WorldWideScience

Sample records for rapidly delivers fentanyl

  1. An anaphylactic reaction to transdermal delivered fentanyl.

    Science.gov (United States)

    Dewachter, P; Lefebvre, D; Kalaboka, S; Bloch-Morot, E

    2009-09-01

    Immediate allergic hypersensitivity reactions with fentanyl are rarely reported. We diagnosed a presumably IgE-mediated allergic hypersensitivity reaction comprising generalized erythema and bronchospasm 4 h after the first-time application of transdermal fentanyl. Prick test remained negative with fentanyl whereas an intradermal test (IDT) with fentanyl was positive (dilution 10(-2)). Cross-reactivity was found with sufentanil but not with remifentanil. The diagnosis was supported by the clinical history and a positive IDT with fentanyl. This case report confirms the need for a systematic allergological investigation in case of immediate hypersensitivity reactions for all drugs and all modes of administration.

  2. Efficacy of rapid-onset oral fentanyl formulations vs. oral morphine for cancer-related breakthrough pain: a meta-analysis of comparative trials.

    Science.gov (United States)

    Jandhyala, Ravi; Fullarton, John R; Bennett, Michael I

    2013-10-01

    Breakthrough cancer pain (BTcP) is widely recognized as a clinically significant complication of chronic cancer pain. With most BTcP episodes peaking in intensity within a few minutes and lasting for approximately 30 minutes, speed of onset is crucial for effective pain management. Although the last decade has seen the development of a number of rapid-onset fentanyl preparations, BTcP is still typically managed by supplemental or rescue doses of the patient's around-the-clock medication, such as oral morphine. Importantly, although the fentanyl preparations, such as fentanyl buccal tablet (FBT), sublingual fentanyl citrate orally disintegrating tablet (ODT), and oral transmucosal fentanyl citrate lozenge (OTFC), have all been proven to be efficacious in clinical studies, oral morphine has never been specifically tested in BTcP, other than as a comparator in studies of OTFC and fentanyl pectin nasal spray. To determine the relative contributions to pain relief from oral morphine and the fentanyl preparations using placebo as a common comparator. Relevant studies were identified by review of the literature and used in a mixed-treatment meta-analysis to indirectly compare fentanyl preparations, morphine, and placebo for the treatment of BTcP. Analysis incorporating the five relevant studies identified revealed that although the fentanyl preparations provide superior pain relief vs. placebo in the first 30 minutes after dosing (FBT provided an 83% probability of superior pain relief, ODT 66%, and OTFC 73% vs. placebo), oral morphine performed little better than placebo (56% probability). This mixed-treatment analysis suggests that FBT, ODT, and OTFC might provide more efficacious treatment options than oral morphine for BTcP. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

  3. Alghedon Fentanyl Transdermal System.

    Science.gov (United States)

    Romualdi, Patrizia; Santi, Patrizia; Candeletti, Sanzio

    2017-04-01

    The efficacy of transdermal fentanyl for cancer pain and chronic non-cancer pain (chronic lower back pain, rheumatoid arthritis, osteoarthritis, neuropathic pain) is well established. Several formulations of fentanyl transdermal systems have been developed to improve the drug delivery and prevent misuse of the active principle. The addition of a rate controlling membrane to the matrix system represented an important advance. The design and functional features of Alghedon patch are compared with other approved generic fentanyl transdermal systems, emphasizing the distinctiveness of Alghedon patch. Alghedon patch has no liquid component in the finished product, therefore no leakage of active ingredient from the system can occur. A rate-controlling membrane provides controlled release of the active substance from the matrix reservoir, ensuring that fentanyl delivery and entry into the microcirculation is not solely controlled by the skin's permeability to this active substance. Alghedon patch contains part of the drug (approximately 15%) in the skin-contact adhesive: this innovative solution allows to overcome a typical drawback of transdermal patches, i.e. the long lag-time before the drug appears in plasma after the first administration, and provides rapid analgesia during the first hours of administration. Alghedon Fentanyl Transdermal System employs materials commonly used in other transdermal applications and having established safety profiles. For each strength level, the fentanyl content - and, thus, the resulting residual fentanyl remaining in the patch after use - is at the lowest end of the range used in commercially available fentanyl patches, minimizing the potential for abuse and misuse.

  4. The history and pharmacology of fentanyl: relevance to a novel, long-acting transdermal fentanyl solution newly approved for use in dogs.

    Science.gov (United States)

    Kukanich, B; Clark, T P

    2012-08-01

    Fentanyl is a potent mu opioid receptor agonist that was discovered to identify an improved human health analgesic over morphine, an opioid frequently associated with histamine-release, bradycardia, hyper- or hypotension, and prolonged postoperative respiratory depression. Historically, the pharmacological features of fentanyl have been described primarily through the study of the human approved fentanyl citrate formulation. In conscious dogs, fentanyl has a wide margin of safety, possesses minimum effects on the cardiovascular and respiratory systems, and is readily reversible. Other pharmacological features include sedation, mild reductions in body temperature, and dose-dependent reduction in food intake. The short duration of effect of available fentanyl citrate solutions has limited its clinical use to perioperative injections or constant rate infusions (CRIs). To extend the analgesic effect, additional fentanyl delivery technologies have been developed for human health including the fentanyl patch that has been used in an extra-label manner in dogs. Beyond the slow onset and variability in fentanyl delivery, several additional disadvantages have precluded common use of patches in dogs. The recent approval of long-acting transdermal fentanyl solution for dogs provides a new approach for sustained delivery of fentanyl for the control of postoperative pain in dogs. It has a rapid onset of action, prolonged duration, and mitigates the disadvantages of oral, parenteral, and patch-delivered opioids. The availability of a safe and effective approved opioid in dogs may allow further optimization of postoperative analgesia in this species. The objective of this review is to summarize the history and pharmacology of fentanyl and to integrate information about the newly approved long-acting transdermal fentanyl solution. © 2012 Blackwell Publishing Ltd.

  5. Contribution of Central μ-Receptors to Switching Pulmonary C-Fibers-Mediated Rapid Shallow Breathing into An Apnea by Fentanyl in Anesthetized Rats

    Science.gov (United States)

    Zhang, Zhenxiong; Zhang, Cancan; Zhuang, Jianguo; Xu, Fadi

    2012-01-01

    Our previous study has shown that activating peripheral μ-receptors is necessary for switching the bronchopulmonary C-fibers (PCFs)-mediated rapid shallow breathing (RSB) into an apnea by systemic administration of fentanyl. The brainstem nuclei, such as the medial nucleus tractus solitarius (mNTS) and the Pre-Botzinger Complex (PBC), are required for completing the PCF-mediated respiratory reflexes. Moreover, these areas contain abundant μ-receptors and their activation prolongs expiratory duration (TE). Thus, we asked if central μ-receptors, especially those in the mNTS and PBC, are involved in fully expressing this RSB-apnea switch by fentanyl. In anesthetized rats, the cardiorespiratory responses to right atrial injection of phenylbiguanide (PBG, 3–6 μg/kg) were repeated after: 1) fentanyl (iv), a μ-receptor agonist, alone (8 μg/kg, iv); 2) fentanyl following microinjection of naloxone methiodide (NXM, an opioid receptor antagonist) into the cisterna magna (10 μg/4 μl); 3) the bilateral mNTS (10 mM, 20 nl); or 4) PBC (10 mM, 20 nl). Our results showed that PBG shortened TE by 37 ± 6 % (RSB, from 0.41 ± 0.05 to 0.26 ± 0.03 s, P fentanyl (iv). Pretreatment with NXM injected into the cisterna magna or the PBC, but not the mNTS, prevented the fentanyl-induced switch. This study, along with our previous results mentioned above, suggests that although peripheral μ-receptors are essential for triggering the fentanyl-induced switch, central μ-receptors, especially those in the PBC, are required to fully exhibit such switch. PMID:22759907

  6. 3-alkyl fentanyl analogues: Structure-activity-relationship study

    OpenAIRE

    Vučković, Sonja; Savić-Vujović, Katarina; Srebro, Dragana; Ivanović, Milovan; Došen-Mićović, Ljiljana; Stojanović, Radan; Prostran, Milica

    2012-01-01

    Introduction. Fentanyl belongs to 4-anilidopiperidine class of synthetic opioid analgesics. It is characterized by high potency, rapid onset and short duration of action. A large number of fentanyl analogues have been synthesized so far, both to establish the structure-activity-relationship (SAR) and to find novel, clinically useful analgesic drugs. Objective. In this study, newly synthesized 3-alkyl fentanyl analogues were examined for analgesic activity and compared with fentanyl. Methods. ...

  7. Deaths Involving Fentanyl, Fentanyl Analogs, and U-47700 - 10 States, July-December 2016.

    Science.gov (United States)

    O'Donnell, Julie K; Halpin, John; Mattson, Christine L; Goldberger, Bruce A; Gladden, R Matthew

    2017-11-03

    Preliminary estimates of U.S. drug overdose deaths exceeded 60,000 in 2016 and were partially driven by a fivefold increase in overdose deaths involving synthetic opioids (excluding methadone), from 3,105 in 2013 to approximately 20,000 in 2016 (1,2). Illicitly manufactured fentanyl, a synthetic opioid 50-100 times more potent than morphine, is primarily responsible for this rapid increase (3,4). In addition, fentanyl analogs such as acetylfentanyl, furanylfentanyl, and carfentanil are being detected increasingly in overdose deaths (5,6) and the illicit opioid drug supply (7). Carfentanil is estimated to be 10,000 times more potent than morphine (8). Estimates of the potency of acetylfentanyl and furanylfentanyl vary but suggest that they are less potent than fentanyl (9). Estimates of relative potency have some uncertainty because illicit fentanyl analog potency has not been evaluated in humans. This report describes opioid overdose deaths during July-December 2016 that tested positive for fentanyl, fentanyl analogs, or U-47700, an illicit synthetic opioid, in 10 states participating in CDC's Enhanced State Opioid Overdose Surveillance (ESOOS) program.* Fentanyl analogs are similar in chemical structure to fentanyl but not routinely detected because specialized toxicology testing is required. Fentanyl was detected in at least half of opioid overdose deaths in seven of 10 states, and 57% of fentanyl-involved deaths also tested positive for other illicit drugs, such as heroin. Fentanyl analogs were present in >10% of opioid overdose deaths in four states, with carfentanil, furanylfentanyl, and acetylfentanyl identified most frequently. Expanded surveillance for opioid overdoses, including testing for fentanyl and fentanyl analogs, assists in tracking the rapidly changing illicit opioid market and informing innovative interventions designed to reduce opioid overdose deaths.

  8. Fentanyl Sublingual Spray

    Science.gov (United States)

    Fentanyl sublingual spray is used to treat breakthrough pain (sudden episodes of pain that occur despite round ... effects of the medication) to narcotic pain medications. Fentanyl is in a class of medications called narcotic ( ...

  9. Fentanyl Transdermal Patch

    Science.gov (United States)

    Fentanyl patches are used to relieve severe pain in people who are expected to need pain medication ... and who cannot be treated with other medications. Fentanyl is in a class of medications called opiate ( ...

  10. Fentanyl Nasal Spray

    Science.gov (United States)

    ... of fentanyl nasal spray out. Remove the protective cap from the bottle tip. Hold the bottle so that the nozzle ... after using fentanyl nasal spray. Replace the protective cap on the bottle and put the bottle back in the child- ...

  11. Nebulized Fentanyl in Acute Pain: A Systematic Review.

    Science.gov (United States)

    Thompson, Joshua P; Thompson, Dennis F

    2016-10-01

    To provide a systematic review of the current role of nebulized fentanyl in acute pain and potentially other conditions. A MEDLINE literature search inclusive of the dates 1946 to May 2016 was performed using the following search terms: fentanyl and administration, inhaled Excerpta Medica was searched from 1980 to May 2016 using the following search terms: exp fentanyl/inhalation drug administration Additionally, Web of Science was searched using the terms fentanyl and pain inclusive of 1945 to May 2016. We utilized the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to select English language, human primary literature, review articles, and supporting data assessing the efficacy of nebulized fentanyl in acute pain. Seven clinical trials have demonstrated no difference in efficacy between nebulized fentanyl and intravenous (IV) opioids. Few adverse effects were reported; however, the trials were of short duration. Nebulized fentanyl appeared to be a rapid-acting analgesic that does not require IV access. Evidence suggests that nebulized fentanyl is as effective as IV opioids in the treatment of acute pain, with relatively few adverse effects. However, questions remain about the extemporaneous preparation of fentanyl nebulized solution, the variability in nebulization devices, and ensuring consistent drug delivery to distal airways in the clinical setting. The abuse potential of nebulized fentanyl should also be considered. © The Author(s) 2016.

  12. Efficacy and safety of fentanyl buccal for cancer pain management by administration through a soluble film: an update

    Directory of Open Access Journals (Sweden)

    Marvin Omar Delgado-Guay

    2010-11-01

    Full Text Available Marvin Omar Delgado-GuayDivision of Geriatrics and Palliative Medicine, The University of Texas, Medical School at Houston, Houston, TX, USAAbstract: More than half of patients receiving prescription medicine for cancer pain have been reported to experience inadequate pain relief or breakthrough pain. Buccal administration can deliver lipophilic opioids rapidly to the systemic circulation through the buccal mucosa, limiting gastrointestinal motility and first-pass metabolism. This review updates the safety and efficacy of fentanyl buccal soluble film (FBSF in patients with cancer pain. Literature was identified through searches of Medline (PubMed. Search terms included combinations of the following: cancer pain, fentanyl, fentanyl buccal soluble film, pharmacology, kinetics, safety, efficacy and toxicity. FBSF is an oral transmucosal form of fentanyl citrate developed as a treatment of breakthrough pain in opioid-tolerant patients with cancer. Studies have shown that it is well tolerated in the oral cavity, with adequate bioavailability and safety in cancer patients. Further studies are warranted to evaluate, in comparison with other short-acting opioids, its efficacy in the management of breakthrough cancer pain, its addictive potential and its economic impact in cancer patients.Keywords: fentanyl buccal soluble film, cancer pain

  13. Fentanyl Formulations in the Management of Pain: An Update.

    Science.gov (United States)

    Schug, Stephan A; Ting, Sonya

    2017-05-01

    Fentanyl is a synthetic, highly selective opioid with many desirable physicochemical properties, including a high lipophilicity and predictable pharmacokinetics. These properties have an established record in the management of pain in a variety of settings, particularly acute pain and breakthrough cancer pain. Fentanyl was initially developed for parenteral use; however, this is invasive and impractical in the outpatient setting. Unfortunately, the high first-pass metabolism of fentanyl makes oral formulations unfeasible. However, its high lipophilicity allows fentanyl to be absorbed via a number of other routes. Thus new formulations were designed to allow non-invasive methods of administration. Transmucosal and transdermal fentanyl formulations are well established, and have proven useful in the settings of breakthrough cancer pain, emergencies and in the paediatric population. The iontophoretic transdermal system was developed to provide a needle-free system of delivering bolus doses of fentanyl on demand, a novel way of delivering patient-controlled opioid analgesia. Transpulmonary administration of fentanyl remains experimental. The aim of this review is to provide an update on current non-parenteral fentanyl formulations, with attention to their particular pharmacokinetics and features relevant to clinical use in pain management.

  14. Opioid Basics: Fentanyl

    Science.gov (United States)

    ... without the user’s knowledge—to increase its euphoric effects. Learn More: Fentanyl Data The Problem Illicitly-made fentanyl use is on the ... other drug users, 9 or family and friend bystanders who have obtained the medication. 10 Health Care Providers: Multiple doses of ...

  15. A retrospective analysis of nebulized versus intravenous fentanyl for renal colic.

    Science.gov (United States)

    Imamoglu, Melih; Aygun, Ali; Bekar, Omer; Erdem, Erkan; Cicek, Mustafa; Tatli, Ozgur; Karaca, Yunus; Sahin, Aynur; Turkmen, Suha; Turedi, Suleyman

    2017-05-01

    To assess the effectiveness of nebulized fentanyl used for analgesia in renal colic. This research was planned as a randomized, blinded study in which prospectively collected data were analyzed retrospectively to compare nebulized and intravenous (iv) fentanyl therapies. Patients with renal colic with 'moderate' or worse pain on a four-point verbal pain score (VPS) or with pain of 20mm or above on a 100-mm visual analogue score (VAS) at time of presentation were randomized into iv fentanyl (n=62) or nebulized fentanyl (n=53) study groups. Decreases in VAS and VPS scores at 15 and 30min compared to baseline, rescue analgesia requirements and side-effects between the groups were compared. Both iv fentanyl and nebulized fentanyl provided effective analgesia in renal colic patients at the end of 30min. However, iv fentanyl provided more rapid and more effective analgesia than nebulized fentanyl. Patients receiving iv fentanyl had lower rescue analgesia requirements than those receiving nebulized fentanyl (37.1% vs 54.7%), although the difference was not statistically significant (p=0.058). In addition, side-effects were more common in the iv fentanyl group compared to the nebulized fentanyl group (22.1% vs 9.4%), although the difference was also not significant (p=0.058). Nebulized fentanyl provides effective analgesia in patients with renal colic. However, iv fentanyl exhibits more rapid and more powerful analgesic effects than nebulized fentanyl. Nonetheless, due to its ease of use and few potential risks and side-effects the nebulized form can be used as an alternative in renal colic. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Clinical Pharmacology of Fentanyl in Preterm Infants. A Review

    Directory of Open Access Journals (Sweden)

    Gian Maria Pacifici

    2015-06-01

    Full Text Available Fentanyl is a synthetic opioid that is very important in anesthetic practice because of its relatively short time to peak analgesic effect and the rapid termination of action after small bolus doses. The objective of this survey is to review the clinical pharmacology of fentanyl in preterm infants. The bibliographic search was performed using PubMed and EMBASE databases as search engines. In addition, the books Neofax: A manual of drugs used in neonatal care and Neonatal formulary were consulted. Fentanyl is N-dealkylated by CYP3A4 into the inactive norfentanyl. Fentanyl may be administered as bolus doses or as a continuous infusion. In neonates, there is a remarkable interindividual variability in the kinetic parameters. In neonates, fentanyl half-life ranges from 317 minutes to 1266 minutes and in adults it is 222 minutes. Respiratory depression occurs when fentanyl doses are >5 μg/kg. Chest wall rigidity may occur in neonates and occasionally is associated with laryngospasm. Tolerance to fentanyl may develop after prolonged use of this drug. Significant withdrawal symptoms have been reported in infants treated with continuous infusion for 5 days or longer. Fentanyl is an extremely potent analgesic and is the opioid analgesic most frequently used in the neonatal intensive care unit.

  17. A review: Fentanyl and non-pharmaceutical fentanyls.

    Science.gov (United States)

    Suzuki, Joji; El-Haddad, Saria

    2017-02-01

    Fentanyl and non-pharmaceutical fentanyls (NPFs) have been responsible for numerous outbreaks of overdoses all over the United States since the 1970s. However, there has been a growing concern in recent years that NPFs are contributing to an alarming rise in the number of opioid-related overdoses. The authors conducted a narrative review of the published and grey literature on fentanyl and NPFs in PubMed, Google Scholar, and Google using the following search terms: "fentanyl", "non-pharmaceutical fentanyl", "fentanyl analogs", "fentanyl laced heroin" and "fentanyl overdose". References from relevant publications and grey literature were also reviewed to identify additional citations for inclusion. The article reviews the emergence and misuse of fentanyl and NPFs, their clinical pharmacology, and the clinical management and prevention of fentanyl-related overdoses. Fentanyl and NPFs may be contributing to the recent rise in overdose deaths in the United States. There is an urgent need to educate clinicians, researchers, and patients about this public health threat. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Fentanyl Buccal Soluble Film: A Review in Breakthrough Cancer Pain.

    Science.gov (United States)

    Garnock-Jones, Karly P

    2016-05-01

    Fentanyl buccal soluble film (Onsolis(®), Breakyl(®), Painkyl™) comprises two layers: a mucoadhesive layer containing the active drug, and an inactive layer with the aim of preventing the diffusion of fentanyl into the oral cavity. It is approved in several countries worldwide, including the USA and those of the EU, for the management of breakthrough cancer pain in opioid-tolerant, adult patients with cancer. This article reviews the pharmacological properties of fentanyl buccal soluble film and its clinical efficacy and tolerability in these patients. Fentanyl buccal soluble film provides an additional option for transmucosal delivery of fentanyl, with approximately half of the dose undergoing an initial, rapid absorption via the buccal mucosa (accounting for its high bioavailability). In clinical trials, fentanyl buccal soluble film was associated with significant improvements in pain intensity scores versus placebo and was generally well tolerated. The most common adverse events were typical opioid-associated adverse events, such as nausea and vomiting. Fentanyl buccal soluble film is a useful option for the treatment of breakthrough cancer pain in opioid-tolerant patients.

  19. The fentanyl family: A distinguished medical history tainted by abuse.

    Science.gov (United States)

    Raffa, R B; Pergolizzi, J V; LeQuang, J A; Taylor, R; Colucci, S; Annabi, M H

    2018-02-01

    Beginning in the 1950s, a family of potent opioids was synthesized and developed (fentanyl and analogues). They continue to serve as valuable analgesic agents. But the recent spike and notoriety of their abuse has raised alarm, even calls for tighter control. We review the trajectory of these compounds. To rectify shortcomings of the then available opioid analgesics, an analogue family of compounds was synthesized having a piperidine ring (presumptive principal active moiety in morphine and meperidine). The result was more potent and rapid-acting compounds, including alfentanil, carfentanil, fentanyl, sufentanil and others. These properties, plus availability in formulations for multiple routes of administration, impart broad therapeutic utility. They also unfortunately favour abuse. The abuse of fentanyl and its analogues (legal and illicit) serves as a case study for the dilemma and difficulties balancing a medical need against psychosocial realities. The fentanyl family provides relief for severe pain, but their very properties also engender abuse. © 2017 John Wiley & Sons Ltd.

  20. Asphyxiation with a Fentanyl Patch

    Directory of Open Access Journals (Sweden)

    Aaron S. Mansfield

    2013-05-01

    Full Text Available Narcotics are frequently prescribed to alleviate pain in patients with serious medical illnesses such as cancer. Because of their nonoral route of administration, fentanyl patches are now being frequently prescribed. However, the widespread use of fentanyl patches has been associated with medication errors and misuse [Butts and Jatoi: J Opioid Manag 2011;7:35-45]. The transdermal delivery of fentanyl may lead to unusual, unanticipated complications. Herein, we describe a fentanyl patch complication, which, to our knowledge, has not been previously reported.

  1. Fatty acids are rapidly delivered to and extracted from membranes by methyl-beta-cyclodextrin.

    Science.gov (United States)

    Brunaldi, Kellen; Huang, Nasi; Hamilton, James A

    2010-01-01

    We performed detailed biophysical studies of transfer of long-chain fatty acids (FAs) from methyl-beta-CD (MBCD) to model membranes (egg-PC vesicles) and cells and the extraction of FA from membranes by MBCD. We used i) fluorescein phosphatidylethanolamine to detect transfer of FA anions arriving in the outer membrane leaflet; ii) entrapped pH dyes to measure pH changes after FA diffusion (flip-flop) across the lipid bilayer; and iii) soluble fluorescent-labeled FA binding protein to measure the concentration of unbound FA in water. FA dissociated from MBCD, bound to the membrane, and underwent flip-flop within milliseconds. In the presence of vesicles, MBCD maintained the aqueous concentration of unbound FA at low levels comparable to those measured with albumin. In studies with cells, addition of oleic acid (OA) complexed with MBCD yielded rapid (seconds) dose-dependent OA transport into 3T3-L1 preadipocytes and HepG2 cells. MBCD extracted OA from cells and model membranes rapidly at concentrations exceeding those required for OA delivery but much lower than concentrations commonly used for extracting cholesterol. Compared with albumin, MBCD can transfer its entire FA load and is less likely to extract cell nutrients and to introduce impurities.

  2. Characteristics of Fentanyl Overdose - Massachusetts, 2014-2016.

    Science.gov (United States)

    Somerville, Nicholas J; O'Donnell, Julie; Gladden, R Matthew; Zibbell, Jon E; Green, Traci C; Younkin, Morgan; Ruiz, Sarah; Babakhanlou-Chase, Hermik; Chan, Miranda; Callis, Barry P; Kuramoto-Crawford, Janet; Nields, Henry M; Walley, Alexander Y

    2017-04-14

    Opioid overdose deaths in Massachusetts increased 150% from 2012 to 2015 (1). The proportion of opioid overdose deaths in the state involving fentanyl, a synthetic, short-acting opioid with 50-100 times the potency of morphine, increased from 32% during 2013-2014 to 74% in the first half of 2016 (1-3). In April 2015, the Drug Enforcement Agency (DEA) and CDC reported an increase in law enforcement fentanyl seizures in Massachusetts, much of which was believed to be illicitly manufactured fentanyl (IMF) (4). To guide overdose prevention and response activities, in April 2016, the Massachusetts Department of Public Health and the Office of the Chief Medical Examiner collaborated with CDC to investigate the characteristics of fentanyl overdose in three Massachusetts counties with high opioid overdose death rates. In these counties, medical examiner charts of opioid overdose decedents who died during October 1, 2014-March 31, 2015 were reviewed, and during April 2016, interviews were conducted with persons who used illicit opioids and witnessed or experienced an opioid overdose. Approximately two thirds of opioid overdose decedents tested positive for fentanyl on postmortem toxicology. Evidence for rapid progression of fentanyl overdose was common among both fatal and nonfatal overdoses. A majority of interview respondents reported successfully using multiple doses of naloxone, the antidote to opioid overdose, to reverse suspected fentanyl overdoses. Expanding and enhancing existing opioid overdose education and prevention programs to include fentanyl-specific messaging and practices could help public health authorities mitigate adverse effects associated with overdoses, especially in communities affected by IMF.

  3. Topically applied methotrexate is rapidly delivered into skin by fractional laser ablation

    DEFF Research Database (Denmark)

    Taudorf, Elisabeth Hjardem; Lerche, Catharina; Vissing, Anne-Cathrine

    2015-01-01

    /v%) was measured from 0.25 to 24 h through AFXL-processed and intact porcine skin in Franz Cells (n = 46). A 2,940 nm fractional Erbium Yttrium Aluminium Garnet laser generated mid-dermal microchannels at 2.4% density, and 256 mJ/microchannel. HPLC quantified MTX-concentrations in extracts from mid-dermal skin...... sections, donor and receiver compartments. Fluorescence microscopy of UVC-activated MTX-fluorescence and desorption electro-spray ionization mass spectrometry imaging (DESI-MSI) evaluated MTX biodistribution. Results: AFXL-processed skin facilitated rapid MTX delivery through cone-shaped microchannels...... of 690 µm ablation depth, lined by the 47 µm thermal coagulation zone (CZ). Quantitatively, MTX was detectable by HPLC in mid-dermis after 15 min, significantly exceeded deposition in intact skin after 1.5 h, and saturated skin after 7 h at a 10-fold increased MTX-deposition versus intact skin (3.08 vs 0...

  4. Safety of fentanyl initiation according to past opioid exposure among patients newly prescribed fentanyl patches

    National Research Council Canada - National Science Library

    Friesen, Kevin J; Woelk, Cornelius; Bugden, Shawn

    2016-01-01

    Although a convenient opioid delivery system, transdermal fentanyl patches have caused several deaths and resulted in safety warnings reminding prescribers that fentanyl patches should be prescribed...

  5. Molecular modeling of fentanyl analogs

    Directory of Open Access Journals (Sweden)

    LJILJANA DOSEN-MICOVIC

    2004-11-01

    Full Text Available Fentanyl is a highly potent and clinically widely used narcotic analgesic. A large number of its analogs have been synthesized, some of which (sufentanil and alfentanyl are also in clinical use. Theoretical studies, in recent years, afforded a better understanding of the structure-activity relationships of this class of opiates and allowed insight into the molecular mechanism of the interactions of fentanyl analogs with their receptors. An overview of the current computational techniques for modeling fentanyl analogs, their receptors and ligand-receptor interactions is presented in this paper.

  6. Fentanyl Patch Can Be Deadly to Children

    Science.gov (United States)

    ... Products For Consumers Home For Consumers Consumer Updates Fentanyl Patch Can Be Deadly to Children Share Tweet ... from accidental exposure to a skin patch containing fentanyl, a powerful pain reliever. As a result of ...

  7. Enhanced Analgesic Responses After Preferential Delivery of Morphine and Fentanyl to the Olfactory Epithelium in Rats

    Science.gov (United States)

    Hoekman, John D.; Ho, Rodney J.Y.

    2011-01-01

    Background Centrally acting opioid analgesics such as morphine and fentanyl are effective, but their efficacy is often limited by a delayed response or side effects resulting from systemic first-pass before reaching the brain and the central nervous system (CNS). It is generally accepted that drugs applied to the nasal cavity can directly access the brain and the CNS, which could provide therapeutic advantages such as rapid onset and lower systemic exposure. The olfactory region of the nasal cavity has been implicated in facilitating this direct nose-to-CNS transfer. If the fraction of opioid administered to the olfactory region could be improved, there could be a larger fraction of drug directly delivered to the CNS, mediating greater therapeutic benefit. Methods We have developed a pressurized olfactory delivery (POD) device to consistently and non-invasively deposit a majority of drug on the olfactory region of the nasal cavity in Sprague-Dawley rats. Using the tail-flick latency test and analysis of plasma and CNS tissue drug exposure, we compared distribution and efficacy of the opioids morphine and fentanyl administered to the nasal olfactory region with the POD device or the nasal respiratory region with nose drops or systemically via intraperitoneal (IP) injection. Results Compared to nose drop, POD administration of morphine resulted in significantly higher overall therapeutic effect (AUCeffect) without a significant increase in plasma drug exposure (AUCplasma). POD delivery of morphine resulted in a nose-to-CNS direct transport percentage of 38–55%. POD delivery of fentanyl led to a faster (5 min vs. 10 min) and more intense analgesic effect compared to nasal respiratory administration. Unlike IP injection or nose drop administration, both morphine and fentanyl given by the POD device to olfactory nasal epithelium exhibited clockwise [plasma] versus effect hysteresis after nasal POD administration, consistent with direct nose-to-CNS drug transport

  8. Anesthesia with Intraperitoneal Propofol, Medetomidine, and Fentanyl in Rats

    Science.gov (United States)

    Alves, Heber Nuno Castro; da Silva, Aura Luísa Maia; Olsson, Ingrid Anna S; Orden, José Manuel Gonzalo; Antunes, Luis Marques

    2010-01-01

    A safe and reliable method for anesthetizing rats has long been a leading concern of biomedical researchers. We recently found that the intraperitoneal administration of propofol combined with medetomidine and fentanyl is safe for mouse anesthesia. Here we studied whether the same combination could be used for general anesthesia in rats. We used male Wistar rats to test 10 combinations of propofol, medetomidine, and fentanyl administered intraperitoneally and reversed with intraperitoneal atipamezole 30 min after induction. The depth of anesthesia, induction time, loss of pedal withdrawal reflex, pulse rate, and respiratory rate were evaluated, along with the duration and quality of induction, surgical anesthesia, and recovery. The combination of propofol and medetomidine provided a predictable induction and sufficient hypnosis and muscle relaxation, but surgical anesthesia (loss of pedal withdrawal reflex) was difficult to achieve with this protocol. The addition of fentanyl increased analgesia, making it possible to achieve surgical anesthesia. In conclusion, combination of propofol (100 mg/kg), medetomidine (0.1 mg/kg), and fentanyl (0.1 mg/kg) is a safe and practical technique for intraperitoneal anesthesia in rats, providing a surgical window of 25 min and restraint for 30 min, with rapid recovery after administration of atipamezole. PMID:20819392

  9. Heroin uncertainties: Exploring users' perceptions of fentanyl-adulterated and -substituted 'heroin'.

    Science.gov (United States)

    Ciccarone, Daniel; Ondocsin, Jeff; Mars, Sarah G

    2017-08-01

    The US is experiencing an unprecedented opioid overdose epidemic fostered in recent years by regional contamination of the heroin supply with the fentanyl family of synthetic opioids. Since 2011 opioid-related overdose deaths in the East Coast state of Massachusetts have more than tripled, with 75% of the 1374 deaths with an available toxicology positive for fentanyl. Fentanyl is 30-50X more potent than heroin and its presence makes heroin use more unpredictable. A rapid ethnographic assessment was undertaken to understand the perceptions and experiences of people who inject drugs sold as 'heroin' and to observe the drugs and their use. A team of ethnographers conducted research in northeast Massachusetts and Nashua, New Hampshire in June 2016, performing (n=38) qualitative interviews with persons who use heroin. (1) The composition and appearance of heroin changed in the last four years; (2) heroin is cheaper and more widely available than before; and (3) heroin 'types' have proliferated with several products being sold as 'heroin'. These consisted of two types of heroin (alone), fentanyl (alone), and heroin-fentanyl combinations. In the absence of available toxicological information on retail-level heroin, our research noted a hierarchy of fentanyl discernment methods, with embodied effects considered most reliable in determining fentanyl's presence, followed by taste, solution appearance and powder color. This paper presents a new 'heroin' typology based on users' reports. Massachusetts' heroin has new appearances and is widely adulterated by fentanyl. Persons who use heroin are trying to discern the substances sold as heroin and their preferences for each form vary. The heroin typology presented is inexact but can be validated by correlating users' discernment with drug toxicological testing. If validated, this typology would be a valuable harm reduction tool. Further research on adaptations to heroin adulteration could reduce risks of using heroin and

  10. A Review of Transbuccal Fentanyl Use in the Emergency Department

    Directory of Open Access Journals (Sweden)

    Annette O. Arthur

    2012-01-01

    Full Text Available Patients with severe, painful injuries and illnesses treated in the emergency department are commonly administered opioid medications. Intravenous administration provides the most rapid onset of pain relief and is readily titrated. Fentanyl, administered intravenously, is well documented as an effective medication for pain management in the emergency department. It is preferred in many settings due to its minimal hemodynamic effects, as compared to other commonly used opioids. However, not all patients require intravenous access. These patients are given orally administered pain medications. The oral route is effective at minimizing pain but has a much slower onset of action when compared to the intravenous route. As an alternative to the slower onset of action seen with oral opioids, this paper discusses the use of fentanyl buccal tablet for pain management in the emergency department. Fentanyl buccal tablets are readily absorbed, with a bioavailability of approximately 65%, and have a more rapid onset of action than achieved with traditional oral opioids used in the emergency department.

  11. Differential development of antinociceptive tolerance to morphine and fentanyl is not linked to efficacy in the ventrolateral periaqueductal gray of the rat

    Science.gov (United States)

    Bobeck, Erin N.; Haseman, Rachel A.; Hong, Dana; Ingram, Susan L.; Morgan, Michael M.

    2012-01-01

    Systemic administration of morphine typically produces greater tolerance than higher efficacy mu-opioid receptor (MOPr) agonists, such as fentanyl. The objective of the present study was to test this relationship by measuring antinociceptive efficacy and tolerance to morphine and fentanyl microinjected into the ventrolateral periaqueductal gray (vlPAG). MOPr agonist efficacy was evaluated by microinjecting the irreversible opioid receptor antagonist β-funaltrexamine hydrochloride (β-FNA) into the vlPAG prior to a dose-response analysis of morphine and fentanyl antinociception. In contrast to systemic administration of morphine and fentanyl, microinjection of these drugs into the vlPAG had similar efficacy as measured by similar reductions in maximal antinociception following β-FNA administration. Analysis of tolerance revealed a rightward shift in the dose-response curve to a single pretreatment with morphine, but not fentanyl. Moreover, the magnitude of tolerance to morphine was comparable following one, four, or eight pretreatments. Tolerance to fentanyl also was evident following four or eight microinjections. These data are surprising in that antinociceptive efficacy appears to vary depending on the site of administration. Moreover, the similar efficacy following microinjection of morphine and fentanyl into the vlPAG was associated with comparable tolerance, with the one exception of no tolerance to acute administration of fentanyl. Perspective These data reveal that antinociceptive tolerance following vlPAG administration of opioids develops rapidly, is evident with both morphine and fentanyl, and the magnitude is relatively consistent regardless of the number of pretreatments. PMID:22766006

  12. Acceptability of using electronic vending machines to deliver oral rapid HIV self-testing kits: a qualitative study.

    Directory of Open Access Journals (Sweden)

    Sean D Young

    Full Text Available Rates of unrecognized HIV infection are significantly higher among Latino and Black men who have sex with men (MSM. Policy makers have proposed that HIV self-testing kits and new methods for delivering self-testing could improve testing uptake among minority MSM. This study sought to conduct qualitative assessments with MSM of color to determine the acceptability of using electronic vending machines to dispense HIV self-testing kits.African American and Latino MSM were recruited using a participant pool from an existing HIV prevention trial on Facebook. If participants expressed interest in using a vending machine to receive an HIV self-testing kit, they were emailed a 4-digit personal identification number (PIN code to retrieve the test from the machine. We followed up with those who had tested to assess their willingness to participate in an interview about their experience.Twelve kits were dispensed and 8 interviews were conducted. In general, participants expressed that the vending machine was an acceptable HIV test delivery method due to its novelty and convenience.Acceptability of this delivery model for HIV testing kits was closely associated with three main factors: credibility, confidentiality, and convenience. Future research is needed to address issues, such as user-induced errors and costs, before scaling up the dispensing method.

  13. Acceptability of using electronic vending machines to deliver oral rapid HIV self-testing kits: a qualitative study.

    Science.gov (United States)

    Young, Sean D; Daniels, Joseph; Chiu, ChingChe J; Bolan, Robert K; Flynn, Risa P; Kwok, Justin; Klausner, Jeffrey D

    2014-01-01

    Rates of unrecognized HIV infection are significantly higher among Latino and Black men who have sex with men (MSM). Policy makers have proposed that HIV self-testing kits and new methods for delivering self-testing could improve testing uptake among minority MSM. This study sought to conduct qualitative assessments with MSM of color to determine the acceptability of using electronic vending machines to dispense HIV self-testing kits. African American and Latino MSM were recruited using a participant pool from an existing HIV prevention trial on Facebook. If participants expressed interest in using a vending machine to receive an HIV self-testing kit, they were emailed a 4-digit personal identification number (PIN) code to retrieve the test from the machine. We followed up with those who had tested to assess their willingness to participate in an interview about their experience. Twelve kits were dispensed and 8 interviews were conducted. In general, participants expressed that the vending machine was an acceptable HIV test delivery method due to its novelty and convenience. Acceptability of this delivery model for HIV testing kits was closely associated with three main factors: credibility, confidentiality, and convenience. Future research is needed to address issues, such as user-induced errors and costs, before scaling up the dispensing method.

  14. 21 CFR 522.800 - Droperidol and fentanyl citrate injection.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Droperidol and fentanyl citrate injection. 522.800... § 522.800 Droperidol and fentanyl citrate injection. (a) Specifications. Droperidol and fentanyl citrate injection is a sterile solution containing 20 milligrams of droperidol and 0.4 milligram of fentanyl citrate...

  15. Acetyl Fentanyl Toxicity: Two Case Reports.

    Science.gov (United States)

    Fort, Chelsea; Curtis, Byron; Nichols, Clay; Niblo, Cheryl

    2016-11-01

    Acetyl fentanyl is an illicit fentanyl analog recently appearing in forensic casework. A quantitative method was created for measuring acetyl fentanyl in various biological matrices acquired post-mortem due to recent positive screening results in casework. Initial detection by immunoassay and standard gas chromatography mass spectrometry (GC/MS) methods have been previously reported for acetyl fentanyl and are examined further here. A Selective Ion Monitoring (SIM) method was created using a GC/MS for quantitation. In two separate cases, acetyl fentanyl was found to be in similar concentrations to those previously reported and ruled to be the cause of death. Acetyl fentanyl concentrations were determined in blood samples, liver, brain, vitreous humor, and urine. Individual 1 had acetyl fentanyl concentrations as follows: heart blood-285 ng/mL, femoral blood-192 ng/mL, liver-1,100 ng/g, brain-620 ng/g, and urine-3,420 ng/mL. Individual 2 had acetyl fentanyl concentrations as follows: heart blood-210 ng/mL, femoral blood-255 ng/mL, urine-2,720 ng/mL and vitreous humor-140 ng/mL. Experimental conditions for screening and quantitation are provided, using immunoassay and GC/MS methods. Due to the recent emergence of acetyl fentanyl, more data will need to be generated to fully differentiate recreational and fatal concentrations of acetyl fentanyl to assist toxicologists accurately understanding its physiological impact. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Characterizing fentanyl use in methadone-maintained clients.

    Science.gov (United States)

    Arfken, Cynthia L; Suchanek, Jessica; Greenwald, Mark K

    2017-04-01

    Deaths attributed to fentanyl have increased in the United States. However, little is known about fentanyl use among substance abuse treatment clients. To fill this gap, we assessed prevalence of fentanyl exposure, characteristics of clients testing positive for fentanyl, other substances detected concurrently or simultaneously with fentanyl, and clients' perception of how many people are actively seeking to use fentanyl. A retrospective chart review was conducted of all clients at one methadone maintenance treatment clinic between January 2015 and May 2016 in Wayne County, Michigan. Urine drug screens (UDS) including fentanyl (and its metabolite norfentanyl) were conducted clinically. To obtain additional data, 113 clients in this clinic subsequently completed an anonymous survey. Of 368 unique clients with UDS, 38.0% had at least one and 26.1% had ≥2 fentanyl-positive UDS results. None had a fentanyl prescription. Clients ever testing positive for fentanyl were significantly (pFentanyl-positive UDS results coincided most commonly with metabolites of cocaine- and heroin-positive UDS results. Of the anonymously surveyed clients, most (67.3%) reported they did not know anyone seeking fentanyl, a proportion significantly higher than for heroin, cocaine, alprazolam, hydrocodone and morphine. Fentanyl was commonly detected during this period with some clients having multiple fentanyl-positive UDS. Most clients did not know anyone seeking to obtain fentanyl. Regardless, the high exposure underscores that naloxone training and distribution is needed. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Stability of Fentanyl Citrate in Polyolefin Bags.

    Science.gov (United States)

    Donnelly, Ronald F

    2016-01-01

    Fentanyl is used to manage pain because it is a potent lipophilic opiate agonist. The stability of fentanyl in polyolefin bags when diluted to either 10 µg/mL or 50 µg/mL with sodium chloride 0.9% has not been studied. The chemical stability of fentanyl 50 µg/mL packaged in polyvinyl chloride bags has been studied, however, the stability in polyolefin bags is lacking. Polyolefin bags were aseptically filled with either 10-µg/mL or 50-µg/mL fentanyl solution. Containers were then stored at either 5°C and protected from light or 22°C and exposed to light for 93 days. Fentanyl peaks were monitored using a stability-indicatin high-performance liquid chromatographic method. Changes to color, clarity, and pH were also monitored. There were no signs of chemical degradation of fentanyl packaged in polyolefin bags at either 5°C or 22°C after storage for 93 days. Over the course of the study, all solutions remained colorless and clear. The pH showed a slight decrease during the 93 days of storage. The stability of both undiluted (50-µg/mL) and diluted (10-µg/mL) fentanyl solutions when packaged in polyolefin bags was 93 days when stored at either 5°C or 22°C. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

  18. A new transmucosal drug delivery system for patients with breakthrough cancer pain: the fentanyl effervescent buccal tablet

    Science.gov (United States)

    Freye, Enno

    2009-01-01

    Breakthrough pain, a transitory severe pain with the background of otherwise controlled persistent pain has a prevalence between 52% and 67% in outpatients with cancer. Medications for such sudden-onset pain require non-invasive delivery of a potent and short-acting opioid for rapid pain relief. Although oral transmucosal delivery of fentanyl citrate (OTFC) has been shown to provide better pain relief than a typical oral opioid administration such as morphine sulfate immediate release (MSIR) in the management of breakthrough pain in patients with cancer-related pain, newer delivery systems offer a potential for further enhancement of pain relief. The fentanyl effervescent buccal tablet (FBT) formulation employs a novel drug delivery system that relies on an effervescence reaction to improve buccal fentanyl absorption. Using the effervescence reaction results in the production and dissipation of carbon dioxide with a dynamic shift in pH as the tablet dissolves. The induced low pH favors dissolution of fentanyl citrate in saliva (higher water solubility). The subsequent increase in pH thereafter favors the buccal absorption of non-ionized fentanyl across the buccal mucosa. Such a pH “pumping” mechanism increases the permeation of fentanyl into and through the buccal to the vascular system from where the agent is transported to the specific opioid receptor sites in the CNS. Compared with OTFC, data in healthy volunteers show that the effervescence reaction employed in FBT increases the total amount and the speed of absorption of fentanyl being absorbed. Compared with OTFC there is an increase in peak fentanyl blood concentrations, and an enhancement of the amount of buccal delivery of fentanyl. Such favorable data are underlined by the results of clinical studies where the FBT technology was studied in patients with breakthrough pain in chronic malignant pathologies. PMID:21197291

  19. Use of Fentanyl in Adolescents with Clinically Severe Obesity Undergoing Bariatric Surgery: A Pilot Study.

    Science.gov (United States)

    Vaughns, Janelle D; Ziesenitz, Victoria C; Williams, Elaine F; Mushtaq, Alvina; Bachmann, Ricarda; Skopp, Gisela; Weiss, Johanna; Mikus, Gerd; van den Anker, Johannes N

    2017-06-01

    The number of obese pediatric patients requiring anesthesia is rapidly increasing. Although fentanyl is a commonly used narcotic during surgery, there are no pharmacokinetic (PK) data available for optimal dosing of fentanyl in adolescents with clinically severe obesity. An institutional review board-approved exploratory pilot study was conducted in six adolescents aged 14-19 years undergoing bariatric surgery. Mean total body weight (TBW) and mean BMI were 137.4 ± 14.3 kg and 49.6 ± 6.4 kg/m2 (99.5th BMI percentile), respectively. Fentanyl was administered intravenously for intraoperative analgesia based on ideal body weight per standard of care. PK blood samples were drawn over a 24-h post-dose period. Fentanyl PK parameters were calculated by non-compartmental analysis. Mean fentanyl AUC0-∞ was 1.5 ± 0.5 h·ng/mL. Systemic clearance of fentanyl was 1522 ± 310 mL/min and 11.2 ± 2.6 mL/min·kg TBW. Volume of distribution was 635 ± 282 L and 4.7 ± 2.1 L/kg TBW. While absolute clearance was increased, absolute volume of distribution was comparable to previously established adult values. These results suggest that fentanyl clearance is enhanced in adolescents with clinically severe obesity while volume of distribution is comparable to previously published studies. NCT01955993 (clinicaltrials.gov).

  20. Trends in fentanyl prescriptions and fentanyl-related mortality in Australia.

    Science.gov (United States)

    Roxburgh, Amanda; Burns, Lucy; Drummer, Olaf H; Pilgrim, Jennifer; Farrell, Michael; Degenhardt, Louisa

    2013-05-01

    The study aims to quantify trends in fentanyl prescribing and fentanyl mortality in Australia within the context of concern among health professionals concerning increasing accessibility of fentanyl, and the harms that may arise as a result. This paper presents data on prescribing patterns of fentanyl by 10 year age group adjusted by population rate, detailed analyses of fentanyl-related deaths from the National Coronial Information System and deaths adjusted for prescribing levels within Australia. Fentany prescriptions have increased and are most prevalent among Australians aged over 80 years. One hundred and thirty-six fentanyl-related deaths were recorded during 2000-2011; 54% of decedents had a history of injecting drug use and, among this group, 95% had injected fentanyl at the time of death; 62% of deaths recorded misuse (most notably injection) of fentanyl; 50% recorded a history of drug dependence and 40% a mental health problem; 37% recorded a history of chronic pain; and 36% recorded fentanyl as being prescribed at the time of death. Deaths were primarily among Australians under 47 years of age. There have been significant increases in fentanyl prescribing in Australia. It is unclear what proportion of this increase represents legitimate treatment of pain. Fentanyl deaths have also increased, although mortality is currently low in Australia. A large proportion of the deaths involved the injection of diverted fentanyl, highlighting the need for messages regarding safer injecting practices targeting people who inject drugs, and strategies to minimise the risks of diversion. © 2013 Australasian Professional Society on Alcohol and other Drugs.

  1. Postmortem Toxicology Findings of Acetyl Fentanyl, Fentanyl, and Morphine in Heroin Fatalities in Tampa, Florida

    OpenAIRE

    Pearson, Julia; Poklis, Justin; Poklis, Alphonse; Wolf, Carl; Mainland, Mary; Hair, Laura; Devers, Kelly; Chrostowski, Leszek; Arbefeville, Elise; Merves, Michele

    2015-01-01

    In the last two years, an epidemic of 40 fatal heroin overdose cases has occurred in the Tampa area of Florida. Of these cases, 14 involved fentanyl and acetyl fentanyl. Victim demographics, case histories, toxicology findings, and causes and manners of death for all 40 deaths are presented. In 26 deaths in which acetyl fentanyl or fentanyl were not involved, free and total peripheral blood morphine concentrations were consistent with fatal heroin intoxications, averaging 0.16 mg/L and 0.35 m...

  2. Fentanyl

    Science.gov (United States)

    ... least 16 years of age if taking Actiq brand lozenges) who are taking regularly scheduled doses of ... hearing voices that do not exist), fever, sweating, confusion, fast heartbeat, shivering, severe muscle stiffness or twitching, ...

  3. Fentanyl

    Science.gov (United States)

    ... Guideline for Opioid Prescribing for Pain. ( March 2017 ) Naloxone for Opioid Overdose: Life-Saving Science This brief fact sheet provides ... Guideline for Opioid Prescribing for Pain. ( March 2017 ) Naloxone for Opioid Overdose: Life-Saving Science This brief fact sheet provides ...

  4. Synthesis and evaluation of fluorinated derivatives of fentanyl as candidates for opiate receptor studies using positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Dahren Hwang; Feliu, A.L.; Wolf, A.P.; MacGregor, R.R.; Fowler, J.S.; Arnett, C.D.

    1986-03-01

    Three fluorinated derivatives of fentanyl, fluorofentanyl (3), keto-fluorofentanyl (5), and fluorofentanol (6), were synthesized and their abilities to compete with /sup 3/diprenorphine for binding sites in guinea pig brain membranes were determined. The relative potencies were fentanyl > 3 approx.= 6 >> 5. On the basis of its apparent affinity for opiate receptors and its relative ease of synthesis, 6 was selected for further study. Fentanyl was slightly better than 6 in its ability to compete with (/sup 3/H)naltrexone for binding sites in rat brain membranes. Both fentayl and 6 exhibited a similar high ''sodium ratio'' (quotient of the IC/sub 50/'s against (/sup 3/H)naltrexone in the presence and absence of sodium chloride) generally characteristic of opiate agonists. The analgesic potencies of fentanyl and 6 were determined in rats by measuring suppression of locomotion and vocalization responses to footshock. 6 appeared slightly less potent than fentanyl, but produced a similar analgesia and catalepsy which was entirely blocked by pretreatment of rats with naloxone, an opiate antagonist. A rapid synthesis of (/sup 18/F)-6 was developed and the tissue distribution of (/sup 18/F)-6 in mice was determined 5, 60, and 120 minutes after intravenous injection. The use of this general route to /sup 18/F-labeled derivatives of fentanyl for studies of the opiate receptor using positron emission tomography is planned.

  5. Fentanyl transmucosal tablets: current status in the management of cancer-related breakthrough pain

    Directory of Open Access Journals (Sweden)

    Prommer E

    2012-06-01

    Full Text Available Eric Prommer, Brandy FicekDivision of Hematology/Oncology, Mayo Clinic College of Medicine, Mayo Clinic Hospital, Scottsdale, AZ, USAAbstract: Breakthrough pain is a newly recognized pain category that was first described by Portenoy and Hagen in 1990. The term describes pain that increases in intensity to “break through” chronic pain that is being controlled by a scheduled opioid regimen. The development of fluctuations in pain intensity is challenging due to their unpredictable nature, rapid onset, and need for rapid treatment intervention. Breakthrough pain has been treated by using an extra opioid dose in addition to the scheduled opioid being used for pain. Recommendations for dose and frequency are based on expert opinion only, and have included dosing based on a percentage of the total opioid dose. Other recommendations include increasing the regularly scheduled opioid dose. Clinical trials have now focused on delivery of opioids that have both potency and a rapid onset of action. Lipophilic opioids have received a substantial amount of study due to their quick absorption and rapid onset of analgesia. Lipophilic opioids that have been studied to date include transmucosal fentanyl, sublingual fentanyl, intranasal sufentanil, and oral and sublingual methadone. Initial clinical trials have established the superiority of transmucosal fentanyl as a breakthrough analgesic when compared with immediate-release oral opioid formulations. Problems with bioavailability have led to a search for newer formulations of transmucosal delivery. Newer formulations, such as fentanyl transmucosal tablets, have been developed to ensure superior delivery for the patient suffering from breakthrough pain. The purpose of this paper is to discuss the current status of transmucosal tablet formulations for cancer breakthrough pain.Keywords: fentanyl, transmucosal, tablets, pain, breakthrough, cancer

  6. Physiologically-based pharmacokinetic model for Fentanyl in support of the development of Provisional Advisory Levels

    Energy Technology Data Exchange (ETDEWEB)

    Shankaran, Harish, E-mail: harish.shankaran@pnnl.gov [Computational Biology and Bioinformatics Group, Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Adeshina, Femi [National Homeland Security Research Center, United States Environmental Protection Agency, Washington, DC 20460 (United States); Teeguarden, Justin G. [Systems Toxicology Group, Pacific Northwest National Laboratory, Richland, WA 99352 (United States)

    2013-12-15

    Provisional Advisory Levels (PALs) are tiered exposure limits for toxic chemicals in air and drinking water that are developed to assist in emergency responses. Physiologically-based pharmacokinetic (PBPK) modeling can support this process by enabling extrapolations across doses, and exposure routes, thereby addressing gaps in the available toxicity data. Here, we describe the development of a PBPK model for Fentanyl – a synthetic opioid used clinically for pain management – to support the establishment of PALs. Starting from an existing model for intravenous Fentanyl, we first optimized distribution and clearance parameters using several additional IV datasets. We then calibrated the model using pharmacokinetic data for various formulations, and determined the absorbed fraction, F, and time taken for the absorbed amount to reach 90% of its final value, t90. For aerosolized pulmonary Fentanyl, F = 1 and t90 < 1 min indicating complete and rapid absorption. The F value ranged from 0.35 to 0.74 for oral and various transmucosal routes. Oral Fentanyl was absorbed the slowest (t90 ∼ 300 min); the absorption of intranasal Fentanyl was relatively rapid (t90 ∼ 20–40 min); and the various oral transmucosal routes had intermediate absorption rates (t90 ∼ 160–300 min). Based on these results, for inhalation exposures, we assumed that all of the Fentanyl inhaled from the air during each breath directly, and instantaneously enters the arterial circulation. We present model predictions of Fentanyl blood concentrations in oral and inhalation scenarios relevant for PAL development, and provide an analytical expression that can be used to extrapolate between oral and inhalation routes for the derivation of PALs. - Highlights: • We develop a Fentanyl PBPK model for relating external dose to internal levels. • We calibrate the model to oral and inhalation exposures using > 50 human datasets. • Model predictions are in good agreement with the available

  7. Addicts Try to Avoid Deadly Fentanyl, but Many Tragically Fail

    Science.gov (United States)

    ... fullstory_166663.html Addicts Try to Avoid Deadly Fentanyl, But Many Tragically Fail Potent synthetic opioid now ... may be caused by the potent synthetic opioid fentanyl. But most opioid addicts are not actively seeking ...

  8. An autopsy case of acetyl fentanyl intoxication caused by insufflation of 'designer drugs'.

    Science.gov (United States)

    Takase, Izumi; Koizumi, Takako; Fujimoto, Ihoko; Yanai, Aya; Fujimiya, Tatsuya

    2016-07-01

    We present a fatal case of intoxication due to insufflation of acetyl fentanyl. His blood concentration of acetyl fentanyl was 270ng/mL, and the manner of death was classified as an accident. This is the first report of an autopsy case of acetyl fentanyl delivered by insufflation, rather than intravenous administration. He had been snoring loudly for at least 12h prior to death, and transport to a hospital during this time and treatment with naloxone may have saved his life. In this sense, it can be said that his death was preventable. This case reemphasizes the risk of death associated with drug overdose and the narrow range of acetyl fentanyl between the effective dose (ED50) and lethal dose (LD50). The case should also raise awareness among medical professionals of the effectiveness of naloxone and the need to establish a comprehensive system for toxicological analysis while keeping the possibility of use of 'designer drugs' in mind. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Fentanyl for neuropathic pain in adults.

    Science.gov (United States)

    Derry, Sheena; Stannard, Cathy; Cole, Peter; Wiffen, Philip J; Knaggs, Roger; Aldington, Dominic; Moore, R Andrew

    2016-10-11

    Opioid drugs, including fentanyl, are commonly used to treat neuropathic pain, and are considered effective by some professionals. Most reviews have examined all opioids together. This review sought evidence specifically for fentanyl, at any dose, and by any route of administration. Other opioids are considered in separate reviews. To assess the analgesic efficacy of fentanyl for chronic neuropathic pain in adults, and the adverse events associated with its use in clinical trials. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from inception to June 2016, together with the reference lists of retrieved articles, and two online study registries. We included randomised, double-blind studies of two weeks' duration or longer, comparing fentanyl (in any dose, administered by any route, and in any formulation) with placebo or another active treatment in chronic neuropathic pain. Two review authors independently searched for studies, extracted efficacy and adverse event data, and examined issues of study quality and potential bias. We did not carry out any pooled analyses. We assessed the quality of the evidence using GRADE. Only one study met our inclusion criteria. Participants were men and women (mean age 67 years), with postherpetic neuralgia, complex regional pain syndrome, or chronic postoperative pain. They were experiencing inadequate relief from non-opioid analgesics, and had not previously taken opioids for their neuropathic pain. The study used an enriched enrolment randomised withdrawal design. It was adequately blinded, but we judged it at unclear risk of bias for other criteria.Transdermal fentanyl (one-day fentanyl patch) was titrated over 10 to 29 days to establish the maximum tolerated and effective dose (12.5 to 50 µg/h). Participants who achieved a prespecified good level of pain relief with a stable dose of fentanyl, without excessive use of rescue medication or intolerable adverse events ('responders

  10. Seizure-like activity during fentanyl anesthesia. A case report.

    OpenAIRE

    Webb, M. D.

    1990-01-01

    Fentanyl induced seizures have been described previously in the literature. Clinical observations has labeled the movements seen in fentanyl anesthesia as seizure activity but electroencephalographic studies have not supported this. A case of seizure-like activity after the administration of fentanyl in a 20-year-old female is reported.

  11. Anaphylaxis related to fentanyl citrate

    Directory of Open Access Journals (Sweden)

    Gaurav Singh Tomar

    2012-01-01

    Full Text Available Anaphylaxis is a fulminant, unexpected, immunoglobulin E-mediated allergic reaction that can be triggered by multiple agents. Common causative agents include neuromuscular blocking drugs, latex, antibiotics, colloids, hypnotics, and opioids. Fentanyl citrate, however, is an extremely unusual cause of anaphylaxis. Pulmonary edema, although uncommon in anaphylaxis, can be a prominent feature, as was in one of the patient. An adverse drug reaction is a noxious or unintended reaction to a drug that is administered in standard doses by the proper route for the purpose of prophylaxis, diagnosis, or treatment. Reactions are classified into two major subtypes: type A, which are dose dependent and predictable; and type B, which are not dose dependent and unpredictable. Unpredictable reactions include immune (allergic or no immune drug hypersensitivity reactions and are related to genetic susceptibilities or undefined mechanisms (formally called idiosyncratic and intolerance reactions. A drug allergy is always associated with an immune mechanism for which evidence of drug-specific antibodies or activated T lymphocytes can be shown. In the last few years, many novel drugs have entered clinical practice (i.e., biologic agents generating novel patterns of drug hypersensitivity reactions. As old drugs continue to be used, new clinical and biologic techniques enable improvement in the diagnosis of these reactions.

  12. Intranasal Fentanyl and Quality of Pediatric Acute Care.

    Science.gov (United States)

    Adelgais, Kathleen M; Brent, Alison; Wathen, Joseph; Tong, Suhong; Massanari, Derrek; Deakyne, Sara; Sills, Marion R

    2017-11-01

    Changes in the manner in which medications can be delivered can have significant effects on the quality of care in the acute care setting. The objective of this study was to evaluate the change in three Institute of Medicine quality indicators (timeliness, safety, and effectiveness) in the pediatric emergency department (ED) after the introduction of the Mucosal Atomizer Device Nasal™ (MADn) for opioid analgesia. This was a retrospective review of patients receiving opioid analgesia for certain conditions over a 5-year period. We compared patients receiving intravenous opioid (IVO) to those receiving intranasal fentanyl (INF). Timeliness outcomes include time from medication order to administration, time from dose to discharge, overall time to analgesia, and ED length of stay. Effectiveness outcomes include change in pain score and frequency of repeat dosing. Safety outcomes were the frequency of reversal agent administration or a documented oxygen desaturation of pediatric ED. Published by Elsevier Inc.

  13. Budget impact analysis of the fentanyl buccal tablet for treatment of breakthrough cancer pain

    Directory of Open Access Journals (Sweden)

    Darbà J

    2013-12-01

    Full Text Available Josep Darbà,1 Lisette Kaskens,2 Rainel Sánchez-de la Rosa31University of Barcelona, Barcelona, 2BCN Health Economics and Outcomes Research SL, Barcelona, 3Medical and HEOR Department, TEVA Pharmaceutical Industries Ltd, Madrid, SpainBackground: The purpose of this study was to assess the economic impact of the fentanyl buccal tablet for the management of breakthrough cancer pain (BTcP in Spain.Methods: A 4-year budget impact model was developed for the period 2012–2015 for patients with BTcP from the perspective of the Spanish National Health System. BTcP products included in this model were rapid-onset opioids containing fentanyl (buccal, sublingual, or nasal transmucosal. Prevalence data on cancer, BTcP, opioid use, and number of BTcP episodes were obtained from the literature. Input data on health care resources associated with opioid use and opioid-induced side effects were obtained by consulting experts in oncology from different Spanish hospitals. Resources used included drugs, medical and emergency visits, other nonpharmacologic treatments, and treatment of opioid-induced side effects. Unit costs were obtained from the literature, and a 3% discount rate was applied to costs. Based on the unit costs for drugs and health care resources, the annual BTcP treatment costs per patient associated with each fentanyl product were determined to estimate the overall budget impact based on the total treatment population and the percentage of drug utilization associated with each product. One-way sensitivity analyses were conducted to test the robustness of the model.Results: Patients treated with oral opioids for BTcP were estimated at 23,291 in 2012, with an increase up to 23,413 in 2015. The average annual budget savings, with an increase of fentanyl buccal tablets, fentanyl sublingual tablets, and intranasal fentanyl spray, and a decrease in oral transmucosal fentanyl citrate, was estimated at €2.6 million, which represents a 0.5% decrease in

  14. Fatal Fentanyl: One Pill Can Kill.

    Science.gov (United States)

    Sutter, Mark E; Gerona, Roy R; Davis, M Thais; Roche, Bailey M; Colby, Daniel K; Chenoweth, James A; Adams, Axel J; Owen, Kelly P; Ford, Jonathan B; Black, Hugh B; Albertson, Timothy E

    2017-01-01

    The current national opioid epidemic is a public health emergency. We have identified an outbreak of exaggerated opioid toxicity caused by fentanyl adulterated tablets purchased on the street as hydrocodone/acetaminophen. Over an 8-day period in late March 2016, a total of 18 patients presented to our institution with exaggerated opioid toxicity. The patients provided a similar history: ingesting their "normal dose" of hydrocodone/acetaminophen tablets but with more pronounced symptoms. Toxicology testing and analysis was performed on serum, urine, and surrendered pills. One of the 18 patients died in hospital. Five patients underwent cardiopulmonary resuscitation, one required extracorporeal life support, three required intubation, and two received bag-valve-mask ventilation. One patient had recurrence of toxicity after 8 hours after naloxone discontinuation. Seventeen of 18 patients required boluses of naloxone, and four required prolonged naloxone infusions (26-39 hours). All 18 patients tested positive for fentanyl in the serum. Quantitative assays conducted in 13 of the sera revealed fentanyl concentrations of 7.9 to 162 ng/mL (mean = 52.9 ng/mL). Pill analysis revealed fentanyl amounts of 600-6,900 μg/pill. The pills are virtually indistinguishable from authentic hydrocodone/acetaminophen tablets and are similar in weight. To date, our county has reported 56 cases of fentanyl opioid toxicity, with 15 fatalities. In our institution, the outbreak has stressed the capabilities and resources of the emergency department and intensive care units. A serious outbreak of exaggerated opioid toxicity caused by fentanyl-adulterated tablets purchased on the street as hydrocodone/acetaminophen is under way in California. These patients required higher dosing and prolonged infusions of naloxone. Additionally, observation periods off naloxone were extended due to delayed, recurrent toxicity. The outbreak has serious ramifications for public health and safety, law

  15. Two Fatal Intoxications Involving Butyryl Fentanyl.

    Science.gov (United States)

    Poklis, Justin; Poklis, Alphonse; Wolf, Carl; Hathaway, Cindie; Arbefeville, Elise; Chrostowski, Leszek; Devers, Kelly; Hair, Laura; Mainland, Mary; Merves, Michele; Pearson, Julia

    2016-10-01

    We present the case histories, autopsy findings and toxicology findings of two fatal intoxications involving the designer drug, butyryl fentanyl. The quantitative analysis of butyryl fentanyl in postmortem fluids and tissues was performed by an ultrahigh-performance liquid chromatography tandem mass spectrometry method. In the first case, butyryl fentanyl was the only drug detected with concentrations of 99 ng/mL in peripheral blood, 220 ng/mL in heart blood, 32 ng/mL in vitreous humor, 590 ng/mL in gastric contents, 93 ng/g in brain, 41 ng/g in liver, 260 ng/mL in bile and 64 ng/mL in urine. The cause of death was ruled fatal intoxication by butyryl fentanyl. In the second case, butyryl fentanyl was detected along with acetyl fentanyl, alprazolam and ethanol. The butyryl fentanyl concentrations were 3.7 ng/mL in peripheral blood, 9.2 ng/mL in heart blood, 9.8 ng/mL in vitreous humor, 4,000 ng/mL in gastric contents, 63 ng/g in brain, 39 ng/g in liver, 49 ng/mL in bile and 2 ng/mL in urine. The acetyl fentanyl concentrations were 21 ng/mL in peripheral blood, 95 ng/mL in heart blood, 68 ng/mL in vitreous humor, 28,000 ng/mL in gastric contents, 200 ng/g in brain, 160 ng/g in liver, 330 ng/mL in bile and 8 ng/mL in urine. In addition, the alprazolam concentration was 40 ng/mL and the ethanol concentration was 0.11 g/dL, both measured in peripheral blood. The cause of death in the second case was ruled a mixed drug intoxication. In both cases, the manner of death was accident. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Fentanyl Buccal Tablet for the Treatment of Breakthrough Pain: Pharmacokinetics of Buccal Mucosa Delivery and Clinical Efficacy

    Directory of Open Access Journals (Sweden)

    Mona Darwish

    2010-06-01

    Full Text Available The treatment of breakthrough pain (BTP, a transitory exacerbation of pain that occurs on a background of otherwise-controlled, persistent pain, requires an opioid formulation and/or method of administration that can provide rapid and extensive systemic exposure. Fentanyl buccal tablet (FBT; FENTORA®, Cephalon, Inc. employs OraVescent® drug delivery technology, which enhances the rate and extent of fentanyl absorption. OraVescent technology enhances the oral dissolution and buccal absorption of fentanyl, which facilitates rapid uptake of fentanyl into the bloodstream, reducing gastrointestinal absorption and minimizing extensive first-pass metabolism. The resulting pharmacokinetic profile of FBT is characterized by greater bioavailability and a higher early systemic exposure compared with the earlier oral transmucosal fentanyl citrate formulation. In clinical studies of opioid-tolerant patients with cancer-related and noncancer- related BTP, FBT has provided consistent and clinically relevant improvements in pain intensity and pain relief relative to placebo, with a safety and tolerability profile that is generally typical of that observed with other potent opioids. The pharmacokinetic properties of FBT allow for meaningful clinical efficacy, with an onset of action that closely matches the onset of BTP.

  17. Fentanyl and its analogues in clinical and forensic toxicology.

    Science.gov (United States)

    Skulska, Agnieszka; Kała, Maria; Parczewski, Andrzej

    2005-01-01

    Fentanyl and its analogues are commonly named synthetic opiates. Some compounds from fentanyl group (e.g. fentanyl, alfentanil, sufentanil, remifentanil) are used as anaesthetic and analgesic of high potency and short duration of action. Effects of acting fentanyls are indistinguishable from those produced by nasal inhalation of street heroin. In view of this, fentanyls are very "attractive" for the narcotic market. In least years an increase in number of reports about illegal production and non-medical use of fentanyl and its analogues have appeared. Numerous fentanyl analogues are sold under one name synthetic heroine or China white. Fentanyl and its analogues also can be used as gas warfare agents. One of fentanyl-related compound was used during action of easing hostages from Dubrovka theatre. Because of respiratory depression, which was caused by used compound, died over 100 hostages. Because of high potency fentanyl-related compounds are used in very low doses. So fentanyls appear in biological material in very low concentrations, not higher than several nanograms per millilitre or per gram. The drugs in these concentrations cannot be detected by means of routinely used screening procedures. Therefore direct methods for determination of this group of compounds are needed. Screening method for determination of fentanyl and its analogues was elaborated and validated. Liquid chromatography-mass spectrometry (LC/MS) technique was applied. The method is characterised by the limit of quantification (LOQ) and the limit of detection (LOD) ranged from 0.6 to 2 ng/ml and from 0.2 to 0.6 ng/ml, respectively for four above-mentioned compounds. The method was used for determination of fentanyl in three forensic cases. The blood, bile and blood from lung samples were taken during autopsy of persons who died shortly after surgical procedure in which fentanyl was used as an adjunct to general anaesthesia.

  18. Illicit Fentanyl-Related Fatalities in Florida: Toxicological Findings.

    Science.gov (United States)

    Lee, Dayong; Chronister, Chris W; Broussard, Wilson A; Utley-Bobak, Suzanne R; Schultz, Daniel L; Vega, Russell S; Goldberger, Bruce A

    2016-10-01

    Fentanyl induces pharmacological effects and abuse liability comparable to other prescription opioids and heroin. A surge in fentanyl-related fatalities has been periodically reported throughout the USA. The University of Florida Forensic Toxicology Laboratory observed a significant increase in fentanyl-related deaths starting in mid-2014. The present report evaluated toxicological findings, demographics of the decedents and circumstances of death in the postmortem cases that were submitted to the laboratory for toxicological analysis from July 2014 to January 2015 and that were tested for fentanyl in biological specimens. The cases originated from 6 of the 24 Florida Medical Examiner Districts, with the majority from District 12 (Desoto, Manatee and Sarasota counties). The specimens were analyzed for fentanyl by gas chromatography-mass spectrometry; the limit of detection (LOD) was 0.62 ng/mL and the limit of quantification (LOQ) was 2.5 ng/mL. During the 7-month period, the laboratory tested 143 postmortem cases for fentanyl and 50% had quantifiable fentanyl in postmortem blood. Fentanyl concentrations ranged from 2.5 to 68 ng/mL (n = 66; median: 9.8 ng/mL); six cases were positive for fentanyl >LOD but fentanyl as a sole or contributing factor for 57 cases (two non-drug intoxication deaths). The median age of the 57 decedents was 35 (range: 19-63) years. Males represented 87% of the deaths and 96% were Whites. Most of the decedents (n = 53) had no prescription for fentanyl. Considering fentanyl's high potency and abuse liability, the recent rise in fentanyl-related deaths is a serious public health concern and signifies the urgent need to establish prevention and treatment efforts. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Comparison of two drug combinations in total intravenous anesthesia: Propofol–ketamine and propofol–fentanyl

    Science.gov (United States)

    Singh Bajwa, Sukhminder Jit; Bajwa, Sukhwinder Kaur; Kaur, Jasbir

    2010-01-01

    Background and Aims: Keeping in consideration the merits of total intravenous anesthesia (TIVA), a genuine attempt was made to find the ideal drug combinations which can be used in general anesthesia. This study was conducted to evaluate and compare two drug combinations of TIVA using propofol–ketamine and propofol–fentanyl and to study the induction, maintenance and recovery characteristics following anesthesia with these techniques. Settings and Design: A case control study was conducted, which included 100 patients, in the department of Anaesthesiology and Intensive care, Government Medical College and Hospital, Patiala. Patients and Methods: A hundred patients between the ages of 20 and 50 years of either gender were divided into two groups of 50 each, and they underwent elective surgery of approximately 1 h duration. Group I received propofol–ketamine while group II received propofol–fentanyl for induction and maintenance of anesthesia. All the results were tabulated and analyzed statistically with student's unpaired t-test and chi-square test. Results: Propofol–fentanyl combination produced a significantly greater fall in pulse rate (PR; 9.28% versus 0.23%) and in both systolic (7.94% versus 0.12%) and diastolic blood pressures (BP; 8.10% versus 0.35%) as compared to propofol–ketamine during induction of anesthesia. Propofol–ketamine combination produced stable hemodynamics during maintenance phase while on the other hand propofol–fentanyl was associated with a slight increase in both PR and BP. During recovery, ventilation score was better in group I while movement and wakefulness score was better in group II. Mean time to protrusion of tongue and lifting of head was shorter in group I. Conclusions: Both propofol–ketamine and propofol–fentanyl combinations produce rapid, pleasant and safe anesthesia with only a few untoward side effects and only minor hemodynamic effects. PMID:20927266

  20. Nebulized fentanyl vs intravenous morphine for ED patients with acute limb pain: a randomized clinical trial.

    Science.gov (United States)

    Farahmand, Shervin; Shiralizadeh, Said; Talebian, Mohammad-Taghi; Bagheri-Hariri, Shahram; Arbab, Mona; Basirghafouri, Hamed; Saeedi, Morteza; Sedaghat, Mojtaba; Mirzababai, Habibolla

    2014-09-01

    Intravenous morphine has been used as a common method of pain control in emergency care. Nebulized fentanyl is also an effective temporary substitute. This study was designed to compare the effectiveness of nebulized fentanyl with intravenous (IV) morphine on management of acute limb pain. This was a placebo-controlled, double-blind randomized clinical trial. Ninety emergency department patients with moderate to severe pain aged 15 to 50 years were blocked randomized and enrolled in this study. Forty-seven patients in the experimental group received nebulized fentanyl (4 μg/kg) and IV normal saline as placebo, and the remaining 43 patients in the control group received IV morphine (0.1 mg/kg) and nebulized normal saline as placebo. All participants' pain scores were assessed by Numerical Rating Scale before and after intervention at 5-, 10-, 15-, 30-, 45-, and 60-minute intervals. Patients' vital sign and possible adverse effects were recorded respectively. Finally, all participants were assessed for their satisfaction. The mean initial pain score in the experimental group was 8.7 and 8.4 in the control group (P = .1). Pain relief in both groups after 5 and 10 minutes were similar (P = .72). Although the pain relief was significantly greater with fentanyl at 15 minutes, this difference is not clinically significant. Pain management in both groups was successful and was more than 3 scores reduction in Numerical Rating Scale. Patient satisfaction in both groups was similar. No adverse effects were reported in the experimental group. This study suggests that nebulized fentanyl is a rapid, safe, and effective method for temporary control of acute limb pain in emergency department patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Efficacy and safety of intravenous fentanyl administered by ambulance personnel

    DEFF Research Database (Denmark)

    Friesgaard, Kristian Dahl; Nikolajsen, Lone; Giebner, Matthias

    2016-01-01

    BACKGROUND: Management of pain in the pre-hospital setting is often inadequate. In 2011, ambulance personnel were authorized to administer intravenous fentanyl in the Central Denmark Region. The aim of this study was to evaluate the efficacy and safety of intravenous fentanyl administered...... by ambulance personnel. METHODS: Pre-hospital medical charts from 2348 adults treated with intravenous fentanyl by ambulance personnel during a 6-month period were reviewed. The primary outcome was the change in pain intensity on a numeric rating scale (NRS) from before fentanyl treatment to hospital arrival....... Secondary outcomes included the number of patients with reduction in pain intensity during transport (NRS ≥ 2), the number of patients with NRS > 3 at hospital arrival, and potential fentanyl-related side effects. RESULTS: Fentanyl reduced pain from before treatment (8, IQR 7-9) to hospital arrival (4, IQR...

  2. An LC-MS-MS Method for the Analysis of Carfentanil, 3-Methylfentanyl, 2-Furanyl Fentanyl, Acetyl Fentanyl, Fentanyl and Norfentanyl in Postmortem and Impaired-Driving Cases.

    Science.gov (United States)

    Sofalvi, Szabolcs; Schueler, Harold E; Lavins, Eric S; Kaspar, Claire K; Brooker, Ian T; Mazzola, Carrie D; Dolinak, David; Gilson, Thomas P; Perch, Steve

    2017-07-01

    In July of 2016, carfentanil (CF) emerged in Northeast Ohio resulting in over 25 deaths within a 30-day period. A total of 125 deaths have occurred in Summit County and Cuyahoga County has reported 40 deaths, relating to the presence of CF either alone, or in combinations with heroin and fentanyl. Prior to this surge in CF cases, positive fentanyl enzyme-linked immunosorbent assay (ELISA) screening results were increasing in number. Many were negative for fentanyl confirmation by gas chromatography-mass spectrometry. Fentanyl analogs such as CF, acetyl fentanyl (AF), 2-furanyl fentanyl (2-Fu-F) and 3-methylfentanyl (3-MF) may be present in these cases. Some fentanyl analogs like CF and 3-MF do not cross-react with the Immunalysis ELISA fentanyl assay. With the emergence of potent synthetic fentanyl analogs, questions arose as to how to interpret their very low concentrations or absence in the blood in relation to cause of death. Driving under the influence of drugs (DUID) blood specimens had also tested positive for CF by reference laboratories. A liquid chromatography-tandem mass spectrometry method was developed to identify and quantify fentanyl, norfentanyl (NF) and four analogs: AF, 2-Fu-F, 3-MF and CF. The method has been utilized to quantify these fentanyl analogs in blood and vitreous humor in authentic antemortem and postmortem cases. Calibration curves were established between 0.10-4.0 ng/mL (NF, AF, 3-MF, 2-Fu-F and CF) and 1.0-40 ng/mL for fentanyl. In total, 98 postmortem cases analyzed produced the following blood concentration ranges: CF (0.11-0.88 ng/mL), 3-MF (0.15-1.7 ng/mL), 2-Fu-F (0.15-0.30 ng/mL), AF (0.14-0.16 ng/mL), fentanyl (1.1-15 ng/mL) and NF (0.10-3.7 ng/mL). Only CF, fentanyl and NF were detected in a statistically significant subset DUID population of 26 cases producing concentration ranges between 0.11 and 0.47 ng/mL, 1.0 and 9.8 ng/mL, and 0.11 and 3.5 ng/mL, respectively. © The Author 2017. Published by Oxford University Press

  3. Response to intravenous fentanyl infusion predicts subsequent response to transdermal fentanyl.

    Science.gov (United States)

    Hayashi, Norihito; Kanai, Akifumi; Suzuki, Asaha; Nagahara, Yuki; Okamoto, Hirotsugu

    2016-04-01

    Prediction of the response to transdermal fentanyl (FENtd) before its use for chronic pain is desirable. We tested the hypothesis that the response to intravenous fentanyl infusion (FENiv) can predict the response to FENtd, including the analgesic and adverse effects. The study subjects were 70 consecutive patients with chronic pain. The response to fentanyl at 0.1 mg diluted in 50 ml of physiological saline and infused over 30 min was tested. This was followed by treatment with FENtd (Durotep MT patch 2.1 mg) at a dose of 12.5 µg/h for 2 weeks. Pain intensity before and after FENiv and 2 weeks after FENtd, and the response to treatment, were assessed by the numerical rating scale (NRS), clinical global impression-improvement scale (CGI-I), satisfaction scale (SS), and adverse effects. The NRS score decreased significantly from 7 (4-9) [median (range)] at baseline to 3 (0-8) after FENiv (p 0.04, each). The analgesic and side effects after intravenous fentanyl infusion can be used to predict the response to short-term transdermal treatment with fentanyl.

  4. Intranasal Fentanyl Intoxication Leading to Diffuse Alveolar Hemorrhage.

    Science.gov (United States)

    Ruzycki, Shannon; Yarema, Mark; Dunham, Michael; Sadrzadeh, Hossein; Tremblay, Alain

    2016-06-01

    Increasing rates of opioid abuse, particularly fentanyl, may lead to more presentations of unusual effects of opioid toxicity. Diffuse alveolar hemorrhage is a rare complication of fentanyl overdose. A 45-year-old male presented in hypoxic respiratory failure secondary to diffuse alveolar hemorrhage requiring intubation. Comprehensive drug screening detected fentanyl without exposure to cocaine. Further history upon the patient's recovery revealed exposure to snorted fentanyl powder immediately prior to presentation. Diffuse alveolar hemorrhage is a potential, though rare, presentation of opioid intoxication. Recognition of less common complications of opioid abuse such as diffuse alveolar hemorrhage is important in proper management of overdoses.

  5. [Epidural fentanyl delayed emergence from anesthesia].

    Science.gov (United States)

    Shintani, Noriyuki; Ishiyama, Tadahiko; Kume, Masaki; Terada, Yoshihide; Shibuya, Kazuhiro; Matsukawa, Takashi

    2012-01-01

    An 83-year-old man (158 cm, 42 kg) was scheduled for cholecystectomy. He had a history of hypertension and atrial fibrillation. The patient received no premedication. An epidural catheter was inserted via the T9-10 interspace and 2% mepivacaine 7 ml was injected, producing a sensory block from T4 to T12. Anesthesia was induced with propofol and remifentanil, and was maintained with propofol, remifentanil, and nitrous oxide in oxygen. Rocuronium was given to provide neuromuscular block. Just before the completion of surgery, a bolus epidural injection of 2% mepivacaine 2 ml with fentanyl 50 microg was performed. Then epidural solution of ropivacaine 0.1% with fentanyl 6.25 microg x ml(-1), and droperidol 25 microg x ml(-1) was infused at 4 ml x hr(-1). Soon after the surgery, the patient developed atrial fibrillation that was treated with external electrocardioversion with 100 watt x sec. After the restoration of sinus rhythm, anesthetics were discontinued. The patient did not emerge from anesthesia though he breathed spontaneously Doxapram was slightly effective, but he did not respond to the verbal command. Epidural infusion was stopped and the patient was transferred to the ward. The patient fully recovered from anesthesia after 2 hours. Epidural infusion was restarted 17 hours later, and the patient fell asleep. He woke up after stopping epidural infusion. Epidurally administered fentanyl must have been the cause of delayed recovery from anesthesia. He could have been highly sensitive to fentanyl. Patient controlled epidural anesthesia may have been useful for this patient.

  6. Can solar power deliver?

    Science.gov (United States)

    Nelson, Jenny; Emmott, Christopher J M

    2013-08-13

    Solar power represents a vast resource which could, in principle, meet the world's needs for clean power generation. Recent growth in the use of photovoltaic (PV) technology has demonstrated the potential of solar power to deliver on a large scale. Whilst the dominant PV technology is based on crystalline silicon, a wide variety of alternative PV materials and device concepts have been explored in an attempt to decrease the cost of the photovoltaic electricity. This article explores the potential for such emerging technologies to deliver cost reductions, scalability of manufacture, rapid carbon mitigation and new science in order to accelerate the uptake of solar power technologies.

  7. Sedation and Analgesia in Intensive Care: A Comparison of Fentanyl and Remifentanil

    Directory of Open Access Journals (Sweden)

    F. Cevik

    2011-01-01

    Full Text Available Optimal sedation and analgesia are of key importance in intensive care. The aim of this study was to assess the quality of sedoanalgesia and outcome parameters in regimens containing midazolam and either fentanyl or remifentanil. A prospective, randomized, open-label, controlled trial was carried out in the ICU unit of a large teaching hospital in Istanbul over a 9-month period. Thirty-four patients were randomly allocated to receive either a remifentanil-midazolam regimen (R group, =17 or a fentanyl-midazolam regimen (F group, =17. A strong correlation between Riker Sedation-Agitation Scale (SAS and Ramsey Scale (RS measurements was observed. Comparatively, remifentanil provided significantly more potent and rapid analgesia based on Behavioral-Physiological Scale (BPS measurements and a statistically nonsignificantly shorter time to discharge. On the other hand, remifentanil also caused a significantly sharper fall in heart rate within the first six hours of treatment.

  8. Multiple fatalities in the North of England associated with synthetic fentanyl analogue exposure: Detection and quantitation a case series from early 2017.

    Science.gov (United States)

    Hikin, Laura; Smith, Paul R; Ringland, Eleanor; Hudson, Simon; Morley, Stephen R

    2018-01-01

    Synthetic fentanyl analogues are highly potent opioid drugs which have no pharmaceutical use in humans. We detected the synthetic fentanyl analogues; carfentanil, butyryl fentanyl, fluorobutyrylfentanyl, furanylfentanyl, and alfentanil as well as fentanyl itself in 25 cases in early 2017. There have been no previous reports of synthetic fentanyl deaths in the United Kingdom (UK). Cases in which the history clearly stated drug use but where a post mortem blood morphine concentration was lower than would be expected to explain the sudden death, were referred for further analysis by high resolution accurate mass (HRAM) mass spectrometry. 25 post mortem cases in which synthetic fentanyl analogues were implicated in the cause of death were reported from January to May 2017. No cases were seen in June 2017. The age range was 21-54 years and 22 were male. There was a history of heroin use, or markers of heroin use on toxicology screening in 21/25 cases. Carfentanil and fentanyl were detected in 7 cases. Multiple synthetic fentanyl analogues were present in 13 cases, with the remaining 5 cases having only carfentanil present. Synthetic fentanyl analogues were detected in combination with other drugs in all cases. Significant concentrations of ethanol were detected in only 2 cases. The concentration range of carfentanil in blood was 90-4004pg/mL. Of note, the 3 cases in which ante mortem carfentanil was quantified ranged from 21 to 98pg/mL. In all cases, death was attributed to combined central nervous system depression. This paper highlights a new and rapid emergence of these drugs into the UK illicit drug arena. Synthetic fentanyl analogues represent a significant challenge both analytically and clinically within the groups who misuse drugs. It is worthwhile considering the possibility of the presence of these drugs in cases in which a toxicological cause of death is not apparent analytically but there is a history of drug use and circumstantial evidence exists to support

  9. Postoperative pain management with transdermal fentanyl after forefoot surgery: a randomized, placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Merivirta R

    2015-01-01

    Full Text Available Riika Merivirta,1 Mikko Pitkänen,2 Jouko Alanen,3 Elina Haapoja,1 Mari Koivisto,4 Kristiina Kuusniemi11Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine of Turku University Hospital and University of Turku, Turku, 2Department of Anaesthesia, Hospital Orton, Invalid Foundation, Helsinki, 3Terveystalo Clinic Hospital, Helsinki, 4Department of Biostatistics, University of Turku, Turku, FinlandBackground: Quality of life is decreased in patients with hallux valgus deformity, mainly because of pain. Significant improvement is usually achieved by surgery. However, postoperative pain can be moderate to severe for 2–3 days. The aim of the present study was to evaluate the use of transdermal fentanyl for postoperative pain management after forefoot surgery.Methods: Sixty patients undergoing hallux valgus or hallux rigidus surgery were allocated to receive a patch delivering either fentanyl 12 µg/hour or placebo for postoperative pain. The consumption of rescue opioid oxycodone, the primary outcome measure, was evaluated daily until the fourth postoperative day. Total consumption of oxycodone during the study period was also assessed. Pain scores and possible adverse effects were evaluated every 6 hours during the first 24 hours and on the fourth postoperative day.Results: The use of rescue opioid was low in both groups, the median (range consumption of oxycodone being 10 (0–50 mg on the day of surgery (no difference between the groups, P=0.31 and 0 (0–35 mg thereafter. The total combined consumption was 10 (0–105 mg in the fentanyl group and 20 (0–70 mg in the placebo group (P=0.23. There were no statistically significant differences in pain scores or adverse effects between the groups.Conclusion: As a part of multimodal analgesia with ibuprofen and acetaminophen, a patch delivering fentanyl 12 µg/hour did not significantly decrease the consumption of rescue opioid or pain scores after forefoot surgery

  10. Prevalence and correlates of fentanyl-contaminated heroin exposure among young adults who use prescription opioids non-medically.

    Science.gov (United States)

    Macmadu, Alexandria; Carroll, Jennifer J; Hadland, Scott E; Green, Traci C; Marshall, Brandon D L

    2017-05-01

    The rate of overdose deaths caused by fentanyl-contaminated heroin (FCH) use is increasing rapidly in the United States. We examined risk factors for exposure to FCH and experiences with FCH use among young adult non-medical prescription opioids (NMPO) users. We analyzed data from the Rhode Island Young Adult Prescription Drug Study (RAPiDS), which enrolled young adults aged 18 to 29 reporting prior 30day NMPO use between January 2015 and February 2016. Participants completed questionnaires ascertaining drug use patterns and risk behaviors, including FCH exposure. Logistic regression was used to assess factors associated with known or suspected FCH exposure. Of 199 participants, the median age was 25 (IQR: 22, 27), 130 (65.3%) were male, and 122 (61.3%) were of White, non-Hispanic race/ethnicity. In total, 22 (11%) reported known or suspected FCH exposure in the prior six months. Several drug use patterns and risk behaviors were associated with FCH exposure, including: regular heroin and cocaine use; diverted pharmaceutical fentanyl use in the prior six months; NMPO use to avoid withdrawal symptoms; longer duration of NMPO use; regular injection drug use; and prior overdose (all pfentanyl prior to last use, 59% reported that FCH provides a better high, and all recognized that fentanyl increases overdose risk. Exposure to fentanyl-contaminated heroin is an emerging trend among young adult NMPO users in Rhode Island. Overdose prevention programs addressing FCH use are urgently needed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Effectiveness of morphine, fentanyl, and methoxyflurane in the prehospital setting.

    Science.gov (United States)

    Middleton, Paul M; Simpson, Paul M; Sinclair, Gary; Dobbins, Timothy A; Math, B; Bendall, Jason C

    2010-01-01

    To compare the effectiveness of intravenous (IV) morphine, intranasal (IN) fentanyl, and inhaled methoxyflurane when administered by paramedics to patients with moderate to severe pain. We conducted a retrospective comparative study of adult patients with moderate to severe pain treated by paramedics from the Ambulance Service of New South Wales who received IV morphine, IN fentanyl, or inhaled methoxyflurane either alone or in combination between January 1, 2004, and November 30, 2006. We used multivariate logistic regression to analyze data extracted from a clinical database containing routinely entered information from patient health care records. The primary outcome measure was effective analgesia, defined as a reduction in pain severity of > or = 30% of initial pain score using an 11-point verbal numeric rating scale (VNRS-11). The study population comprised 52,046 patients aged between 16 and 100 years with VNRS-11 scores of > or = 5. All analgesic agents were effective in the majority of patients (81.8%, 80.0%, and 59.1% for morphine, fentanyl, and methoxyflurane, respectively). There was very strong evidence that methoxyflurane was inferior to both morphine and fentanyl (p methoxyflurane, IN fentanyl, and IV morphine are all effective analgesic agents in the out-of-hospital setting. Morphine and fentanyl are significantly more effective analgesic agents than methoxyflurane. Morphine appears to be more effective than IN fentanyl; however, the benefit of IV morphine may be offset to some degree by the ability to administer IN fentanyl without the need for IV access.

  12. Identification of Unique Metabolites of the Designer Opioid Furanyl Fentanyl.

    Science.gov (United States)

    Goggin, Melissa M; Nguyen, An; Janis, Gregory C

    2017-06-01

    The illicit drug market has seen an increase in designer opioids, including fentanyl and methadone analogs, and other structurally unrelated opioid agonists. The designer opioid, furanyl fentanyl, is one of many fentanyl analogs clandestinely synthesized for recreational use and contributing to the fentanyl and opioid crisis. A method has been developed and validated for the analysis of furanyl fentanyl and furanyl norfentanyl in urine specimens from pain management programs. Approximately 10% of samples from a set of 500 presumptive heroin-positive urine specimens were found to contain furanyl fentanyl, with an average concentration of 33.8 ng/mL, and ranging from 0.26 to 390 ng/mL. Little to no furanyl norfentanyl was observed; therefore, the furanyl fentanyl specimens were further analyzed by untargeted high-resolution mass spectrometry to identify other metabolites. Multiple metabolites, including a dihydrodiol metabolite, 4-anilino-N-phenethyl-piperidine (4-ANPP) and a sulfate metabolite were identified. The aim of the presented study was to identify the major metabolite(s) of furanyl fentanyl and estimate their concentrations for the purpose of toxicological monitoring. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Clonidine versus fentanyl as adjuvants to bupivacaine in peribulbar anesthesia

    Directory of Open Access Journals (Sweden)

    Maha M.I. Youssef

    2014-07-01

    Conclusion: The addition of either clonidine or fentanyl to the local anesthetic during peribulbar block results in a faster onset and longer duration of the block with a longer period of postoperative analgesia. The addition of clonidine was found to prolong the duration of the block more than fentanyl.

  14. Fentanyl-induced cough--pathophysiology and prevention.

    Science.gov (United States)

    El Baissari, Mabelle C Tannous; Taha, Samar K; Siddik-Sayyid, Sahar M

    2014-06-01

    Many reports have demonstrated that intravenous administration of a bolus of fentanyl at induction of anesthesia can cause coughing with varying degrees. This cough can be benign, but sometimes it causes undesirable side effects including an increase in intraabdominal, intracranial or intraocular pressure. Many studies demonstrated that the incidence and severity of fentanyl-induced cough could be related to age, ethnicity, history of smoking, as well as to the rate, route, dose and concentration of fentanyl administered. This cough was described by several mechanisms including an inhibition of central sympathetic system leading to vagal predominance, reflex bronchonstriction after the stimulation of tracheobronchial tree receptors, or histamine release. The efficacy of several measures to avoid fentanyl-induced cough have been demonstrated, and several anesthetics adjuncts can be given prior to fentanyl administration aiming at decreasing this unwanted side effect.

  15. Population Pharmacokinetics of Fentanyl in the Critically Ill.

    Science.gov (United States)

    Choi, Leena; Ferrell, Benjamin A; Vasilevskis, Eduard E; Pandharipande, Pratik P; Heltsley, Rebecca; Ely, E Wesley; Stein, C Michael; Girard, Timothy D

    2016-01-01

    To characterize fentanyl population pharmacokinetics in patients with critical illness and identify patient characteristics associated with altered fentanyl concentrations. Prospective cohort study. Medical and surgical ICUs in a large tertiary care hospital in the United States. Patients with acute respiratory failure and/or shock who received fentanyl during the first 5 days of their ICU stay. We collected clinical and hourly drug administration data and measured fentanyl concentrations in plasma collected once daily for up to 5 days after enrollment. Among 337 patients, the mean duration of infusion was 58 hours at a median rate of 100 μg/hr. Using a nonlinear mixed-effects model implemented by NONMEM, we found that fentanyl pharmacokinetics were best described by a two-compartment model in which weight, severe liver disease, and congestive heart failure most affected fentanyl concentrations. For a patient population with a mean weight of 92 kg and no history of severe liver disease or congestive heart failure, the final model, which performed well in repeated 10-fold cross-validation, estimated total clearance, intercompartmental clearance (Q), and volumes of distribution for the central (V1) and peripheral compartments (V2) to be 35 L/hr (95% CI, 32-39 L/hr), 55 L/hr (95% CI, 42-68 L/hr), 203 L (95% CI, 140-266 L), and 523 L (95% CI, 428-618 L), respectively. Severity of illness was marginally associated with fentanyl pharmacokinetics but did not improve the model fit after liver and heart diseases were included. In this study, fentanyl pharmacokinetics during critical illness were strongly influenced by severe liver disease, congestive heart failure, and weight, factors that should be considered when dosing fentanyl in the ICU. Future studies are needed to determine if data-driven fentanyl dosing algorithms can improve outcomes for ICU patients.

  16. Population Pharmacokinetics of Fentanyl in the Critically Ill

    Science.gov (United States)

    Choi, Leena; Ferrell, Benjamin A; Vasilevskis, Eduard E; Pandharipande, Pratik P; Heltsley, Rebecca; Ely, E Wesley; Stein, C Michael; Girard, Timothy D

    2016-01-01

    Objective To characterize fentanyl population pharmacokinetics in patients with critical illness and identify patient characteristics associated with altered fentanyl concentrations. Design Prospective cohort study. Setting Medical and surgical ICUs in a large tertiary care hospital in the United States. Patients Patients with acute respiratory failure and/or shock who received fentanyl during the first five days of their ICU stay. Measurements and Main Results We collected clinical and hourly drug administration data and measured fentanyl concentrations in plasma collected once daily for up to five days after enrollment. Among 337 patients, the mean duration of infusion was 58 hours at a median rate of 100 µg/hr. Using a nonlinear mixed-effects model implemented by NONMEM, we found fentanyl pharmacokinetics were best described by a two-compartment model in which weight, severe liver disease, and congestive heart failure most affected fentanyl concentrations. For a patient population with a mean weight of 92 kg and no history of severe liver disease or congestive heart failure, the final model, which performed well in repeated 10-fold cross-validation, estimated total clearance (CL), intercompartmental clearance (Q), and volumes of distribution for the central (V1) and peripheral compartments (V2) to be 35 (95% confidence interval: 32 to 39) L/hr, 55 (42 to 68) L/hr, 203 (140 to 266) L, and 523 (428 to 618) L, respectively. Severity of illness was marginally associated with fentanyl pharmacokinetics but did not improve the model fit after liver and heart disease were included. Conclusions In this study, fentanyl pharmacokinetics during critical illness were strongly influenced by severe liver disease, congestive heart failure, and weight, factors that should be considered when dosing fentanyl in the ICU. Future studies are needed to determine if data-driven fentanyl dosing algorithms can improve outcomes for ICU patients. PMID:26491862

  17. Detection of illicit online sales of fentanyls via Twitter.

    Science.gov (United States)

    Mackey, Tim K; Kalyanam, Janani

    2017-01-01

    A counterfeit fentanyl crisis is currently underway in the United States.  Counterfeit versions of commonly abused prescription drugs laced with fentanyl are being manufactured, distributed, and sold globally, leading to an increase in overdose and death in countries like the United States and Canada.  Despite concerns from the U.S. Drug Enforcement Agency regarding covert and overt sale of fentanyls online, no study has examined the role of the Internet and social media on fentanyl illegal marketing and direct-to-consumer access.  In response, this study collected and analyzed five months of Twitter data (from June-November 2015) filtered for the keyword "fentanyl" using Amazon Web Services.  We then analyzed 28,711 fentanyl-related tweets using text filtering and a machine learning approach called a Biterm Topic Model (BTM) to detect underlying latent patterns or "topics" present in the corpus of tweets.  Using this approach we detected a subset of 771 tweets marketing the sale of fentanyls online and then filtered this down to nine unique tweets containing hyperlinks to external websites.  Six hyperlinks were associated with online fentanyl classified ads, 2 with illicit online pharmacies, and 1 could not be classified due to traffic redirection.  Importantly, the one illicit online pharmacy detected was still accessible and offered the sale of fentanyls and other controlled substances direct-to-consumers with no prescription required at the time of publication of this study.   Overall, we detected a relatively small sample of Tweets promoting illegal online sale of fentanyls.  However, the detection of even a few online sellers represents a public health danger and a direct violation of law that demands further study.

  18. Efficacy and Safety of Oral or Nasal Fentanyl for Treatment of Breakthrough Pain in Cancer Patients: A Systematic Review.

    Science.gov (United States)

    Rogríguez, Dulce; Urrutia, Gerard; Escobar, Yolanda; Moya, Jordi; Murillo, Maite

    2015-09-01

    Formulations of fentanyl that use buccal, sublingual, or nasal transmucosal routes of administration have been developed for the treatment of BTP in opioid-tolerant patients with cancer. The purposes of this analysis were to identify and review published data describing the efficacy and safety of different oral or nasal transmucosal fentanyl formulations for treatment of cancer-related BTP, based on a critical analysis of scientific literature. Oral transmucosal or intranasal fentanyl is an effective treatment for management of BTP episodes due to a potent analgesic effect, rapid onset of action, and sustained effect. Furthermore, it is a reasonably safe treatment, causing generally mild adverse events not leading to treatment discontinuation. Nevertheless, further progress in standardizing methodology, definitions, and criteria used both in research and in clinical practice is needed in order to generate quality information allowing a better understanding of the comparable efficacy of available formulations of fentanyl. A more rigorous assessment of long-term safety is also needed to establish a balance between benefits and risks of the available options.

  19. Trends in the use and abuse of branded and generic extended release oxycodone and fentanyl products in the United States.

    Science.gov (United States)

    Cicero, Theodore J; Inciardi, James A; Surratt, Hilary

    2007-12-01

    A great deal of previous work on the pharmacoeconomics of alcohol, tobacco and illicit drug abuse indicates that as cost decreases, abuse increases and vice versa. The application of these cost principles to the abuse of prescribed medications is largely unknown. In this paper we assessed whether the introduction of generic products in the U.S. increased the therapeutic use and illicit abuse of extended release oxycodone products and the fentanyl patch. As an index of therapeutic use, we purchased prescription data for each of the ZIP codes in which we had corresponding abuse data. To gather information about prescription drug abuse, we elicited cases with quarterly questionnaires completed by a key informant network. The introduction of generic extended release (ER) oxycodone and fentanyl patch did not significantly change the total prescriptions written for these products, but markedly altered the composition of sales: branded sales dropped precipitously over a very short time and this was compensated for by a corresponding increase in sales of generics. Surprisingly, the introduction of generic products did not increase the abuse of ER oxycodone or fentanyl products; the branded version was the drug of choice for at least 2 years. Our data suggest that drug costs alone do not increase the overall likelihood that a prescription opioid analgesic will be used therapeutically or abused. However, while generics are rapidly endorsed by insurance companies as a prescribed entity, abuse of the branded versions of ER oxycodone and fentanyl remains predominant for some time.

  20. Topical fentanyl stimulates healing of ischemic wounds in diabetic rats

    Science.gov (United States)

    FAROOQUI, Mariya; ERICSON, Marna E; GUPTA, Kalpna

    2016-01-01

    Background Topically applied opioids promote angiogenesis and healing of ischemic wounds in rats. We examined if topical fentanyl stimulates wound healing in diabetic rats by stimulating growth-promoting signaling, angiogenesis, lymphangiogenesis and nerve regeneration. Methods We used Zucker diabetic fatty rats that develop obesity and diabetes on a high fat diet due to a mutation in the Leptin receptor. Fentanyl blended with hydrocream was applied topically on ischemic wounds twice daily, and wound closure was analyzed regularly. Wound histology was analyzed by hematoxylin and eosin staining. Angiogenesis, lymphangiogenesis, nerve fibers and phospho-PDGFR-β were visualized by CD31-, lymphatic vessel endothelium-1, protein gene product 9.5- and anti-phospho PDGFR-β-immunoreactivity, respectively. Nitric oxide synthase (NOS) and PDGFR-β signaling were analyzed using Western immunoblotting. Results Fentanyl significantly promoted wound closure as compared to PBS. Histology scores were significantly higher in fentanyl-treated wounds, indicative of increased granulation tissue formation, reduced edema and inflammation, and increased matrix deposition. Fentanyl treatment resulted in increased wound angiogenesis, lymphatic vasculature, nerve fibers, nitric oxide, NOS and PDGFR-β signaling as compared to PBS. Phospho PDGFR-β co-localized with CD31 co-staining for vasculature. Conclusions Topically applied fentanyl promotes closure of ischemic wounds in diabetic rats. Increased angiogenesis, lymphangiogenesis, peripheral nerve regeneration, NO and PDGFR-β signaling are associated with fentanyl-induced tissue remodeling and wound healing. PMID:25266258

  1. Randomized Controlled Study Comparing Use of Propofol Plus Fentanyl versus Midazolam Plus Fentanyl as Sedation in Diagnostic Endoscopy in Patients with Advanced Liver Disease

    National Research Council Canada - National Science Library

    Sameh Abdelkhalik Ahmed; Amal Selim; Nehad Hawash; Ahmed Khaled Tawfik; Mohamed Yousef; Abdelrahman Kobtan; Rehab Badawi; Sally Elnawasany; Reham Abdelkader Elkhouly; Amr Shaaban Hanafy; Fatma H. Rizk; Loai Mansour; Sherief Abd-Elsalam

    2017-01-01

    Objectives. We aimed to investigate the safety and efficacy of propofol plus fentanyl versus midazolam plus fentanyl as sedative for patients with advanced liver disease presented for gastrointestinal endoscopy. Methods...

  2. Rationales behind the choice of administration form with fentanyl

    DEFF Research Database (Denmark)

    Jacobsen, Ramune; Møldrup, Claus; Christrup, Lona

    2010-01-01

    BACKGROUND AND AIM: The aim of this study was to describe the rationale behind the choice of fentanyl administration forms among Danish general practitioners (GPs). METHODS: Thirty-eight Danish GPs were contacted via an Internet survey system to perform a Delphi survey. In the brainstorming phase...... for not choosing OTFCs were intolerance to fentanyl and price. The most important possible rationale to choose fentanyl nasal spray was easy administration. The most important possible reasons to not choose fenanyl nasal spray were application side effects. CONCLUSIONS: The rationale behind the choice...

  3. Transdermal fentanyl matrix patches Matrifen and Durogesic DTrans are bioequivalent

    DEFF Research Database (Denmark)

    Kress, Hans G; Boss, Hildegard; Delvin, Thomas

    2010-01-01

    AIM: The pharmacokinetic profiles of the two commercially available transdermal fentanyl patches Matrifen (100 microg/h) and Durogesic DTrans (100 microg/h), used to manage severe chronic pain, were compared regarding their systemic exposure, rate of absorption, and safety. METHODS: Transdermal...... matrix fentanyl patches [Matrifen or Durogesic DTrans (100 microg/h)] were applied for 72 h to 30 healthy male subjects in a randomized, four-period (two replicated treatment sequences), crossover study; 28 subjects completed the study. The pharmacokinetic parameters of fentanyl were determined for 144 h...

  4. Swallowing action immediately before intravenous fentanyl at induction of anesthesia prevents fentanyl-induced coughing: a randomized controlled study.

    Science.gov (United States)

    Sako, Saori; Tokunaga, Shoji; Tsukamoto, Masanori; Yoshino, Jun; Fujimura, Naoyuki; Yokoyama, Takeshi

    2017-04-01

    Fentanyl is a strong µ-opioid analgesic which attenuates the stimulation of surgical invasion and tracheal intubation. However, intravenous fentanyl often induces coughing [fentanyl-induced coughing (FIC)] during induction of anesthesia. We found that the swallowing action, when requested at induction of anesthesia, attenuated FIC. In the current study, we investigated the relationship between the occurrence of FIC and the swallowing action. The study included American Society of Anesthesiologists physical status I or II patients, aged 20-64 years, who were undergoing elective surgery. They were divided into two groups-one group was urged to perform the swallowing action immediately before intravenous fentanyl (S group), and the other group performed no swallowing action (non-S group). The patients first received intravenous fentanyl and were observed for 90 s. Each patient's background, dose of fentanyl and occurrence of coughing were investigated from their records and a motion picture recording. The incidence of FIC was evaluated by chi-squared test, and severity was tested by Wilcoxon rank-sum test. P fentanyl may be a simple and clinically feasible method for preventing FIC effectively. Clinical trial number: UMIN000012086 ( https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=Rn000014126&language=J ).

  5. Randomized Controlled Study Comparing Use of Propofol Plus Fentanyl versus Midazolam Plus Fentanyl as Sedation in Diagnostic Endoscopy in Patients with Advanced Liver Disease

    OpenAIRE

    Sameh Abdelkhalik Ahmed; Amal Selim; Nehad Hawash; Ahmed Khaled Tawfik; Mohamed Yousef; Abdelrahman Kobtan; Rehab Badawi; Sally Elnawasany; Reham Abdelkader Elkhouly; Amr Shaaban Hanafy; Fatma H. Rizk; Loai Mansour; Sherief Abd-Elsalam

    2017-01-01

    Objectives. We aimed to investigate the safety and efficacy of propofol plus fentanyl versus midazolam plus fentanyl as sedative for patients with advanced liver disease presented for gastrointestinal endoscopy. Methods. A total of 100 patients with liver cirrhosis referred for upper endoscopy were enrolled and divided equally in two groups, midazolam plus fentanyl group and propofol plus fentanyl group. All patients were subjected to history taking, estimation of level of sedation, endoscopi...

  6. Fentanyl sublingual spray for breakthrough cancer pain in patients receiving transdermal fentanyl.

    Science.gov (United States)

    Alberts, David S; Smith, Christina Cognata; Parikh, Neha; Rauck, Richard L

    2016-10-01

    To investigate the relationship between effective fentanyl sublingual spray (FSS) doses for breakthrough cancer pain (BTCP) and around-the-clock (ATC) transdermal fentanyl patch (TFP). Adults tolerating ATC opioids received open-label FSS for 26 days, followed by a 26-day double-blind phase for patients achieving an effective dose (100-1600 µg). Out of 50 patients on ATC TFP at baseline, 32 (64%) achieved an effective dose. FSS effective dose moderately correlated with mean TFP dose (r = 0.4; p = 0.03). Patient satisfaction increased during the study. Common adverse event included nausea (9%) and peripheral edema (9%). FSS can be safely titrated to an effective dose for BTCP in patients receiving ATC TFP as chronic cancer pain medication. ClinicalTrials.gov identifier: NCT00538850.

  7. Life-threatening coma and full-thickness sunburn in a patient treated with transdermal fentanyl patches: a case report

    Directory of Open Access Journals (Sweden)

    Sindali Katia

    2012-07-01

    Full Text Available Abstract Introduction Fentanyl transdermal patches have been widely used in the treatment of chronic pain and in palliative care settings since 1991 in cases where prolonged opioid use is often necessary. Transdermal drug delivery is deemed safe and effective with the advantages of delivering a steady dose of the drug and improving patient compliance due to its ease of use. However, intentional and unintentional misuse and overdose using transdermal opioid patches has been widely reported in the literature. Case presentation We describe the case of a 77-year-old Caucasian woman who developed severe opioid toxicity while sun tanning, likely due to altered fentanyl transdermal patch function in a heated environment. As a result of prolonged sun exposure due to an opioid-induced coma she then sustained hyperthermia and severe burns to her abdomen and lower limbs. This inadvertent fentanyl overdose necessitated initial treatment in intensive care and follow on care in a specialist burn unit. Conclusion Patients who are using fentanyl patches and their relatives should be educated about how to use the patch safely. Healthcare practitioners should warn patients about the possibility of overdosing on transdermally delivered drugs if used incorrectly. They should avoid strenuous activities and external heat sources such as warming blankets, hot water bottles, saunas, hot tubs or sunbathing and should seek medical attention if they develop a fever. Additionally, any burns sustained in the context of altered consciousness levels such as in this case with opioid overdose should raise suspicion about a potential deeper burn injury than is usually observed.

  8. Comparison of equivalent doses of fentanyl buccal tablets and arteriovenous differences in fentanyl pharmacokinetics.

    Science.gov (United States)

    Darwish, Mona; Kirby, Mary; Robertson, Philmore; Hellriegel, Edward; Jiang, John G

    2006-01-01

    The fentanyl buccal tablet (FBT) is designed to enhance the rate and extent of fentanyl absorption through the buccal mucosa. To evaluate the bioequivalence of microg-equivalent doses of FBT administered as single and multiple tablets and assess differences in the arterial and venous pharmacokinetics of FBT in healthy volunteers. Twenty-seven healthy adults, aged 19-45 years, participated in the randomised, open-label, three-period, crossover study. In the first two periods, FBT was administered as four 100 microg tablets simultaneously or one FBT 400 microg to assess bioequivalence. Venous blood samples were obtained over a 72-hour period to measure plasma fentanyl concentrations. In the third period, arterial and venous blood samples were obtained simultaneously from before administration of one FBT 400 microg through 4 hours after administration to evaluate the impact of arterial versus venous sampling on the pharmacokinetic profile. As subjects were not opioid tolerant, naltrexone was administered to block opioid receptor-mediated effects of fentanyl. Adverse events were recorded throughout. Maximum plasma concentration (C(max)) and area under the plasma concentration-time curve from time zero to infinity (AUC(infinity)) on average were approximately 12% and 13% higher, respectively, for FBT administered as four 100 microg tablets simultaneously compared with one FBT 400 microg. Maximum plasma concentrations in the arterial circulation were approximately 60% higher and occurred 15 minutes earlier than those measured from the venous circulation. No serious adverse events were reported during the study. Despite small differences in C(max) and AUC(infinity) (on average 12% and 13%, respectively), FBT administered as four 100 microg tablets simultaneously compared with one 400 microg tablet did not meet the criteria for bioequivalence. An increased surface area exposure with four tablets compared with one tablet may account for the slightly higher maximum

  9. Resurgence of Fentanyl as a Drug of Abuse

    Directory of Open Access Journals (Sweden)

    Lauren P Tamburro

    2016-01-01

    Full Text Available Fentanyl, a powerful opioid analgesic introduced over 50 years ago, has a major role in modern anesthesia and chronic pain relief but has also gained a major role in illicit use. After a spike in fentanyl abuse between 2005 and 2007, fentanyl deaths decreased until 2010, with the introduction of “abuse-deterrent” OxyContin. Our data indicate a recent rise in fentanyl-related deaths beginning in 2013, which follows national trends. With the re-emergence of the synthetic narcotic analgesic of high potency as a popular drug of abuse and the alarmingly increasing mortality associated with its abuse, there are profound implications for public health, health care providers, law enforcement, and the society in general.

  10. Neurotoxic effects of levobupivacaine and fentanyl on rat spinal cord

    Directory of Open Access Journals (Sweden)

    Yesim Cokay Abut

    2015-02-01

    Full Text Available BACKGROUND: The purpose of the study was to compare the neurotoxic effects of intrathecally administered levobupivacaine, fentanyl and their mixture on rat spinal cord. METHODS: In experiment, there were four groups with medication and a control group. Rats were injected 15 µL saline or fentanyl 0.0005 µg/15 µL, levobupivacaine 0.25%/15 µL and fentanyl 0.0005 µg + levobupivacaine 0.25%/15 µL intrathecally for four days. Hot plate test was performed to assess neurologic function after each injection at 5th, 30th and 60th min. Five days after last lumbal injection, spinal cord sections between the T5 and T6 vertebral levels were obtained for histologic analysis. A score based on subjective assessment of number of eosinophilic neurons - Red neuron - which means irreversible neuronal degeneration. They reflect the approximate number of degenerating neurons present in the affected neuroanatomic areas as follows: 1, none; 2, 1-20%; 3, 21-40%; 4, 41-60%; and 5, 61-100% dead neurons. An overall neuropathologic score was calculated for each rat by summating the pathologic scores for all spinal cord areas examined. RESULTS: In the results of HPT, comparing the control group, analgesic latency statistically prolonged for all four groups.In neuropathologic investment, the fentanyl and fentanyl + levobupivacaine groups have statistically significant high degenerative neuron counts than control and saline groups. CONCLUSIONS: These results suggest that, when administered intrathecally in rats, fentanyl and levobupivacaine behave similar for analgesic action, but fentanyl may be neurotoxic for spinal cord. There was no significant degeneration with levobupivacaine, but fentanyl group has had significant degeneration.

  11. Fentanyl-induced respiratory depression is attenuated in pregnant patients

    OpenAIRE

    Cao, Xiaofei; Liu, Shijiang; Sun, Jie; Yu, Min; Fang, Yin; Ding, Zhengnian

    2017-01-01

    Xiaofei Cao,* Shijiang Liu,* Jie Sun, Min Yu, Yin Fang, Zhengnian Ding Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China *These authors contributed equally to this work Background: Respiratory depression is a complication of intravenous fentanyl administration. The effect of pregnancy on respiratory depression following opioid administration is unclear. This study investigated the effect of pregnancy on fentanyl-indu...

  12. Intravenous lidocaine suppresses fentanyl-induced cough in Children

    OpenAIRE

    Gecaj-Gashi, Agreta; Nikolova-Todorova, Zorica; Ismaili-Jaha, Vlora; Gashi, Musli

    2013-01-01

    Objective Fentanyl-induced cough is usually mild and transitory, but it can be undesirable in patients with increased intracranial pressure, open wounds of the eye, dissecting aortic aneurism, pneumothorax, and reactive airway disease. The aim of this study is to evaluate the efficacy of lidocaine in suppressing fentanyl-induced cough in children during induction in general anesthesia. Methods One hundred and eighty-six children of both sexes, aged between 4?10?years, ASA physical status I an...

  13. Self-identification of nonpharmaceutical fentanyl exposure following heroin overdose.

    Science.gov (United States)

    Griswold, Matthew K; Chai, Peter R; Krotulski, Alex J; Friscia, Melissa; Chapman, Brittany; Boyer, Edward W; Logan, Barry K; Babu, Kavita M

    2018-01-01

    To compare user self-identification of nonpharmaceutical fentanyl exposure with confirmatory urine drug testing in emergency department (ED) patients presenting after heroin overdose. This was a cross-sectional study of adult ED patients who presented after a heroin overdose requiring naloxone administration. Participants provided verbal consent after which they were asked a series of questions regarding their knowledge, attitudes and beliefs toward heroin and nonpharmaceutical fentanyl. Participants also provided urine samples, which were analyzed using liquid chromatography coupled to quadrupole time-of-flight mass spectrometry to identify the presence of fentanyl, heroin metabolites, other clandestine opioids, common pharmaceuticals and drugs of abuse. Thirty participants were enrolled in the study period. Ten participants (33%) had never required naloxone for an overdose in the past, 20 participants (67%) reported recent abstinence, and 12 participants (40%) reported concomitant cocaine use. Naloxone was detected in all urine drug screens. Heroin or its metabolites were detected in almost all samples (93.3%), as were fentanyl (96.7%) and its metabolite, norfentanyl (93.3%). Acetylfentanyl was identified in nine samples (30%) while U-47700 was present in two samples (6.7%). Sixteen participants self-identified fentanyl in their heroin (sensitivity 55%); participants were inconsistent in their qualitative ability to identify fentanyl in heroin. Heroin users presenting to the ED after heroin overdose requiring naloxone are unable to accurately identify the presence of nonpharmaceutical fentanyl in heroin. Additionally, cutting edge drug testing methodologies identified fentanyl exposures in 96.7% of our patients, as well as unexpected clandestine opioids (like acetylfentanyl and U-47700).

  14. Plasma Concentrations of Fentanyl Achieved With Transdermal Application in Chickens.

    Science.gov (United States)

    Delaski, Kristina M; Gehring, Ronette; Heffron, Brendan T; Negrusz, Adam; Gamble, Kathryn C

    2017-03-01

    Providing appropriate analgesia is an important concern in any species. Fentanyl, a μ-receptor specific opioid, use is common in mammalian species but has been incompletely evaluated for this purpose in avian species. Transdermal fentanyl patches were applied to domestic chickens (n = 10) of varying breeds for 72 hours. Repeated blood samples were collected from the birds to assess time-concentration of fentanyl and norfentanyl in plasma, as assayed by liquid chromatography-mass spectrometry, throughout patch application and for 48 hours after patch removal. Compartmental modeling was used to characterize the elimination profiles. Evaluation as a large bolus, followed by slower elimination rates over the remaining time, best fit the data as a one-compartment open model. Although maximum plasma fentanyl concentrations varied substantially by individual birds, chickens trended into 2 general groups of maximum plasma concentration, clearance, and volume of distribution, which was attributed to absorption variability. For all birds, harmonic mean of elimination half-life was 7.2 ± 3.7 hours and showed less individual variation than the other pharmacokinetic parameters. Because the application of transdermal fentanyl patches in the chickens achieved plasma fentanyl concentrations considered therapeutic in people, this approach could provide an additional analgesic option for avian patients.

  15. Fentanyl bolus induces muscle tremors in sevoflurane-anaesthetized piglets.

    Science.gov (United States)

    Ringer, S K; Spielmann, N; Weiss, M; Mauch, J Y

    2016-08-01

    Intravenous fentanyl (10 mcg/kg) or saline (control) was randomly administered to 10 healthy sevoflurane-mono-anaesthetized piglets. Trembling was assessed by two blinded observers using a visual analogue scale (VAS) and a simple ordinal scale at baseline and 5 min (T5) after drug administration. If no trembling was observed at that time point, the opposite treatment was administered and piglets were re-evaluated after another 5 min (T10). Four out of five piglets showed trembling after fentanyl (T5), while none given saline showed any trembling. With fentanyl the VAS scores were significantly higher at T5 compared either with baseline or with the control treatment. Control animals received fentanyl after the 5 min evaluation and all piglets showed clear trembling afterwards. The median time after fentanyl administration until first muscle tremors was 51 (20-840) s. In summary, nine out of 10 sevoflurane-anaesthetized piglets showed muscle tremors after intravenous fentanyl. Tremors subsided over time and no specific treatment was necessary. © The Author(s) 2015.

  16. Effect of fentanyl target-controlled infusions on isoflurane minimum anaesthetic concentration and cardiovascular function in red-tailed hawks (Buteo jamaicensis).

    Science.gov (United States)

    Pavez, Juan C; Hawkins, Michelle G; Pascoe, Peter J; Knych, Heather K DiMaio; Kass, Philip H

    2011-07-01

    To determine the impact of three different target plasma concentrations of fentanyl on the minimum anaesthetic concentration (MAC) for isoflurane in the red-tailed hawk and the effects on the haemodynamic profile. Experimental study. Six healthy adult red-tailed hawks (Buteo jamaicensis) of unknown sex with body weights (mean ± SD) of 1.21 ± 0.15 kg. This study was undertaken in two phases. In the first phase anaesthesia was induced with isoflurane in oxygen via facemask and maintained with isoflurane delivered in oxygen via a Bain circuit. Following instrumentation baseline determination of the MAC for isoflurane was made for each animal using the bracketing method and a supramaximal electrical stimulus. End-tidal isoflurane concentration (E'Iso) was then set at 0.75 × MAC and after an appropriate equilibration period a bolus of fentanyl (20 μg kg(-1)) was administered intravenously (IV) in order to determine the pharmacokinetics of fentanyl in the isoflurane-anaesthetized red-tailed hawk. During the second phase anaesthesia was induced in a similar manner and E'Iso was set at 0.75 × MAC for each individual. Fentanyl was infused IV to achieve target plasma concentrations between 8 and 32 ng mL(-1). At each fentanyl plasma concentration, the MAC for isoflurane and cardiovascular variables were determined. Data were analyzed by use of repeated-measures anova. Mean ± SD fentanyl plasma concentrations and isoflurane MACs were 0 ± 0, 8.51 ± 4, 14.85 ± 4.82 and 29.25 ± 11.52 ng mL(-1), and 2.05 ± 0.45%, 1.42 ± 0.53%, 1.14 ± 0.31% and 0.93 ± 0.32% for the target concentrations of 0, 8, 16 and 32 ng mL(-1), respectively. At these concentrations fentanyl significantly (p = 0.0016) decreased isoflurane MAC by 31%, 44% and 55%, respectively. Dose had no significant effect on heart rate, systolic, diastolic or mean arterial blood pressure. Fentanyl produced a dose-related decrease of isoflurane MAC with minimal effects on measured cardiovascular parameters in

  17. 78 FR 44432 - New Animal Drugs; Change of Sponsor; Fentanyl; Iron Injection

    Science.gov (United States)

    2013-07-24

    ... Sponsor; Fentanyl; Iron Injection AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY... interest in, NADA 141-337 for RECUVYRA (fentanyl) Transdermal Solution to Elanco Animal Health, A Division...

  18. Levobupivacaine plus fentanyl versus racemic bupivacaine plus fentanyl in epidural anaesthesia for lower limb surgery.

    Science.gov (United States)

    Casimiro, C; Rodrigo, J; Mendiola, M A; Rey, F; Barrios, A; Gilsanz, F

    2008-01-01

    To compare the anaesthetic epidural effects of levobupivacaine plus fentanyl versus bupivacaine plus fentanyl in patients undergoing lower limb surgery. A single blind, randomised, prospective, multicentre study was designed to compare both therapies. The study was conducted in 10 tertiary hospitals. A total of 96 patients who were ASA I or II, who required at least a 24-hour-stay in the hospital and who were subjected to surgery of lower limbs with epidural anaesthesia were enrolled in this study. Treatments were administered at a dosage of 1.2 ml per metamera,including a test dose (3 mL) and the dose of fentanyl (100 mg). Patients were then randomly allocated to receive either Levobupivacaine (n = 49) or bupivacaine (N.= 47). The primary endpoint was sensory blockade (SB) duration. Secondary evaluations included motor blockade (MB), post-surgery analgesic medication usage, safety and the investigator global evaluation. SB duration was similar for both interventions: 195 min (165-205) in the bupivacaine group versus 170 min (140-185) in the levobupivicaine group (log-rank test, P=0.884). However, the lack of MB as evaluated by the modified Bromage scale was significantly higher in the levobupivacaine group than in the bupivacaine group (39% vs 13%, P=0.017). Although no significant differences in MB duration were observed between the groups, a trend was observed in the levobupivacaine group, which had a lesser MB (P=0.093). Investigator satisfaction was high and was assessed to a similar extent for both interventions. Forty-one adverse events were detected in 28 patients, with no differences between groups: 15 (33%) with bupivacaine and 13 (27%) with levobupivacaine, P=0.516. Although both interventions showed similar anaesthetic effects, a higher proportion of patients receiving levobupivacaine lacked MB.

  19. Increases in Fentanyl-Related Overdose Deaths - Florida and Ohio, 2013-2015.

    Science.gov (United States)

    Peterson, Alexis B; Gladden, R Matthew; Delcher, Chris; Spies, Erica; Garcia-Williams, Amanda; Wang, Yanning; Halpin, John; Zibbell, Jon; McCarty, Carolyn Lullo; DeFiore-Hyrmer, Jolene; DiOrio, Mary; Goldberger, Bruce A

    2016-08-26

    In March and October 2015, the Drug Enforcement Administration (DEA) and CDC issued nationwide alerts identifying fentanyl, particularly illicitly manufactured fentanyl (IMF), as a threat to public health and safety (1,2). IMF is pharmacologically similar to pharmaceutical fentanyl (PF), but is unlawfully produced in clandestine laboratories, obtained via illicit drug markets, and includes fentanyl analogs. Fentanyl is a synthetic opioid 50-100 times more potent than morphine and approved for the management of surgical/postoperative pain, severe chronic pain, and breakthrough cancer pain.* DEA's National Forensic Laboratory Information System (NFLIS) collects drug identification results from drug cases analyzed by federal, state, and local forensic laboratories throughout the United States.(†) In 2014, 80% of fentanyl submissions (i.e., drug products obtained by law enforcement that tested positive for fentanyl) in NFLIS were identified from 10 states, including Florida and Ohio (2), and seven of these 10 states reported sharp increases in fentanyl-related overdose deaths (fentanyl deaths) (3). This report presents findings of increased fentanyl deaths during 2013-2015 from investigations conducted by the University of Florida and the Ohio Department of Public Health, in collaboration with CDC. Analyses examined the association between trends in fentanyl-related law enforcement submissions and fentanyl deaths and describes groups at risk for fentanyl death using medical examiner and coroner reports. The marked increases in fentanyl death in Florida and Ohio during 2013-2015 were closely associated with parallel increases in fentanyl submissions, with the largest impact on persons who use heroin, consistent with reports that IMF is commonly mixed with or sold as heroin (1,4). In Ohio, circumstances associated with fentanyl deaths included a current diagnosed mental health disorder(§) and recent release from an institution such as a jail, rehabilitation facility

  20. Treatment with subcutaneous and transdermal fentanyl: Results from a population pharmacokinetic study in cancer patients

    NARCIS (Netherlands)

    A.W. Oosten (Astrid); J.A. Abrantes (João A.); S. Jönsson (Siv); P. de Bruijn (Peter); E.J.M. Kuip (Evelien); A. Falcão (Amílcar); C.C.D. van der Rijt (Carin); A.H.J. Mathijssen (Ron)

    2016-01-01

    textabstractPurpose: Transdermal fentanyl is effective for the treatment of moderate to severe cancer-related pain but is unsuitable for fast titration. In this setting, continuous subcutaneous fentanyl may be used. As data on the pharmacokinetics of continuous subcutaneous fentanyl are lacking, we

  1. Treatment with subcutaneous and transdermal fentanyl: results from a population pharmacokinetic study in cancer patients

    NARCIS (Netherlands)

    Oosten, A.W.; Abrantes, J.A.; Jonsson, S.; Bruijn, P. de; Kuip, E.J.M.; Falcao, A.; Rijt, C.C. van der; Mathijssen, R.H.

    2016-01-01

    PURPOSE: Transdermal fentanyl is effective for the treatment of moderate to severe cancer-related pain but is unsuitable for fast titration. In this setting, continuous subcutaneous fentanyl may be used. As data on the pharmacokinetics of continuous subcutaneous fentanyl are lacking, we studied the

  2. 77 FR 47511 - New Animal Drugs; Cephalexin; Fentanyl; Milbemycin Oxime and Praziquantel

    Science.gov (United States)

    2012-08-09

    ... Drug Administration 21 CFR Parts 510, 520, and 524 New Animal Drugs; Cephalexin; Fentanyl; Milbemycin...-337 Nexcyon RECUVYRA (fentanyl) Original approval for New yes CE \\1\\ Pharmaceuticals, Transdermal... follows: Authority: 21 U.S.C. 360b. 0 10. Add Sec. 524.916 to read as follows: Sec. 524.916 Fentanyl. (a...

  3. Single-dose and steady-state pharmacokinetics of fentanyl buccal tablet in healthy volunteers.

    Science.gov (United States)

    Darwish, Mona; Kirby, Mary; Robertson, Philmore; Hellriegel, Edward; Jiang, John G

    2007-01-01

    This study evaluated the single-dose and steady-state pharmacokinetics of fentanyl buccal tablet 400 microg in healthy adult volunteers. After receiving naltrexone 50 mg to block opioid receptor-mediated effects of fentanyl, subjects received fentanyl buccal tablet 400 microg on day 1, then every 6 hours from day 4 to day 9 (21 doses). Naltrexone 50 mg was administered every 12 hours throughout the study. Plasma fentanyl concentrations were determined for 72 hours after administration of fentanyl buccal tablet 400 microg on day 1 and the last dose of fentanyl buccal tablet 400 microg on day 9. Following single- and multiple-dose administration of fentanyl buccal tablet, the median time to maximum concentration (tmax) was 52.2 and 49.8 minutes, respectively. Peak plasma concentration of fentanyl (Cmax) was 0.88 ng/mL for the single-dose regimen and 1.77 ng/mL for the multiple-dose regimen. Steady state was reached within 5 days, consistent with the observed median half-life of approximately 22 hours following multiple doses. Observed accumulation of fentanyl after multiple doses of fentanyl buccal tablet was slightly greater than would be expected based on the single-dose data. This was attributed to the redistribution of fentanyl from a deep tissue compartment into the plasma. This study indicates that fentanyl buccal tablet has predictable pharmacokinetics following multiple-dose administration.

  4. Effectiveness of prehospital morphine, fentanyl, and methoxyflurane in pediatric patients.

    Science.gov (United States)

    Bendall, Jason C; Simpson, Paul M; Middleton, Paul M

    2011-01-01

    To compare the effectiveness of intravenous morphine, intranasal (IN) fentanyl, and inhaled methoxyflurane for managing moderate to severe pain in pediatric patients in the out-of-hospital setting. We conducted a retrospective comparative study of 3,312 pediatric patients aged between 5 and 15 years who had moderate to severe pain (pain score ≥ 5) and who received intravenous morphine, IN fentanyl, or inhaled methoxyflurane, either alone or in combination, between January 1, 2004, and November 30, 2006. Multivariate logistic regression was used to analyze data extracted from a clinical database containing routinely entered information from patient health care records. The primary outcome measure was effective analgesia, defined as a reduction in pain severity of ≥ 30% of initial pain score using an 11-point verbal numeric rating scale. Effective analgesia was achieved in 82.5% of cases overall. All analgesic agents were effective in the majority of patients (87.5%, 89.5%, and 78.3% for morphine, fentanyl, and methoxyflurane, respectively). There was evidence that methoxyflurane was less effective than both morphine (odds ratio [OR] 0.52; 95% confidence interval [CI] 0.36-0.74) and fentanyl (OR 0.43; 95% CI 0.29-0.62; p Methoxyflurane is less effective in comparison with both morphine and fentanyl, but is an effective analgesic in the majority of children.

  5. Significant Bradycardia in Critically Ill Patients Receiving Dexmedetomidine and Fentanyl

    Directory of Open Access Journals (Sweden)

    Channing Hui

    2017-01-01

    Full Text Available Purpose. To report a case series of three patients who developed significant bradycardia while receiving the combination of dexmedetomidine and fentanyl for sedation and analgesia. Materials and Methods. This is a case series of patients obtained from a mixed medical, surgical, and cardiac ICU in a community teaching hospital. Three intubated patients receiving fentanyl and dexmedetomidine infusion developed sudden bradycardia requiring intervention. In all three cases, adjustments to therapy were required. Results. All three patients experienced significant bradycardia, with a heart rate less than 50 bpm, and one patient briefly developed asystole. In Case  1, the fentanyl infusion rate was reduced by 67% and the dexmedetomidine infusion rate was reduced by 25%. In Case  2, the sedation was changed to midazolam, and in Case  3, both fentanyl and dexmedetomidine were discontinued. In all three cases, there were no further incidences of significant bradycardia following intervention. Conclusions. Fentanyl used in combination with dexmedetomidine can result in clinically significant bradycardia. Further study is warranted to identify risk factors and elucidate the mechanisms that result in life-threatening bradycardia.

  6. Efficacy and safety of sublingual fentanyl orally disintegrating tablets in patients with breakthrough pain: multicentre prospective study.

    Science.gov (United States)

    Guitart, Jordi; Vargas, Isabel; De Sanctis, Vicente; Ferreras, Julia; Fuentes, Jose; Salazar, Rafael; Vázquez, Juan M; Folch, Jordi; Moya, Jordi; Ribera, Hermann; Rodelas, Francisco; Tomás, Albert; Arilla, María; Coma, Joan; Aberasturi, Teresa; Sintes, Dolores; Lombán, Ester

    2013-09-01

    number of daily BTP episodes decreased in both groups, but it was statistically significant in BTcP. 114 patients (62.64 %) experienced AEs during the study. AEs recorded included nausea, vomiting, somnolence and constipation, and seven (4.49 %) were considered severe. No death or discontinuation was considered related to AEs. Sublingual fentanyl ODT provided rapid and consistent relief from BTP, both in cancer and non-cancer patients. It was well-tolerated and well-accepted by patients in routine clinical practice.

  7. Bronchial mucus transport velocity in patients receiving desflurane and fentanyl vs. sevoflurane and fentanyl.

    Science.gov (United States)

    Ledowski, T; Manopas, A; Lauer, S

    2008-09-01

    Sevoflurane has been shown to distinctly reduce bronchial mucus transport velocity, an essential determinant of mucociliary clearance and pulmonary complications. However, sevoflurane is regarded as one of the least irritant volatile anaesthetics, especially when compared with desflurane. Hence, the aim of this double-blind, randomized, controlled trial was to assess differences in bronchial mucus transport velocity between sevoflurane and desflurane. Twenty patients listed for general surgery were randomized to receive either maintenance of anaesthesia with desflurane and fentanyl, or sevoflurane and fentanyl. Thirty minutes after tracheal intubation, bronchial mucus transport velocity was assessed by fibreoptic observation of the movement of methylene blue dye applied to the dorsal surface of the right main bronchus. Both agents distinctly reduced bronchial mucus transport velocity when compared with previous studies, but the degree of impairment did not significantly differ between the investigated groups (median [25%/75% percentile]): desflurane 1.5 [0.5/4.2] vs. sevoflurane 1.3 [0.3/2.9] mm min(-1), P = 0.343). Desflurane is commonly regarded as more irritant to the airway, but as far as bronchial mucus transport velocity is concerned, the choice between sevoflurane and desflurane does not seem to matter.

  8. Saliva versus Plasma for Pharmacokinetic and Pharmacodynamic Studies of Fentanyl in Patients with Cancer.

    Science.gov (United States)

    Bista, Sudeep R; Haywood, Alison; Norris, Ross; Good, Phillip; Tapuni, Angela; Lobb, Michael; Hardy, Janet

    2015-11-01

    Fentanyl is widely used to relieve cancer pain. However there is great interpatient variation in the dose required to relieve pain and little knowledge about the pharmacokinetic and pharmacodynamic (PK/PD) relationship of fentanyl and pain control. Patients with cancer are fragile and there is reluctance on the part of health professionals to take multiple plasma samples for PK/PD studies. The relationship between plasma and saliva fentanyl concentrations was investigated to determine whether saliva could be a valid substitute for plasma in PK/PD studies. One hundred sixty-three paired plasma and saliva samples were collected from 56 patients prescribed transdermal fentanyl (Durogesic, Janssen-Cilag Pty Limited, NSW, Australia) at varying doses (12-200 µg/h). Pain scores were recorded at the time of sampling. Fentanyl and norfentanyl concentrations in plasma and saliva were quantified using HPLC-MS/MS. Saliva concentrations of fentanyl (mean = 4.84 μg/L) were much higher than paired plasma concentrations of fentanyl (mean = 0.877 μg/L). Both plasma and saliva mean concentrations of fentanyl were well correlated with dose with considerable interpatient variation at each dose. The relationship between fentanyl and norfentanyl concentrations was poor in both plasma and saliva. No correlation was observed between fentanyl concentration in plasma and saliva (r(2) = 0.3743) or free fentanyl in plasma and total saliva concentrations (r(2) = 0.1374). Pain scores and fentanyl concentration in either of the matrices were also not correlated. No predictive correlation was observed between plasma and saliva fentanyl concentration. However the detection of higher fentanyl concentrations in saliva than plasma, with a good correlation to dose, may allow saliva to be used as an alternative to plasma in PK/PD studies of fentanyl in patients with cancer. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

  9. Postmortem Tissue Distribution of Acetyl Fentanyl, Fentanyl and their Respective Nor-Metabolites Analyzed by Ultrahigh Performance Liquid Chromatography with Tandem Mass Spectrometry

    Science.gov (United States)

    Poklis, Justin; Poklis, Alphonse; Wolf, Carl; Mainland, Mary; Hair, Laura; Devers, Kelly; Chrostowski, Leszek; Arbefeville, Elise; Merves, Michele; Pearson, Julia

    2015-01-01

    In the last two years, an epidemic of fatal narcotic overdose cases has occurred in the Tampa area of Florida. Fourteen of these deaths involved fentanyl and/or the new designer drug, acetyl fentanyl. Victim demographics, case histories, toxicology findings and causes and manners of death, as well as, disposition of fentanyl derivatives and their nor-metabolites in postmortem heart blood, peripheral blood, bile, brain, liver, urine and vitreous humor are presented. In the cases involving only acetyl fentanyl (without fentanyl, n=4), the average peripheral blood acetyl fentanyl concentration was 0.467 mg/L (range 0.31 to .60 mg/L) and average acetyl norfentanyl concentration was 0.053 mg/L (range 0.002 to 0.086 mg/L). In the cases involving fentanyl (without acetyl fentanyl, n=7), the average peripheral blood fentanyl concentration was 0.012 mg/L (range 0.004 to 0.027 mg/L) and average norfentanyl blood concentration was 0.001 mg/L (range 0.0002 to 0.003 mg/L). In the cases involving both acetyl fentanyl and fentanyl (n=3), the average peripheral blood acetyl fentanyl concentration was 0.008 mg/L (range 0.006 to 0.012 mg/L), the average peripheral blood acetyl norfentanyl concentration was 0.001 mg/L (range 0.001 to 0.002 mg/L), the average peripheral blood fentanyl concentration was 0.018 mg/L (range 0.015 to 0.021 mg/L) and the average peripheral blood norfentanyl concentration was 0.002 mg/L (range 0.001 mg/L to 0.003 mg/L). Based on the toxicology results, it is evident that when fentanyl and/or acetyl fentanyl were present, they contributed to the cause of death. A novel ultrahigh performance liquid chromatography (UPLC) tandem mass spectrometry (MS/MS) method to identify and quantify acetyl fentanyl, acetyl norfentanyl, fentanyl and norfentanyl in postmortem fluids and tissues is also presented. PMID:26583960

  10. Whole fentanyl patch ingestion: a multi-center case series.

    Science.gov (United States)

    Mrvos, Rita; Feuchter, Alexander C; Katz, Kenneth D; Duback-Morris, Lynn F; Brooks, Daniel E; Krenzelok, Edward P

    2012-05-01

    Fentanyl is a potent synthetic opioid with large abuse potential. A common preparation of fentanyl is a sustained-release transdermal patch. To our knowledge, there are only two published case reports of whole patch ingestion. A case series of 76 patients with a history of whole patch ingestion is reported. To characterize whole fentanyl patch ingestion to develop a clinical guideline for management. This was a retrospective review of all patients who ingested intact fentanyl patches as reported to three regional poison information centers (RPIC) from 2000 to 2008. The three RPIC medical record databases were queried for all exposures with a substance code matching the Micromedex® (Thomson Reuters, New York, NY) fentanyl product codes. Collected data included: age, gender, reason for the exposure, number of patches ingested, dose (μg/h), symptoms, symptom onset and duration, treatment hospital flow (level of care), and outcome. A total of 76 patients met the inclusion criteria. Two patients had both time of onset and symptom duration documented. In both patients, the signs and symptoms developed within 2 h of the exposure, and the patients were asymptomatic at 6½ and 9 h, respectively. Fifty-eight (78.3%) patients were admitted. Of those patients who were admitted, 56 (96.5%) were admitted to a critical care unit. Fourteen patients required intubation, and naloxone infusions were documented in eight cases. Ingestion of whole fentanyl patches may lead to prolonged and significant toxicity based on these poison center data. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Schedules of Controlled Substances: Temporary Placement of ortho-Fluorofentanyl, Tetrahydrofuranyl Fentanyl, and Methoxyacetyl Fentanyl Into Schedule I. Temporary amendment; temporary scheduling order.

    Science.gov (United States)

    2017-10-26

    The Administrator of the Drug Enforcement Administration is issuing this temporary scheduling order to schedule the synthetic opioids, N-(2-fluorophenyl)-N-(1-phenethylpiperidin-4-yl)propionamide (ortho-fluorofentanyl or 2-fluorofentanyl), N-(1-phenethylpiperidin-4-yl)-N-phenyltetrahydrofuran-2-carboxamide (tetrahydrofuranyl fentanyl), and 2-methoxy-N-(1-phenethylpiperidin-4-yl)-N-phenylacetamide (methoxyacetyl fentanyl), into Schedule I. This action is based on a finding by the Administrator that the placement of ortho-fluorofentanyl, tetrahydrofuranyl fentanyl, and methoxyacetyl fentanyl into Schedule I of the Controlled Substances Act is necessary to avoid an imminent hazard to the public safety. As a result of this order, the regulatory controls and administrative, civil, and criminal sanctions applicable to Schedule I controlled substances will be imposed on persons who handle (manufacture, distribute, reverse distribute, import, export, engage in research, conduct instructional activities or chemical analysis, or possess), or propose to handle, ortho-fluorofentanyl, tetrahydrofuranyl fentanyl, and methoxyacetyl fentanyl.

  12. Treatment of tetralogy of Fallot hypoxic spell with intranasal fentanyl.

    Science.gov (United States)

    Tsze, Daniel S; Vitberg, Yaffa M; Berezow, Joel; Starc, Thomas J; Dayan, Peter S

    2014-07-01

    We present the case of a 3-month-old girl who had unrepaired Tetralogy of Fallot who presented to the emergency department with an acute hypoxic episode. The patient was hyperpneic and cyanotic, with an initial oxygen saturation of 56%. She did not respond to knee-to-chest positioning. A single dose of intranasal fentanyl was administered with subsequent resolution of her symptoms and improvement of her oxygen saturation to 78% within 10 minutes. To our knowledge, this is the first report of the successful treatment of a hypoxic episode of Tetralogy of Fallot using intranasal fentanyl. Copyright © 2014 by the American Academy of Pediatrics.

  13. An efficient, optimized synthesis of fentanyl and related analogs.

    Directory of Open Access Journals (Sweden)

    Carlos A Valdez

    Full Text Available The alternate and optimized syntheses of the parent opioid fentanyl and its analogs are described. The routes presented exhibit high-yielding transformations leading to these powerful analgesics after optimization studies were carried out for each synthetic step. The general three-step strategy produced a panel of four fentanyls in excellent yields (73-78% along with their more commonly encountered hydrochloride and citric acid salts. The following strategy offers the opportunity for the gram-scale, efficient production of this interesting class of opioid alkaloids.

  14. Pharmacokinetic Interaction Between Tacrolimus and Fentanyl in Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Kitazawa, Fumiaki; Fuchida, Shin-Ichi; Kado, Yoko; Ueda, Kumi; Kokufu, Takatoshi; Okano, Akira; Hatsuse, Mayumi; Murakami, Satoshi; Nakayama, Yuko; Takara, Kohji; Shimazaki, Chihiro

    2017-09-26

    BACKGROUND Tacrolimus and fentanyl are well-known cytochrome P450 (CYP) 3A4 substrates with a narrow therapeutic range. However, the pharmacokinetic interaction between tacrolimus and fentanyl is unclear. The aim of this study was to determine whether drug interaction exists between tacrolimus and fentanyl. MATERIAL AND METHODS A retrospective study was performed in 6 patients who had received allogeneic hematopoietic stem cell transplantation between April 2010 and March 2015. The patients received continuous intravenous infusion of fentanyl with concomitant use of tacrolimus, and the blood concentrations of tacrolimus were evaluated using fluorescence polarization immunoassay. RESULTS The clearance (CL) of tacrolimus decreased significantly from 1.28 to 0.68 mL/min/kg with concomitant use of fentanyl. The CL changed with time and dose of fentanyl administration. In addition, the CL of tacrolimus was reverted by stopping fentanyl infusion. Horn's drug interaction probability scale indicated a probable category or possible category, suggesting a drug interaction between tacrolimus and fentanyl. No patient showed a difference in hepatic or renal function before and after fentanyl administration. No additional administration of other CYP3A4 inhibitors was observed, suggesting that the drug interaction was mediated by CYP3A4. CONCLUSIONS The influence of fentanyl on the pharmacokinetics of tacrolimus was demonstrated to be of clinical importance. It is proposed that the dose of tacrolimus be reduced by 40% when used in combination with fentanyl.

  15. A review of factors explaining variability in fentanyl pharmacokinetics; focus on implications for cancer patients.

    Science.gov (United States)

    Kuip, Evelien J M; Zandvliet, Maarten L; Koolen, Stijn L W; Mathijssen, Ron H J; van der Rijt, Carin C D

    2017-02-01

    Fentanyl is a strong opioid that is available for various administration routes, and which is widely used to treat cancer-related pain. Many factors influence the fentanyl pharmacokinetics leading to a wide inter- and intrapatient variability. This systematic review summarizes multiple studied factors that potentially influence fentanyl pharmacokinetics with a focus on implications for cancer patients. The use of CYP3A4 inhibitors and inducers, impaired liver function, and heating of the patch potentially influence fentanyl pharmacokinetics in a clinically relevant way. In elderly patients, current data suggest that we should carefully dose fentanyl due to alterations in absorption and metabolism. The influence of BMI and gender on fentanyl pharmacokinetics is questionable, most probably due to a large heterogeneity in the published studies. Pharmacogenetics, e.g. the CYP3A5*3 gene polymorphism, may influence fentanyl pharmacokinetics as well, although further study is warranted. Several other factors have been studied but did not show significant and clinically relevant effects on fentanyl pharmacokinetics. Unfortunately, most of the published papers that studied factors influencing fentanyl pharmacokinetics describe healthy volunteers instead of cancer patients. Results from the studies in volunteers may not be simply extrapolated to cancer patients because of multiple confounding factors. To handle fentanyl treatment in a population of cancer patients, it is essential that physicians recognize factors that influence fentanyl pharmacokinetics, thereby preventing potential side-effects and increasing its efficacy. © 2016 The British Pharmacological Society.

  16. A physiologically-based recirculatory meta-model for nasal fentanyl in man

    DEFF Research Database (Denmark)

    Upton, RN; Foster, DJR; Christrup, Lona Louring

    2012-01-01

    Pharmacokinetic (PK) and pharmacodynamic (PD) data were available from a study of a nasal delivery system for the opioid analgesic fentanyl, together with data on the kinetics of fentanyl in arterial blood in man, and in the lung and brain of sheep. Our aim was to reconcile these data using...... a physiologically-based population recirculatory PK-PD model, with emphasis on achieving a meta-model that could simultaneously account for the arterial and venous (arm) concentrations of fentanyl, could relate PD effects (pain scores) to the CNS concentrations of fentanyl, and could account for the effect of body...... size and age on fentanyl kinetics. Data on the concentration gradients of fentanyl across brain, lung and muscle were used to develop sub-models of fentanyl kinetics in these organs. The sub-models were incorporated into a "whole body" recirculatory model by adding additional sub-models for a venous...

  17. Comparison between Infusion Pumps: Fentanyl/Ketamine and Fentanyl/Paracetamol in Pain control Following Tight and Leg Surgeries

    Directory of Open Access Journals (Sweden)

    Behnam Mahmoodiyeh

    2016-08-01

    Full Text Available Background: Adjuvants such as ketamine, promethazine and paracetamol could bring up patients satisfaction and control harmful effects of opioids besides lessening their needed doses, as seen by fentanyl/paracetamol and fentanyl/ketamine combination before. The current study headed to compare paracetamol and ketamine in addition to fentanyl applied by infusion pumps in order to pain relief following major surgery.Methods: Through a double blinded randomized clinical trial, patients between18 and 65 with elective surgery for tight or leg fractures with ASA Class 1 and 2 referring to a university hospital in Arak, a town in central region of Iran, were recruited and used infusion pump for their postoperative pain control. The participants were divided into cases and controls regarding using ketamine/fentanyl (KF or paracetamol/fentanyl (PF infusion pumps.Results: The mean pain score was totally 3.87 with higher value in KF (5.06 and lower in PF (4.5 immediately after finishing surgery and getting conscious when started using infusion pump. There was no statistical difference between the groups in this regard. Concerning the side effects of the applied medications, blood pressure and heart rate had no differences comparing the groups.Conclusion: This study showed that paracetamol used in infusion pump can be brilliant in pain control after major surgeries like what done in lower extremities and joint replacement while lessens opioid use. Although paracetamol was more effective than ketamine in the current trial, more qualified studies at bigger size and in other fields of surgery beside orthopedic ones would be useful to support the effects if applicable.Keywords: Infusion pump, Ketamine, Paracetamol, Fentanyl, Postoperative pain

  18. A randomized controlled trial comparing intranasal fentanyl to intravenous morphine for managing acute pain in children in the emergency department.

    Science.gov (United States)

    Borland, Meredith; Jacobs, Ian; King, Barbara; O'Brien, Debra

    2007-03-01

    We compare the efficacy of intranasal fentanyl versus intravenous morphine in a pediatric population presenting to an emergency department (ED) with acute long-bone fractures. We conducted a prospective, randomized, double-blind, placebo-controlled, clinical trial in a tertiary pediatric ED between September 2001 and January 2005. A convenience sample of children aged 7 to 15 years with clinically deformed closed long-bone fractures was included to receive either active intravenous morphine (10 mg/mL) and intranasal placebo or active intranasal concentrated fentanyl (150 microg/mL) and intravenous placebo. Exclusion criteria were narcotic analgesia within 4 hours of arrival, significant head injury, allergy to opiates, nasal blockage, or inability to perform pain scoring. Pain scores were rated by using a 100-mm visual analog scale at 0, 5, 10, 20, and 30 minutes. Routine clinical observations and adverse events were recorded. Sixty-seven children were enrolled (mean age 10.9 years [SD 2.4]). Fractures were radius or ulna 53 (79.1%), humerus 9 (13.4%), tibia or fibula 4 (6.0%), and femur 1 (1.5%). Thirty-four children received intravenous (i.v.) morphine and 33 received intranasal fentanyl. Statistically significant differences in visual analog scale scores were not observed between the 2 treatment arms either preanalgesia or at 5, 10, 20, or 30 minutes postanalgesia (P=.333). At 10 minutes, the difference in mean visual analog scale between the morphine and fentanyl groups was -5 mm (95% confidence interval -16 to 7 mm). Reductions in combined pain scores occurred at 5 minutes (20 mm; P=.000), 10 minutes (4 mm; P=.012), and 20 minutes (8 mm; P=.000) postanalgesia. The mean total INF dose was 1.7 microg/kg, and the mean total i.v. morphine dose was 0.11 mg/kg. There were no serious adverse events. Intranasal fentanyl delivered as 150 microg/mL at a dose of 1.7 microg/kg was shown to be an effective analgesic in children aged 7 to 15 years presenting to an ED with

  19. Efficacy of intrathecal midazolam versus fentanyl for endoscopic ...

    African Journals Online (AJOL)

    Background: This prospective randomized double-blind study was designed to compare the analgesic efficacy and safety of intrathecal midazolam versus fentanyl as an adjunct to bupivacaine for endoscopic urology surgery. Methods: Sixty adult ASA grade I–II patients undergoing transurethral resection of prostate or ...

  20. Intrathecal tramadol versus intrathecal fentanyl for visceral pain ...

    African Journals Online (AJOL)

    2013-10-29

    Oct 29, 2013 ... local anesthetic agents during management of visceral pain of appendicectomy in Africa in general and in Nigeria in particular. Intrathecal tramadol versus intrathecal fentanyl for visceral pain control during bupivacaine subarachnoid block for open appendicectomy. JM Afolayan, TO Olajumoke1, ...

  1. Efficacy of intrathecal midazolam versus fentanyl for endoscopic

    African Journals Online (AJOL)

    intrathecal midazolam versus fentanyl as an adjunct to bupivacaine for endoscopic urology surgery. Methods: Sixty adult ASA grade I–II patients undergoing transurethral resection of prostate or bladder tumor under spinal block. Postoperative analgesia was provided with intravenous diclofenac. The onset and duration of ...

  2. [Analgesic effect of fentanyl in neonates during mechanical ventilation].

    Science.gov (United States)

    Chen, Shu-Shu; Liu, Ling; Hu, Pin; Shi, Bi-Zhen; Fu, Yi-Kang; Luo, Rui; Xie, Cai

    2015-10-01

    To study the analgesic effect and safety of fentanyl in neonates receiving mechanical ventilation. Thirty neonates receiving mechanical ventilation between December 2010 and February 2011 were randomized into drug intervention group and control group (n=15 each). In addition to the conventional treatment for both groups, the drug intervention group received fentanyl as the analgesic treatment. Heart rate, respiratory rate, blood pressure changes, and premature infant pain profile (PIPP) score before treatment and at 30 minutes, 2 hours, and 4 hours after treatment were recorded in both groups. Follow-up visits were performed for these infants after discharge, and the CDCC intellectual development scale for infants was applied to measure mental development index (MDI) and psychomotor development index (PDI) at 3, 6, 9, and 12 months of age. The respiratory rate and heart rate decreased in the drug intervention group after fentanyl treatment compared with the control group (Pcontrol group (Pcontrol groups (P>0.05). Fentanyl can relieve the pain response in neonates receiving mechanical ventilation, with no long-term adverse effects on neurodevelopment.

  3. Fatalities Involving Carfentanil and Furanyl Fentanyl: Two Case Reports.

    Science.gov (United States)

    Swanson, Dina M; Hair, Laura S; Strauch Rivers, Selly R; Smyth, Brianna C; Brogan, Sara C; Ventoso, Alexis D; Vaccaro, Samantha L; Pearson, Julia M

    2017-07-01

    Carfentanil is a fentanyl analog frequently used in large animal veterinary medicine. Recently, carfentanil has been discovered in postmortem and antemortem cases throughout the United States in the heroin supply either alone or mixed with heroin and/or other fentanyl analogs. The potency of carfentanil is ~10,000 times greater than morphine and 100 times greater than fentanyl. In two recent cases, carfentanil was identified and ruled to be the cause of death, either alone or in combination with other drugs. Case 1 involved a known heroin user. He was discovered slumped over in a running van blocking the bays of a carwash. Two syringes, a spoon with cotton and residue and a yellow baggie of powder were found in the van. Case 2 involved a man living in a tent in a park with his mother. He was last heard from by a sister via phone who stated he sounded very intoxicated and by his mother who noted him to be "itching all over" and upset over his girlfriend. When the mother returned from work, she discovered him unresponsive with a small baggie of brown powder next to him. Routine drug and volatile screening tests were performed on heart blood using headspace gas chromatography, immunoassay and gas chromatography mass spectrometry methods. Results from initial testing on both cases did not have any significant toxicological findings. However, due to the history, scene photos, toxicological findings in blood and urine and analysis of the drug paraphernalia on one of the cases which identified carfentanil and furanyl fentanyl, fentanyl analogues were suspected. Heart blood was sent to a reference laboratory for carfentanil and furanyl fentanyl analysis. Case 1 had a carfentanil concentration of 1.3 ng/mL and a furanyl fentanyl concentration of 0.34 ng/mL. Case 2 had a carfentanil concentration of 0.12 ng/mL. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Radioreceptor assay for analysis of fentanyl and its analogs in biological samples

    Energy Technology Data Exchange (ETDEWEB)

    Alburges, M.E.

    1988-01-01

    The assay is based on the competition of these drugs with ({sup 3}H) fentanyl for opioid receptors in membrane preparations of rat forebrain in vitro. The binding in stereospecific, reversible and saturable. Scatchard plots of saturation suggest the presence of high and low affinity binding sites. Morphine and hydromorphone complete with ({sup 3}H)fentanyl for the opioid receptor, but other morphine-like compounds were relatively weak displacers of ({sup 3}H)fentanyl. Many other commonly abused drugs do not compete with ({sup 3}H)fentanyl for the opioid receptors. Urine samples from animals injected with fentanyl, ({plus minus})-cis-3-methylfentanyl, alpha-methylfentanyl, butyrylfentanyl and benzylfentanyl were analyzed by radioreceptor assay, radioimmunoassay, and gas chromatography/mass spectrometry. Urinary analysis of fentanyl showed a good correlation with these three methods; however, discrepancies were observed in the analysis of fentanyl analogs. This radioreceptor assay is well-suited as an initial assay for the detection of active analogs of fentanyl in urine with good correlation with other techniques in the analysis of fentanyl; however, there is substantial disagreement between techniques in the quantitation of fentanyl analogs. The implications of these discrepancies are discussed.

  5. Pharmacokinetics of 2 Formulations of Transdermal Fentanyl in Cynomolgus Macaques (Macaca fascicularis)

    Science.gov (United States)

    Carlson, Amy M; Kelly, Richard; Fetterer, David P; Rico, Pedro J; Bailey, Emily J

    2016-01-01

    Fentanyl is a μ-opioid agonist that often is used as the analgesic component for balanced anesthesia in both human and veterinary patients. Minimal information has been published regarding appropriate dosing, and the pharmacokinetics of fentanyl are unknown in NHP. The pharmacokinetic properties of 2 transdermal fentanyl delivery methods, a solution (2.6 and 1.95 mg/kg) and a patch (25 µg/h), were determined when applied topically to the dorsal scapular area of cynomolgus macaques (Macaca fascicularis). Serum fentanyl concentrations were analyzed by using liquid chromatography–mass spectrometry. Compared with the patch, the transdermal fentanyl solution generated higher drug concentrations over longer time. Adverse reactions occurred in the macaques that received the transdermal fentanyl solution at 2.6 mg/kg. Both preparations showed significant interanimal variability in the maximal serum drug levels, time to achieve maximal fentanyl levels, elimination half-life, and AUC values. Both the maximal concentration and the time at which this concentration occurred were increased in macaques compared with most other species after application of the transdermal fentanyl patch and compared with dogs after application of the transdermal fentanyl solution. The pharmacokinetic properties of transdermal fentanyl in macaques are markedly different from those in other veterinary species and preclude its use as a long-acting analgesic drug in NHP. PMID:27423151

  6. Study of the newborn feeding behaviors and fentanyl concentration in colostrum after an analgesic dose of epidural and intravenous fentanyl in cesarean section.

    Science.gov (United States)

    Goma, Hala M; Said, Reem N; El-Ela, Amr M

    2008-05-01

    To compare the effects of epidural and intravenous fentanyl on breast feeding behaviors and fentanyl concentration in the colostrum after an analgesic dose. This study was conducted at the Obstetrics Department of Kasr El-Aini Hospital-Cairo University, Cairo, Egypt. The studied mothers were 100 multipara, who have been subjected to cesarean section, and have a previous history of successful breast feeding. The study was conducted from May 2005 to May 2007. They were divided into 2 groups: group I included 50 patients who received epidural anesthesia with fentanyl, and group II included 50 patients who received spinal anesthesia with intravenous fentanyl, and both groups were observed for initial breast feeding behaviors of newborns, and fentanyl concentration in the colostrum at 45 minutes, and 24 hours after birth. The study included 100 multipara, 2 samples of colostrum were taken from each patients at 45 minutes, and at 24 hours. The levels of fentanyl concentration were greatest at 45 minutes of the initial sampling time, reaching 0.40+/-0.059 ng/ml in the epidural group, and 0.19+/-0.019 ng/ml in intravenous fentanyl group. There was no statistical difference in breast feeding behaviors at birth, or at 24 hours of age in both groups. Although the levels of fentanyl concentration were greatest at 45 minutes of the initial sampling time, it can be used safely as intravenous or epidural without affecting the initial breast feeding behaviors of the newborn.

  7. Prehospital intravenous fentanyl to patients with hip fracture: an observational cohort study of risk factors for analgesic non-treatment.

    Science.gov (United States)

    Friesgaard, Kristian D; Christensen, Erika F; Kirkegaard, Hans; Bendtsen, Mette D; Jensen, Flemming B; Nikolajsen, Lone

    2017-01-19

    Patients with proximal femoral neck fracture have a high short-term mortality, a high risk of postoperative complications, and impaired quality of life. One of the challenges related to the prehospital treatment of these patients is to administer systemic opioids fast and properly. Effective analgesic prehospital treatment ought be initiated rapidly in order to alleviate the stress that follows acute pain, to facilitate transportation, and to improve quality of care. The objectives of this study were to explore the prevalence of prehospital administration of intravenous fentanyl to patients with proximal femoral neck fracture in the ambulances and to assess risk factors for analgesic non-treatment. This was a register-based observational cohort study of patients with proximal femoral neck fracture from the North Denmark Region transported by ambulance. The patients were identified via the Danish Interdisciplinary Hip Fracture Registry over a 3-year period from 1 July 2011 to 30 June 2014. This hospital registry contains data on several patient characteristics used for the risk factor analysis. Data on prehospital treatment (intravenous fentanyl) and patient monitoring were registered in an electronic prehospital patient record. A modified Poisson regression with robust standard errors was carried out with intravenous fentanyl as the primary binary outcome and the following explanatory variables: age, sex, Charlson Comorbidity Index score, housing, body mass index, type of fracture, fracture displacement, prior consultation with general practitioner, dispatch triage level, and time with ambulance personnel. In total, 2,140 patients with proximal femoral neck fracture were transported by ambulance, of which 584 (27.3%, 95% CI: 25.4-29.2) were treated with intravenous fentanyl. Risk factors for non-treatment were: older age, male sex (RR 0.77, 95% CI: 0.64-0.91), institutional housing (RR 0.72, 95% CI: 0.56-0.92), medial fracture (RR 0.74, 95% CI: 0.60-0.92), short

  8. Comparison of remifentanil and low-dose fentanyl for fast-track cardiac anesthesia

    DEFF Research Database (Denmark)

    Khanykin, Boris; Siddiqi, Rizwan; Jensen, Per F

    2013-01-01

    BACKGROUND: Different anesthetic techniques have been used for fast tracking in cardiac anesthesia. Remifentanil, with its unique pharmacokinetic profile, could be an ideal drug for fast tracking. Possible limitations of remifentanil are rapid onset of postoperative pain after discontinuation...... of the drug infusion, which may increase the risk of an ischemic event. We conducted this randomized study to compare the efficacy of remifentanil versus low doses of fentanyl in fast-track cardiac anesthesia. It has been hypothesized that remifentanil would provide a safe anesthesia with no impact...... anesthesia. The study was designed as a prospective randomized study. The primary outcomes were changes in the cardiac index and creatine kinase MB fraction (CKMB), extubation times, mobilization times, and lengths of stay in the intensive care unit (ICU) and the hospital. Frequency of myocardial infarction...

  9. [Treatment of pain with opioid analgesics and the role of TTS-fentanyl (Durogesic)].

    Science.gov (United States)

    Persoli-Gudelj, M

    2001-01-01

    Current opinions in chronic pain treatment with opioid analgesics are presented in this review. Justified use of opioid analgesics in treatment of chronic non-malignant pain in inflammatory and degenerative processes is emphasised. Advantages of opioid analgesics compared with non-opiod analgesics are stressed. New form of opioid--a patch, Durogesic TTS, recently registered in Croatia, is described. After brief review of pharmacodynamics and pharmacokinetics of Durogesic, authors experiences in both chronic malignant pain and chronic non-malignant pain treatment with this analgesic are described. Trial was performed in Pain clinic of Karlovac General Hospital as a part of international multicentric clinical trial. Regarding efficacy, compared to the previous therapy, TTS fentanyl was evaluated positively by patients, both in pain control and ease of use, and by the author, for around the clock, non-invasive administration. Slow dose adjustment in rapid illness progression was recognised as disadvantage.

  10. Effect of buccal dwell time on the pharmacokinetic profile of fentanyl buccal tablet.

    Science.gov (United States)

    Darwish, M; Kirby, M; Jiang, J G

    2007-09-01

    The time fentanyl buccal tablet (FBT) takes to completely dissolve after placement on the buccal mucosa (i.e., 'dwell time') could exceed the time to onset of analgesia. To examine the relationship between FBT dwell time and fentanyl pharmacokinetic parameters. This was a post hoc exploratory analysis of data from two randomized, open-label, crossover, pharmaco-kinetic studies that were designed to assess dose proportionality within the anticipated therapeutic dose range. Healthy adults received single FBT doses of 200-1080 microg in Study 1 (n = 28) and 270-1300 microg in Study 2 (n = 42). Assessments included buccal dwell time, defined as the duration of FBT presence in the oral cavity, and the following pharmacokinetic measures: maximum serum concentration (C(max)), time to C(max) (T(max)) and area under the concentration-time curve (AUC; exposure) from 0 minutes to median T(max) adjusted for the dose (T(max')) (AUC(0 T(max'))). Spontaneously reported adverse events were recorded. Mean buccal dwell time for FBT across the dose range varied from 14 to 25 minutes (range 3 - 62 minutes). There was no evidence of an association between FBT dwell time and values for T(max) (medians 45 - 60 minutes), dose-normalized C(max) (means 0.42-0.66 pg/ml/200 microg) or dose-normalized AUC(0 T(max')) (means 0.24-0.38 pg x h/ml/200 microg) over the range of FBT doses delivered. All adverse events reported were mild to moderate; none were unexpected or serious. The pharmacokinetic parameters of FBT did not appear to be related to its buccal dwell time.

  11. Effect of fentanyl and lidocaine on the end-tidal sevoflurane concentration preventing motor movement in dogs.

    Science.gov (United States)

    Suarez, Martin A; Seddighi, Reza; Egger, Christine M; Rohrbach, Barton W; Cox, Sherry K; KuKanich, Butch K; Doherty, Thomas J

    2017-01-01

    OBJECTIVE To determine effects of fentanyl, lidocaine, and a fentanyl-lidocaine combination on the minimum alveolar concentration of sevoflurane preventing motor movement (MACNM) in dogs. ANIMALS 6 adult Beagles. PROCEDURES Dogs were anesthetized with sevoflurane in oxygen 3 times (1-week intervals). Baseline MACNM (MACNM-B) was determined starting 45 minutes after induction of anesthesia. Dogs then received 1 of 3 treatments IV: fentanyl (loading dose, 15 μg/kg; constant rate infusion [CRI], 6 μg/kg/h), lidocaine (loading dose, 2 mg/kg; CRI, 6 mg/kg/h), and the fentanyl-lidocaine combination at the same doses. Determination of treatment MACNM (MACNM-T) was initiated 90 minutes after start of the CRI. Venous blood samples were collected at the time of each treatment MACNM measurement for determination of plasma concentrations of fentanyl and lidocaine. RESULTS Mean ± SEM overall MACNM-B for the 3 treatments was 2.70 ± 0.27 vol%. The MACNM decreased from MACNM-B to MACNM-T by 39%, 21%, and 55% for fentanyl, lidocaine, and the fentanyl-lidocaine combination, respectively. This decrease differed significantly among treatments. Plasma fentanyl concentration was 3.25 and 2.94 ng/mL for fentanyl and the fentanyl-lidocaine combination, respectively. Plasma lidocaine concentration was 2,570 and 2,417 ng/mL for lidocaine and the fentanyl-lidocaine combination, respectively. Plasma fentanyl and lidocaine concentrations did not differ significantly between fentanyl and the fentanyl-lidocaine combination or between lidocaine and the fentanyl-lidocaine combination. CONCLUSIONS AND CLINICAL RELEVANCE CRIs of fentanyl, lidocaine, and the fentanyl-lidocaine combination at the doses used were associated with clinically important and significant decreases in the MACNM of sevoflurane in dogs.

  12. Fentanyl Initiated Polymers Prepared by ATRP for Targeted Delivery.

    Science.gov (United States)

    Cohen-Karni, Devora; Kovaliov, Marina; Li, Shaohua; Jaffee, Stephen; Tomycz, Nestor D; Averick, Saadyah

    2017-04-19

    The targeted delivery of polymers to neurons is a challenging yet important goal for polymer based drug delivery. We prepared a fentanyl based atom transfer radical polymerization (ATRP) initiator to target the Mu opioid receptor (MOR) for neuronal targeting. We incorporated our recently discovered rigid acrylate linking group into the initiator to retain a high degree of binding to the MOR and grafted random or block copolymers of poly(oligo(ethylene oxide) methacrylate)-block-(glycidyl methacrylate). Trifluoroethanol promoted amine ring opening of the glycidyl methacrylate was used for post-polymerization modification of the fentanyl initiated polymers to attach a near-infrared fluorescent dye (ADS790WS) or to build a targeted siRNA delivery system via modification with secondary amines. We examined the biocompatibility, cellular internalization, and siRNA binding properties of our polymer library in a green fluorescent protein expressing SY SH5Y neuroblastoma cell-line.

  13. Intravenous lidocaine suppresses fentanyl-induced cough in Children.

    Science.gov (United States)

    Gecaj-Gashi, Agreta; Nikolova-Todorova, Zorica; Ismaili-Jaha, Vlora; Gashi, Musli

    2013-01-01

    Fentanyl-induced cough is usually mild and transitory, but it can be undesirable in patients with increased intracranial pressure, open wounds of the eye, dissecting aortic aneurism, pneumothorax, and reactive airway disease. The aim of this study is to evaluate the efficacy of lidocaine in suppressing fentanyl-induced cough in children during induction in general anesthesia. One hundred and eighty-six children of both sexes, aged between 4-10 years, ASA physical status I and II, and scheduled for elective surgery, were recruited for the study. Patients with a history of bronchial asthma, obstructive pulmonary disease, or infections of the respiratory tract were excluded. Patients were randomly allocated to three equal groups (n = 62) to receive 1.0 mg/kg lidocaine (Group I), 0.5 mg/kg lidocaine (Group II), or placebo (equal volume of 0.9% saline; Group III). Each was administered over 5 s one minute before intravenous (IV) administration of fentanyl 2-3 μg/kg during induction in general anesthesia. The severity of coughing was graded by counting the number of episodes of cough: mild (1-2), moderate (3-4) or severe (5 or more). Demographic information was comparable between groups. The most frequent coughing was observed in the placebo group (Group III; 43.5%), of whom 4.8% (three patients) were graded with severe cough. In Group II, 22.6% patients had cough, of which 1.6% (one patient) was graded as severe. In Group I, 16.1% patients had cough, none of whom were graded as severe. Our results demonstrate that IV lidocaine can markedly suppress fentanyl-induced cough in children, even in doses as low as 0.5 mg/kg.

  14. "Supplemental Pethidine and Fentanyl to local anesthetics in supraclavicular block "

    Directory of Open Access Journals (Sweden)

    Sadeghi SA

    2003-06-01

    Full Text Available It has been sugeested since long that peripheral nerves possess opiod receptors and this has tempted clinicans in adding narcotics to local anesthetics to prolong the analgesic effects of these solutions. In this regard, we studied 45 patients undergoing surgical procedures on upper extremities. The patients scheduled for surgery were divided in to three groups, each comprising of 15 patients and all the patients underwent supraclavicular block. In goup A, we used 5 mg/kg of 1.5 percent lidocaine, in group B the same dose of lidocaine along with 1 mcg/kg of fentanyl solution was use. Lidocaine in the above dosage and pethidine 1mg/kg were injected to the patients in group C to facilitate supraclavicular block. The average length of analgesia was 180 minutes in group A, 300 minutes in group B and 406 minutes in group C. In conclusion: Adding pethidine or fentanyl to local anesthetics can increase the analgesia period 2-3 times. Although pethidine implies longer effect than fentanyl, but this difference is not significant (P>0.05.

  15. The effectiveness of a long-acting transdermal fentanyl solution compared to buprenorphine for the control of postoperative pain in dogs in a randomized, multicentered clinical study.

    Science.gov (United States)

    Linton, D D; Wilson, M G; Newbound, G C; Freise, K J; Clark, T P

    2012-08-01

    A prospective, double-blinded, positive-controlled, multicenter, noninferiority clinical study was conducted to evaluate the safety and effectiveness of a long-acting transdermal fentanyl solution (TFS) for the control of postoperative pain. Four hundred forty-five client-owned dogs of various breeds were randomly assigned to receive a single dose of TFS (2.6 mg/kg [∼50 μL/kg]) (N = 223) applied 2-4 h prior to surgery or buprenorphine (20 μg/kg) (N = 222) administered intramuscularly 2-4 h prior to surgery and every 6 h through 90 h. There were 159 (35.7%) males and 286 (64.3%) females ranging from 0.5 to 16 years of age and 3 to 98.5 kg enrolled. Pain was scored using the modified Glasgow Composite Pain Scale with an a priori dropout criteria of ≥ 8 (20 maximum score). The one-sided upper 95% confidence interval of the mean difference between fentanyl and buprenorphine treatment failures was 5.6%, which was not greater than the a priori selected margin difference of 15%. Adverse events attributed to either treatment were minimal in impact and were approximately equal between groups. Sustained plasma fentanyl concentrations provided by a single pre-emptive dose of TFS are safe and effective and are noninferior to repeated injections of buprenorphine in controlling postoperative pain over 4 days. This long-acting fentanyl formulation provides veterinarians with a novel, registered option for the control of postoperative pain in dogs that improves dosing compliance and potentially mitigates the disadvantages of oral, parenteral, and patch delivered opioids. © 2012 Blackwell Publishing Ltd.

  16. Effectiveness of fentanyl transdermal patch (fentanyl-TTS, durogegic) for radiotherapy induced pain and cancer pain: multi-center trial

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Seong Soo; Choi, Eun Kyung [University of Ulsan College of Medicine, Seoul (Korea, Republic of); Huh, Seung Jae [Sungkyunkwan University College of Medicine, Seoul (Korea, Republic of)] (and others)

    2006-12-15

    To evaluate the effectiveness and safety of fentanyl-TTS in the management of radiotherapy induced acute pain and cancer pain treated with radiotherapy. Our study was open labelled prospective phase IV multi-center study, the study population included patients with more 4 numeric rating scale (NRS) score pain although managed with other analgesics or more than 6 NRS score pain without analgesics. Patients divided into two groups: patients with radiotherapy induced pain (Group A) and patients with cancer pain treated with radiotherapy (Group B). All patients received 25 ug/hr of fentanyl transdermal patch. Primary end point was pain relief: second end points were change in patient quality of life, a degree of satisfaction for patients and clinician, side effects. Between March 2005 and June 2005, 312 patients from 26 participating institutes were registered, but 249 patients completed this study. Total number of patients in each group was 185 in Group A, 64 in Group B. Mean age was 60 years and male to female ratio was 76:24. Severe pain NRS score at 2 weeks after the application of fentanyl was decreased from 7.03 to 4.01, {rho} = 0.003. There was a significant improvement in insomnia, social functioning, and quality of life. A degree of satisfaction for patients and clinician was very high. The most common reasons of patients' satisfactions was good pain control. Ninety six patients reported side effect. Nausea was the most common side effect. There was no serious side effect. Fentanyl-TTS was effective in both relieving pain with good tolerability and improving the quality of life for patients with radiotherapy induced acute pain and cancer pain treated with radiotherapy. The satisfaction of the patients and doctors was good. There wa no major side effect.

  17. Genetic, pathological and physiological determinants of transdermal fentanyl pharmacokinetics in 620 cancer patients of the EPOS study

    DEFF Research Database (Denmark)

    Barratt, Daniel T; Bandak, Benedikte; Klepstad, Pål

    2014-01-01

    This study aimed to investigate whether CYP3A4/5 genetic variants, together with clinical and patient factors, influence serum fentanyl and norfentanyl concentrations and their ratio in cancer pain patients receiving transdermal fentanyl.......This study aimed to investigate whether CYP3A4/5 genetic variants, together with clinical and patient factors, influence serum fentanyl and norfentanyl concentrations and their ratio in cancer pain patients receiving transdermal fentanyl....

  18. Analgesia and side effects of the addition of 10 or 20 µg fentanyl to articaine in spinal anesthesia for knee arthroscopy: a randomized and observer-blinded study.

    Science.gov (United States)

    Stenman, Paula; Salonen, Merja; Tarkkila, Pekka; Rosenberg, Per

    2017-06-01

    Articaine, a popular and rapidly acting local anesthetic in dentistry, has been also found to be beneficial in ambulatory spinal anesthesia. Analgesia in the intraoperative and immediate postoperative period may be further improved by adding fentanyl to the local anesthetic solution for spinal anesthesia. The aim was to evaluate dose-dependency of analgesia and side effects associated with intrathecal fentanyl additive to articaine for spinal anesthesia in knee arthroscopy patients. In this randomized, observer- and patient-blinded study, 90 adult patients scheduled for elective ambulatory knee arthroscopy under spinal anesthesia were randomized into three groups: plain articaine 60 mg with saline (group AF0), articaine 60 mg with fentanyl 10 µg (group AF10) or 20 µg (group AF20) in a total volume of 1.9 ml. The blinded observer tested the sensory and the motor block, and performed telephone interviews on the first and seventh postoperative days. The median (IQR) duration of sensory block at the dermatomal level of T10 was significantly longer in groups AF10, 69 min (56) and AF20, 69 min (45) than in group AF0, 41 min (35) (p = 0.013). Motor block duration was similar in all groups (median 120 min). Group AF20 patients experienced pruritus significantly more often than patients in the other groups (p = 0.039). No acute or late anesthetic side effects occurred, and satisfaction with the anesthetic technique was the same in all groups (97% satisfied). Fentanyl 10 or 20 µg as additive to articaine for spinal anesthesia prolonged the duration of sensory block significantly and similarly. Fentanyl 20 µg was more often associated with pruritus than fentanyl 10 µg.

  19. A review of factors explaining variability in fentanyl pharmacokinetics; focus on implications for cancer patients

    NARCIS (Netherlands)

    Kuip, E.J.M.; Zandvliet, M.L.; Koolen, S.L.; Mathijssen, R.H.; Rijt, C.C. van der

    2017-01-01

    Fentanyl is a strong opioid that is available for various administration routes, and which is widely used to treat cancer-related pain. Many factors influence the fentanyl pharmacokinetics leading to a wide inter- and intrapatient variability. This systematic review summarizes multiple studied

  20. Fentanyl Utility Function: A Risk-Benefit Composite of Pain Relief and Breathing Responses

    NARCIS (Netherlands)

    van der Boom, M.; Olofsen, E.; Neukirchen, M.; Fussen, R.; Hay, J.; Groeneveld, G.J.; Aarts, L.; Sarton, E.; Dahan, A.

    2013-01-01

    INTRODUCTION:: Integrating opioid risk and benefit into a single function may give a useful single measure of the opioid's positive and negative effects. An explorative study on the effects of fentanyl on antinociception and respiratory depression was performed to construct fentanyl risk-benefit

  1. Intrathecal sufentanil versus fentanyl for lower limb surgeries - A randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Poonam Motiani

    2010-01-01

    Conclusions: Intrathecal sufentanil (5 μg and fentanyl (25 μg, as adjuvants lead to an earlier onset and prolonged duration of sensory block. The duration of effective analgesia with intrathecal sufentanil and fentanyl as adjuvants to hyperbaric bupivacaine is longer than that of bupivacaine alone.

  2. Intranasal fentanyl in the treatment of acute pain--a systematic review

    DEFF Research Database (Denmark)

    Hansen, M S; Mathiesen, O; Trautner, S

    2012-01-01

    population. The objective of this systematic review was to evaluate the current evidence of IN fentanyl in the treatment of acute pain. Reports of randomized controlled trials (RCTs) of IN fentanyl in treatment of pain were systematically sought using the PubMed database, Embase, Google scholar, Cochrane...

  3. In vitro and in vivo evaluation of a sublingual fentanyl wafer formulation

    Science.gov (United States)

    Lim, Stephen CB; Paech, Michael J; Sunderland, Bruce; Liu, Yandi

    2013-01-01

    Background The objective of this study was to prepare a novel fentanyl wafer formulation by a freeze-drying method, and to evaluate its in vitro and in vivo release characteristics, including its bioavailability via the sublingual route. Methods The wafer formulation was prepared by freeze-drying an aqueous dispersion of fentanyl containing sodium carboxymethylcellulose and amylogum as matrix formers. Uniformity of weight, friability, and dissolution testing of the fentanyl wafer was achieved using standard methods, and the residual moisture content was measured. The fentanyl wafer was also examined using scanning electron microscopy and x-ray diffraction. The absolute bioavailability of the fentanyl wafer was evaluated in 11 opioid-naïve adult female patients using a randomized crossover design. Results In vitro release showed that almost 90% of the fentanyl dissolved in one minute. In vivo, the first detectable plasma fentanyl concentration was observed after 3.5 minutes and the peak plasma concentration between 61.5 and 67 minutes. The median absolute bioavailability was 53.0%. Conclusion These results indicate that this wafer has potential as an alternative sublingual fentanyl formulation. PMID:23596347

  4. Efficacy and safety of continuous infusion of fentanyl for pain control in preterm newborns on mechanical ventilation.

    Science.gov (United States)

    Ancora, Gina; Lago, Paola; Garetti, Elisabetta; Pirelli, Anna; Merazzi, Daniele; Mastrocola, Maura; Pierantoni, Luca; Faldella, Giacomo

    2013-09-01

    To evaluate the analgesic superiority and the safety equivalence of continuous fentanyl infusions versus fentanyl boluses in preterm infants on mechanical ventilation. In this multicenter, double-blind, randomized controlled trial, mechanically ventilated newborns (≤ 32(+6) weeks gestational age) were randomized to fentanyl (continuous infusion of fentanyl plus open-label boluses of fentanyl) or placebo (continuous infusion of placebo plus open-label boluses of fentanyl). The primary endpoint was analgesic efficacy, as evaluated by the Echelle Douleur Inconfort Nouveau-Né (EDIN) and Premature Infant Pain Profile scales. Safety variables were evaluated as well. Sixty-four infants were allocated to the fentanyl group, and 67 were allocated to the placebo group. The need for open-label boluses of fentanyl was similar in the 2 groups (P = .949). EDIN scores were comparable in the 2 groups; 65 of 961 (6.8%) EDIN scores were >6 in the fentanyl group and 91 of 857 (10.6%) in the placebo group (P = .003). The median Premature Infant Pain Profile score was clinically and statistically higher in the placebo group compared with the fentanyl group on days 1, 2, and 3 of treatment (P Mechanical ventilation at age 1 week was required in 27 of 64 infants in the fentanyl group (42.2%), compared with 17 of 67 infants in the placebo group (25.4%) (P = .042). The first cycle of mechanical ventilation was longer and the first meconium passage occurred later in the fentanyl group (P = .019 and .027, respectively). In very preterm infants on mechanical ventilation, continuous fentanyl infusion plus open-label boluses of fentanyl does not reduce prolonged pain, but does reduce acute pain and increase side effects compared with open-label boluses of fentanyl alone. Copyright © 2013 Mosby, Inc. All rights reserved.

  5. Foetal Fentanyl Exposure and Ion Trapping after Intravenous and Transdermal Administration to the Ewe.

    Science.gov (United States)

    Heikkinen, Emma M; Kokki, Hannu; Heikkinen, Aki; Ranta, Veli-Pekka; Räsänen, Juha; Voipio, Hanna-Marja; Kokki, Merja

    2017-02-01

    Opioids given to pregnant and parturient women are relatively freely transferred across the placenta. Spinal, epidural and intravenous fentanyl has been studied in pregnant women and neonates, but foetal safety of fentanyl dosing with transdermal patch during pregnancy and labour is not sufficiently studied. Foetal pH is physiologically lower than maternal pH, and thus, opioids, which are weak bases, are ionized and may cumulate to foetus. Foetal asphyxia may further worsen acidosis, and ion trapping induced by low pH is assumed to increase the foetal exposure to opioids. Here, we show that no correlation between foetal acidosis and ion trapping of fentanyl could be found. In three experiments, 29 pregnant sheep were administered fentanyl with 2 μg/kg/h patch supplemented with IV boluses/infusion. Foetal exposure to fentanyl was extensive, median 0.34 ng/ml (quartiles 0.21, 0.42), yet drug accumulation to foetus was not observed, and median of foetal/maternal concentration (F/M) ratio was 0.63 (0.43, 0.75) during the first hours after the fentanyl administration. Low foetal pH and pH difference between ewe and the foetus did not correlate with fentanyl concentration in the foetus or F/M ratio. At steady-state during the second patch worn, foetal plasma fentanyl was low, 0.13 ng/ml, and the median of F/M ratio was 0.69. Our results demonstrate that drug accumulation to foetus caused by ion trapping seen with some weak base opioids may not be that significant with fentanyl. These results have a clinical relevance when fentanyl is dosed to pregnant woman and the foetus is acidemic. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  6. Randomized Controlled Study Comparing Use of Propofol Plus Fentanyl versus Midazolam Plus Fentanyl as Sedation in Diagnostic Endoscopy in Patients with Advanced Liver Disease

    Directory of Open Access Journals (Sweden)

    Sameh Abdelkhalik Ahmed

    2017-01-01

    Full Text Available Objectives. We aimed to investigate the safety and efficacy of propofol plus fentanyl versus midazolam plus fentanyl as sedative for patients with advanced liver disease presented for gastrointestinal endoscopy. Methods. A total of 100 patients with liver cirrhosis referred for upper endoscopy were enrolled and divided equally in two groups, midazolam plus fentanyl group and propofol plus fentanyl group. All patients were subjected to history taking, estimation of level of sedation, endoscopist rating, and hemodynamic parameters including oxygen saturation, heart rate, mean arterial pressure, incidence of side effect as (bradycardia, hypotension, hypoxia, nausea and vomiting, cough, shivering, or diplopia, time needed for complete recovery, and time needed for discharge. Results. There was no statistical significant difference between the studied groups regarding age, sex, weight, Child–Pugh classification score, type and duration of endoscopic intervention, time needed for complete recovery, or time needed for discharge. Complication rates were similar in both groups except for mean arterial blood pressure which was significantly lower in group of patients receiving propofol and fentanyl (P=0.001. Conclusion. The use of either propofol or midazolam in combination to fentanyl is effective in sedation of patients with advanced liver diseases presented for upper GIT endoscope. The trial is registered with ClinicalTrials.gov Identifier: NCT03063866.

  7. Fentanyl-associated fatalities among illicit drug users in Wayne County, Michigan (July 2005-May 2006).

    Science.gov (United States)

    Algren, D Adam; Monteilh, Carolyn P; Punja, Mohan; Schier, Joshua G; Belson, Martin; Hepler, Bradford R; Schmidt, Carl J; Miller, Corinne E; Patel, Manish; Paulozzi, Leonard J; Straetemans, Masja; Rubin, Carol

    2013-03-01

    During the summer of 2005, multiple cities in the United States began to report outbreaks of fentanyl-associated fatalities among illicit drug users. The objectives of this study were to (1) determine if an outbreak of fentanyl-associated fatalities occurred in mid-2005 to mid-2006 and (2) to examine trends and compare features of fentanyl-contaminated heroin-associated fatalities (FHFs) with non-fentanyl, heroin-associated fatalities (NFHFs) among illicit drug users. Baseline prevalence of fentanyl- and heroin-associated deaths was estimated from January to May 2005 based on recorded cause of death (determined by the medical examiner (ME)) using the Wayne County, MI, USA toxicology database. The database was then queried for both FHFs and NFHFs between July 1, 2005 and May 12, 2006. A FHF was defined as having fentanyl or norfentanyl (metabolite) detected in any postmortem biological sample and either (1) detection of heroin or its metabolite (6-acetylmorphine) and/or cocaine or its metabolite (benzoylecgonine) in a postmortem biological specimen or (2) confirmation of fentanyl abuse as the cause of death by the ME or a medical history available sufficient enough to exclude prescription fentanyl or other therapeutic opioid use. A NFHF was defined as detection of heroin, 6-acetylmorphine (heroin metabolite) or morphine in any postmortem biological specimen, heroin overdose listed as the cause of death by the ME, and absence of fentanyl detection on postmortem laboratory testing. Information was systematically collected, trended for each group and then compared between the two groups with regard to demographic, exposure, autopsy, and toxicology data. Logistic regression was performed using SAS v 9.1 examining the effects of age, gender, and marital status with fentanyl group status. Monthly prevalence of fentanyl-associated fatalities among illicit drug users increased from an average of two in early 2005 to a peak of 24 in May, 2006. In total, 101 FHFs and 90 NFHFs

  8. Treatment of Severe Cancer Pain by Transdermal Fentanyl

    Directory of Open Access Journals (Sweden)

    Dženita Ljuca

    2010-05-01

    Full Text Available The goal of research was to determine the frequency, intensity, time of occurrence, duration and causes of breakthrough pain (BTP in patients whose carcinoma pain was treated by transdermal fentanyl. (TDF. A prospective study was conducted in a hospice for recumbent patients of the Centre for Palliative Care (hospice University Clinical Centre Tuzla from October 2009 to December 2010. 33 patients in terminal stage of carcinoma, who had been treated by transdermal fentanyl due to their excruciating pain (7-10 mark on numerica! scale with initial dosage of 25 μg as a strong opiate analgesic, were monitored within the time period of 10 days. In the statistics we used the even T - test, the Wilcox test and Mann -Whitney test. The difference was seen to be significant at p < 0,05. Treatment by transdermal fentanyl significantly reduces the intensity of strong carcinoma pain (p < 0.0001, with a frequent requirement for dose increase with bone metastasis. The intensity of BTP is higher compared to the pain experienced upon reception. The frequency and intensity of BTP are significantly reduced already in the second day of treatment by transdermal fentanyl (p = 0,0024. The BTP is most intense in patients with neck and head tumours (9,26 ± 0,66, and most frequent with abdomen and pelvic tumour. The biggest number of BTP (68.3 % occurs within first three days of treatment. BTP most frequently occurs in the evening or at night (between 18:00 and 06:00 h in 62,2 % of the cases, with the duration of usually less than 15 minutes (65,2% of the cases. In 61,6 % cases the occurrence of BTP is related to physical activities or psychosocial incidents, while the cause is undetermined in 38,4 % of examinees.BTP is most frequent within first three days of treatment by TDF. Using the optimal dosage a good control of carcinoma pain is enabled, regardless of the occurrence of bone metastasis, while it also helps reduce the frequency and intensity of BTP.

  9. Oral trasmucosal fentanyl citrate for breakthrough pain treatment in cancer patients.

    Science.gov (United States)

    Mercadante, Sebastiano

    2012-04-01

    Breakthrough cancer pain has been defined as a transitory increase in pain intensity that occurs either spontaneously or in relation to a specific predictable or unpredictable trigger, despite relatively stable and adequately controlled background pain. The availability of supplemental doses of oral opioids, in addition to the continuous analgesic medication, is the main treatment suggested to manage pain flares. Oral transmucosal fentanyl citrate (OTFC) is the first product of a new generation of delivery systems, named rapid-onset opioids (ROOs), characterized by rapidity of effect and the short duration of analgesia. Controlled studies and long-term experience have shown that OTFC is an effective treatment for breakthrough pain management and its use should be considered in any patient experiencing breakthrough pain related to cancer. The onset of action of OTFC - demonstrated to start within 15 min - and the short time to maximum concentration make it a useful indication for breakthrough pain; dose titration is commonly recommended. However, it is likely that patients receiving high doses of opioids for background analgesia will not be candidates for titration with minimal initial doses of OTFC, as they are opioid tolerant and the process would be time consuming.

  10. Fentanyl Law Enforcement Submissions and Increases in Synthetic Opioid-Involved Overdose Deaths - 27 States, 2013-2014.

    Science.gov (United States)

    Gladden, R Matthew; Martinez, Pedro; Seth, Puja

    2016-08-26

    In March and October 2015, the Drug Enforcement Administration (DEA) and CDC, respectively, issued nationwide alerts identifying illicitly manufactured fentanyl (IMF) as a threat to public health and safety (1,2). IMF is unlawfully produced fentanyl, obtained through illicit drug markets, includes fentanyl analogs, and is commonly mixed with or sold as heroin (1,3,4). Starting in 2013, the production and distribution of IMF increased to unprecedented levels, fueled by increases in the global supply, processing, and distribution of fentanyl and fentanyl-precursor chemicals by criminal organizations (3). Fentanyl is a synthetic opioid 50-100 times more potent than morphine (2).* Multiple states have reported increases in fentanyl-involved overdose (poisoning) deaths (fentanyl deaths) (2). This report examined the number of drug products obtained by law enforcement that tested positive for fentanyl (fentanyl submissions) and synthetic opioid-involved deaths other than methadone (synthetic opioid deaths), which include fentanyl deaths and deaths involving other synthetic opioids (e.g., tramadol). Fentanyl deaths are not reported separately in national data. Analyses also were conducted on data from 27 states(†) with consistent death certificate reporting of the drugs involved in overdoses. Nationally, the number of fentanyl submissions and synthetic opioid deaths increased by 426% and 79%, respectively, during 2013-2014; among the 27 analyzed states, fentanyl submission increases were strongly correlated with increases in synthetic opioid deaths. Changes in fentanyl submissions and synthetic opioid deaths were not correlated with changes in fentanyl prescribing rates, and increases in fentanyl submissions and synthetic opioid deaths were primarily concentrated in eight states (high-burden states). Reports from six of the eight high-burden states indicated that fentanyl-involved overdose deaths were primarily driving increases in synthetic opioid deaths. Increases in

  11. Rationales behind the choice of administration form with fentanyl: Delphi survey among Danish general practitioners.

    Science.gov (United States)

    Jacobsen, Ramune; Møldrup, Claus; Christrup, Lona

    2010-01-01

    The aim of this study was to describe the rationale behind the choice of fentanyl administration forms among Danish general practitioners (GPs). Thirty-eight Danish GPs were contacted via an Internet survey system to perform a Delphi survey. In the brainstorming phase, the main reasons for prescribing and not prescribing fentanyl patches, oral transmucosal systems (OTFCs), and nasal sprays were identified. In the second phase, GPs were asked to rate the importance of each reason. Thirty-three GPs responded in the brainstorming phase, and 33 and 31 in two rating rounds, respectively. The most important reason to choose fentanyl patches was that patients' clinical condition did not allow them to take analgesia orally. OTFCs were primarily seen as a self-administrative alternative to injections in case of breakthrough pain. The main reasons for not choosing OTFCs were intolerance to fentanyl and price. The most important possible rationale to choose fentanyl nasal spray was easy administration. The most important possible reasons to not choose fenanyl nasal spray were application side effects. The rationale behind the choice of administration form with fentanyl partly differed from those overviewed in the literature. Fentanyl nasal spray was seen as a better option for treatment of breakthrough pain among terminally ill patients if compared with OTFCs.

  12. Optimization of the radioimmunoassays for measuring fentanyl and alfentanil in human serum

    Energy Technology Data Exchange (ETDEWEB)

    Schuettler, J.; White, P.F.

    1984-09-01

    Measurement of serum fentanyl and alfentanil concentrations by radioimmunoassay (RIA) may result in significant errors and high variability when the technique described in the available fentanyl and alfentanil RIA kits is used. The authors found a 29-94% overestimation of measured fentanyl and alfentanil serum levels when 3H-fentanyl or 3H-alfentanil was added lastly to the mixture of antiserum and sample. This finding is related to a reduction in binding sites for the labeled compounds after preincubation of sample and antiserum. If this sequence is used, it becomes necessary to extend the incubation period up to 6 h for fentanyl and up to 10 h for alfentanil in order to achieve equilibration between unlabeled and labeled drug with respect to antiserum binding. However, when antiserum is added lastly to the mixture of sample and labeled drug, measurement accuracy and precision for fentanyl and alfentanil serum concentrations are enhanced markedly. In addition, it is important to perform the calibration curves and sample measurements using the same medium (i.e., serum alone or a serum/buffer dilution). In summary, to optimize the RIA for fentanyl and alfentanil, the authors recommend the following: 1) adding the antiserum lastly to the mixture of sample and labeled drug; 2) performing calibration curves using patient's blank serum when possible; 3) carefully examining and standardizing each step of the RIA procedure to reduce variability, and, finally; 4) comparing results with those of other established RIA laboratories.

  13. Myocardial protection induced by fentanyl in pigs exposed to high-dose adrenaline.

    Science.gov (United States)

    da Luz, Vinicius Fernando; Otsuki, Denise Aya; Gonzalez, Maria Margarita Castro; Negri, Elnara Marcia; Caldini, Elia Garcia; Damaceno-Rodrigues, Nilsa Regina; Malbouisson, Luiz Marcelo Sá; Viana, Bruno Gonçalves; Vane, Matheus Fachini; Carmona, Maria Jose Carvalho

    2015-10-01

    The use of high doses of adrenaline is common in critical patients, especially during cardiac arrest. During these situations, myocardial dysfunction can be a result of multiple factors, including adrenaline use. In addition, opioids have been shown to have anti-arrhythmic and anti-ischemic mechanisms that may confer cardiac protection. This study aimed to evaluate the effects of fentanyl on myocardial function in pigs exposed to high-dose adrenaline. After institutional ethics committee approval, 26 pigs were randomly allocated to receive either 20 μg/kg fentanyl (n = 10; fentanyl group) administered 5 min before five doses of adrenaline (20 μg/kg), equivalent-volume saline (n = 10; saline group) using the same adrenaline dosing protocol, or neither fentanyl nor adrenaline (n = 6; sham group). The fentanyl group showed lower levels of troponin at the end of the sixth hour compared with the saline group (1.91 ± 1.47 vs 5.44 ± 5.35 ng/mL, P = 0.019). Transmission electron microscopy and immunohistochemistry also showed less myocardial injury in the fentanyl group. The conclusion was reached that fentanyl attenuates myocardial injury caused by high-dose adrenaline without blunting the hemodynamic effect of adrenaline. © 2015 Wiley Publishing Asia Pty Ltd.

  14. Oxidative treatment of fentanyl compounds in water by sodium bromate combined with sodium sulphite.

    Science.gov (United States)

    Xu, Lin; Ren, Lijun; Wang, Zhihua; Tian, Xingtao; Qi, Lihong; Fan, Qiping; Xiang, Yulian

    2015-01-01

    As narcotic analgesics, fentanyl compounds have been commonly produced and widely used during surgical procedures. The residual and waste of fentanyl compounds have potential harmful impacts on the environment and human health. The oxidative degradation of fentanyl compounds by sodium bromate mixed systems was studied. Factors influencing the oxidation reaction, including molar ratio of NaBrO3/H(+)/SO3(2-), molar ratio of NaBrO3/fentanyl and pH, were investigated. Fentanyl, carfentanil and 3-methylfentanyl were able to be completely degraded in 30 minutes by a NaBrO3 mixed system under optimum conditions, the molar ratio of NaBrO3/H(+)/SO3(2-) equal to 20:3:10, the molar ratio of NaBrO3:fentanyl compounds 50:1 and pH = 4. Sufentanil was only able to be degraded by 74% under the same conditions. The degradation products of the fentanyl compounds detected and identified by gas chromatography/mass spectrometry suggested several possible degradation pathways.

  15. In vitro and in vivo evaluation of a sublingual fentanyl wafer formulation

    Directory of Open Access Journals (Sweden)

    Lim SCB

    2013-04-01

    Full Text Available Stephen CB Lim,1,3 Michael J Paech,2 Bruce Sunderland,3 Yandi Liu3 1Pharmacy Department, Armadale Health Service, Armadale, 2School of Medicine and Pharmacology, University of Western Australia, and Department of Anaesthesia and Pain Medicine, King Edward Memorial Hospital for Women, Subiaco, 3School of Pharmacy, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia Background: The objective of this study was to prepare a novel fentanyl wafer formulation by a freeze-drying method, and to evaluate its in vitro and in vivo release characteristics, including its bioavailability via the sublingual route. Methods: The wafer formulation was prepared by freeze-drying an aqueous dispersion of fentanyl containing sodium carboxymethylcellulose and amylogum as matrix formers. Uniformity of weight, friability, and dissolution testing of the fentanyl wafer was achieved using standard methods, and the residual moisture content was measured. The fentanyl wafer was also examined using scanning electron microscopy and x-ray diffraction. The absolute bioavailability of the fentanyl wafer was evaluated in 11 opioid-naïve adult female patients using a randomized crossover design. Results: In vitro release showed that almost 90% of the fentanyl dissolved in one minute. In vivo, the first detectable plasma fentanyl concentration was observed after 3.5 minutes and the peak plasma concentration between 61.5 and 67 minutes. The median absolute bioavailability was 53.0%. Conclusion: These results indicate that this wafer has potential as an alternative sublingual fentanyl formulation. Keywords: absolute bioavailability, fentanyl wafer, in vitro dissolution, in vivo study, pharmacokinetics, sublingual

  16. Detection of illicit online sales of fentanyls via Twitter [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Tim K. Mackey

    2017-11-01

    Full Text Available A counterfeit fentanyl crisis is currently underway in the United States.  Counterfeit versions of commonly abused prescription drugs laced with fentanyl are being manufactured, distributed, and sold globally, leading to an increase in overdose and death in countries like the United States and Canada.  Despite concerns from the U.S. Drug Enforcement Agency regarding covert and overt sale of fentanyls online, no study has examined the role of the Internet and social media on fentanyl illegal marketing and direct-to-consumer access.  In response, this study collected and analyzed five months of Twitter data (from June-November 2015 filtered for the keyword “fentanyl” using Amazon Web Services.  We then analyzed 28,711 fentanyl-related tweets using text filtering and a machine learning approach called a Biterm Topic Model (BTM to detect underlying latent patterns or “topics” present in the corpus of tweets.  Using this approach we detected a subset of 771 tweets marketing the sale of fentanyls online and then filtered this down to nine unique tweets containing hyperlinks to external websites.  Six hyperlinks were associated with online fentanyl classified ads, 2 with illicit online pharmacies, and 1 could not be classified due to traffic redirection.  Importantly, the one illicit online pharmacy detected was still accessible and offered the sale of fentanyls and other controlled substances direct-to-consumers with no prescription required at the time of publication of this study.   Overall, we detected a relatively small sample of Tweets promoting illegal online sale of fentanyls.  However, the detection of even a few online sellers represents a public health danger and a direct violation of law that demands further study.

  17. Disposition, behavioural and physiological effects of escalating doses of intravenously administered fentanyl to young foals.

    Science.gov (United States)

    Knych, H K; Steffey, E P; Casbeer, H C; Mitchell, M M

    2015-09-01

    Foal responses to a broader range of plasma fentanyl concentrations than currently reported are desirable to support (or not) clinical use. To describe fentanyl plasma concentrations following an escalating i.v. fentanyl dosing schedule in foals aged 5-13 days and describe selected, associated dose- and time-related behavioural and physiological responses to plasma fentanyl concentration. Experimental. Fentanyl was administered i.v. in an escalating fashion (2, 4, 8, 16 and 32 μg/kg bwt) at 10-min intervals. Blood samples were collected before and at selected times until 24 h post administration. Blood samples were analysed for fentanyl and metabolite concentrations and correlated with behavioural and physiological observations and selected blood analytes. Foals mostly appeared to be unaffected following 2 μg/kg bwt (1.09 ± 0.41 μg/l; average maximal plasma concentration) of fentanyl, but 6 of the 8 foals appeared to be sedated following 4 μg/kg bwt (3.07 ± 1.11 μg/l). Ataxia with increased locomotor activity, muscle rigidity and head pressing posture was observed in many foals at 8 (7.24 ± 3.22 μg/l) and 16 μg/kg bwt (17.4 ± 5.67 μg/l). All foals were heavily sedated after 32 μg/kg bwt (34.5 ± 10.3 μg/l); 3 of the 8 foals became recumbent. The average (± s.d.) terminal half-life following administration of the final dose was 44.2 ± 9.85 min. Behavioural and physiological responses to i.v. fentanyl in young foals are dose related. As with mature horses, the window of fentanyl plasma concentrations related to possible clinically desirable actions appears relatively narrow. © 2014 EVJ Ltd.

  18. Effect of low-dose naloxone infusion on fentanyl requirements in critically ill children.

    Science.gov (United States)

    Darnell, Cindy Maria; Thompson, Jennifer; Stromberg, Daniel; Roy, Lonnie; Sheeran, Paul

    2008-05-01

    Sedating critically ill patients often involves prolonged opioid infusions causing opioid tolerance. Naloxone has been hypothesized to limit opioid tolerance by decreasing adenylate cyclase/cyclic adenosine monophosphate activation. The study purpose was to investigate the effect of low-dose naloxone on the maximum cumulative daily fentanyl dose in critically ill children. We conducted a double-blinded, randomized, placebo-control trial from December 2002 through July 2004 in a university PICU. We enrolled 82 children age 1 day to 18 years requiring mechanical ventilation and fentanyl infusions anticipated to last for >4 days were eligible for enrollment. Those receiving additional oral analgesia or sedation, having a history of drug dependence or withdrawal, or having significant neurologic, renal, or hepatic disease were excluded. In addition to fentanyl infusions, patients received low-dose naloxone or placebo infusions. Medications were adjusted using the Modified Motor Activity Assessment Scale. Withdrawal was monitored using the Modified Narcotic Withdrawal Scale. Intervention was a low-dose naloxone infusion (0.25 microg/kg per hour) and the main outcome variable was the maximum cumulative daily fentanyl dose (micrograms per kilogram per day). There was no difference in the maximum cumulative daily fentanyl dose between patients treated with naloxone (N = 37) or those receiving placebo (N = 35). Adjustment for the starting fentanyl dose also failed to reveal group differences. Total fentanyl dose received throughout the study in the naloxone group (360 microg/kg) versus placebo (223 microg/kg) was not statistically different. Placebo patients trended toward fewer rescue midazolam boluses (10.7 vs 17.8), lower total midazolam dose (11.6 mg/kg vs 23.9 mg/kg), and fewer rescue fentanyl boluses (18.5 vs 23.9). We conclude that administration of low-dose naloxone (0.25 microg/kg per hour) does not decrease fentanyl requirements in critically ill, mechanically

  19. A Cluster of Fentanyl-Laced Heroin Deaths in 2015 in Melbourne, Australia.

    Science.gov (United States)

    Rodda, Luke N; Pilgrim, Jennifer L; Di Rago, Matthew; Crump, Kerryn; Gerostamoulos, Dimitri; Drummer, Olaf H

    2017-05-01

    The prevalence of opioid use in therapeutic and recreational settings has steadily increased throughout the western world. The addition of fentanyl into heroin products can produce potentially dangerous consequences, even to opioid tolerant individuals who may be unaware of such additions. Following an observed spike of heroin-fentanyl related deaths in Melbourne, Australia, a study was undertaken to determine the prevalence of these cases. All reportable deaths occurring in Victoria during 2015 and submitted to the toxicology laboratory were analysed using LC-MS-MS to confirm the combination of the heroin marker 6-acetylmorphine and/or morphine, and fentanyl. Over 4,000 coronial cases in 2015 underwent toxicological analysis for these drugs, there were nine cases identified that involved fentanyl-laced heroin. There was no specific mention of fentanyl use in any of these cases. All occurred within 2 months and in two distinct locations. The first four deaths occurred within 3 days of each other, in neighboring suburbs. The ages ranged from 25 to 57 years with an average of 40 and median of 37 years, and consisted of eight males and one female. The average and median femoral blood concentration of fentanyl was 18 and 20 ng/mL (range: fentanyl, which supported the likelihood of fentanyl-laced heroin. This is the first reported case series of fatalities involving heroin and fentanyl outside of North America in published literature. These findings may help inform public health and prevention strategies serving to decrease the potential for such fatalities in the future. © Crown copyright 2017.

  20. Fentanyl inhibits proliferation and invasion of colorectal cancer via β-catenin

    Science.gov (United States)

    Zhang, Xiu-Lai; Chen, Min-Li; Zhou, Sheng-Li

    2015-01-01

    Background and aim: Fentanyl is widely used for relieving pain and narcotizing in cancer patients. However, there are few published reports regarding the effects of fentanyl on tumor control and treatment. Here we investigated the effects of fentanyl on tumor growth and cell invasion in the human colorectal carcinoma (HCT116) cells. Methods: Nude mice xenografts of HCT116 cells were established to assess the inhibition effect on tumor growth by fentanyl. MTT and Transwell were employed to determine the cell survival rate and cell invasion, respectively. MicroRNAs and mRNAs expression were quantified by real-time PCR. β-catenin and matrix metalloproteinases (MMP-2 and MMP-9) expression were assayed by western blotting. β-Catenin-specific small interfering RNA (Si-β-catenin) and miR-182 mimics were transfected in cells to investigate the mechanism underlying the effects of fentanyl on the colorectal tumor and HCT116 cells. Results: Treatment with fentanyl inhibited the tumor growth and HCT116 cells invasion. Fentanyl also downregulated the expression of β-catenin and miR-182 in both xenograft tumors and HCT116 cells, and decreased the protein level of MMP-9 in HCT116 cells. Downregulation of β-Catenin resulted in the decrease of miR-182 expression in colorectal cells. In addition, the overexpression of miR-182 reversed the effect of fentanyl on MMP-9 expression and cell invasion of HCT116 cells. Conclusions: The current study demonstrated that the inhibition of tumor growth and cell invasion in colorectal cancer by fentanyl is probably due to downregulation of miR-182 and MMP-9 expression by β-catenin. PMID:25755709

  1. Epidural Labor Analgesia-Fentanyl Dose and Breastfeeding Success: A Randomized Clinical Trial.

    Science.gov (United States)

    Lee, Amy I; McCarthy, Robert J; Toledo, Paloma; Jones, Mary Jane; White, Nancy; Wong, Cynthia A

    2017-10-01

    Breastfeeding is an important public health concern. High cumulative doses of epidural fentanyl administered for labor analgesia have been reported to be associated with early termination of breastfeeding. We tested the hypothesis that breastfeeding success is adversely influenced by the cumulative epidural fentanyl dose administered for labor analgesia. The study was a randomized, double-blind, controlled trial of parous women at greater than 38 weeks gestation who planned to breastfeed, had successfully breastfed a prior infant, and who received neuraxial labor analgesia. Participants were randomized to receive one of three epidural maintenance solutions for labor analgesia (bupivacaine 1 mg/ml, bupivacaine 0.8 mg/ml with fentanyl 1 μg/ml, or bupivacaine 0.625 mg/ml with fentanyl 2 μg/ml). The primary outcome was the proportion of women breastfeeding at 6 weeks postpartum. Maternal and umbilical venous blood fentanyl and bupivacaine concentration at delivery were measured. A total of 345 women were randomized and 305 had complete data for analysis. The frequency of breastfeeding at 6 weeks was 97, 98, and 94% in the groups receiving epidural fentanyl 0, 1, and 2 μg/ml, respectively (P = 0.34). The cumulative fentanyl dose (difference: 37 μg [95% CI of the difference, -58 to 79 μg], P = 0.28) and maternal and umbilical cord venous fentanyl and bupivacaine concentrations did not differ between women who discontinued breastfeeding and those who were still breastfeeding at 6 weeks postpartum. Labor epidural solutions containing fentanyl concentrations as high as 2 μg/ml do not appear to influence breastfeeding rates at 6 weeks postpartum.

  2. A COMPARATIVE STUDY OF HEAMOD Y NAMIC PARAMETERS IN LSCS WITH INTRATHECAL FENTANYL - BUPIVACAINE COMBINATION AND BUPIVACAINE ALONE

    Directory of Open Access Journals (Sweden)

    Ramana Prasad

    2015-10-01

    Full Text Available BACKGROUND: Caesarean section is considered as a major abdominal surgery, which requires profound blockade of spinal segments. Spinal anaesthesia is the most elegant approach providing profound anaesthesia and excellent operative conditions. Hypotension, the most clinically significant effect of spinal anaesthesia can occur rapidly and have a significant impact on neonatal outcome. There has been interest in using analgesic additives to local anaesthetics to decrease the dose of local anaesthetics and reduce in incidence of hypotension without compromising intra - operative analgesia, enabling faster motor recovery and providing efficient post - operative analgesia. This study was conducted t o compare the incidence of hypotension between intrathecal fentanyl - bupivacaine combinations with bupivacaine alone in patients undergoing elective LSCS. INTRODUCTION: In Caesarean section, the surgery is major and profound blockade of many spinal segments is required. Strong visceral stimulation is present, sudden cardiovascular changes is compounded by posture and fetal wellbeing may be influenced by several physiologic variables and drugs. Spinal anaesthesia is perhaps the most efficient and elegant appr oach to this challenge. With a small needle and little amount of drug, profound anaesthesia and excellent operating conditions can be readily provided for this major intrabdominal surgery. Spinal hypotension, the most clinically significant aspect of spina l anaesthesia can occur rapidly and may have a significant impact on the neonatal outcome. Recently, there has been an interest in using analgesic additives to subarachnoid local anaesthetic dose so as to reduce the incidence and degree of hypotension but at the same time without compromising intraoperative analgesia and also to enable faster recovery and providing efficient post - operative analgesia. Opioids were the first clinically used selective spinal analgesics after the discovery of opioids

  3. A new once-a-day fentanyl citrate patch (Fentos Tape) could be a new treatment option in patients with end-of-dose failure using a 72-h transdermal fentanyl matrix patch.

    Science.gov (United States)

    Koike, Kazuhiko; Terui, Takeshi; Nagasako, Tomokazu; Horiuchi, Iori; Machino, Takayuki; Kusakabe, Toshiro; Hirayama, Yasuo; Mihara, Hiroyoshi; Yamakage, Michiaki; Kato, Junji; Nishisato, Takuji; Ishitani, Kunihiko

    2016-03-01

    The recommended dosing interval for transdermal fentanyl is every 72 h. However, some patients will have "end-of-dose failure," which may be seen as an increase of episodes of severe pain flares at the third day after application of the patch. A new once-a-day fentanyl patch was developed in Japan since 2010. This study aimed to assess the efficacy of the once-a-day fentanyl citrate patch for patients with cancer-related pain receiving the 72-h transdermal fentanyl not lasting 72 h. We performed a cross-sectional retrospective analysis of 445 inpatients with the 72-h transdermal fentanyl at Higashi Sapporo Hospital. We could switch to the once-a-day fentanyl citrate patch if patients reported inadequate pain relief beyond 48 h after application of the 72-h transdermal fentanyl. Patients recorded baseline scores for background pain intensity (PI) and the frequency of use of daily rescue medication for breakthrough cancer pain (BTcP). Of all patients, 10.1% showed the increase in PI of 30% or more baseline PI on the third day after application of the 72-h transdermal fentanyl. Of patients, 84.4% were converted from equivalent dose of the 72-h transdermal fentanyl to the once-a-day fentanyl citrate patch. On the third day after switching, 60.5% of patients showed a reduction of more than 30% from baseline PI. Switching to the once-a-day fentanyl citrate patch significantly reduced the mean frequency of daily rescue dose for BTcP. A once-a-day fentanyl citrate patch provided stable pain control. Its use may be considered as the dominant strategy for patients receiving a 72-h transdermal fentanyl not lasting 72 h.

  4. Prophylactic Effect of Ondansetron for Intrathecal Fentanyl-Induced Pruritus

    Directory of Open Access Journals (Sweden)

    Mehdi Fathi

    2014-01-01

    Full Text Available Background: Using opioids along with local analgesic increase anesthesia duration and provide appropriate postoperative analgesia. However, intrathecal injection of opioids is associated with upsetting side effects including pruritus. Ondansetron (5-HT3 receptor agonist has anti-pruritus effects. Therefore, we conducted a double blind randomized case-control study to evaluate prophylactic effects of ondansetron for preventing intrathecal fentanyl-induced pruritus. Materials and Methods: Two hundred seven patients with ASA status I, II or III, who were candidate for pelvic or lower extremity surgery with spinal anesthesia (SA using bupivacaine hyperbaric (10-15 mg and fentanyl (25 μg were included in the study. Patients were randomly assigned to two groups of case (ondansetron 8 mg IV and control (4 ml normal saline IV. Patients’ hemodynamic indexes and side effects were evaluated at 5, 10, 30, 60 minutes and then hourly up to 6 hours after SA. Pruritus presence, degree, and site were evaluated after two and six hours. Data were analyzed using Kolmogorov-Smirnov test, student t-test, Mann–Whitney U, χP2P, Fisher exact test, and Spearman linear correlation coefficient. Results: The pruritus incidence was 60% in control and 34% in case group. Severe pruritus was observed in 18% of control group and 6% of case group. Ninety four percent of patients with pruritus in control group expressed it in above TR6R dermatomes and 74% of patients with pruritus in case group had pruritus in TR6R-LR1R dermatomes. The incidence of pruritus in LR1R-lower dermatomes was similar in two groups. Headache and nausea after anesthesia were more common in control group (p=0.035. Conclusion: Ondansetron decrease incidence and degree of intrathecal fentanyl-induced pruritus. This reduction was more significant around injection area TR6R-LR1R dermatomes. Ondansetron injection does not influence systolic blood pressure, duration of anesthesia and analgesia, and does not

  5. Chronological age affects the permeation of fentanyl through human skin in vitro

    DEFF Research Database (Denmark)

    Holmgaard, R; Benfeldt, E; Sorensen, J A

    2013-01-01

    AIM: To study the influence of chronological age on fentanyl permeation through human skin in vitro using static diffusion cells. Elderly individuals are known to be more sensitive to opioids and obtain higher plasma concentrations following dermal application of fentanyl compared to younger...... individuals. The influence of age - as an isolated pharmacokinetic term - on the absorption of fentanyl has not been previously studied. METHOD: Human skin from 30 female donors was mounted in static diffusion cells, and samples were collected during 48 h. Donors were divided into three age groups: ... and old age groups: 5,922 and 4,050 ng, respectively). Furthermore, the lag time and absorption rate were different between the three groups, with a significantly higher rate in the young participants versus the oldest participants. CONCLUSION: We demonstrate that fentanyl permeates the skin of young...

  6. Safety and efficiency of prehospital pain management with fentanyl administered by emergency medical technicians

    DEFF Research Database (Denmark)

    Nielsen, Niels Dalsgaard; Brogaard, Kjeld; Dahl, Michael

    2007-01-01

    Introduction: In our region Advanced Emergency Medical Technicians (AEMTs) respond to acutely ill or injured patients in rural areas. The AEMTs have been authorized to administer fentanyl intravenously in doses up to 2 μg/kg to selected groups of patients in pain. Higher doses can be allowed...... by a physician after a teleconference. We examined the effect of intravenous (IV) fentanyl treatment, expressed as pain reduction on a 10-point Numeric Rating Scale (NRS). Moreover we examined the occurrence of negative coincident events to assess whether it was safe to let non-medical staff administer potent...... opioids intravenously.   Methods: Retrospectively we collected the case sheets for all patients treated with IV fentanyl by the AEMTs in 2005 and 2006. We excluded all patients where a physician had been directly involved in the prehospital treatment. We recorded the IV fentanyl dose, NRS-score before...

  7. The hidden web and the fentanyl problem: Detection of ocfentanil as an adulterant in heroin

    National Research Council Canada - National Science Library

    Quintana, Pol; Ventura, Mireia; Grifell, Marc; Palma, Alvaro; Galindo, Liliana; Fornís, Iván; Gil, Cristina; Carbón, Xoán; Caudevilla, Fernando; Farré, Magí; Torrens, Marta

    2017-01-01

    .... The aims of this paper are to report the presence of ocfentanil, a novel, potent, non-controlled fentanyl analog, in samples sold as heroin in the hidden web, and to summarize the effects reported by users. Methods...

  8. Fentanyl-midazolam vs. midazolam-ketamine regarding patient sedation analgesia for emergency orthopedic procedures

    National Research Council Canada - National Science Library

    Ali Abdolrazaghnejad; Mohsen Banaie

    2017-01-01

    The aim of the present study was to investigate two pharmaceutical groups including fentanyl-midazolam and midazolam-ketamine used as patient seda-tion analgesia for the orthopedic emergency procedures...

  9. Schedules of Controlled Substances: Temporary Placement of 4-Fluoroisobutyryl Fentanyl into Schedule I. Temporary scheduling order.

    Science.gov (United States)

    2017-05-03

    The Administrator of the Drug Enforcement Administration is issuing this temporary scheduling order to schedule the synthetic opioid, N-(4-fluorophenyl)-N-(1-phenethylpiperidin-4-yl)isobutyramide (4-fluoroisobutyryl fentanyl or para-fluoroisobutyryl fentanyl), and its isomers, esters, ethers, salts and salts of isomers, esters, and ethers, into schedule I pursuant to the temporary scheduling provisions of the Controlled Substances Act. This action is based on a finding by the Administrator that the placement of 4-fluoroisobutyryl fentanyl into schedule I of the Controlled Substances Act is necessary to avoid an imminent hazard to the public safety. As a result of this order, the regulatory controls and administrative, civil, and criminal sanctions applicable to schedule I controlled substances will be imposed on persons who handle (manufacture, distribute, reverse distribute, import, export, engage in research, conduct instructional activities or chemical analysis, or possess), or propose to handle, 4-fluoroisobutyryl fentanyl.

  10. Synthesis and analysis of the opioid analgesic [[sup 14]C]-fentanyl

    Energy Technology Data Exchange (ETDEWEB)

    Bagley, J.R.; Wilhelm, J.A. (Anaquest Inc., Murray Hill, NJ (United States))

    1992-11-01

    The synthesis of [[sup 14]C]-fentanyl, the radiolabelled congener of the potent opioid analgesic chosen for utilization in drug disposition studies, is described. [[sup 14]C]-Labelling was achieved in the first of two steps, a room temperature reduction of the in situ generated Schiff base from 1-phenylethyl-4-piperidone and [UL-[sup 14]C]-aniline hydrochloride with sodium triacetoxyborohydride. A nearly instantaneous production of fentanyl was accomplished at room temperature with the addition of propionyl chloride. The overall radiochemical yield was 18%. The method described is efficiently adaptable for submicromolar scale while yielding a product of sufficient specific activity for in vivo studies. Our solvent system for thin layer chromatography was superior to the USP system reported for chromatographic analysis of fentanyl. This is the first reported preparation of [[sup 14]C]-fentanyl with the radiolabel in the aniline benzene ring. (author).

  11. Combination of Continuous Dexmedetomidine Infusion with Titrated Ultra-Low-Dose Propofol-Fentanyl for an Awake Craniotomy; Case report

    Directory of Open Access Journals (Sweden)

    Samaresh Das

    2016-08-01

    Full Text Available An awake craniotomy is a continuously evolving technique used for the resection of brain tumours from the eloquent cortex. We report a 29-year-old male patient who presented to the Khoula Hospital, Muscat, Oman, in 2016 with a two month history of headaches and convulsions due to a space-occupying brain lesion in close proximity with the left motor cortex. An awake craniotomy was conducted using a scalp block, continuous dexmedetomidine infusion and a titrated ultra-low-dose of propofol-fentanyl. The patient remained comfortable throughout the procedure and the intraoperative neuropsychological tests, brain mapping and tumour resection were successful. This case report suggests that dexmedetomidine in combination with titrated ultra-low-dose propofolfentanyl are effective options during an awake craniotomy, ensuring optimum sedation, minimal disinhibition and a rapid recovery. To the best of the authors’ knowledge, this is the first awake craniotomy conducted successfully in Oman.

  12. Epidural versus intravenous fentanyl for postoperative analgesia following orthopedic surgery: randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Marcelo Soares Privado

    Full Text Available CONTEXT AND OBJECTIVE: Controversy exists regarding the site of action of fentanyl after epidural injection. The objective of this investigation was to compare the efficacy of epidural and intravenous fentanyl for orthopedic surgery. DESIGN AND SETTING: A randomized double-blind study was performed in Hospital São Paulo. METHODS: During the postoperative period, in the presence of pain, 29 patients were divided into two groups: group 1 (n = 14 received 100 µg of fentanyl epidurally and 2 ml of saline intravenously; group 2 (n = 15 received 5 ml of saline epidurally and 100 µg of fentanyl intravenously. The analgesic supplementation consisted of 40 mg of tenoxicam intravenously and, if necessary, 5 ml of 0.25% bupivacaine epidurally. Pain intensity was evaluated on a numerical scale and plasma concentrations of fentanyl were measured simultaneously. RESULTS: The percentage of patients who required supplementary analgesia with tenoxicam was lower in group 1 (71.4% than in group 2 (100%: 95% confidence interval (CI = 0.001-0.4360 (P = 0.001, Fisher's exact test; relative risk, RR = 0.07. Epidural bupivacaine supplementation was also lower in group 1 (14.3% than in group 2 (53.3%: 95% CI = 0.06-1.05 (P = 0.03, Fisher's exact test; RR = 0.26. There was no difference in pain intensity on the numerical scale. Mean fentanyl plasma concentrations were similar in the two groups. CONCLUSION: Intravenous and epidural fentanyl appear to have similar efficacy for reducing pain according to the numerical scale, but supplementary analgesia was needed less frequently when epidural fentanyl was used. CLINICAL TRIAL REGISTRATION NUMBER: NCT00635986

  13. Synergistic effect of intrathecal fentanyl and bupivacaine in spinal anesthesia for cesarean section

    Directory of Open Access Journals (Sweden)

    Srivastava Pratima

    2005-05-01

    Full Text Available Abstract Background Potentiating the effect of intrathecal local anesthetics by addition of intrathecal opiods for intra-abdominal surgeries is known. In this study by addition of fentanyl we tried to minimize the dose of bupivacaine, thereby reducing the side effects caused by higher doses of intrathecal bupivacaine in cesarean section. Methods Study was performed on 120 cesarean section parturients divided into six groups, identified as B8, B10 and B 12.5 8.10 and 12.5 mg of bupivacaine mg and FB8, FB10 and FB 12.5 received a combination of 12.5 μg intrathecal fentanyl respectively. The parameters taken into consideration were visceral pain, hemodynamic stability, intraoperative sedation, intraoperative and postoperative shivering, and postoperative pain. Results Onset of sensory block to T6 occurred faster with increasing bupivacaine doses in bupivacaine only groups and bupivacaine -fentanyl combination groups. Alone lower concentrations of bupivacaine could not complete removed the visceral pain. Blood pressure declined with the increasing concentration of Bupivacaine and Fentanyl. Incidence of nausea and shivering reduces significantly whereas, the postoperative pain relief and hemodynamics increased by adding fentanyl. Pruritis, maternal respiratory depression and changes in Apgar score of babies do not occur with fentanyl. Conclusion Spinal anesthesia among the neuraxial blocks in obstetric patients needs strict dose calculations because minimal dose changes, complications and side effects arise, providing impetus for this study. Here the synergistic, potentiating effect of fentanyl (an opiod on bupivacaine (a local anesthetic in spinal anesthesia for cesarian section is presented, fentanyl is able to reduce the dose of bupivacaine and therefore its harmful effects.

  14. Neither xenon nor fentanyl induces neuroapoptosis in the newborn pig brain.

    Science.gov (United States)

    Sabir, Hemmen; Bishop, Sarah; Cohen, Nicki; Maes, Elke; Liu, Xun; Dingley, John; Thoresen, Marianne

    2013-08-01

    Some inhalation anesthetics increase apoptotic cell death in the developing brain. Xenon, an inhalation anesthetic, increases neuroprotection when combined with therapeutic hypothermia after hypoxic-ischemic brain injury in newborn animals. The authors, therefore, examined whether there was any neuroapoptotic effect of breathing 50% xenon with continuous fentanyl sedation for 24 h at normothermia or hypothermia on newborn pigs. Twenty-six healthy pigs (inhaled xenon with fentanyl at hypothermia (Trec = 33.5 °C), (2) 24 h of 50% inhaled xenon with fentanyl at normothermia (Trec = 38.5 °C), (3) 24 h of fentanyl at normothermia, or (4) nonventilated juvenile controls at normothermia. Five additional nonrandomized pigs inhaled 2% isoflurane at normothermia for 24 h to verify any proapoptotic effect of inhalation anesthetics in our model. Pathological cells were morphologically assessed in cortex, putamen, hippocampus, thalamus, and white matter. To quantify the findings, immunostained cells (caspase-3 and terminal deoxynucleotidyl transferase-mediated deoxyuridine-triphosphate nick-end labeling) were counted in the same brain regions. For groups (1) to (4), the total number of apoptotic cells was less than 5 per brain region, representing normal developmental neuroapoptosis. After immunostaining and cell counting, regression analysis showed that neither 50% xenon with fentanyl nor fentanyl alone increased neuroapoptosis. Isoflurane caused on average a 5- to 10-fold increase of immunostained cells. At normothermia or hypothermia, neither 24 h of inhaled 50% xenon with fentanyl sedation nor fentanyl alone induces neuroapoptosis in the neonatal pig brain. Breathing 2% isoflurane increases neuroapoptosis in neonatal pigs.

  15. Increase in Drug Overdose Deaths Involving Fentanyl-Rhode Island, January 2012-March 2014.

    Science.gov (United States)

    Mercado, Melissa C; Sumner, Steven A; Spelke, M Bridget; Bohm, Michele K; Sugerman, David E; Stanley, Christina

    2017-03-06

     This study identified sociodemographic, substance use, and multiple opioid prescriber and dispenser risk factors among drug overdose decedents in Rhode Island, in response to an increase in overdose deaths (ODs) involving fentanyl.  This cross-sectional investigation comprised all ODs reviewed by Rhode Island's Office of the State Medical Examiners (OSME) during January 2012 to March 2014. Data for 536 decedents were abstracted from OSME's charts, death certificates, toxicology reports, and Prescription Monitoring Program (PMP) databases. Decedents whose cause of death involved illicit fentanyl (N = 69) were compared with decedents whose causes of death did not involve fentanyl (other drug decedents; N = 467). Illicit-fentanyl decedents were younger than other drug decedents ( P  = 0.005). While more other-drug decedents than illicit fentanyl decedents had postmortem toxicological evidence of consuming heroin (31.9% vs 19.8%, P  fentanyl decedents (62.3% vs 45.6%, P  = 0.002). Approximately 35% of decedents filled an opioid prescription within 90 days of death; of these, one-third had a mean daily dosage greater than 100 morphine milligram equivalents (MME/day). Most decedents' opioid prescriptions were filled at one to two dispensers (83.9%) and written by one to two prescribers (75.8%). Notably, 29.2% of illicit fentanyl and 10.5% of other drug decedents filled prescriptions for buprenorphine, which is used to treat opioid use disorders. Illicit-fentanyl deaths frequently involved other illicit drugs (e.g., cocaine, heroin). The proportion of all decedents acquiring greater than 100 MME/day prescription dosages written and/or filled by few prescribers and dispensers is concerning. To protect patients, prescribers and dispensers should review PMP records and substance abuse history prior to providing opioids.

  16. Fatal Overdose due to Confusion of an Transdermal Fentanyl Delivery System

    OpenAIRE

    Ingo Voigt

    2013-01-01

    Background. The use of transdermal fentanyl systems has increased over recent years, especially in patients with chronic pain. Large misuse potential and fatal outcomes have been described. Case Presentation. A 58-year-old patient presenting with clinical signs of opioid poisoning (hypoventilation, bradycardia, hypotension, and miosis) was admitted to our ICU. The first body check revealed a 75 mcg per hour fentanyl patch at the patient's right scapula. Some months ago, patient's aunt died af...

  17. Effects of fentanyl on serotonin syndrome-like behaviors in rats.

    Science.gov (United States)

    Kitamura, Sonoe; Kawano, Takashi; Kaminaga, Satomi; Yamanaka, Daiki; Tateiwa, Hiroki; Locatelli, Fabricio M; Yokoyama, Masataka

    2016-02-01

    Emerging evidence from case reports suggests that fentanyl may precipitate potentially life-threatening serotonin syndrome in patients taking serotonergic drugs. However, the underlying mechanism of the association between serotonin syndrome and fentanyl remains under investigation. We therefore investigated the pharmacological effects of an analgesic dose of fentanyl (0.2 mg/kg) injected subcutaneously (s.c.) on serotonergic toxicity-like responses in rats. Rats were s.c. injected with 0.75 mg/kg 8-OH-DPAT, a full 5-HT1A agonist, as an animal model of serotonin syndrome. The 8-OH-DPAT-treated rats showed well-characterized serotonin syndrome-like behaviors (low body posture, forepaw treading), hyperlocomotion, and decreased body temperature. Rats injected s.c. with fentanyl alone showed no significant changes in any of the parameters measured, while concomitant administration of fentanyl + 8-OH-DPAT resulted in exaggerated 8-OH-DPAT-induced serototoxic responses. A separate dose-response experiment showed that the serototoxic effect of fentanyl was dose-dependent. Pretreatment with naloxone [2.0 mg/kg, intraperitoneal (i.p.) injection], an opioid receptor antagonist, failed to antagonize the fentanyl-induced exaggerated serotonin syndrome-like behaviors. In contrast, pretreatment with WAY-100653, a serotonin 5-HT1A receptor antagonist (0.5 mg/kg, i.p. injection) completely inhibited all responses. Our findings provide preclinical proof-of-concept that an analgesic dose of fentanyl enhances serotonin toxicity, likely via its serotonin-reuptake inhibitory activity, independently of interaction with the opioid receptors.

  18. Continuous intravenous analgesia with fentanyl or morphine after gynecological surgery: a cohort study.

    Science.gov (United States)

    Russo, Andrea; Grieco, Domenico Luca; Bevilacqua, Francesca; Anzellotti, Gian Marco; Scarano, Annamaria; Scambia, Giovanni; Costantini, Barbara; Marana, Elisabetta

    2017-02-01

    This retrospective study aims to compare postoperative pain relief offered by continuous intravenous infusion of either fentanyl or morphine. Sixty American Society of Anesthesiologists Physical Status I and II women who had undergone open gynecological surgery were enrolled. All patients received total intravenous postoperative analgesia for 24 h with continuous infusion of either fentanyl or morphine at comparable doses (38 patients received 0.3 µg/kg/h fentanyl and 22 received 0.02 mg/kg/h morphine). The primary endpoint was the need for analgesic rescue therapy during the postoperative period as assessed by an experienced nurse blinded to the design of the study, while the time to gastrointestinal bowel recovery was the main safety outcome measure. Visual analog scale was used to evaluate postoperative pain. Ramsay sedation score, multiparametric monitoring, bowel function and adverse effects were also recorded at 1, 6, 12, 18 and 24 h after the end of surgery. Data analysis showed that four patients (10 %) in the fentanyl group versus eight patients (36 %) in the morphine group needed to be treated with analgesic rescue drugs [unadjusted OR for fentanyl 0.2 (0.05-0.80); p = 0.02]. Patients treated with fentanyl showed a faster gastrointestinal recovery [1 (1-2) vs 3 (2.7-4) days; p fentanyl and morphine for postoperative pain relief is effective. In our cohort of patients, continuous intravenous infusion of fentanyl was associated with lower need for analgesic rescue drug, faster bowel recovery and shorter hospital length of stay.

  19. Functionally Selective Signaling for Morphine and Fentanyl Antinociception and Tolerance Mediated by the Rat Periaqueductal Gray

    Science.gov (United States)

    Morgan, Michael M.; Reid, Rachel A.; Saville, Kimber A.

    2014-01-01

    Functionally selective signaling appears to contribute to the variability in mechanisms that underlie tolerance to the antinociceptive effects of opioids. The present study tested this hypothesis by examining the contribution of G protein-coupled receptor kinase (GRK)/Protein kinase C (PKC) and C-Jun N-terminal kinase (JNK) activation on both the expression and development of tolerance to morphine and fentanyl microinjected into the ventrolateral periaqueductal gray of the rat. Microinjection of morphine or fentanyl into the periaqueductal gray produced a dose-dependent increase in hot plate latency. Microinjection of the non-specific GRK/PKC inhibitor Ro 32-0432 into the periaqueductal gray to block mu-opioid receptor phosphorylation enhanced the antinociceptive effect of morphine but had no effect on fentanyl antinociception. Microinjection of the JNK inhibitor SP600125 had no effect on morphine or fentanyl antinociception, but blocked the expression of tolerance to repeated morphine microinjections. In contrast, a microinjection of Ro 32-0432 blocked the expression of fentanyl, but not morphine tolerance. Repeated microinjections of Ro 32-0432 blocked the development of morphine tolerance and inhibited fentanyl antinociception whether rats were tolerant or not. Repeated microinjections of SP600125 into the periaqueductal gray blocked the development of tolerance to both morphine and fentanyl microinjections. These data demonstrate that the signaling molecules that contribute to tolerance vary depending on the opioid and methodology used to assess tolerance (expression vs. development of tolerance). This signaling difference is especially clear for the expression of tolerance in which JNK contributes to morphine tolerance and GRK/PKC contributes to fentanyl tolerance. PMID:25503060

  20. Sufentanil Vs Fentanyl for Fast-Track Cardiac Anaesthesia

    Directory of Open Access Journals (Sweden)

    C M Deshpande

    2009-01-01

    Full Text Available A perioperative anaesthetic management that aims to facilitate tracheal extubation of patients within 1-6 hrs after cardiac surgery is called "fast-track′. Main advantage of ′fast-track" method is better usage of medical resources and lowering hospital costs without increasing morbidity and mortality of the patients. Standard fast-track protocols contain short acting anaesthetic agents, smaller incisions and decreased pump times without hypothermia. In this study we compared two short acting opioid drugs, fentanyl versus Sufentanil when used as a part of the balanced anaesthesia technique for fast track in cardiac surgery patients& evaluated the time taken for extubation, haemodynamic stability, analgesia requirements& incidence of awareness. The results from the study show thatboth agents provide good haemodynamic stability and postoperative analgesia. Although Sufentanil provides earlier extuba-tion, both agents reduce the ICU stay equally. In conclusion both agents can be used effectively for fasttrack cardiac anaesthesia.

  1. Influence of fentanyl and morphine on intestinal circulation

    Energy Technology Data Exchange (ETDEWEB)

    Tverskoy, M.; Gelman, S.; Fowler, K.C.; Bradley, E.L.

    1985-06-01

    The influence of fentanyl and morphine on the intestinal circulation was evaluated in an isolated loop preparation in 37 dogs anesthetized with pentobarbital intravenously. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mm Hg. A mixture of /sup 86/Rb and 9-micron spheres labeled with /sup 141/Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A strong correlation was found between the clearances of rubidium and microspheres (r = 0.97, P less than 0.0001), suggesting that the shunting of 9-micron spheres through the intestines reflects the shunting of blood through nonnutritive vessels. Intravenous fentanyl decreased oxygen uptake (O/sub 2/up), and vascular resistance (VR), and increased blood flow (BF), rubidium and microsphere clearances (Cl-Rb, Cl-Sph, respectively), and permeability--surface area product (PS) in a dose-related fashion. Intravenous morphine in a dose of 1 mg X kg-1 increased Cl-Rb (nutritive BF) without changes in total (nutritive and nonnutritive) BF. This increase in nutritive BF is probably related to morphine-induced histamine release. Morphine in a dose of 5 mg X kg-1 was accompanied by vasoconstriction that was completely abolished by alpha-adrenoceptor blockade. The data suggest that morphine-induced intestinal vasoconstriction is mediated via a release of epinephrine, apparently from the adrenal medulla. It is concluded that changes in the intestinal circulation during anesthesia with narcotics might play a certain role in the cardiovascular homeostasis during anesthesia and surgery. An increase in oxygen content in portal venous blood, resulting from a decrease in intestinal oxygen uptake, should facilitate hepatic oxygenation.

  2. Evaluation of fentanyl disposition and effects in newborn piglets as an experimental model for human neonates.

    Science.gov (United States)

    Rey-Santano, Carmen; Mielgo, Victoria; Valls-I-Soler, Adolfo; Encinas, Esther; Lukas, John C; Vozmediano, Valvanera; Suárez, Elena

    2014-01-01

    Fentanyl is widely used off-label in NICU. Our aim was to investigate its cerebral, cardiovascular and pulmonary effects as well as pharmacokinetics in an experimental model for neonates. Fentanyl (5 µg/kg bolus immediately followed by a 90 minute infusion of 3 µg/kg/h) was administered to six mechanically ventilated newborn piglets. Cardiovascular, ventilation, pulmonary and oxygenation indexes as well as brain activity were monitored from T = 0 up to the end of experiments (T = 225-300 min). Also plasma samples for quantification of fentanyl were drawn. A "reliable degree of sedation" was observed up to T = 210-240 min, consistent with the selected dosing regimen and the observed fentanyl plasma levels. Unlike cardiovascular parameters, which were unmodified except for an increasing trend in heart rate, some of the ventilation and oxygenation indexes as well as brain activity were significantly altered. The pulmonary and brain effects of fentanyl were mostly recovered from T = 210 min to the end of experiment. The newborn piglet was shown to be a suitable experimental model for studying fentanyl disposition as well as respiratory and cardiovascular effects in human neonates. Therefore, it could be extremely useful for further investigating the drug behaviour under pathophysiological conditions.

  3. Evaluation of fentanyl disposition and effects in newborn piglets as an experimental model for human neonates.

    Directory of Open Access Journals (Sweden)

    Carmen Rey-Santano

    Full Text Available BACKGROUND: Fentanyl is widely used off-label in NICU. Our aim was to investigate its cerebral, cardiovascular and pulmonary effects as well as pharmacokinetics in an experimental model for neonates. METHODS: Fentanyl (5 µg/kg bolus immediately followed by a 90 minute infusion of 3 µg/kg/h was administered to six mechanically ventilated newborn piglets. Cardiovascular, ventilation, pulmonary and oxygenation indexes as well as brain activity were monitored from T = 0 up to the end of experiments (T = 225-300 min. Also plasma samples for quantification of fentanyl were drawn. RESULTS: A "reliable degree of sedation" was observed up to T = 210-240 min, consistent with the selected dosing regimen and the observed fentanyl plasma levels. Unlike cardiovascular parameters, which were unmodified except for an increasing trend in heart rate, some of the ventilation and oxygenation indexes as well as brain activity were significantly altered. The pulmonary and brain effects of fentanyl were mostly recovered from T = 210 min to the end of experiment. CONCLUSION: The newborn piglet was shown to be a suitable experimental model for studying fentanyl disposition as well as respiratory and cardiovascular effects in human neonates. Therefore, it could be extremely useful for further investigating the drug behaviour under pathophysiological conditions.

  4. Intrathecal sufentanil versus fentanyl for lower limb surgeries - A randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Poonam Motiani

    2011-01-01

    Full Text Available Background:To compare the efficacy and safety of intrathecal sufentanil or fentanyl as adjuvants to hyperbaric bupivacaine in patients undergoing major orthopaedic lower limb surgeries in terms of onset and duration of sensory block, motor block and post-operative pain relief. Patients & Methods: Ninety patients were recruited in this Prospective, randomized double blind study to receive either intrathecal sufentanil 5 μg (Group S, fentanyl 25 μg (Group F or normal saline 0.5 ml (Group C as adjuvants to 15 mg of 0.5% hyperbaric bupivacaine. The onset and duration of sensory and motor block were assessed intraoperatively. The pain scores were assessed postoperatively. Duration of complete and effective analgesia was recorded. The incidence of side effects such as nausea, vomiting, pruritus, shivering and PDPH was recorded. Results: The Demographic data, hemodynamic and respiratory parameters were comparable in the three groups. There was a significantly earlier onset and prolonged duration of sensory block in the sufentanil and fentanyl groups. The duration of complete and effective analgesia were also significantly prolonged in the fentanyl and sufentanil groups. Pruritus was noticed in the study groups (Groups S&F. Conclusions: Intrathecal sufentanil (5 μg and fentanyl (25 μg, as adjuvants lead to an earlier onset and prolonged duration of sensory block. The duration of effective analgesia with intrathecal sufentanil and fentanyl as adjuvants to hyperbaric bupivacaine is longer than that of bupivacaine alone.

  5. Time to opioid administration after implementation of an intranasal fentanyl protocol.

    Science.gov (United States)

    Schaefer, Jared A; Mlekoday, Tamara J

    2015-12-01

    Prompt and effective analgesia is a mainstay of emergency department (ED) medicine; however, it is often delayed in times of overcrowding and by the need to establish intravenous (IV) access. Thus, noninvasive analgesic administration by means of the intranasal route could potentially reduce time to analgesic administration by eliminating IV line insertion. This retrospective study evaluated time from physician entry into patient's room to opioid administration after implementation of an intranasal fentanyl protocol. Data were collected on pediatric patients who received intranasal fentanyl in the ED 225 days after protocol implementation. Time to opioid administration was then evaluated against historical controls given IV opioids in the same ED 90 days before protocol implementation. Seven patients were included in the intranasal fentanyl group and were evaluated against 47 patients given IV opioids. Time from physician entry into patient's room to opioid administration was significantly reduced for intranasal fentanyl (20.43 ± 11.54 minutes) vs IV opioids (42.04 ± 31.55 minutes; P = .002), and IV line insertion was avoided in all 7 intranasal fentanyl patients. No significant differences in adverse events were noted. This study provides evidence that administration of fentanyl via the intranasal route in the ED decreases time to administration of opioids in pediatric patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Exposure to Fentanyl After Transdermal Patch Administration for Cancer Pain Management.

    Science.gov (United States)

    Bista, Sudeep R; Haywood, Alison; Hardy, Janet; Norris, Ross; Hennig, Stefanie

    2016-06-01

    This study aimed to describe exposure after fentanyl transdermal patch administration in patients with advanced cancer to quantify variability around the exposure. Patients (n  =  56) with advanced cancer who received transdermal fentanyl (Durogesic®; median dose, 50 μg/h; range, 12-200 μg/h) provided venous blood samples (n  =  163) at various times (0.5-72 hours) during several patch application intervals. Plasma fentanyl concentration was determined (median, 0.9 μg/L; range, 0.04-9.7 μg/L) by high-performance liquid chromatography coupled to tandem mass spectrometry. Pharmacokinetic analysis was performed using nonlinear mixed-effects modeling with NONMEM. A 1-compartment distribution model with first-order absorption and elimination described fentanyl exposure after transdermal patch administration. Fentanyl apparent clearance (between-subject variability [BSV], %) was estimated at 122 L/h/70 kg and 38.5%, respectively. The absorption rate constant was 0.013 h(-1) . Between-occasion variability on apparent clearance was 22.0%, which was lower than BSV, suggesting predictable exposure within the same patient and justifying therapeutic drug monitoring. Except for weight-based dosing, no other patient characteristic could be identified to guide initial fentanyl dose selection in patients with advanced cancer. © 2015, The American College of Clinical Pharmacology.

  7. Comparative pharmacokinetics of intravenous fentanyl and buprenorphine in healthy greyhound dogs.

    Science.gov (United States)

    KuKanich, B; Allen, P

    2014-12-01

    The purpose of this study was to compare the pharmacokinetics of two highly protein-bound, lipophilic opioid drugs. Fentanyl (10 μg/kg) and buprenorphine (20 μg/kg) were administered intravenously (IV) to six healthy greyhound dogs (three males and three females). The doses were based on clinically administered doses for dogs. Plasma drug concentrations were determined using liquid chromatography with mass spectrometry, and noncompartmental pharmacokinetics were estimated with computer software. The volume of distribution (area) was larger for fentanyl (7.42 L/kg) compared to buprenorphine (3.54 L/kg). The plasma clearance of fentanyl (38.6 mL·min/kg) was faster than buprenorphine (10.3 mL·min/kg). The terminal half-life of fentanyl (2.22 h) was shorter than buprenorphine (3.96 h). Despite similar physicochemical properties including octanol-water partition coefficient and pKa, the pharmacokinetics of fentanyl and buprenorphine were not similar. Both fentanyl (84%) and buprenorphine (95-98%) are considered highly protein bound, but the differences in protein binding may contribute to the lack of similarity of pharmacokinetics in healthy dogs. © 2014 John Wiley & Sons Ltd.

  8. An Acute Acetyl Fentanyl Fatality: A Case Report With Postmortem Concentrations.

    Science.gov (United States)

    McIntyre, Iain M; Trochta, Amber; Gary, Ray D; Malamatos, Mark; Lucas, Jonathan R

    2015-01-01

    In this case report, we present an evaluation of the distribution of postmortem concentrations of acetyl fentanyl in a fatality attributed to the drug. A young man who had a history of heroin abuse was found deceased at his parents' home. Toxicology testing, which initially screened positive for fentanyl by ELISA, subsequently confirmed acetyl fentanyl by gas chromatography-mass spectrometry specific ion monitoring (GC-MS SIM) analysis following liquid-liquid extraction. No other drugs or medications, including fentanyl, were detected. The acetyl fentanyl peripheral blood concentration was quantified at 260 ng/mL compared with the central blood concentration of 250 ng/mL. The liver concentration was 1,000 ng/kg, the vitreous was 240 ng/mL and the urine was 2,600 ng/mL. The cause of death was certified due to acute acetyl fentanyl intoxication, and the manner of death was certified as an accident. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. The effects of secondhand smoke on postoperative pain and fentanyl consumption.

    Science.gov (United States)

    Aydogan, Mustafa Said; Ozturk, Erdogan; Erdogan, Mehmet Ali; Yucel, Aytac; Durmus, Mahmut; Ersoy, Mehmet Ozcan; Colak, Cemil

    2013-08-01

    Although the need for increased postoperative analgesia in smokers has been described, the effect of secondhand smoke on postoperative analgesia requirements has not been studied. We examined the effects of secondhand smoke on fentanyl consumption and postoperative pain. In this study, 101 patients (American Society of Anesthesiology physical status I and II) who underwent abdominal hysterectomy were divided into 3 groups according to history of exposure to cigarette smoke as per medical records which was retrospectively confirmed by measurement of serum cotinine: smokers (n = 28), nonsmokers (n = 31), and secondhand smokers (n = 32). All patients received propofol-remifentanil total intravenous anesthesia and used fentanyl patient controlled analgesia for postoperative pain. The fentanyl consumption visual analogue scale-pain intensity (VAS-PI) score and side effects were recorded in the postanesthesia care unit (PACU) and at 2, 4, 6, and 24 h after surgery. Fentanyl consumption at all the evaluation time points was significantly higher in secondhand smokers than in nonsmokers (P fentanyl consumption in secondhand smokers was lower than that in smokers in the PACU and at 24 h (P 0.05). Secondhand smoking was associated with increased postoperative fentanyl consumption, and increased VAS-PI scores. These findings may be beneficial for managing postoperative pain in secondhand smokers.

  10. Crystallographic and theoretical studies of an inclusion complex of β-cyclodextrin with fentanyl.

    Science.gov (United States)

    Ogawa, Noriko; Nagase, Hiromasa; Loftsson, Thorsteinn; Endo, Tomohiro; Takahashi, Chisato; Kawashima, Yoshiaki; Ueda, Haruhisa; Yamamoto, Hiromitsu

    2017-10-15

    The crystal structure of an inclusion complex of β-cyclodextrin (β-CD) with fentanyl was determined by single crystal X-ray diffraction analysis. The crystal belongs to the triclinic space group P1 and the complex comprises one fentanyl, two β-CD, and several water molecules. β-CD and fentanyl form a host-guest inclusion complex at a ratio of 2:1 and the asymmetric unit of the complex contains two host molecules (β-CDs) in a head-to-head arrangement that form dimers through hydrogen bonds between the secondary hydroxyl groups of β-CD and one guest molecule. Fentanyl is totally contained within the β-CD cavity and the structure of the phenylethyl part of fentanyl inside the dimeric cavity of the complex is disordered. Furthermore, theoretical molecular conformational calculations were conducted to clarify the mobility of the guest molecule in the β-CD cavity using CONFLEX software. Crystal optimization and crystal energy calculations were also conducted. The results of the theoretical calculations confirmed that the conformation of disorder part 1, which was high in occupancy by crystal structure analysis, was more stable. The phenylethyl part of fentanyl existed in several stable conformations. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. THERMAL SENSITIVITY ACROSS AGES AND DURING CHRONIC FENTANYL ADMINISTRATION IN RATS

    Science.gov (United States)

    Mitzelfelt, Jeremiah D.; Carter, Christy S.; Morgan, Drake

    2013-01-01

    Rationale Chronic pain is becoming a more common medical diagnosis and is especially prevalent in older individuals. As such, prescribed use of opioids is on the rise, even though the efficacy for pain management in older individuals is unclear. Objectives Thus the present preclinical study assessed the effectiveness of chronic fentanyl administration to produce antinociception in aging rats (16, 20, 24 months). Methods Animals were tested in a thermal sensitivity procedure known to involve neural circuits implicated in chronic pain in humans. Sensitivity to heat and cold thermal stimulation was assessed during 28 days of fentanyl administration (1.0 mg/kg/day), and 28 days of withdrawal. Results Fentanyl resulted in decreased thermal sensitivity to heat but not cold stimulation indicated by more time spent in the hot compartment relative to time spent in the cold or neutral compartments. Unlike previous findings using a hot-water tail withdrawal procedure, tolerance did not develop to the antinociceptive effects of fentanyl over a 28-day period of drug administration. The oldest animals were least sensitive, and the youngest animals most sensitive to the locomotor-stimulating effects of fentanyl. The effect on the antinociceptive response to fentanyl in the oldest group of rats was difficult to interpret due to profound changes in the behavior of saline-treated animals. Conclusions Overall, aging modifies the behavioral effects of opioids, a finding that may inform future studies for devising appropriate treatment strategies. PMID:23900640

  12. Evaluation of Fentanyl Disposition and Effects in Newborn Piglets as an Experimental Model for Human Neonates

    Science.gov (United States)

    Valls-i-Soler, Adolfo; Encinas, Esther; Lukas, John C.; Vozmediano, Valvanera; Suárez, Elena

    2014-01-01

    Background Fentanyl is widely used off-label in NICU. Our aim was to investigate its cerebral, cardiovascular and pulmonary effects as well as pharmacokinetics in an experimental model for neonates. Methods Fentanyl (5 µg/kg bolus immediately followed by a 90 minute infusion of 3 µg/kg/h) was administered to six mechanically ventilated newborn piglets. Cardiovascular, ventilation, pulmonary and oxygenation indexes as well as brain activity were monitored from T = 0 up to the end of experiments (T = 225–300 min). Also plasma samples for quantification of fentanyl were drawn. Results A “reliable degree of sedation” was observed up to T = 210–240 min, consistent with the selected dosing regimen and the observed fentanyl plasma levels. Unlike cardiovascular parameters, which were unmodified except for an increasing trend in heart rate, some of the ventilation and oxygenation indexes as well as brain activity were significantly altered. The pulmonary and brain effects of fentanyl were mostly recovered from T = 210 min to the end of experiment. Conclusion The newborn piglet was shown to be a suitable experimental model for studying fentanyl disposition as well as respiratory and cardiovascular effects in human neonates. Therefore, it could be extremely useful for further investigating the drug behaviour under pathophysiological conditions. PMID:24595018

  13. Evaluation of the Coat-A-Count sup 125 I fentanyl RIA: Comparison of sup 12 5I RIA and GC/MS-SIM for quantification of fentanyl in case urine specimens

    Energy Technology Data Exchange (ETDEWEB)

    Watts, V.W.; Caplan, Y.H. (Mesa Police Crime Laboratory, AZ (USA))

    1990-09-01

    The Coat-A-Count solid phase {sup 125}I Fentanyl Radioimmunoassay was evaluated with respect to linearity and precision using equine urine fortified with fentanyl and then compared with a gas chromatographic/mass spectrometric method for quantification of fentanyl in urine. The RIA assay was found to be linear over the urine fentanyl concentration range of 0.25 to 7.5 ng/mL and precise with coefficients of variation (CV) ranging from 9.6 to 19.3%. The RIA calibrators, ranging in fentanyl concentrations from 0.25 to 7.5 ng/mL, and controls, at mean fentanyl concentrations of 0.46 and 1.32 ng/mL, were compared by both the RIA and GC/MS methods. The cross-reactivity with the {sup 125}I RIA test was determined for the fentanyl metabolites, norfentanyl and hydroxyfentanyl, and found to be 5% and 35%, respectively. The illicit fentanyl analogs were found to show significant cross-reactivity, ranging from 20 to 100%. The {sup 125}I RIA was compared to GC/MS quantifications of fentanyl in 35 positive and 20 negative case urine specimens.

  14. Limited evidence for intranasal fentanyl in the emergency department and the prehospital setting--a systematic review

    DEFF Research Database (Denmark)

    Hansen, Morten Sejer; Dahl, Jørgen Berg

    2013-01-01

    The intranasal (IN) mode of application may be a valuable asset in non-invasive pain management. Fentanyl demonstrates pharmacokinetic and pharmacodynamic properties that are desirable in the management of acute pain, and IN fentanyl may be of value in the prehospital setting. The aim...... of this systematic review was to evaluate the current evidence for the use of IN fentanyl in the emergency department (ED) and prehospital setting....

  15. [Anesthesia with flunitrazepam/fentanyl and isoflurane/fentanyl. Unconscious perception and mid-latency auditory evoked potentials].

    Science.gov (United States)

    Schwender, D; Kaiser, A; Klasing, S; Faber-Züllig, E; Golling, W; Pöppel, E; Peter, K

    1994-05-01

    There is a high incidence of intraoperative awareness during cardiac surgery. Mid-latency auditory evoked potentials (MLAEP) reflect the primary cortical processing of auditory stimuli. In the present study, we investigated MLAEP and explicit and implicit memory for information presented during cardiac anaesthesia. PATIENTS AND METHODS. Institutional approval and informed consent was obtained in 30 patients scheduled for elective cardiac surgery. Anaesthesia was induced in group I (n = 10) with flunitrazepam/fentanyl (0.01 mg/kg) and maintained with flunitrazepam/fentanyl (1.2 mg/h). The patients in group II (n = 10) received etomidate (0.25 mg/kg) and fentanyl (0.005 mg/kg) for induction and isoflurane (0.6-1.2 vol%)/fentanyl (1.2 mg/h) for maintenance of general anaesthesia. Group III (n = 10) served as a control and patients were anaesthetized as in I or II. After sternotomy an audiotape that included an implicit memory task was presented to the patients in groups I and II. The story of Robinson Crusoe was told, and it was suggested to the patients that they remember Robinson Crusoe when asked what they associated with the word Friday 3-5 days postoperatively. Auditory evoked potentials were recorded awake and during general anaesthesia before and after the audiotape presentation on vertex (positive) and mastoids on both sides (negative). Auditory clicks were presented binaurally at 70 dBnHL at a rate of 9.3 Hz. Using the electrodiagnostic system Pathfinder I (Nicolet), 1000 successive stimulus responses were averaged over a 100 ms poststimulus interval and analyzed off-line. Latencies of the peak V, Na, Pa were measured. V belongs to the brainstem-generated potentials, which demonstrates that auditory stimuli were correctly transduced. Na, Pa are generated in the primary auditory cortex of the temporal lobe and are the electrophysiological correlate of the primary cortical processing of the auditory stimuli. RESULTS. None of the patients had an explicit memory

  16. Influence of endotoxin-induced sepsis on the requirements of propofol-fentanyl infusion rate in pigs

    DEFF Research Database (Denmark)

    Bollen, Peter; Nielsen, Bjørn J; Toft, Palle

    2007-01-01

    Endotoxin-induced sepsis in pigs is a recognized experimental model for the study of human septic shock. Generally, pigs are brought into general anaesthesia before sepsis is induced. It is our experience that drug dosages of propofol and fentanyl need to be reduced during endotoxin-induced sepsis......, in order to prevent respiratory and cardiovascular depression, but the scientific evidence for this observation is lacking. Therefore, we measured the consumption of propofol and fentanyl at equal level of anaesthesia in pigs with (n = 5) and without (n = 5) endotoxin-induced sepsis, using the cerebral...... state index (CSI) as measure of anaesthetic depth. Infusion rates of propofol (P fentanyl (P fentanyl, whereas...

  17. 1000th magnet delivered!

    CERN Multimedia

    2006-01-01

    On Monday 20 February members of the AT Department marked the delivery of the 1000th superconducting dipole magnet to CERN. Only 232 more of the dipole magnets are needed for the LHC. The 35 tonne-dipoles are 15 meters long and are being manufactured by three companies: Babcock Noell Nuclear in Germany (which finished its contract in November 2005), Ansaldo Superconduttori in Italy and Alstom-Jeumont in France. "The production is proceeding well and we expect to be complete in October as previously foreseen," said Lucio Rossi, Head of the Magnets and Superconductors Group (AT-MAS). In total, 1650 main magnets are needed for the LHC, of which 1300 have been delivered.

  18. 1000th magnet delivered!

    CERN Multimedia

    2006-01-01

    On Monday 20 February members of the AT Department marked the delivery of the 1000th superconducting dipole magnet to CERN. Only 232 more of the dipole magnets are needed for the LHC. The 35-tonne-dipoles are 15 meters long and are being manufactured by three companies: Babcock Noell Nuclear in Germany (which completed its contract in November 2005), Ansaldo Superconduttori in Italy and Alstom-Jeumont in France. 'The production is proceeding well and we expect to be complete in October as foreseen,' said Lucio Rossi, Head of the Magnets and Superconductors Group (AT-MAS). In total, 1650 main magnets are needed for the LHC, of which 1300 have already been delivered.

  19. Effects of acepromazine or dexmedetomidine on fentanyl disposition in dogs during recovery from isoflurane anesthesia.

    Science.gov (United States)

    Keating, Stephanie; Kerr, Carolyn; McDonell, Wayne; Valverde, Alexander; Johnson, Ron; Knych, Heather; Edginton, Andrea

    2016-01-01

    To describe fentanyl pharmacokinetics during isoflurane anesthesia and on recovery from anesthesia with concurrent administration of acepromazine, dexmedetomidine or saline in dogs. Experimental blinded, randomized, crossover study. Seven adult hound dogs. Dogs were administered intravenous (IV) fentanyl as a bolus (5 μg kg(-1)) followed by an infusion (5 μg kg(-1) hour(-1)) for 120 minutes during isoflurane anesthesia and emergence from anesthesia, and for 60 minutes after extubation during recovery from anesthesia. At the time of extubation, dexmedetomidine (2.5 μg kg(-1)), acepromazine (0.05 mg kg(-1)) or saline were administered IV. Venous blood was sampled during the maintenance and recovery periods. Fentanyl plasma concentrations were measured using high-performance liquid chromatography-mass spectrometry and population pharmacokinetic analyses were performed. Mean fentanyl plasma concentrations were 1.6-4.5 ng mL(-1) during isoflurane anesthesia and 1.6-2.0 ng mL(-1) during recovery from anesthesia. Recovery from isoflurane anesthesia without sedation was associated with an increase in the volume of the central compartment from 0.80 to 1.02 L kg(-1). After administration of acepromazine, systemic clearance of fentanyl increased from 31.5 to 40.3 mL minute(-1) kg(-1) and the volume of the central compartment increased from 0.70 to 0.94 L kg(-1). Administration of dexmedetomidine did not significantly change fentanyl pharmacokinetics. Inter-individual variability for fentanyl parameter estimates in all treatments ranged from 2.2% to 54.5%, and residual error ranged from 6.3% to 13.4%. The dose rates of fentanyl used in this study achieved previously established analgesic plasma concentrations for the duration of the infusion. Despite alterations in fentanyl pharmacokinetics, differences in fentanyl plasma concentrations among treatments during recovery from anesthesia were small and were unlikely to be of clinical significance. © 2015 Association of

  20. The influence of a fentanyl and dexmedetomidine combination on external respiratory functions in acute hemorrhage model

    Directory of Open Access Journals (Sweden)

    Nikolay G. Vengerovich

    2017-01-01

    Full Text Available Background. The synthetic opioid analgesic fentanyl is widely used for prophylaxis and therapy of traumatic shock associated with massive bleeding. Its side effects – skeletal muscle rigidity and respiratory center depression – are especially pronounced with repeated administration. It is rational to apply fentanyl in diminished doses in combination with non-opioid analgesics in order to reduce respiratory disturbances risk.Aim. The aim of the work is to justify the influence of opioid analgesic fentanyl and α2 -adrenomimetic dexmedetomidine combination on external respiratory functions in acute hemorrhage model.Materials and methods. Acute loss of 35–40% of circulating blood volume was modeled in experiments on 75 white mongrel male rats. The external respiratory functions (respiratory rate, respiratory volume, breath volume per minute were estimated in animals of 5 groups: 1 – rats without analgesic help (controls; 2–3 – rats receiving a single fentanyl intramuscular injection (ED99 98,96 mcg/kg or fentanyl together with dexme detomidine (ED99 of combination 67,94 mcg/kg 15 min after acute blood loss; 4–5 – rats receiving the same drugs 15 min, 30, 45 and 60 min later.Results. In experimental acute loss of 35–40% of circulating blood volume, 15 min later a secondary acute respiratory failure developed with a drop of respiratory rate, respiratory volume and volume of breath per minute by 30%, 21 and 47% (p < 0,05. The external respiratory functions recoverеd after 4 h mainly due to the increase of respiratory volume. A single intramuscular injection of fentanyl caused respiratory depression 15 min after experimental blood loss which resulted in the decrease of breath volume per minute to 30–61% (p < 0,05 for 90 min. Four intramuscular injections of fentanyl 15 min, 30, 45 and 60 min after hemorrhage caused a severe respiratory dysfunction, accompanied by apnea periods and Biot’s respiration. Respiratory rate was reduced

  1. Demonstration of analgesic effect of intranasal ketamine and intranasal fentanyl for postoperative pain after pediatric tonsillectomy.

    Science.gov (United States)

    Yenigun, Alper; Yilmaz, Sinan; Dogan, Remzi; Goktas, Seda Sezen; Calim, Muhittin; Ozturan, Orhan

    2018-01-01

    Tonsillectomy is one of the oldest and most commonly performed surgical procedure in otolaryngology. Postoperative pain management is still an unsolved problem. In this study, our aim is to demonstrate the efficacy of intranasal ketamine and intranasal fentanyl for postoperative pain relief after tonsillectomy in children. This randomized-controlled study was conducted to evaluate the effects of intranasal ketamine and intranasal fentanyl in children undergoing tonsillectomy. Tonsillectomy performed in 63 children were randomized into three groups. Group I received: Intravenous paracetamol (10 mg/kg), Group II received intranasal ketamine (1.5 mg/kg ketamine), Group III received intranasal fentanyl (1.5 mcg/kg). The Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and Wilson sedation scale scores were recorded at 15, 30, 60 min, 2 h, 6hr, 12 h and 24 h postoperatively. Patients were interviewed on the day after surgery to assess the postoperative pain, nightmares, hallucinations, nausea, vomiting and bleeding. Intranasal ketamine and intranasal fentanyl provided significantly stronger analgesic affects compared to intravenous paracetamol administration at postoperative 15, 30, 60 min and at 2, 6, 12 and 24 h in CHEOPS (p ketamine administration group. No such sedative effect was seen in the groups that received intranasal fentanyl and intravenous paracetamol in Wilson Sedation Scale (p ketamine and intranasal fentanyl were more effective than paracetamol for postoperative analgesia after pediatric tonsillectomy. Sedative effects were observed in three patients with the group of intranasal ketamine. There was no significant difference in the efficacy of IN Ketamine and IN Fentanyl for post-tonsillectomy pain. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. The role of thiopental and fentanyl in the production of balanced anaesthesia.

    Science.gov (United States)

    Tammisto, T; Aromaa, U; Korttila, K

    1980-01-01

    In order to clarify the interactions between various doses of thiopental and fentanyl in producing "balanced anaesthesia", their effects on consciousness, superficial nociception, and respiration and circulation were studied during N2O+O2 inhalation in connection with the induction of anaesthesia. Altogether 60 patients were studied; the drug combinations used were thiopental 5 mg/kg (TP5), thipental 3 mg/kg (TP3), thiopental 3 mg/kg and fentanyl 0.5 micrograms/kg (TP3F0.5), thiopental 2 mg/kg and fentanyl 1 micrograms/kg (TP2F1), thiopental 1 mg/kg and fentanyl 2 micrograms/kg (TP1F2), and fentanyl 3 micrograms/kg (F3). Five minutes after the i.v. supplementation of N2O+O2 anaesthesia, the depth of anaesthesia and analgesia (antinociception) were evaluated from the eyelid reflex and by pinching an inguinal skin fold. Cardiorespiratory parameters were measured during this study period at 1-min intervals. The balance between antinociception and anaesthesia was closest to optimum in groups TP2F1 and TP2F0.5. In pure thiopental groups, the analgesia was poor; only four patients did not respond to the nociceptive stimulus, whereas in group F3 anaesthesia (disappearance of the eyelid reflex) was obtained in only two patients. The respiratory depression was most pronounced in groups receiving 3, 2 and 1 micrograms/kg fentanyl and weakest in groups where only thiopental was used. Blood pressure decreased in all groups but no statistically significant differences were noted. On the basis of the results it seems obvious that attempts to achieve what is called "balanced anaesthesia" by the supplementation of an N2O+O2 mixture with fentanyl only leads to an unnecessarily prnounced respiratory depression, whereas supplementation with thiopental alone does not offer adequate antinociception.

  3. Correlation of ADRB1 rs1801253 Polymorphism with Analgesic Effect of Fentanyl After Cancer Surgeries

    Science.gov (United States)

    Wei, Wei; Tian, Yanli; Zhao, Chunlei; Sui, Zhifu; Liu, Chang; Wang, Congmin; Yang, Rongya

    2015-01-01

    Background Our study aimed to explore the association between β1-adrenoceptor (ADRB1) rs1801253 polymorphism and analgesic effect of fentanyl after cancer surgeries in Chinese Han populations. Material/Methods Postoperative fentanyl consumption of 120 patients for analgesia was recorded. Genotype distributions were detected by allele specific amplification-polymerase chain reaction (ASA-PCR) method. Postoperative pain was measured by visual analogue scale (VAS) method. Differences in postoperative VAS score and postoperative fentanyl consumption for analgesia in different genotype groups were compared by analysis of variance (ANOVA). Preoperative cold pressor-induced pain test was also performed to test the analgesic effect of fentanyl. Results Frequencies of Gly/Gly, Gly/Arg, Arg/Arg genotypes were 45.0%, 38.3%, and 16.7%, respectively, and passed the Hardy-Weinberg Equilibrium (HWE) test. The mean arterial pressure (MAP) and the heart rate (HR) had no significant differences at different times. After surgery, the VAS score and fentanyl consumption in Arg/Arg group were significantly higher than in other groups at the postoperative 2nd hour, but the differences were not obvious at the 4th hour, 24th hour, and the 48th hour. The results suggest that the Arg/Arg homozygote increased susceptibility to postoperative pain. The preoperative cold pressor-induced pain test suggested that individuals with Arg/Arg genotype showed worse analgesic effect of fentanyl compared to other genotypes. Conclusions In Chinese Han populations, ADRB1 rs1801253 polymorphism might be associated with the analgesic effect of fentanyl after cancer surgery. PMID:26694722

  4. Effects of fentanyl anesthesia and sufentanil anesthesia on regulatory T cells frequencies

    Science.gov (United States)

    Gong, Li; Qin, Qian; Zhou, Lei; Ouyang, Wen; Li, Yanshuang; Wu, Yuhui; Li, Yunli

    2014-01-01

    Background: CD4+CD25+Foxp3+ regulatory T cells (Tregs) can inhibit anti-tumor immune responses and opioids were also immunosuppressive. We set out to compare the effects of sufentanil and fentanyl on Tregs frequencies both in vitro and in breast cancer (BC) patients undergoing eradicative operation. Methods: PBMCs from 12 BC patients were activated in vitro in the presence of fentanyl or sufentanil. The percentage of Tregs was detected by flow cytometry after seven days culture. Other 38 patients who underwent eradicative operation were prospectively randomized to sufentanil anesthesia and fentanyl anesthesia. Blood samples were collected for Tregs quantification by flow cytometry analysis and for Foxp3 mRNA expression by RT-PCR, at 10 min before anesthesia (D0), 24h (D1), and 168 h (D7) after the operation respectively. Results: Activation of PBMCs in the presence of either fentanyl or sufentanil increased the Tregs number, and the effect of sufentanil was more significant under the same analgesic effect with fentanyl. In the 38 operated cases, both the Tregs frequencies and Foxp3 mRNA expression on D1 decreased in comparison to those on D0, but then recovered on D7. By comparing SF and F group, there ware no significant differences in Tregs frequencies and Foxp3 mRNA expression on D0, D1 and D7. Conclusion: With the same analgesic potency, sufentanil is more powerful in increasing the Tregs quantity than fentanyl in vitro. But there are no significant differences as to Tregs frequencies between sufentanil anesthesia and fentanyl anesthesia perioperatively. Further studies are needed to determine the differences in the Tregs function and long-term outcome of these patients. PMID:25550807

  5. Pharmacokinetics and dose proportionality of fentanyl effervescent buccal tablets in healthy volunteers.

    Science.gov (United States)

    Darwish, Mona; Tempero, Kenneth; Kirby, Mary; Thompson, Jeffrey

    2005-01-01

    Fentanyl effervescent buccal tablets (FEBT) are designed to enhance the rate and efficiency of fentanyl absorption through the buccal mucosa. This study was undertaken to characterise the pharmacokinetics and assess the dose proportionality of FEBT in healthy volunteers within the potential therapeutic dose range. Twenty-five healthy adults (mean age 33 years) completed a single-dose, randomised, open-label, four-dose, four-period, crossover study of FEBT. They were administered FEBT 200, 500, 810 or 1080microg. The subjects in this study were not opioid tolerant; therefore, naltrexone was administered to block any opioid receptor-mediated effects of fentanyl. Venous blood samples for measurement of serum fentanyl concentrations were obtained over 36 hours following dosing. Adverse events were recorded throughout the study. The pharmacokinetics of FEBT were characterised by an absorption phase with a median time to reach maximum serum concentration (tmax) of 0.75-0.99 hours that was consistent irrespective of dose. Mean serum fentanyl concentrations exhibited a biexponential decline from peak after FEBT 200 and 500microg doses and a triexponential decline after FEBT 810 and 1080microg doses. The maximum serum concentration (Cmax) of fentanyl was proportional up to and including the 810microg dose. The increase in Cmax was 20% less than proportional at the 1080microg dose. Systemic exposure to fentanyl, as measured by the area under the serum concentration-time curve from time zero to infinity (AUCinfinity), increased proportionally with increasing doses of FEBT (200-1080microg). No serious adverse events were reported during the study. The pharmacokinetics of FEBT were characterised by a high early fentanyl concentration as a result of absorption across the buccal mucosa of the oral cavity, which results in bypassing first-pass metabolism. This high early tmax contributed to enhanced early systemic fentanyl exposure. Maximum concentration and AUCinfinity of FEBT

  6. A COMPARISON OF SPINAL ANAESTHESIA WITH LEVOBUPIVACAINE AND HYPERBARIC BUPIVACAINE COMBINED WITH FENTANYL IN CAESAREAN SECTION

    Directory of Open Access Journals (Sweden)

    Kurmanadh Kalepalli

    2016-10-01

    Full Text Available BACKGROUND Recent trends in obstetric anaesthesia show increased popularity of regional anaesthesia among obstetric anaesthetists. General anaesthesia in caesarean section is associated with high morbidity and mortality rate when compared with regional anaesthesia. Regional anaesthesia has its own demerits which are primarily related to excessively high spinal blocks and toxicity of local anaesthetics. Reduction in doses and improvement in technique to avoid high level blocks and increased awareness of toxicity of local anaesthetics have contributed to reduction in complications related to regional anaesthesia. The challenges presented by a parturient requiring anaesthesia or analgesia, or both, make the role of obstetric anaesthesiologist both challenging and rewarding. Spinal anesthesia is a popular technique for caesarean delivery. Hyperbaric Bupivacaine in 8% glucose is often used. Plain or glucose-free, Bupivacaine has been frequently referred to as “Isobaric” in the literature, even after Blomqvist and Nilsson demonstrated its hypobaricity. More recently, several studies have confirmed that plain Bupivacaine is indeed hypobaric in comparison with human CSF. Although hyperbaric local anesthetic solutions have a remarkable record of safety, their use is not totally without risk. To prevent unilateral or saddle blocks, patients should move from the lateral or sitting position rapidly to supine position. Hyperbaric solutions may cause sudden cardiac arrest after spinal anesthesia because of the extension of the sympathetic block. The use of truly isobaric solutions may prove less sensitive to position issues. Hyperbaric solutions may cause hypotension or bradycardia after mobilization. Isobaric solutions are favored with respect to their less sensitivity to postural changes. MATERIALS AND METHODS 60 full term parturients of ASA Grade 1 and 2 posted for elective caesarean section under spinal anaesthesia were divided in to two groups. GROUP

  7. Effects of Parecoxib and Fentanyl on nociception-induced cortical activity

    Directory of Open Access Journals (Sweden)

    Wang Ying-Wei

    2010-01-01

    Full Text Available Abstract Background Analgesics, including opioids and non-steroid anti-inflammatory drugs reduce postoperative pain. However, little is known about the quantitative effects of these drugs on cortical activity induced by nociceptive stimulation. The aim of the present study was to determine the neural activity in response to a nociceptive stimulus and to investigate the effects of fentanyl (an opioid agonist and parecoxib (a selective cyclooxygenase-2 inhibitor on this nociception-induced cortical activity evoked by tail pinch. Extracellular recordings (electroencephalogram and multi-unit signals were performed in the area of the anterior cingulate cortex while intracellular recordings were made in the primary somatosensory cortex. The effects of parecoxib and fentanyl on induced cortical activity were compared. Results Peripheral nociceptive stimulation in anesthetized rats produced an immediate electroencephalogram (EEG desynchronization resembling the cortical arousal (low-amplitude, fast-wave activity, while the membrane potential switched into a persistent depolarization state. The induced cortical activity was abolished by fentanyl, and the fentanyl's effect was reversed by the opioid receptor antagonist, naloxone. Parecoxib, on the other hand, did not significantly affect the neural activity. Conclusion Cortical activity was modulated by nociceptive stimulation in anesthetized rats. Fentanyl showed a strong inhibitory effect on the nociceptive-stimulus induced cortical activity while parecoxib had no significant effect.

  8. Dexmedetomidine versus standard therapy with fentanyl for sedation in mechanically ventilated premature neonates.

    Science.gov (United States)

    O'Mara, Keliana; Gal, Peter; Wimmer, John; Ransom, J Laurence; Carlos, Rita Q; Dimaguila, Mary Ann V T; Davanzo, Christie C; Smith, McCrae

    2012-07-01

    To compare the efficacy and safety of dexmedetomidine and fentanyl for sedation in mechanically ventilated premature neonates. This was a retrospective, observational case-control study in a level III neonatal intensive care unit. Forty-eight premature neonates requiring mechanical ventilation were included. Patients received fentanyl (n=24) or dexmedetomidine (n=24) for pain or sedation. Each group also received fentanyl and lorazepam boluses as needed for agitation. The primary outcomes were efficacy and frequency of acute adverse events associated with each drug. Days on mechanical ventilation, stooling patterns, feeding tolerance, and neurologic outcomes were also evaluated. There were no significant differences in baseline demographics between the dexmedetomidine and fentanyl patients. Patients in the dexmedetomidine group required less adjunctive sedation and had more days free of additional sedation in comparison to fentanyl (54.1% vs. 16.5%, psedation in the premature neonates included in this study. Prospective randomized-controlled trials are needed before routine use of dexmedetomidine can be recommended.

  9. Identification of Chemical Attribution Signatures of Fentanyl Syntheses Using Multivariate Statistical Analysis of Orthogonal Analytical Data

    Energy Technology Data Exchange (ETDEWEB)

    Mayer, B. P. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Mew, D. A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); DeHope, A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Spackman, P. E. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Williams, A. M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-09-24

    Attribution of the origin of an illicit drug relies on identification of compounds indicative of its clandestine production and is a key component of many modern forensic investigations. The results of these studies can yield detailed information on method of manufacture, starting material source, and final product - all critical forensic evidence. In the present work, chemical attribution signatures (CAS) associated with the synthesis of the analgesic fentanyl, N-(1-phenylethylpiperidin-4-yl)-N-phenylpropanamide, were investigated. Six synthesis methods, all previously published fentanyl synthetic routes or hybrid versions thereof, were studied in an effort to identify and classify route-specific signatures. 160 distinct compounds and inorganic species were identified using gas and liquid chromatographies combined with mass spectrometric methods (GC-MS and LCMS/ MS-TOF) in conjunction with inductively coupled plasma mass spectrometry (ICPMS). The complexity of the resultant data matrix urged the use of multivariate statistical analysis. Using partial least squares discriminant analysis (PLS-DA), 87 route-specific CAS were classified and a statistical model capable of predicting the method of fentanyl synthesis was validated and tested against CAS profiles from crude fentanyl products deposited and later extracted from two operationally relevant surfaces: stainless steel and vinyl tile. This work provides the most detailed fentanyl CAS investigation to date by using orthogonal mass spectral data to identify CAS of forensic significance for illicit drug detection, profiling, and attribution.

  10. The impact of interprofessional collaboration on nurses' satisfaction and comfort with intranasal fentanyl.

    Science.gov (United States)

    Moadebi, Susanne; Kwan, Fiona; Stackhouse, Sherry; Reddekopp, Lisa

    2013-01-01

    Healthcare providers' beliefs and comfort with analgesics can impact medication decisions. Interprofessional educational interventions (IPE) improve medication delivery processes ultimately resulting in better patient care. The purpose of this study was to determine the impact on nurses' satisfaction and comfort with administering intranasal fentanyl for pediatric pain management in the Emergency Department (ED) before and following IPE. A protocol for administering intranasal fentanyl for children age 1-15 years with acute pain was introduced to the ED Nursing staff by an educational session conducted by a clinical pharmacist. Nurses' level of satisfaction and comfort was surveyed prior to and following IPE. Compliance with patient monitoring was determined by chart review. Eighty percentage of the nurses were very satisfied with the analgesic effect of intranasal fentanyl but barriers for its use included personal comfort, nurse monitoring time and age appropriateness. Most nurses felt comfortable administering intranasal fentanyl but showed increased comfort with intravenous morphine (83% versus 98%, pintranasal fentanyl. The use of IPE facilitated knowledge sharing to improve nurses' comfort with administering analgesic medication and the quality of patient care services. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Effect of Modulated Electrohyperthermia on the Pharmacokinetics of Oral Transmucosal Fentanyl Citrate in Healthy Volunteers.

    Science.gov (United States)

    Lee, Sun Young; Kim, Min-Gul

    2016-12-01

    This study aimed to determine whether changes occur in fentanyl absorption and disposition when administered in conjunction with modulated electrohyperthermia (mEHT) treatment. A randomized, single-dose, crossover, open-label study was used to investigate the effect of mEHT on the pharmacokinetic properties of fentanyl in 12 healthy volunteers. The 12 healthy volunteers were each administered a single dose of oral transmucosal fentanyl citrate (OTFC) or a single dose of OTFC with mEHT. mEHT was performed on the abdomen for 1 hour. Blood samples were collected for 24 hours after dosing. The temperature of the abdominal skin surface was assessed before dosing and at 10, 20, and 60 minutes after dosing. Geometric mean ratios (ratio of fentanyl with mEHT to fentanyl alone) for the Cmax and AUC0-last were 1.20 (90% CI, 1.09-1.32) and 1.15 (90% CI, 0.99-1.33), respectively. The mean temperature of the abdominal skin surface increased by approximately 4°C. There was an increase in the overall exposure to the drug without implications of any clinical significance. OTFC can be administered without limitations in combination with mEHT, and it is not necessary to modify the dosing regimen. cris.nih.go,kr Identifier: KCT0001286. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

  12. [Withdrawal syndrome in a critically ill child after sedation with midazolam and fentanyl].

    Science.gov (United States)

    Takara, Itaru; Tomiyama, Hiroshi; Tokumine, Joho; Sugahara, Kazuhiro

    2004-07-01

    A 7-year-old girl suffered from withdrawal syndrome with systemic convulsion after sedation with midazolam and fentanyl. She had a history of severe accidental alkaline esophagitis, and under went polysurgeries. This time, she was scheduled to receive reconstruction of the esophagus with small intestine in order to resolve esophageal stenosis. Operation and anesthesia lasted for 14 hours, and 17 hours, respectively. In the postoperative period, she was under heavy sedation with midazolam and fentanyl in order to keep neck position immobile. Her sedation persisted for 14 postoperative days, and the total doses of midazolam and fentanyl were more than 100 mg x kg(-1), and 6.4 mg x kg(-1), respectively. Thereafter, her sedation was tapered and discontinued within about 24 hours. After 12 hours, she suddenly developed systemic convulsion with loss of consciousness. There was no evidence of obvious organic central nervous system abnormality. We suspected withdrawal syndrome, and gradual decrease of midazolam and fentanyl prevented her from going into withdrawal syndrome. We have to pay attention to withdrawal syndrome when heavy and long sedation with midazolam and fentanyl was employed and the drugs were then tapered and discontinued.

  13. [Has the transdermal patch gone up in smoke? A fatal fentanyl intoxication].

    Science.gov (United States)

    Oechsler, Stephanie; Zimmer, Gisela; Pedal, Ingo; Skopp, Gisela

    2009-01-01

    Recently, there has been an increase in fentanyl-related overdoses following administration of transdermal patches by the buccal, oral or intravenous route or via inhalation. A fatal intoxication is reported with clear evidence from toxicological analysis. However, the administration route and the fate of the patch remained elusive at the end of the investigations. Alcohol was present in the blood in small quantity (0.024%), whereas no other drug could be detected by basic strategies. Autopsy and microscopic examination failed to find sufficient evidence for a diagnosis. Fentanyl and norfentanyl were determined from body fluids and tissues by LC/MS/MS following liquid/liquid extraction. Both analytes were detectable in all specimens under investigation except muscle tissue where norfentanyl was absent. While the fentanyl concentration in the blood was considered potentially life-threatening on the basis of data obtained from living persons and fentanyl-related deaths, it was difficult to assess the other values because no comparative data were available. The history and circumstances of the case together with the toxicological findings suggest an intravenous or inhalative application of the patch. The latter assumption is supported by the fact that the body was found holding a cigarillo butt in his right hand. The case underlines the necessity to study fentanyl-related deaths more closely to allow a better interpretation of potential intoxications.

  14. Chemical Attribution of Fentanyl Using Multivariate Statistical Analysis of Orthogonal Mass Spectral Data.

    Science.gov (United States)

    Mayer, Brian P; DeHope, Alan J; Mew, Daniel A; Spackman, Paul E; Williams, Audrey M

    2016-04-19

    Attribution of the origin of an illicit drug relies on identification of compounds indicative of its clandestine production and is a key component of many modern forensic investigations. The results of these studies can yield detailed information on method of manufacture, starting material source, and final product, all critical forensic evidence. In the present work, chemical attribution signatures (CAS) associated with the synthesis of the analgesic fentanyl, N-(1-phenylethylpiperidin-4-yl)-N-phenylpropanamide, were investigated. Six synthesis methods, all previously published fentanyl synthetic routes or hybrid versions thereof, were studied in an effort to identify and classify route-specific signatures. A total of 160 distinct compounds and inorganic species were identified using gas and liquid chromatographies combined with mass spectrometric methods (gas chromatography/mass spectrometry (GC/MS) and liquid chromatography-tandem mass spectrometry-time of-flight (LC-MS/MS-TOF)) in conjunction with inductively coupled plasma mass spectrometry (ICPMS). The complexity of the resultant data matrix urged the use of multivariate statistical analysis. Using partial least-squares-discriminant analysis (PLS-DA), 87 route-specific CAS were classified and a statistical model capable of predicting the method of fentanyl synthesis was validated and tested against CAS profiles from crude fentanyl products deposited and later extracted from two operationally relevant surfaces: stainless steel and vinyl tile. This work provides the most detailed fentanyl CAS investigation to date by using orthogonal mass spectral data to identify CAS of forensic significance for illicit drug detection, profiling, and attribution.

  15. CGRP 4218T/C polymorphism correlated with postoperative analgesic effect of fentanyl

    Science.gov (United States)

    Yi, Yusheng; Zhao, Mingqiang; Xu, Fenghe; Liu, Chuansheng; Yin, Yanwei; Yu, Junmin

    2015-01-01

    Purpose: Our study aimed at evaluating the association between α-calcitonin gene-related peptide (CGRP) 4218T/C polymorphism and the patient-controlled analgesic (PCA) effect of fentanyl on Chinese Han population. Methods: 98 patients were involved in the experiment, but only 92 patients completed the experiment. 0.1 mg/kg fentanyl was given to the patients through intravenous injection ten minutes before the ending of surgery. The patients achieved PCA by controlling the fentanyl infusion pump and a single dose was 1 mg. The CGRP 4218T/C polymorphism was genotyped with polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. The fentanyl consumption within the 72 hours after the surgery was recorded and the pain was assessed with numeric rating scale (NRS) method. Results: The patients were divided into three groups of wild homozygote (T/T), heterozygote (T/C), and mutant homozygote (C/C). At the 6th hour and the 12th hour after the surgery, the fentanyl consumption for PCA of the T/C group was significantly higher than the T/T group (Pfentanyl consumption of the C/C group was much higher than the T/T group (Pfentanyl consumption of the C/C group was more than the T/C group (Pfentanyl consumption for analgesia. PMID:26191294

  16. Fentanyl and Spiradoline Interactions in a Place-Conditioning Black-White Shuttle-Box

    Directory of Open Access Journals (Sweden)

    David J. Mokler

    2010-12-01

    Full Text Available Rats were trained for multiple sessions in a place-conditioning shuttle-box to explore motivational interactions of mu and kappa opioid agonists, specifically fentanyl reward and spiradoline aversion. In Phase 1, groups of rats received various doses of mu or kappa agonists, or placebo, testing for preference or aversion. Group A always received saline SC before 15-minute sessions. Group B received fentanyl SC (0.003, 0.006, 0.012 mg/kg, Group C received low and medium doses of agonists SC, and Group D received spiradoline (0.3, 0.6, 1.2 mg/kg SC during Training Sessions 1-4, rats being restricted to the drug-associated compartment. Rats received saline when restricted to the placebo-associate compartment and on test days with access to both shuttle-box compartments. In Phase 2 of the study, Training Session 5, Combinations of mu and kappa agonists were substituted in Groups B, C, and D. Dose-related preference to fentanyl and aversion to spiradoline occurred during Test Sessions 1-4. During Test Session 5, fentanyl preference in Group B was suppressed by spiradoline, rats in Group C had a saline-like response to combined agonists, and spiradoline aversion in Group D was attenuated by fentanyl. These findings suggest that combined doses of mu and kappa agonists, while additive for antinociception, offset the rewarding and punishing effects of each other.

  17. Diluent volume for epidural fentanyl and its effect on analgesia in early labor.

    Science.gov (United States)

    Connelly, Neil Roy; Parker, Robert K; Pedersen, Thomas; Manikantan, Thenu; Lucas, Tanya; Serban, Stelian; El-Mansouri, Mervat; DuBois, Scott; Santos, Edgar Delos; Rizvi, Asad; Gibson, Charles

    2003-06-01

    Epidural fentanyl after a lidocaine and epinephrine test dose provides adequate analgesia and allows for ambulation during early labor. We designed the current study to determine the influence of the diluent volume of the epidural fentanyl bolus (e.g., whether it has an effect on the onset and duration of analgesia). Sixty laboring primigravid women received a 3-mL epidural test dose of lidocaine with epinephrine and then received a fentanyl 100- micro g bolus in either a 2-mL, 10-mL, or 20-mL volume. Pain scores and side effects were recorded for each patient. The onset of analgesia was similar in all three groups. The mean duration before re-dose was not significantly different in the 2-mL group (108 +/- 40 min), the 10-mL group (126 +/- 57 min), or the 20-mL group (126 +/- 41 min). No patient in any group experienced any detectable motor block; one patient (2-mL group) complained of mild knee weakness and was not allowed to ambulate. In early laboring patients, the volume in which 100 micro g of epidural fentanyl (after a lidocaine-epinephrine test dose) is administered does not affect the onset or duration of analgesia, nor does it affect the ability to ambulate. In early laboring patients, the volume in which 100 micro g of epidural fentanyl (after a lidocaine-epinephrine test dose) is administered does not affect the onset or duration of ambulatory analgesia.

  18. 75 FR 37295 - Control of Immediate Precursor Used in the Illicit Manufacture of Fentanyl as a Schedule II...

    Science.gov (United States)

    2010-06-29

    ...), Department of Justice. ACTION: Final Rule. SUMMARY: The Drug Enforcement Administration (DEA) is designating... behavioral measure, the route of administration, and other factors. The legitimate medical use of fentanyl is... Interim Final Rule, ``Control of a Chemical Precursor Used in the Illicit Manufacture of Fentanyl as a...

  19. Exacerbation of asthma secondary to fentanyl transdermal patch.

    Science.gov (United States)

    Parmar, Malvinder S

    2009-01-01

    Asthma is a common chronic inflammatory disorder of the airways associated with hyperresponsiveness, reversible airflow limitation and respiratory symptoms.1 All patients with asthma are at risk for exacerbations that may range from mild to life threatening. Different triggers cause asthma exacerbation by inducing airway inflammation and/or provoking bronchospasm. Allergen-induced bronchospasm results from IgE-dependent release of mediators including histamine, prostaglandins and leukotrienes.2 Opiates are commonly used to treat chronic pain.3 Although hypersensitivity to opiates or accumulation of opiates can cause respiratory depression, opiates are also used in the management of cough and dyspnoea associated with advanced COPD and heart failure.4(,)5 Here, a report is presented on a patient who developed persistent exacerbation of underlying stable asthma after initiating fentanyl transdermal therapy for chronic low back pain. He underwent extensive investigations and a detailed reassessment of history, especially medication history, led to the possible causative factor; once recognised, removal of the offending agent (fenatnyl) resulted in complete improvement in his symptoms within 72 h.

  20. Limited evidence for intranasal fentanyl in the emergency department and the prehospital setting--a systematic review

    DEFF Research Database (Denmark)

    Hansen, Morten Sejer; Dahl, Jørgen Berg

    2013-01-01

    The intranasal (IN) mode of application may be a valuable asset in non-invasive pain management. Fentanyl demonstrates pharmacokinetic and pharmacodynamic properties that are desirable in the management of acute pain, and IN fentanyl may be of value in the prehospital setting. The aim of this sys......The intranasal (IN) mode of application may be a valuable asset in non-invasive pain management. Fentanyl demonstrates pharmacokinetic and pharmacodynamic properties that are desirable in the management of acute pain, and IN fentanyl may be of value in the prehospital setting. The aim...... of this systematic review was to evaluate the current evidence for the use of IN fentanyl in the emergency department (ED) and prehospital setting....

  1. Inhaled methoxyflurane and intranasal fentanyl for prehospital management of visceral pain in an Australian ambulance service.

    Science.gov (United States)

    Johnston, Steven; Wilkes, Garry J; Thompson, Jennifer A; Ziman, Mel; Brightwell, Richard

    2011-01-01

    This study analysed the analgesic effect and changes in vital signs associated with administration of inhaled Methoxyflurane (MTX) and/or intranasal Fentanyl (INF) for prehospital management of visceral pain. A retrospective, observational study reviewing 1024 randomly selected records of patients with presumed visceral pain administered MTX (465), INF (397) or both (162) by the Western Australian Ambulance Service between January 2004 and February 2006. Clinical variables assessed included systolic blood pressure, pulse rate, respiration rate and Glasgow Coma Scale score. Pain was assessed utilising Visual/Verbal Analogue Scale pain scores. Overall effects on vital signs appeared favourable 5 min after use and at hospital arrival with either agent alone or in combination. As sole agents, MTX produced the greatest initial pain scores reduction (2.0 (1.7 to 2.2) vs 1.6 (1.4 to 1.8)) (mean (95% CI), and INF provided greater pain reduction by hospital arrival (3.2 (2.9 to 3.5) vs 2.5 (2.1 to 2.9)). While both agents were effective, INF provided a greater pain score reduction for cardiac (3.0 (2.6 to 3.4) vs 2.3 (1.8 to 2.8)), female (3.4 (2.9 to 4.0) v 2.5 (2.0 to 3.0)) and age 75+ patients (3.2 (2.5 to 3.8) vs 1.8 (1.0 to 2.5)). Combined use of agents was not advantageous. MTX and INF are effective agents for providing visceral pain analgesia in the prehospital setting. While MTX provided a more rapid onset of pain relief, INF provided superior analgesia after subsequent doses and in female, cardiac and older patients.

  2. Comparing anesthesia with isoflurane and fentanyl/fluanisone/midazolam in a rat model of cardiac arrest

    DEFF Research Database (Denmark)

    Secher, Niels; Malte, Christian Lind; Tønnesen, Else

    2016-01-01

    CA model. We hypothesize that isoflurane anesthesia improves short-term outcome following resuscitation from CA compared with a subcutaneous fentanyl/fluanisone/midazolam anesthesia. METHODS: Male Sprague Dawley rats were randomized to anesthesia with isoflurane (n=11) or fentanyl...... samples for Endothelin-1 and cathecolamines were drawn before and after CA. KEY FINDINGS: Compared with fentanyl/fluanisone/midazolam anesthesia, isoflurane resulted in a shorter time to return of spontaneous circulation (ROSC), less use of epinephrine, increased coronary perfusion pressure during CPR......, higher mean arterial pressure post ROSC, increased plasma levels of Endothelin-1 and decreased levels of epinephrine. The choice of anesthesia did not affect ROSC rate or systemic O2 consumption. CONCLUSION: Isoflurane reduces time to ROSC, increases coronary perfusion pressure, and improves hemodynamic...

  3. Fentanyl inhibits the invasion and migration of colorectal cancer cells via inhibiting the negative regulation of Ets-1 on BANCR.

    Science.gov (United States)

    Li, Ai-xiang; Xin, Wen-qi; Ma, Chuan-gen

    2015-09-25

    Recent studies have shown the potential anti-tumor effect of fentanyl on colorectal cancer (CRC). However, its underling mechanism is still unclear. Since studies indicates the abnormal expression of transcription factor Ets-1 and BRAF-activated lncRNA (BANCR) in CRC progress, the relationship between Ets-1 and BANCR was investigated here to illustrate the fentanyl-induced mechanism on CRC in vitro. The expression levels of Ets-1 and BANCR were first detected in fentanyl-treated CRC cells. The interaction between Ets-1 and BANCR promoter was verified with chromatin immunoprecipitation assays, as well as corresponding acetylation of histones. The regulation of Ets-1 on BANCR expression was confirmed through luciferase assays and RT-PCR analysis. And, cell clone formation, cell migration and invasion were observed to evaluate the anti-tumor effects of fentanyl. Ets-1 overexpression or co-overexpression with BANCR was further performed by plasmids transfection to show the regulatory role of Ets-1 in fentanyl-induced mechanism. Fentanyl induced BANCR upregulation and Ets-1 downregulation in CRC cells. Further studies showed that Ets-1 negatively regulated BANCR expression via the deacetylation of histones H3 within BANCR promoter. Moreover, fentanyl induced less cell clone formation, as well as inhibited cell migration and invasion in vitro, while Ets-1 overexpression inhibited fentanyl-induced effects that could be reversed by BANCR co-overexpression. Fentanyl showed anti-tumor like effects on CRC cells, including less cell clone formation and inhibited cell migration and invasion. Furthermore, the regulatory role of Ets-1 on BANCR influenced fentanyl-induced mechanism, indicating their potential application in the therapeutic treatment of CRC. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Qualitative Identification of Fentanyl Analogs and Other Opioids in Postmortem Cases by UHPLC-Ion Trap-MSn.

    Science.gov (United States)

    Shoff, Elisa N; Zaney, M Elizabeth; Kahl, Joseph H; Hime, George W; Boland, Diane M

    2017-07-01

    Since 2013, the Miami-Dade County Medical Examiner Department has experienced an increase in the number of opioid-related deaths. The majority of cases coincided with the introduction of fentanyl into the local heroin supply. From 2014 to 2015, Miami-Dade County experienced a near 600% increase in fentanyl-related deaths, followed by an additional 200% increase in 2016. In 2015, two novel fentanyl analogs were identified in medical examiner cases: beta-hydroxythiofentanyl and acetyl fentanyl. In 2016, four additional fentanyl analogs emerged: para-fluoroisobutyryl fentanyl, butyryl fentanyl, furanyl fentanyl and carfentanil, as well as the synthetic opioid U-47700. In order to address this epidemic, a method was developed and validated to identify 44 opioid-related and analgesic compounds in postmortem samples using ultra high performance liquid chromatography ion trap mass spectrometry with MSn capabilities. The limit of detection for all compounds ranged from 0.1 to 5 ng/mL, with a majority having MS3 spectral fragmentation. Blood, urine, liver or brain specimens from ~500 postmortem cases were submitted for analysis based on case history and/or initial screening results. Of those cases, 375 were positive for illicit fentanyl and/or one or more fentanyl analogs. Due to the potency of these compounds, they were almost always included in the cause of death. Worth emphasizing and extremely alarming is the detection of carfentanil in 134 cases, 104 of which were initially missed by gas chromatography mass spectrometry. By incorporating this sensitive, highly specific, and evolving screening procedure into the workflow, the toxicology laboratory continues to effectively assist the medical examiners in determining the cause and manner of death of decedents in Miami-Dade County. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Conscious sedation for balloon mitral valvotomy: A comparison of fentanyl versus sufentanil.

    Science.gov (United States)

    Modak, Shailendra Deochandra; Kane, Deepa G

    2017-01-01

    Analgesia and sedation are required for the comfort of patient and the cardiologist during balloon mitral valvotomy. In this study, efficacy of analgesia, sedation, and patient satisfaction with sufentanil was compared with fentanyl. Single-centered, prospective single-blind study of sixty patients. Patients between 15 and 45 years of rheumatic mitral stenosis with valve area of 0.8-1 cm2 undergoing elective balloon mitral valvotomy, randomly divided to receive bolus injection fentanyl 1 mcg/kg (Group 1, n = 30) followed by infusion at 1 mcg/kg/h or bolus of injection sufentanil 0.1 mcg/kg (Group 2, n = 30) followed by continuous infusion at 0.1 mcg/h. Both the groups received injection midazolam bolus 0.02 mg/kg followed by infusion at 15 mcg/kg/h. Pain intensity (by visual analog score [VAS]), level of sedation (by Ramsay sedation scale), overall patient and operator's satisfaction, effect on cardiorespiratory parameters, and discharge score (by modified Aldrete score) were assessed. Statistical analysis used Student's unpaired t-test and Chi-square test. P fentanyl group was 0.9 versus 0.13 in sufentanil group (P fentanyl group was 83.52 mmHg versus 88 mmHg in sufentanil group (P fentanyl group was 8.97 versus 9.53 in sufentanil group (P fentanyl group was 17.87 versus 18.23 in sufentanil group (P < 0.05). No statistically significant difference was found with respect to heart rate, respiratory rate, oxygen saturation, PaCO2values, and anxiety scores. Sufentanil was found to be better with respect to analgesia, patient satisfaction, and recovery however not cost-effective for continuous infusion technique.

  6. A COMPARATIVE STUDY OF INTRATHECAL DEXMEDETOMIDINE AND FENTANYL AS ADJUVANTS TO BUPIVACAINE

    Directory of Open Access Journals (Sweden)

    Gollapalli Hanumanth

    2016-02-01

    Full Text Available INTRODUCTION Uncontrolled postoperative pain may produce a range of detrimental acute and chronic effects. Spinal anaesthesia provided by bupivacaine may be too short for providing postoperative analgesia. This study is conducted to evaluate the efficacy of intrathecal fentanyl and intrathecal dexmedetomidine as an adjuvant to hyperbaric bupivacaine with regards to the onset and duration of sensory and motor blockade, as well as postoperative analgesia and adverse effects. Hundred patients aged 18-55 years were randomly divided into two groups, each group consisting of 50 patients of either sex belonging to ASA class I and II posted for elective lower abdominal surgeries were given spinal anaesthesia using bupivacaine 0.5%, heavy 2.5 ml with either fentanyl 25µg (group F or 5µg of preservative free dexmedetomidine (group D. Assessment of the sensory and motor blockade were done at the end of each minute till the maximum level achieved. Measurement of blood pressure, pulse rate, respiratory rate and arterial oxygen saturation were obtained. Postoperatively the patients were observed for the duration of analgesia, time taken for complete regression of sensory blockade to S1 and time taken for complete recovery of motor power. RESULTS Our results showed a statistically highly significant prolongation of sensory and motor blockade, and postoperative analgesia in the dexmedetomidine group compared to the fentanyl group. In dexmedetomidine group four out of fifty patients, and in fentanyl group two out of fifty patients developed hypotension. In dexmedetomidine group five out of fifty patients, and in fentanyl group two out of fifty patients developed bradycardia. Incidence of pruritis is significantly high in fentanyl group.

  7. Synthesis and biological evaluation of some novel 1-substituted fentanyl analogs in Swiss albino mice

    Directory of Open Access Journals (Sweden)

    Yadav Shiv Kumar

    2014-06-01

    Full Text Available Fentanyl [N-(1-phenethyl-4-piperidinylpropionanilide] is a potent opioid analgesic agent, but a has narrow therapeutic index. We reported earlier on the synthesis and bioefficacy of fentanyl and its 1-substituted analogs (1-4 in mice. Here we report the synthesis and biological evaluation of four additional analogs, viz. N-isopropyl-3-(4-(N-phenylpropionamidopiperidin-1-ylpropanamide (5, N-tbutyl- 3-(4-(N-phenylpropionamidopiperidin-1-ylpropanamide (6, isopropyl 2-[4-(N-phenylpropionamidopiperidin-1-yl]propionate (7 and t-butyl 2-[4-(N-phenylpropionamidopiperidin-1-yl]propionate (8. The median lethal dose (LD50 determined by intravenous, intraperitoneal and oral routes suggests these analogs to be comparatively less toxic than fentanyl. On the basis of observational assessment on spontaneous activities of the central, peripheral, and autonomic nervous systems, all the analogs were found to be similar to fentanyl. Naloxone hydrochloride abolished the neurotoxic effects of these analogs, thereby ascertaining their opioid receptor-mediated effects. All the analogs displayed significant analgesic effects, measured by formalin-induced hind paw licking and tail immersion tests at their respective median effective dose (ED50. They also exhibited 8-12 fold increase in therapeutic index over fentanyl. However, 5 and 6 alone produced lower ED50 (20.5 and 21.0 μg/kg, respectively and higher potency ratio (1.37 and 1.33, respectively compared to fentanyl. They could thus be considered for further studies on pain management

  8. A structural study of fentanyl by DFT calculations, NMR and IR spectroscopy

    Science.gov (United States)

    Asadi, Zahra; Esrafili, Mehdi D.; Vessally, Esmail; Asnaashariisfahani, Manzarbanou; Yahyaei, Saeideh; Khani, Ali

    2017-01-01

    N-(1-(2-phenethyl)-4-piperidinyl-N-phenyl-propanamide (fentanyl) is synthesized and characterized by FT-IR, 1H NMR, 13C NMR, mass spectroscopy and elemental analyses. The geometry optimization is performed using the B3LYP and M06 density functionals with 6-311 + G(d) and 6-311++G(d,p) basis sets. The complete assignments are performed on the basis of the potential energy distribution (PED) of the all vibrational modes. Almost a nice correlation is found between the calculated 13C chemical shifts and experimental data. The frontier molecular orbitals and molecular electrostatic potential of fentanyl are also obtained.

  9. Fentanyl-related compounds and derivatives: current status and future prospects for pharmaceutical applications

    Science.gov (United States)

    Vardanyan, Ruben S; Hruby, Victor J

    2014-01-01

    Fentanyl and its analogs have been mainstays for the treatment of severe to moderate pain for many years. In this review, we outline the structural and corresponding synthetic strategies that have been used to understand the structure–biological activity relationship in fentanyl-related compounds and derivatives and their biological activity profiles. We discuss how changes in the scaffold structure can change biological and pharmacological activities. Finally, recent efforts to design and synthesize novel multivalent ligands that act as mu and delta opioid receptors and NK-1 receptors are discussed. PMID:24635521

  10. Overdose Deaths Related to Fentanyl and Its Analogs - Ohio, January-February 2017.

    Science.gov (United States)

    Daniulaityte, Raminta; Juhascik, Matthew P; Strayer, Kraig E; Sizemore, Ioana E; Harshbarger, Kent E; Antonides, Heather M; Carlson, Robert R

    2017-09-01

    Ohio is experiencing unprecedented loss of life caused by unintentional drug overdoses (1), with illicitly manufactured fentanyl (IMF) emerging as a significant threat to public health (2,3). IMF is structurally similar to pharmaceutical fentanyl, but is produced in clandestine laboratories and includes fentanyl analogs that display wide variability in potency (2); variations in chemical composition of these drugs make detection more difficult. During 2010-2015, unintentional drug overdose deaths in Ohio increased 98%, from 1,544 to 3,050.* In Montgomery County (county seat: Dayton), one of the epicenters of the opioid epidemic in the state, unintentional drug overdose deaths increased 40% in 1 year, from 249 in 2015 to 349 in 2016 (estimated unadjusted mortality rate = 57.7 per 100,000) (4). IMFs have not been part of routine toxicology testing at the coroner's offices and other types of medical and criminal justice settings across the country (2,3). Thus, data on IMF test results in the current outbreak have been limited. The Wright State University and the Montgomery County Coroner's Office/Miami Valley Regional Crime Laboratory (MCCO/MVRCL) collaborated on a National Institutes of Health study of fentanyl analogs and metabolites and other drugs identified in 281 unintentional overdose fatalities in 24 Ohio counties during January-February 2017. Approximately 90% of all decedents tested positive for fentanyl, 48% for acryl fentanyl, 31% for furanyl fentanyl, and 8% for carfentanil. Pharmaceutical opioids were identified in 23% of cases, and heroin in 6%, with higher proportions of heroin-related deaths in Appalachian counties. The majority of decedents tested positive for more than one type of fentanyl. Evidence suggests the growing role of IMFs, and the declining presence of heroin and pharmaceutical opioids in unintentional overdose fatalities, compared with 2014-2016 data from Ohio and other states (3-5). There is a need to include testing for IMFs as part

  11. Efficacy, safety, and tolerability of fentanyl pectin nasal spray in patients with breakthrough cancer pain

    Directory of Open Access Journals (Sweden)

    Ueberall MA

    2016-08-01

    for 79.4%. By the end of the study, there had been significant improvements versus baseline in BTcP-related daily life activities (28.3±16.9 vs 53.1±11.9, physical (35.9±8.4 vs 26.8±6.5, and mental quality of life (38.7±8.5 vs 29.9±7.9 (P<0.001 for each comparison vs baseline; in addition, health care resource utilization requirements directly related to BTcP were reduced by 67.5%. FPNS was well tolerated; seven patients (3.2% experienced eight treatment-emergent adverse events of which none was serious. There were no indicators of misuse or abuse.Conclusion: FPNS provided rapid and highly effective BTcP relief in opioid-tolerant cancer patients with substantial improvements in daily functioning and quality of life. FPNS was well tolerated and associated with significant reductions in health care resource utilization and nursing assistance. Keywords: breakthrough pain, cancer, fentanyl pectin nasal spray, intranasal administration, efficacy, safety, quality of life

  12. A COMPARATIVE STUDY OF DEXMEDETOMIDINE AND FENTANYL COMBINED WITH ROPIVACAINE FOR EPIDURAL ANAESTHESIA IN LOWER LIMB ORTHOPAEDIC SURGERIES

    Directory of Open Access Journals (Sweden)

    Ravi Vasupalli

    2016-09-01

    Full Text Available BACKGROUND Intrathecal anaesthesia and epidural anaesthesia are the most popular regional anaesthesia techniques used for lower limb surgeries. Intrathecal anaesthesia also called as subarachnoid block. It has few limitations like short duration of anaesthesia, extension of anaesthesia cannot be made for prolonged surgeries, rapid onset of sympathetic blockade, shorter duration of postoperative analgesia and troublesome complication of Post-Dural Puncture Headache (PDPH. Hence, epidural anaesthesia is the most preferred anaesthetic technique for lower limb surgeries these days. METHODS TIME FRAME The study was conducted during period spanning December 2013 to November 2014. STUDY POPULATION Patients who met all inclusion criteria were randomly selected. No distinction is made between males and females. STUDY DESIGN A prospective, randomised, double blind, case control, observational, interventional comparative study is designed after getting the informed written consent was obtained from the patient. RANDOMISATION Randomisation was done using a computer generated random number table. One hundred patients scheduled for various elective lower limb surgical procedures belonging to ASA class I and II were included in the study. 1. Group RD (n=50 15 mL of 0.75% ropivacaine + 0.6 µg/kg of dexmedetomidine (Inj. DEXTOMID-1 mL=100 mcg, 1 mL ampoule; 2. Group RF (n=50 15 mL of 0.75% ropivacaine (ropivacaine 0.75% preservative free-ROPIN 0.75%, 20 mL ampoules-Neon Laboratories, India, fentanyl 1 µg/kg Inj. FENTANYL-1 mL=50 mcg, 2 mL ampoule. The patients were premedicated with tablet alprazolam 0.5 mg and tablet ranitidine 150 mg orally at bedtime on the previous night before surgery. They were kept nil orally 10 p.m. onwards on the previous night. On the day of surgery, patient’s basal pulse rate and blood pressure were recorded. A peripheral intravenous line with 18 gauge cannula after local anaesthesia was secured in one of the upper limbs. All the

  13. Quantitative determination of fentanyl in newborn pig plasma and cerebrospinal fluid samples by HPLC-MS/MS.

    Science.gov (United States)

    Blanco, M E; Encinas, E; González, O; Rico, E; Vozmediano, V; Suárez, E; Alonso, R M

    2015-09-01

    In this study, a selective and sensitive high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method requiring low sample volume (≤100 μL) was developed and validated for the quantitative determination of the opioid drug fentanyl in plasma and cerebrospinal fluid (CSF). A protein precipitation extraction with acetonitrile was used for plasma samples whereas CSF samples were injected directly on the HPLC column. Fentanyl and (13) C6 -fentanyl (Internal Standard) were analyzed in an electrospray ionization source in positive mode, with multiple reaction monitoring (MRM) of the transitions m/z 337.0/188.0 and m/z 337.0/105.0 for quantification and confirmation of fentanyl, and m/z 343.0/188.0 for (13) C6 -fentanyl. The respective lowest limits of quantification for plasma and CSF were 0.2 and 0.25 ng/mL. Intra- and inter-assay precision and accuracy did not exceed 15%, in accordance with bioanalytical validation guidelines. The described analytical method was proven to be robust and was successfully applied to the determination of fentanyl in plasma and CSF samples from a pharmacokinetic and pharmacodynamic study in newborn piglets receiving intravenous fentanyl (5 µg/kg bolus immediately followed by a 90-min infusion of 3 µg/kg/h). Copyright © 2015 John Wiley & Sons, Ltd.

  14. Intrathecal fentanyl added to bupivacaine and morphine for cesarean delivery may induce a subtle acute opioid tolerance.

    Science.gov (United States)

    Carvalho, B; Drover, D R; Ginosar, Y; Cohen, S E; Riley, E T

    2012-01-01

    Previous studies have demonstrated that the addition of intrathecal fentanyl to a spinal anesthetic for cesarean delivery improves intraoperative analgesia. However, intrathecal fentanyl may induce acute tolerance to opioids. The objective of this study was to investigate whether the addition of intrathecal fentanyl to spinal anesthesia with intrathecal morphine increases postoperative analgesic requirements and pain scores. In this randomized, double-blinded study, 40 women having elective cesarean delivery were enrolled. Patients received spinal anesthesia with hyperbaric bupivacaine 12 mg, morphine 200 μg, and fentanyl 0, 5, 10 or 25 μg. Each patient received intravenous patient-controlled analgesia morphine for 24h postoperatively. Outcome measures included postoperative morphine usage and pain scores, as well as intraoperative pain, nausea, hypotension and vasopressor use. Total morphine use over the 24-h post-spinal study period was similar among the study groups (P=0.129). Postoperative pain scores were higher in patients receiving fentanyl 5, 10 and 25 μg compared to fentanyl 0 μg control group (P=0.003). The study results suggest that intrathecal fentanyl may induce acute tolerance to intrathecal morphine. However, because there was no difference in postoperative analgesia requirement and the difference in pain scores was small, the clinical significance of this finding is uncertain. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Fentanyl postmortem redistribution: preliminary findings regarding the relationship among femoral blood and liver and heart tissue concentrations.

    Science.gov (United States)

    Luckenbill, Kristin; Thompson, Jonathan; Middleton, Owen; Kloss, Julie; Apple, Fred

    2008-10-01

    Postmortem redistribution refers to the process of drugs diffusing from tissues into blood along a concentration gradient between death and time of specimen collection at autopsy. Anatomical site-to-site variation can exist for drug concentrations. The purpose of this study was twofold. First femoral blood, liver, and heart fentanyl concentrations were compared in medical examiner cases to assist in determining which specimen most appropriately should be used for interpretation. Nine fentanyl-positive cases were identified by history of drug use over a 15-month period (2007-2008). Femoral blood fentanyl concentrations (n = 9) ranged from 2.7 to 52.5 microg/L, liver fentanyl tissue (n = 9) ranged from 37.0 to 179 microg/kg, and heart fentanyl tissue (n = 3) ranged from 52.8 to 179 microg/kg. Liver tissue to femoral blood ratios ranged from 0.85 to 35.8, and heart tissue to femoral blood ratios ranged from 1.9 to 5.4. Second, utilizing a published compendium of multiple postmortem drugs, liver and heart tissues to femoral blood drug ratios were compared to known volumes of distribution, solubilities, and pKa. No significant relationships were observed. In conclusion, establishing a larger evidence-based database using liver fentanyl concentrations may be more optimal than blood concentrations for interpretation of postmortem fentanyl concentrations in medical examiner and coroner cases.

  16. Myocardial metabolism during anaesthesia with propofol--low dose fentanyl for coronary artery bypass surgery

    NARCIS (Netherlands)

    Vermeyen, K. M.; de Hert, S. G.; Erpels, F. A.; Adriaensen, H. F.

    1991-01-01

    We have studied the haemodynamic and myocardial effects of propofol-fentanyl anaesthesia in 12 patients undergoing coronary artery bypass surgery during the pre-bypass period. The induction dose of propofol was 1.5 mg kg-1 and mean infusion rate during maintenance was 4.48 mg kg-1 h-1 (range

  17. Comparison of fentanyl, sufentanil, and alfentanil anesthesia in patients undergoing valvular heart surgery

    NARCIS (Netherlands)

    Bovill, J. G.; Warren, P. J.; Schuller, J. L.; van Wezel, H. B.; Hoeneveld, M. H.

    1984-01-01

    The hemodynamic responses to anesthesia and surgery were studied in three groups of 20 patients undergoing valve replacement surgery. Anesthesia was induced with either fentanyl (75 micrograms/kg), sufentanil (15 micrograms/kg), or alfentanil (125 micrograms/kg). Pancuronium (8 mg) was given for

  18. Frontal lobe oxygenation is maintained during hypotension following propofol-fentanyl anesthesia

    DEFF Research Database (Denmark)

    Nissen, P.; Lieshout, J.J. van; Nielsen, H.B.

    2009-01-01

    Near-infrared spectroscopy (NIRS) assesses cerebral oxygen saturation (Sco2) as a balance between cerebral oxygen delivery and consumption. In 71 patients, we evaluated whether marked reduction in mean arterial pressure (MAP) during propofol-fentanyl anesthesia induction affects frontal lobe Sco2...

  19. Remifentanil versus Fentanyl/Midazolam in Painless Reduction of Anterior Shoulder Dislocation; a Randomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    Mohammad Gharavifard

    2016-04-01

    Full Text Available Introduction: Performance of painful diagnostic and therapeutic procedures is common in emergency department(ED, and procedural sedation and analgesia (PSA is a fundamental skill for every emergency physician.This studywas aim to compare the efficacy of remifentanil with fentanyl/midazolam in painless reduction of anteriorshoulder dislocation. Methods: In this randomized, double blind, clinical trial the procedural characteristics,patients satisfaction as well as adverse events were compared between fentanyl/midazolamand remifentanilfor PSA of 18–64 years old patients, which were presented to ED following anterior shoulder dislocation.Results: 96 cases were randomly allocated to two groups (86.5% male. There were no significant difference betweengroups regarding baseline characteristics. Remifentanil group had lower duration of procedure (2.5§1.6versus 4.6§1.8 minutes, p Ç 0.001, higher pain reduction (53.7§13.3 versus 33.5§19.6, p Ç 0.001, lower failurerate (1 (2.1% versus 15 (31.3%, p Ç 0.001, higher satisfaction (p Æ 0.005. Adverse events were seen in 12 (25%patients in midazolam/fentanyl and 8 (16.7% cases in remifentanil group (p Æ 0.122. Conclusion: It seemsthat use of remifentanil resulted in lower procedural time, lower failure rate, and lower pain during procedureas well as higher patient satisfaction in comparison with midazolam/fentanyl combination in anterior shoulderdislocation.

  20. Comparison of the effects of lidocaine and fentanyl in epidural anesthesia in dogs.

    Science.gov (United States)

    Saritas, Z K; Saritas, T B; Pamuk, K; Korkmaz, M; Demirkan, I; Yaprakci, M V; Sivaci, R G

    2014-01-01

    The study included 12 clinically healthy, adult male dogs of various breeds, admitted to our clinic for castration. After general anesthesia with sevoflurane, we administered epidural fentanyl (1 mcg/kg) to fentanyl group, while lidocaine group was given Lidocaine (3 mg/kg) through epidural administration. When hemodynamic parameters were stabilized, first measurements were recorded at minutes 0, 15, 30, 60 in both groups, which included Heart Rate (HR), body temperature, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), sodium (Na+), potassium (K+), glucose (GLC), and hemoglobin (HB) measurements. In addition, serum samples were obtained from arterial blood at the same measurement times, and pH, pO₂, pCO₂, HCO₃, %O₂ Saturation, BE levels were measured. For hematological analysis, WBC, RBC, HCT, THR counts were performed. For serum biochemical analysis, venous blood samples were collected at minutes 0 and 60 and CK, TP, UREA, ALT, AST, ALB, GGT, CRE, CK-MB parameters were assessed using auto-analyzer. Moreover, cortisol levels were measured in the samples collected at minutes 0, 30, and 60.Mean arterial blood pressure values measured at minutes 15, 30 and 60 were found significantly lower in the fentanyl group (p<0.01). In conclusion, we suggest that epidural anesthesia with lidocaine and fentanyl can provide an effective and safe option in high-risk groups (Tab. 5, Fig. 1, Ref. 24).

  1. Fatal Overdose due to Confusion of an Transdermal Fentanyl Delivery System

    Directory of Open Access Journals (Sweden)

    Ingo Voigt

    2013-01-01

    Full Text Available Background. The use of transdermal fentanyl systems has increased over recent years, especially in patients with chronic pain. Large misuse potential and fatal outcomes have been described. Case Presentation. A 58-year-old patient presenting with clinical signs of opioid poisoning (hypoventilation, bradycardia, hypotension, and miosis was admitted to our ICU. The first body check revealed a 75 mcg per hour fentanyl patch at the patient's right scapula. Some months ago, patient's aunt died after suffering from an oncological disease. During breaking up of her household, the patches were saved by the patient. Not knowing the risk of this drug, he mistook it as a heat plaster. Investigations. Laboratory test showed an impaired renal function and metabolic acidosis. Urine drug test was negative at admittance and 12 h later. CCT scan presented a global hypoxic brain disease. Treatment and Outcome. The patient was discharged 30 days after admittance in a hemodynamic stable condition but a vegetative state and transferred to a rehabilitation center. Learning Points. With the ongoing increase in fentanyl patch prescriptions for therapeutic reasons, it is likely that misuse cases will become more relevant. Conventional urine drug screening tests are not able to exclude the diagnosis fentanyl intoxication. History taking should include family member's drug prescriptions.

  2. The role of halothane and fentanyl in the production of balanced anaesthesia.

    Science.gov (United States)

    Tammisto, T; Aromaa, U

    1982-06-01

    The aim of the study was to quantitate the degree of respiratory depression when tolerance of superficial nociception and of an endotracheal tube was achieved by supplementing N2O + O2 anaesthesia either with halothane alone or with halothane in combination with fentanyl. Eighty-four patients, matched into seven groups, were studied after induction of anaesthesia with thiopental (4 mg/kg) and suxamethonium (3 mg/kg) using the following supplementation: 0.8, 0.6, 0.4% halothane alone or 0.4, 0.2, 0% halothane with 0.5-2 micrograms/kg fentanyl. After 10 min administration of the anaesthetic mixture using manual intermittent positive pressure ventilation (IPPV) (end-tidal CO2 c. 5.5%), IPPV was discontinued and spontaneous respiration allowed to return. When the end-tidal CO2 had stabilized, samples for blood gas analysis were taken and superficial antinociception was tested by pinching an inguinal skin fold. Supplementation of an N2O + O2 mixture with 0.8% halothane without fentanyl or with 0.4% halothane with 0.5 microgram/kg fentanyl seemed to come closest to the optimum in producing tolerance of an endotracheal tube and of superficial nociception (in about 85% of cases with an increase in PCO2 to only 7 kPa.

  3. Validation of the Neogen® Fentanyl ELISA Kit for Blood and Urine.

    Science.gov (United States)

    Tiscione, Nicholas B; Wegner, Kristin

    2017-05-01

    The Neogen® Fentanyl ready-to-use enzyme-linked immunosorbent assay kit was validated following the Scientific Working Group for Forensic Toxicology Standard Practices for Method Validation in Forensic Toxicology Laboratory Guidelines. Two decision points, 0.5 and 1 ng/mL, were successfully validated for whole blood. For urine, two decision points, 1 and 5 ng/mL, were also successfully validated. The validation included the evaluation of sensitivity, precision, specificity, carryover, plate drift, ruggedness/robustness and a case sample evaluation. The empirically determined limit of detection was 0.25 ng/mL for blood and 0.5 ng/mL for urine. Precision was determined at five different concentrations ranging from 0.25 to 1.5 ng/mL with 15 replicates at each level for whole blood and demonstrated a fentanyl, 4-anilino-N-phenethylpiperidine, beta-hydroxythiofentanyl, butyryl fentanyl and furanyl fentanyl. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Safety of Intranasal Fentanyl in the Out-of-Hospital Setting

    DEFF Research Database (Denmark)

    Karlsen, Anders P H; Pedersen, Danny M B; Trautner, Sven

    2014-01-01

    : In this prospective observational study, we administered intranasal fentanyl in the out-of-hospital setting to adults and children older than 8 years with severe pain resulting from orthopedic conditions, abdominal pain, or acute coronary syndrome refractory to nitroglycerin spray. Patients received 1 to 3 doses...

  5. Fatal Overdose due to Confusion of an Transdermal Fentanyl Delivery System.

    Science.gov (United States)

    Voigt, Ingo

    2013-01-01

    Background. The use of transdermal fentanyl systems has increased over recent years, especially in patients with chronic pain. Large misuse potential and fatal outcomes have been described. Case Presentation. A 58-year-old patient presenting with clinical signs of opioid poisoning (hypoventilation, bradycardia, hypotension, and miosis) was admitted to our ICU. The first body check revealed a 75 mcg per hour fentanyl patch at the patient's right scapula. Some months ago, patient's aunt died after suffering from an oncological disease. During breaking up of her household, the patches were saved by the patient. Not knowing the risk of this drug, he mistook it as a heat plaster. Investigations. Laboratory test showed an impaired renal function and metabolic acidosis. Urine drug test was negative at admittance and 12 h later. CCT scan presented a global hypoxic brain disease. Treatment and Outcome. The patient was discharged 30 days after admittance in a hemodynamic stable condition but a vegetative state and transferred to a rehabilitation center. Learning Points. With the ongoing increase in fentanyl patch prescriptions for therapeutic reasons, it is likely that misuse cases will become more relevant. Conventional urine drug screening tests are not able to exclude the diagnosis fentanyl intoxication. History taking should include family member's drug prescriptions.

  6. A fatality involving an unusual route of fentanyl delivery: Chewing and aspirating the transdermal patch.

    Science.gov (United States)

    Carson, Henry J; Knight, Laura D; Dudley, Mary H; Garg, Uttam

    2010-05-01

    We recently encountered a subject who died from an uncommon misuse of a fentanyl transdermal patch, chewing, followed by complications of aspiration of the patch. We report this case to alert medical examiners to the troubling trend of increased fentanyl patch abuse and its expanding range of misuses and associated morbidities. The decedent was a 28-year-old white male with a past medical history of prescription drug abuse who was pronounced dead in the emergency department shortly after arrival. An autopsy was completed and a tough but stretchy beige foreign body was identified lodged in a mainstem bronchus. Toxicological analysis of femoral blood showed methamphetamine, fentanyl and norfentanyl concentrations of 1456, 8.6 and 1.4 ng/mL, respectively. Individuals who abuse prescription medications often modify the route of administration of the drug from the intended method. As this case demonstrates, this choice can be fatal. The novel findings include a chewed patch, aspiration of a drug patch, and combination with an illicit drug at potentially lethal blood levels for both methamphetamine and fentanyl in a novice user. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  7. Fatal overdose after ingestion of a transdermal fentanyl patch in two non-human primates.

    Science.gov (United States)

    Deschamps, Jack-Yves; Gaulier, Jean-Michel; Podevin, Guillaume; Cherel, Yan; Ferry, Nicolas; Roux, Françoise A

    2012-11-01

    CASE HISTORY AND PRESENTATION: Two non-human primates (Macaca fascicularis), weight 3.5 kg, enrolled in an experimental protocol received a 25 μg hour(-1) transdermal fentanyl patch for postoperative analgesia. The following day both animals were clinically normal, but after a new induction of anaesthesia with ketamine, they developed severe and prolonged respiratory distress, profound coma and myosis. MANAGEMENT AND FOLLOW-UP: Attempted reversal with naloxone was ineffective. After several hours of ventilation, both primates eventually died, 7 and 15 hours after ketamine injection, respectively. In both cases, the patch was discovered in the animal's cheek pouch. Subsequent fentanyl serum concentration measurements (8.29 and 14.80 μg L(-1) ) confirmed fentanyl overdose. This report of two fatal intoxications in non-human primates secondary to ingestion of a transdermal fentanyl patch demonstrates that this method of analgesia is inappropriate for non-human primates, because of their tendency to chew almost anything they can reach. © 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

  8. Grand mal seizure induced by low-dose fentanyl and lidocaine in a young child.

    Science.gov (United States)

    Hsieh, Xhang-Xian; Hsu, Yung-Chi; Cherng, Chen-Hwan; Lin, Chun-Chieh; Huang, Go-Shine; Lin, Shinn-Long; Wu, Zhi-Fu; Yeh, Chun-Chang

    2015-09-01

    Surgical procedures require general anesthesia using combinations of drugs including fentanyl and/or lidocaine. Because many of these drugs have bimodal anticonvulsant/proconvulsant effects, they must be administered carefully. We herein report a case of seizure attack during anesthesia induction with low-dose fentanyl and lidocaine in a young child with no history of seizures. A 10-year-old girl was scheduled to receive an elective tenectomy. After a few seconds of fentanyl and lidocaine administration for anesthesia induction, she developed generalized tonic-clonic seizures. Seizures subsided spontaneously after 3 minutes. The patient's blood sugar, serum electrolytes, and arterial blood gas analysis were normal immediately after the event. She remained hemodynamically stable; however, the surgery was postponed after communication and discussion with the surgeon. Postoperatively, there was no evidence of postictal phase, and serum electrolytes and magnetic resonance imaging of the brain were normal. The patient had an uneventful recovery. However, electroencephalogram showed that hyperventilation stimulation test induced isolated epileptiform spikes over O1, suggesting a potential paroxysmal disorder over the left occipital area. This report is on a rare complication likely caused by fentanyl or lidocaine, which suggests that these drugs should be used cautiously in children whose clinical epileptic activities have been verified or are strongly suspected. Copyright © 2015. Published by Elsevier B.V.

  9. Patient considerations in the use of transdermal iontophoretic fentanyl for acute postoperative pain

    Directory of Open Access Journals (Sweden)

    Hartrick CT

    2016-04-01

    Full Text Available Craig T Hartrick,1 Cecile R Pestano,1 Li Ding,2 Hassan Danesi,2 James B Jones,2 1Beaumont Health System, Troy, MI, 2The Medicines Company, Parsippany, NJ, USA Abstract: Opioids are commonly used in the management of moderate-to-severe postoperative pain. Patient-controlled analgesic techniques are recognized as preferred administration methods. Previously, research has focused on intravenously administered opioids via a programmable pump. More recently, an iontophoretic transdermal system (ITS, which is patient controlled, has been developed. The focus of this review is on pain management using the fentanyl ITS during the 24–72-hour time period immediately following surgery. Fentanyl ITS offers a needle-free alternative to traditional intravenous (IV patient-controlled analgesia (PCA system that is as effective and safe as IV PCA. This system is easy to use for both patients and nurses. The use of fentanyl ITS is generally associated with a better ease-of-care profile, including a greater ease of mobility, from a patients' perspective when compared with morphine IV PCA. Keywords: patient-controlled analgesia, fentanyl iontophoretic transdermal system, ease of care, mobility, patient perspective, review

  10. Intravenous Fentanyl for Dyspnea at the End of Life: Lessons for Future Research in Dyspnea.

    Science.gov (United States)

    Pang, G S; Qu, L M; Tan, Y Y; Yee, A C P

    2016-04-01

    To determine the efficacy of intravenous (IV) Fentanyl in dyspnoeic patients with advanced cancer. Dyspnoeic patients with advanced cancer satisfying the selection criteria received (IV) Fentanyl and were evaluated for response 24 hours post-administration in a prospective observational study. Altogether 36 patients were enrolled into the study. However, data from only 16 patients could be analysed as 20 patients had died or were too sick to self-report scores. Seven out of 16 patients responded to IV Fentanyl although the result was not statistically significant (non-responders versus responders: 56.3% vs 43.8%, p = 0.33). The strongest correlations for variables predictive of responder status were the absence of anxiety and lung metastases. This exploratory study shows that IV Fentanyl can alleviate dyspnea in some patients but is an example of the difficulties conducting dyspnea research. Future studies would benefit from novel developments in the areas of measuring dyspnea in dying patients and statistical analysis of small sample sizes. © The Author(s) 2014.

  11. Iontophoretic transdermal fentanyl for the management of acute perioperative pain in hospitalized patients.

    Science.gov (United States)

    Fanelli, Andrea; Sorella, Maria Cristina; Chelly, Jacques E

    2016-01-01

    Intravenous (I.V.) morphine administered through a patient-controlled system currently represents the gold standard treatment for moderate to severe acute postoperative pain. To fix the limitations showed by the available I.V. patient-controlled analgesia (PCA) systems that may restrict its use in the clinical practice a needle-free, iontophoretic, fentanyl patient-controlled transdermal system has been developed and recently approved by the United States Food and Drug Administration (FDA) and by the European Medicines Agency (EMA). This review aims at describing the technology, pharmacology and clinical efficacy of fentanyl iontophoretic transdermal system (ITS) in the treatment of acute pain. A literature search was conducted in the PUBMED database using the term 'fentanyl iontophoretic transdermal system' through September 2015 and results from the main clinical trials are discussed. In 2015, the appropriate treatment of acute pain after surgery is still a challenge and it represents a primary goal in the care of the surgical patient. When regional analgesia techniques are not applicable and systemic analgesia is required, patient controlled systems represent the standard of care for opioid administration. The fentanyl ITS presents several potential advantages compared to the currently used PCA devices. In particular, it does not require intravenous lines and eliminates the potential for drug administration errors, observed with manually programmed standard PCA devices. Nevertheless, further studies are needed to address eventual inter-individual variability especially for opioid tolerant patients.

  12. The analgesic efficacy of oxycodone hydrochloride versus fentanyl during outpatient artificial abortion operation: A randomized trial.

    Science.gov (United States)

    Xie, Kangjie; Zhang, Wen; Fang, Wumei; Lian, Yanhong; Lin, Sufeng; Fang, Jun

    2017-06-01

    Problems like body movement, respiratory depression, and complained of pain are still common phenomenon in outpatient artificial abortion general anesthesia. Oxycodone hydrochloride is a semisynthetic opioid and has a good therapeutic effect on visceral pain. We hypothesize that oxycodone hydrochloride would be superior to fentanyl in outpatient artificial abortion surgery. In this clinical trial 149 American Society of Anesthesiologists (ASA) I or II female outpatients scheduled for elective artificial abortion surgeries under general anesthesia were randomly divided into 3 groups: oxycodone hydrochloride 0.06 mg/kg group (group A), oxycodone hydrochloride 0.08 mg/kg group (group B), and control group fentanyl 2 ug/kg (group C). The primary outcome was level body movement and respiratory depression during the surgery, the second outcome included the visual analogue scale (VAS) score 30 minutes after waking. A total of 120 participants completed the study, n = 40 in each group. There was no significant difference in patients' age, body mass index (BMI), preoperative heart rate, mean arterial blood pressure, consumption dose of propofol, intraoperative body movement type and times, and duration of surgery among the 3 groups (P > .05). Comparing the incidence of intraoperative respiratory depression and SPO2 fentanyl, but the incidence of intraoperative respiratory depression and hypoxemia is significantly lower than fentanyl.

  13. Fentanyl-Norfentanyl Concentrations During Transdermal Patch Application: LC-MS-MS Urine Analysis.

    Science.gov (United States)

    Cummings, Oneka T; Enders, Jeffrey R; McIntire, Gregory L; Backer, R; Poklis, A

    2016-10-01

    Poklis and Backer published a survey of the concentrations of fentanyl and norfentanyl that could be expected in urine from patients using Duragesic®, a transdermal fentanyl patch. That study employed a relatively small number of patient data points and analysis by Gas Chromatography/Mass Spectrometry. This work examines a larger population of patient positives for fentanyl and norfentanyl to determine whether more than a decade later the original report remains accurate in predicting the range and median levels of fentanyl and norfentanyl concentrations physicians can expect to see from their patients. Additionally, these data were transformed to develop a model that results in a near Gaussian distribution of urine drug test results. This retrospective approach was developed to transform and normalize urine drug testing results to provide a historical picture of expected patient values for this important analgesic. The resulting near Gaussian distribution is dose independent and as such should be of value to physicians in quickly assessing whether their patient is consistent with this historical population in the broad terms of this model. While this comparison alone is not definitive for adherence with a treatment regimen, together with patient interviews, prescription history and other clinical criteria, it can add an idea of expected patient values from urine drug testing. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Frontal lobe oxygenation is maintained during hypotension following propofol-fentanyl anesthesia

    NARCIS (Netherlands)

    Nissen, Peter; van Lieshout, Johannes J.; Nielsen, Henning B.; Secher, Niels H.

    2009-01-01

    Near-infrared spectroscopy (NIRS) assesses cerebral oxygen saturation (Sco2) as a balance between cerebral oxygen delivery and consumption. In 71 patients, we evaluated whether marked reduction in mean arterial pressure (MAP) during propofol-fentanyl anesthesia induction affects frontal lobe Sco2.

  15. Disaster after the plaster. Fentanyl withdrawal symptoms in a curable hospice patient.

    NARCIS (Netherlands)

    Maathuis, M.H.; Dijkstra, D.D.

    2011-01-01

    Opioids have been used for thousands of years for pain relief. Transdermal fentanyl (TDF) is a synthetic opioid that is prescribed for the treatment of chronic pain. This clinical lesson demonstrates that TDF may be easy to start but sometimes difficult to stop. Like any other opioid there is a

  16. Fentanyl and Midazolam Are Ineffective in Reducing Episodic Intracranial Hypertension in Severe Pediatric Traumatic Brain Injury.

    Science.gov (United States)

    Welch, Timothy P; Wallendorf, Michael J; Kharasch, Evan D; Leonard, Jeffrey R; Doctor, Allan; Pineda, Jose A

    2016-04-01

    To evaluate the clinical effectiveness of bolus-dose fentanyl and midazolam to treat episodic intracranial hypertension in children with severe traumatic brain injury. Retrospective cohort. PICU in a university-affiliated children's hospital level I trauma center. Thirty-one children 0-18 years of age with severe traumatic brain injury (Glasgow Coma Scale score of ≤ 8) who received bolus doses of fentanyl and/or midazolam for treatment of episodic intracranial hypertension. None. The area under the curve from high-resolution intracranial pressure-time plots was calculated to represent cumulative intracranial hypertension exposure: area under the curve for intracranial pressure above 20 mm Hg (area under the curve-intracranial hypertension) was calculated in 15-minute epochs before and after administration of fentanyl and/or midazolam for the treatment of episodic intracranial hypertension. Our primary outcome measure, the difference between predrug and postdrug administration epochs (Δarea under the curve-intracranial hypertension), was calculated for all occurrences. We examined potential covariates including age, injury severity, mechanism, and time after injury; time after injury correlated with Δarea under the curve-intracranial hypertension. In a mixed-effects model, with patient as a random effect, drug/dose combination as a fixed effect, and time after injury as a covariate, intracranial hypertension increased after administration of fentanyl and/or midazolam (overall aggregate mean Δarea under the curve-intracranial hypertension = +17 mm Hg × min, 95% CI, 0-34 mm Hg × min; p = 0.04). The mean Δarea under the curve-intracranial hypertension increased significantly after administration of high-dose fentanyl (p = 0.02), low-dose midazolam (p = 0.006), and high-dose fentanyl plus low-dose midazolam (0.007). Secondary analysis using age-dependent thresholds showed no significant impact on cerebral perfusion pressure deficit (mean Δarea under the curve

  17. Inappropriate Fentanyl Prescribing Among Nursing Home Residents in the United States.

    Science.gov (United States)

    Fain, Kevin M; Castillo-Salgado, Carlos; Dore, David D; Segal, Jodi B; Zullo, Andrew R; Alexander, G Caleb

    2017-02-01

    We quantified transdermal fentanyl prescribing in elderly nursing home residents without prior opioid use or persistent pain, and the association of individual and facility traits with opioid-naïve prescribing. Cross-sectional study. Linked Minimum Data Set (MDS) assessments; Online Survey, Certification and Reporting (OSCAR) records; and Medicare Part D claims. From a cross-section of all long-stay US nursing home residents in 2008 with an MDS assessment and Medicare Part D enrollment, we identified individuals (≥65 years old) who initiated transdermal fentanyl, excluding those with Alzheimer disease, severe cognitive impairment, cancer, or receipt of hospice care. We used Medicare Part D to select beneficiaries initiating transdermal fentanyl in 2008 and determined whether they were "opioid-naïve," defined as no opioid dispensing during the previous 60 days. We obtained resident and facility characteristics from MDS and OSCAR records and defined persistent pain as moderate-to-severe, daily pain on consecutive MDS assessments at least 90 days apart. We estimated associations of patient and facility attributes and opioid-naïve fentanyl initiation using multilevel mixed effects logistic regression modeling. Among 17,052 residents initiating transdermal fentanyl, 6190 (36.3%) were opioid-naïve and 15,659 (91.8%) did not have persistent pain. In the regression analysis with adjustments, residents who were older (ages ≥95 odds ratio [OR] 1.69, 95% confidence interval [CI] 1.46-1.95) or more cognitively impaired (moderate-to-severe cognitive impairment, OR 1.99, 95% CI 1.73-2.29) were more likely to initiate transdermal fentanyl without prior opioid use. Most nursing home residents initiating transdermal fentanyl did not have persistent pain and many were opioid-naïve. Changes in prescribing practices may be necessary to ensure Food and Drug Administration warnings are followed, particularly for vulnerable subgroups, such as the cognitively impaired

  18. Investigating the Effects of Adding Fentanyl to Bupivacaine in Spinal Anesthesia of Opium-addicted Patients

    Directory of Open Access Journals (Sweden)

    H Satari

    2014-10-01

    Full Text Available Introduction: Spinal anesthesia in opium-addicted patients can be associated with many complications. Hence, this study aimed to investigate sensory and motor block characteristics, duration of postoperative analgesia, hemodynamic and side effects by adding Fentanyl to bupivacaine in spinal Anesthesia of opium-addicted patients. Methods: In a double-blind randomized clinical trial, 60 American society of Anesthesiology (ASA class I and II opium-addicted patients under spinal anesthesia in lower abdominal and lower limb operations were randomly classified into two groups of spinal anesthesia with bupivacaine and bupivacaine-fentanyl. Clinical symptoms, side effects, the duration of sensory and motor block, initiation of analgesia requirement and sensory block were assessed. Results: The study results indicated no significant difference between bupivacaine and bupivacaine-fentanyl groups in regard with demographic, side effects, blood pressure and heart rate, though a significant difference was observed in respiratory rate 5min, 10min, 45min, 75min and 90 min after block. Duration of sensory (100.33 to 138.83 and motor block (93.43 to 107.66 and , initiation of analgesia requirement (165.33 to 187.76 was significantly longer in bupivacaine-fentanyl, though initiation of sensory block (8.83 to 4.93 was significantly longer in bupivacaine. Conclusion: Addition of fentanyl to bupivacaine in spinal anesthesia increases the duration of sensory and motor block and initiation of analgesia requirement in opium-addicted patients and also decreases initiation of sensory block in these patients.

  19. Comparison of Clonidin, Pethedin and Fentanyl for Post-spinal Anesthesia Shivering in Elective Caesarian Sections

    Directory of Open Access Journals (Sweden)

    F Javaherforoosh

    2006-10-01

    Full Text Available ABSTRACT: Introduction & Objective: Post operative shivering is a prevalent complication of general and spinal anesthesia. Many drugs were used for prevention and treatment of shivering. The objective of this study was the comparison of clonidin, pethedin and fentanyl for treatment of post spinal anesthesia shivering. Materials & Methods: In this double blind randomized clinical trial, we compared the effects of 3 drug regimens to treat post operative shivering after spinal anesthesia in 60 elective caesarian sections with ASA class 1. Patients were divided into 3 groups (20 patients for each group. Each group received intravenously either pethedin 25 mg, clonidine 30 μg or fentanyl 50 μg. If a patient did not respond to the first dose, the same dose would be repeated up to a total of 3 times (with 5 minute intervals. Homodynamic changes, treatment responses and side effects were recorded. Then the resulting data were analyzed by SPSS software and chi-square test. Results: Considering control of shivering after first injection with pethedin 70%, clonidin 50% and fentanyl 30% with (p=0.04 major side effects in pethedin group were tachycardia 10%, nausea & vomiting 15%. In clonidine group the main side effects were dry mouth & drowsiness (16.7% & 3.3% respectively. Fentanyl group had only 3.3% nausea vomiting accounting for the fewest number of side effects (p< 0.05. Homodynamic was stable in fentanyl & clonidine groups. Conclusion: We concluded that, clonidine offers better thermodynamics along with modest failure rate but pethedin was most effective with more serious side effects.

  20. The role of diazepam and fentanyl in the production of balanced anaesthesia.

    Science.gov (United States)

    Aromaa, U; Korttila, K; Tammisto, T

    1980-01-01

    The effects of diazepam-fentanyl combinations on consciousness, superficial nociception, respiration and circulation during N2O+O2 inhalation were studied in 40 premedicated patients during induction of anaesthesia. The balance between antinociception and anaesthesia was closest to the optimum in patients receiving 0.2 mg/kg of diazepam plus 1 micrograms/kg of fentanyl; the eyelid reflex was negative in all patients and only two out of ten patients reacted to abdominal pinching. When only 0.2 mg/kg of diazepam was given with N2O+O2, the eyelid reflex was negative in all patients, but half of them reacted to pinching. When the dose of diazepam was reduced to 0.1 mg/kg and patients received 1 or 2 micrograms/kg of fentanyl, the balance between anaesthesia and antinociception was good, but 30-50% of patients had a positive eyelid reflex and reacted to pinching. No distinct respiratory depression was observed in patients given 0.2 mg/kg of diazepam, whereas seven patients given 0.1mg/kg of diazepam plus 2 micrrograms/kg of fentanyl had apnoea lasting more than 60 s associated with a significant (P less than 0.05-0.001) increase in end-tidal CO2 and PCO2 in arterialised venous blood. No significant changes were observed in blood pressure or heart rate after any of the drug combinations studied. It appears that an optimal balance between anaesthesia and antinociception with minimal side-effects during balanced general anaesthesia requires reinforcement of N2O+O2 anaesthesia not only with fentanyl but also with hypnotics for sedatives.

  1. Death by band-aid: fatal misuse of transdermal fentanyl patch.

    Science.gov (United States)

    Bakovic, Marija; Nestic, Marina; Mayer, Davor

    2015-11-01

    We present a case of fatal intoxication by the application of a transdermal fentanyl patch upon a superficial bleeding abrasion of a 2-year-old girl. The grandmother discovered the body of the child in bed at approximately 7 a.m. External examination revealed a properly developed, nourished, and hydrated child, with some vomit in the nostrils and inside the mouth. There was no evidence of trauma besides small contusions and abrasions on the knees, with a patch placed over the largest abrasion. Closer inspection revealed that this was transdermal fentanyl patch. Internal examination and microscopic analysis revealed regurgitation of stomach content, cerebral and pulmonary edema, and liver congestion. Toxicology analysis revealed trace levels of fentanyl in the blood just above the limit of detection (2 ng/mL), while concentrations in the urine, liver, and kidney were approximately 102, 28, and 10 ng/mL, respectively. Investigation discovered that the child injured her knee while playing the evening before. The grandmother applied the patch to cover the injury, unaware that she had used a fentanyl transdermal patch instead of simple band-aid. Although fatal intoxications are uncommon among young children in high-income countries, it is of major interest to raise awareness of such events especially since a great majority of these are preventable. The presented case points at the need for more thorough education of users and more strict rules in prescribing and handling of this potent medicine. As well, we find this case to be a useful contribution to the evaluation of postmortem fentanyl concentrations in fatal intoxication in a small child.

  2. Impact of allergic rhinitis and its treatment on the pharmacokinetics of nasally administered fentanyl.

    Science.gov (United States)

    Perelman, Michael; Fisher, Anthony N; Smith, Alan; Knight, Alastair

    2013-05-01

    Fentanyl pectin nasal spray (FPNS, Lazanda® in the US and PecFent® in Europe and Australia) is a novel analgesic approved for the management of breakthrough pain in cancer patients. Given that the fentanyl is nasally administered, it is important to understand whether concomitant allergic rhinitis, or its treatment with a vasoconstrictor, would affect its absorption and, potentially, its efficacy or safety. Subjects with a history of allergic rhinitis were screened to identify subjects who developed at least moderate rhinitis symptoms on exposure to pollen allergen (either ragweed or tree) in an environmental exposure chamber (EEC). These were entered into a randomized, three-way crossover study in which each subject received 100 μg of FPNS under three exposure conditions; Control (no rhinitis), Rhinitis (symptomatic without decongestant), Treated (symptomatic with concomitant oxymetazoline). Blood samples for fentanyl were collected over a 24-hour period. A total of 132 subjects was screened to identify 54 for inclusion in the study; 31 were evaluable for pharmacokinetics. Measures of fentanyl absorption (mean or median) were similar between Control and Rhinitis conditions: Cmax 453.0 vs. 467.8 pg/ml; AUCt 1,292.3 vs. 1,325.4 pg×h/ml, AUC0-∞ 1,430.6 vs. 1,387 pg×h/ml and tmax 20 vs. 17 minutes. When oxymetazoline was co-administered, overall fentanyl absorption was slightly reduced (AUC0-∞ 1,362.4 pg×h/ml); but, more clinically relevant were the delayed rate of absorption (tmax 53 minutes) and reduced Cmax (235.3 pg/ml). Patients treated with FPNS will be unaffected by the development of allergic rhinitis; but, if oxymetazoline is prescribed, the patient would benefit from added supervision when oxymetazoline is started and stopped.

  3. Comparison of adding neostigmine and fentanyl to bupivacaine in caudal analgesia in pediatric inguinal herniorrhaphy

    Directory of Open Access Journals (Sweden)

    Omid Aghadavoudi

    2017-12-01

    Full Text Available AbstractObjective: The aim of the present trial was to compare efficacy and adverse effects of neostigmine against fentanyl when used as adjuvant to bupivacaine in caudal anesthesia.Method: A total of 140 children, aged 1-6 year scheduled to elective herniorrhaphy, were enrolled. Exclusion criteria were sacral area infection, history of allergic reactions to local anesthetics, bleeding tendency, neurological or spinal disease and lack of parent consent. Patients were assigned, using permuted block randomization method, into four groups of 35. Children in the first group received a caudal injection of 0.5 ml/kg bupivacaine 0.25% plus fentanyl 1µ/kg. The second group received 0.5 ml/kg bupivacaine 0.25% plus neostigmine 1µ/kg. Patients in the third group received 0.5 ml/kg bupivacaine 0.25% plus combination of fentanyl 1µ/kg and neostigmine 1µ/kg, and those in the fourth group only received 0.5 ml/kg bupivacaine 0.25% concentration. To assess pain intensity, Wong-Baker Scale was used. Time to first analgesic request and the dosage of analgesic agent was recorded. Data were analyzed using SPSS 17.0.Results:Significant differences were observed among groups in terms of number of patients needing analgesic (p=0.01, time to first analgesic request (p=0.005 and analgesic dose. (p=0.05 The lowest number of requests for analgesia, lowest dose of pethidine and longest time to first analgesic request were in patients receiving combination of bupivacaine, neostigmine and fentanyl.Conclusion: The present study shows that the combination of fentanyl and neostigmine, could prolong duration of analgesia, and decrease severity of pain when added to bupivacaine

  4. Discomfort during bronchoscopy performed after endobronchial intubation with fentanyl and midazolam: a prospective study.

    Science.gov (United States)

    Minami, Daisuke; Takigawa, Nagio; Kano, Hirohisa; Ninomiya, Takashi; Kubo, Toshio; Ichihara, Eiki; Ohashi, Kadoaki; Sato, Akiko; Hotta, Katsuyuki; Tabata, Masahiro; Tanimoto, Mitsune; Kiura, Katsuyuki

    2017-05-01

    Although endobronchial intubation during a bronchoscopic examination is useful for invasive procedures, it is not routine practice in Japan. The present study evaluated discomfort due to endobronchial intubation using fentanyl and midazolam sedation during bronchoscopy. Thirty-nine patients were enrolled prospectively from November 2014 to September 2015 at Okayama University Hospital. Fentanyl (20 µg) was administered to the patients just before endobronchial intubation, and fentanyl (10 µg) and midazolam (1 mg) were added as needed during the procedure. A questionnaire survey was administered 2 h after the examination. In the questionnaire, patient satisfaction was scored using a visual analog scale as follows: excellent (1 point), good (2 points), normal (3 points), uncomfortable (4 points) and very uncomfortable (5 points). An additional question ('Do you remember the bronchoscopic examination?') was also asked. Predefined parameters (blood pressure, heart rate, oxygen saturation and complications) were recorded. The enrolled patients included 22 males and 17 females; their median age was 70 (range: 28-88) years. The patients received a mean dose of 47.9 µg of fentanyl (range: 30-90 µg) and 2.79 mg of midazolam (range: 1-7 mg). In total, 28 patients (71.7%) agreed to undergo a second bronchoscopic examination; the mean levels of discomfort and for the re-examination were 2.07 points each. About 41% of the patients remembered the bronchoscopic examination. No severe complications were reported. Endobronchial intubation using fentanyl and midazolam sedation during an invasive bronchoscopic procedure might be recommended. UMIN000015578 in the UMIN Clinical Trials Registry.

  5. A COMPARATIVE STUDY OF INTRATHECAL DEXMEDETOMIDINE AND FENTANYL AS ADJUVANTS TO BUPIVACAINE FOR LOWER ABDOMINAL SURGERIES

    Directory of Open Access Journals (Sweden)

    Hari Kishore

    2015-01-01

    Full Text Available INTRODUCTION: Various adjuvants have been used with local anesthetics in spinal anesthesia to improve the quality of block and to provide prolonged postoperative analgesia. Dexmedetomidine, the new highly selective α2 - agonist drug, is now being used as a neuraxial adju vant. AIM: The aim of this study was to evaluate the onset and duration of sensory and motor block, hemodynamic effect, postoperative analgesia, and adverse effects of dexmedetomidine or fentanyl given intrathecally with hyperbaric 0.5% bupivacaine. METHOD OLOGY: Fifty patients classified in American Society of Anesthesiologists classes I and II scheduled for lower abdominal surgeries were included in this prospective cohort study at Amala Institute of Medical Sciences. Patients received either 15 mg hyperba ric bupivacaine plus 25 μg fentanyl (group 1, n = 25 or 15 mg hyperbaric bupivacaine plus 5 μg dexmedetomidine (group 2, n = 25 intrathecally . RESULTS : Patients in dexmedetomidine group (2 had a significantly longer duration of motor and sensory block t han patients in fentanyl group . (1 The mean time regression of motor block to reach Bromage 0 was 17 6 . 2± 5.71 min in d exmeditomid ine group and 16 6 . 36 ± 5.97 min in fentanyl group (P<0.05. Duration of analgesia was 2 39.52 ± 9.05 min in D exmed i tomidine gro up and 189.96 ± 5.35 min in fentanyl group ( p< 0.05. A significant decrease in heart rate was noted in dexmedetomidine group. CONCLUSION : Intrathecal dexmedetomidine is associated with prolonged duration of analgesia and motor block along with significant dec rease in heart rate.

  6. COMPARISON OF DEXMEDETOMIDINE WITH FENTANYL IN ATTENUATION OF PRESSOR RESPONSE TO LARYNGOSCOPY AND INTUBATION

    Directory of Open Access Journals (Sweden)

    Sumathi Natta

    2017-07-01

    Full Text Available BACKGROUND Direct laryngoscopy and endotracheal intubation elicits a haemodynamic response associated with increased heart rate and blood pressure. The aim of the study is to compare the efficacy of intravenous dexmedetomidine and fentanyl in attenuation of stress response to laryngoscopy and intubation. MATERIALS AND METHODS Study was carried out on 60 patients belonging to ASA grade I & II, aged 15 to 65 years including either gender scheduled for elective surgical procedures under general anaesthesia in Osmania General Hospital. Patients were randomly divided into two groups of 30 each. Group D received 0.6g/kg dexmedetomidine and Group F received 2 g/kg fentanyl diluted in 10 mL normal saline 10 minutes before laryngoscopy and intubation. Anaesthesia was standardised in both groups and vital parameters heart rate, systolic blood pressure, diastolic blood pressure and mean arterial pressure were recorded preoperatively, during intubation and up to 10 minutes after intubation. RESULTS The groups were well matched for their demographic data. It was observed that increase in heart rate, systolic blood pressure, diastolic blood pressure and mean arterial pressure after intubation was highly significant in fentanyl group as compared to dexmedetomidine. There was a statistically significant difference (P <0.05 between dexmedetomidine and fentanyl groups in heart rate, systolic, diastolic blood pressure and mean arterial pressure at all time points after tracheal intubation. CONCLUSION Both the drugs attenuated the pressor response. Among the two drugs administered dexmedetomidine 0.6 µg/kg provides reliable and effective attenuation of pressor response to laryngoscopy and tracheal intubation when compared to fentanyl in a dose of 2 µg/kg.

  7. Comparison of clonidine and fentanyl as adjuvant to ropivacaine in spinal anesthesia in lower abdominal surgeries.

    Science.gov (United States)

    Sharan, Radhe; Verma, Rajan; Dhawan, Akshay; Kumar, Jugal

    2016-01-01

    Ropivacaine, a newer local anesthetic, is gaining increased acceptance due to its improved safety profile over bupivacaine and lignocaine. Analgesic adjuvants have proved to be valuable in improving the quality of anesthesia and duration of analgesia. To compare the efficacy of clonidine and fentanyl as adjuvants to ropivacaine in spinal anesthesia in lower abdominal surgeries. A randomized, double-blind control study was carried out in 100 patients who were randomly divided into two groups. Ropivacaine-clonidine group (RC) received 30 μg of clonidine with 18.75 mg of 0.75% isobaric ropivacaine, Ropivacaine-fentanyl group (RF) received 25 μg of fentanyl with 18.75 mg of 0.75% isobaric ropivacaine intrathecally. The onset and duration of sensory and motor block, hemodynamic parameters, quality of surgical analgesia, total analgesia time, sedation score, and side effects were statistically analyzed using SPSS statistical package, paired and unpaired t-tests and Chi-square test. The duration of sensory block in RC (240.00 ± 20.99), RF (196.80 ± 18.34), and motor block in RC (192.20 ± 17.36), RF (139.20 ± 17.93) outlasted the duration of surgery. In clonidine group, there was significant prolongation of sensory block, motor block and the total analgesia time. Hypotension and bradycardia occurred more commonly in RC group, whereas pruritus was more in RF group. Ropivacaine when combined with either clonidine or fentanyl provided an adequate subarachnoid block for lower abdominal surgeries. As an adjuvant, clonidine has advantage over fentanyl as it increased the duration of the subarachnoid block and the postoperative analgesia.

  8. Relative bioavailability of the fentanyl effervescent buccal tablet (FEBT) 1,080 pg versus oral transmucosal fentanyl citrate 1,600 pg and dose proportionality of FEBT 270 to 1,300 microg: a single-dose, randomized, open-label, three-period study in healthy adult volunteers.

    Science.gov (United States)

    Darwish, Mona; Tempero, Kenneth; Kirby, Mary; Thompson, Jeffrey

    2006-05-01

    , 17 men; mean [SD] age, 27 [11] years; mean [SD] weight, 68.4 [8.7] kg); 39 completed the study. Total systemic exposure (as measured using AUC(0-infinity))) was statistically similar between FEBT 1,080 microg and OTFC 1,600 microg (mean [SD], 18.0 [5.4] vs 18.0 [7.1] ng x h/mL). However, the mean (SD) C(max) with FEBT 1,080 microg was 2.7 (0.9) ng/mL compared with 2.2 (0.7) ng/mL with OTFC 1,600 microg (P = NS), and the T(max) of 1.0 hour with FEBT was significantly less compared with OTFC (2.0 hours; P 810 microg. Definitive attribution of adverse events (AEs) to FEBT or OTFC was generally not possible because these medications were coadministered with naltrexone. With naltrexone alone, there were reports of headache (3 [7%] subjects), nausea (1 [2%]), upset stomach (1 [2%]), and low systolic blood pressure (1 [2%]) after naltrexone administration, but before FEBT or OTFC administration. The AEs were typical of opioids (ie, headache, nausea, lightheadedness), and most (89.6%) were mild. One case each of mild oral irritation and redness were reported after the administration of FEBT Both occurrences resolved within 4.5 hours after study drug administration. No irritation or redness was reported after the administration of OTFC. In this pharmacokinetic study in healthy volunteers, total systemic exposure increased in a dose-proportional manner up to FEBT 1,300 microg, whereas doses above 810 microg showed a less-than-dose-proportional increase in C(max). The results suggest that fentanyl enters the systemic circulation to a significantly greater extent (C(max) and AUC(0-Tmax')) and significantly more rapidly (T(max)) with FEBT compared with OTFC.

  9. Intracranial pressure and cerebral hemodynamic in patients with cerebral tumors: a randomized prospective study of patients subjected to craniotomy in propofol-fentanyl, isoflurane-fentanyl, or sevoflurane-fentanyl anesthesia.

    Science.gov (United States)

    Petersen, Kurt D; Landsfeldt, Uffe; Cold, Georg Emil; Petersen, Carsten B; Mau, Søren; Hauerberg, John; Holst, Peter; Olsen, Karsten Skovgaard

    2003-02-01

    A critical point during craniotomy is opening of dura, where a high intracranial pressure (ICP) results in swelling of cerebral tissue. Controlled studies concerning ICP, degree of dural tension, and degree of cerebral swelling are therefore warranted. In an open-label study, 117 patients with supratentorial cerebral tumors were randomized to propofol-fentanyl (group 1), isoflurane-fentanyl (group 2), or sevoflurane-fentanyl anesthesia (group 3). Normo- to moderate hypocapnia was applied, with a target level of arterial carbon dioxid tension of 30-40 mmHg. Mean arterial blood pressure was stabilized with intravenous ephedrine (2.5-5 mg) if necessary. Subdural ICP, mean arterial blood pressure, cerebral perfusion pressure (CPP), arteriovenous oxygen difference (AVDo2), internal jugular vein oxygen saturation were monitored before and after a 10-min period of hyperventilation, and the carbon dioxide reactivity was calculated. Furthermore, the tension of dura before and during hyperventilation and the degree of cerebral swelling during hyperventilation and after opening of the dura were estimated by the neurosurgeon. No differences were found between groups with regard to demographics, neuroradiologic examination, positioning of the head, and time to ICP measurement. Before and during hyperventilation, ICP was significantly lower and mean arterial blood pressure and CPP significantly higher in group 1 compared with groups 2 and 3 (P hyperventilation was significantly lower in group 1 compared with group2 (P hyperventilation, subdural ICP and AVDo2 are lower and CPP higher in propofol-anesthetized patients compared with patients anesthetized with isoflurane or sevoflurane. These findings were associated with less tendency for cerebral swelling after opening of dura in the propofol group. The carbon dioxide reactivity in patients anesthetized with isoflurane and sevoflurane was significantly higher than in the propofol group. The differences in subdural ICP between the

  10. A comparison of intrathecal dexmedetomidine verses intrathecal fentanyl with epidural bupivacaine for combined spinal epidural labor analgesia

    Directory of Open Access Journals (Sweden)

    P K Dilesh

    2014-01-01

    Conclusion: 10 μg dexmedetomidine intrathecally provides a longer duration of analgesia with lesser incidence of pruritus compared to 20 μg fentanyl intrathecally for CSE labor analgesia with comparable neonatal side-effects.

  11. Development of the fentanyl iontophoretic transdermal system (ITS) for patient-controlled analgesia of postoperative pain management.

    Science.gov (United States)

    Minkowitz, Harold S; Danesi, Hassan; Ding, Li; Jones, James B

    2015-09-01

    The fentanyl iontophoretic transdermal system (ITS) is a needle-free, patient-activated drug delivery system used for patient-controlled analgesia in adult hospitalized patients with postoperative pain. The system design has been updated to a separated system consisting of a Controller and a Drug Unit, and has had regulatory submissions in USA and Europe in 2014. Fentanyl ITS has been shown to be therapeutically equivalent to morphine intravenous (iv.) patient-controlled analgesia. One of the advantages of fentanyl ITS is that patients have better mobility as there is no need for an iv. pump, iv. lines and pole. The introduction of the updated fentanyl ITS will add a versatile tool to the postoperative pain management armamentarium.

  12. Comparative study between dexmedetomidine and fentanyl for sedation during mechanical ventilation in post-operative paediatric cardiac surgical patients

    OpenAIRE

    Prasad, SR; Simha, Parimala Prasanna; Jagadeesh, AM

    2012-01-01

    Aims and Objectives: To compare the efficacy of sedation and time taken for extubation using dexmedetomidine and fentanyl sedation in post-operative paediatric cardiac surgical patients. Methods: A prospective randomized double-blind study involving 60 children undergoing open heart surgery was conducted. The patients were divided into two groups, each involving 30 patients. One group received fentanyl at 1 ?g/kg/h (Group A) and the other received dexmedetomidine at 0.5 ?g/kg/h (Group B) for ...

  13. The rate-decreasing effects of fentanyl derivatives in pigeons before, during and after chronic morphine treatment.

    Science.gov (United States)

    Gauthier, C A; Gerak, L R; Bagley, J R; Brockunier, L L; France, C P

    1998-05-01

    Mirfentanil is a fentanyl derivative with non-opioid actions, including non-opioid antinociceptive effects in rhesus monkeys. The current study examined the rate-altering effects of mirfentanil and several other compounds in pigeons to assess: 1) the opioid and non-opioid actions of acutely-administered fentanyl derivatives; and 2) the development of cross-tolerance between each of these compounds and morphine. Seven pigeons responded under a fixed-ratio 20 (FR20) schedule of food delivery. In untreated pigeons, fentanyl, morphine, naltrexone, ketamine and three fentanyl derivatives (mirfentanil, OHM3463 and OHM3295) decreased rates of key pecking in a dose-related manner. Naltrexone (0.1-1.0 mg/kg) attenuated the effects of OHM3463 and not mirfentanil or OHM3295, suggesting non-opioid mediation of the rate-decreasing effects for the latter two fentanyl derivatives. Subjects were treated daily with morphine for 9 weeks, up to a dose of 100 mg/kg per day, during which time the dose-effect curves for morphine, fentanyl and OHM3463 shifted rightward 6-, 10- and 2-fold, respectively, indicating the development of tolerance to morphine and cross-tolerance to fentanyl and OHM3463. Dose-effect curves for ketamine, OHM3295 and mirfentanil were not shifted to the right during morphine treatment, and the dose-effect curve for naltrexone was shifted leftward 180-fold. To the extent that rate-decreasing effects are predictive of antinociceptive effects, these data suggest that some fentanyl derivatives might be useful therapeutics under conditions where tolerance develops to morphine-like opioids.

  14. Efficacy, safety, and tolerability of fentanyl pectin nasal spray in patients with breakthrough cancer pain.

    Science.gov (United States)

    Ueberall, Michael A; Lorenzl, Stefan; Lux, Eberhard A; Voltz, Raymond; Perelman, Michael

    2016-01-01

    Assessment of analgesic effectiveness, safety, and tolerability of fentanyl pectin nasal spray (FPNS) in the treatment of breakthrough cancer pain (BTcP) in routine clinical practice. A prospective, open-label, noninterventional study (4-week observation period, 3 month follow-up) of opioid-tolerant adults with BTcP in 41 pain and palliative care centers in Germany. Standardized BTcP questionnaires and patient diaries were used. Evaluation was made of patient-reported outcomes with respect to "time to first effect", "time to maximum effect", BTcP relief, as well as changes in BTcP-related impairment of daily life activities, quality-of-life restrictions, and health care resource utilization. A total of 235 patients were recruited of whom 220 completed all questionnaires and reported on 1,569 BTcP episodes. Patients reported a significant reduction of maximum BTcP intensity (11-stage numerical rating scale [0= no pain, 10= worst pain conceivable]) with FPNS (mean ± standard deviation = 2.8±2.3) compared with either that reported at baseline (8.5±1.5), experienced immediately before FPNS application (7.4±1.7), or that achieved with previous BTcP medication (6.0±2.0; P<0.001 for each comparison). In 12.3% of BTcP episodes, onset of pain relief occurred ≤2 minutes and in 48.4% ≤5 minutes; maximum effects were reported within 10 minutes for 37.9% and within 15 minutes for 79.4%. By the end of the study, there had been significant improvements versus baseline in BTcP-related daily life activities (28.3±16.9 vs 53.1±11.9), physical (35.9±8.4 vs 26.8±6.5), and mental quality of life (38.7±8.5 vs 29.9±7.9) (P<0.001 for each comparison vs baseline); in addition, health care resource utilization requirements directly related to BTcP were reduced by 67.5%. FPNS was well tolerated; seven patients (3.2%) experienced eight treatment-emergent adverse events of which none was serious. There were no indicators of misuse or abuse. FPNS provided rapid and highly

  15. Comparative study between dexmedetomidine and fentanyl for sedation during mechanical ventilation in post-operative paediatric cardiac surgical patients

    Directory of Open Access Journals (Sweden)

    S R Prasad

    2012-01-01

    Full Text Available Aims and Objectives: To compare the efficacy of sedation and time taken for extubation using dexmedetomidine and fentanyl sedation in post-operative paediatric cardiac surgical patients. Methods: A prospective randomized double-blind study involving 60 children undergoing open heart surgery was conducted. The patients were divided into two groups, each involving 30 patients. One group received fentanyl at 1 μg/kg/h (Group A and the other received dexmedetomidine at 0.5 μg/kg/h (Group B for post-operative sedation with intermittent rescue fentanyl 0.5 μg/kg bolus in either group as per requirement during suctioning. The efficacy of sedation was assessed using the Ramsay sedation score, paediatric intensive care unit sedation score and the tracheal suction score. The time taken for extubation from the stoppage of infusion was noted. Results: Haemodynamic parameters between the two groups were comparable. All sedation scores were comparable in the fentanyl and dexmedetomidine groups. Average time (in minutes required for extubation was 131.0 (±51.06 SD in the dexmedetomidine group compared with 373.0 (±121.4 SD in the fentanyl group. The difference in mean time for extubation was statistically significant. Conclusions: Dexmedetomidine facilitates adequate sedation for mechanical ventilation and also early extubation as compared with fentanyl.

  16. Comparative study between dexmedetomidine and fentanyl for sedation during mechanical ventilation in post-operative paediatric cardiac surgical patients.

    Science.gov (United States)

    Prasad, S R; Simha, Parimala Prasanna; Jagadeesh, A M

    2012-11-01

    To compare the efficacy of sedation and time taken for extubation using dexmedetomidine and fentanyl sedation in post-operative paediatric cardiac surgical patients. A prospective randomized double-blind study involving 60 children undergoing open heart surgery was conducted. The patients were divided into two groups, each involving 30 patients. One group received fentanyl at 1 μg/kg/h (Group A) and the other received dexmedetomidine at 0.5 μg/kg/h (Group B) for post-operative sedation with intermittent rescue fentanyl 0.5 μg/kg bolus in either group as per requirement during suctioning. The efficacy of sedation was assessed using the Ramsay sedation score, paediatric intensive care unit sedation score and the tracheal suction score. The time taken for extubation from the stoppage of infusion was noted. Haemodynamic parameters between the two groups were comparable. All sedation scores were comparable in the fentanyl and dexmedetomidine groups. Average time (in minutes) required for extubation was 131.0 (±51.06 SD) in the dexmedetomidine group compared with 373.0 (±121.4 SD) in the fentanyl group. The difference in mean time for extubation was statistically significant. Dexmedetomidine facilitates adequate sedation for mechanical ventilation and also early extubation as compared with fentanyl.

  17. Inhibitory effect of fentanyl citrate on the release of endothlin-1 induced by bradykinin in melanoma cells.

    Science.gov (United States)

    Andoh, Tsugunobu; Shinohara, Akira; Kuraishi, Yasushi

    2017-02-01

    Our previous study showed that the μ-opioid receptor agonist fentanyl citrate inhibits endothelin-1-and bradykinin-mediated pain responses in mice orthotopically inoculated with melanoma cells. We also demonstrated that bradykinin induces endothelin-1 secretion in melanoma cells. However, the analgesic mechanisms of fentanyl citrate remain unclear. Thus, the present study was conducted to determine whether fentanyl citrate affects bradykinin-induced endothelin-1 secretion in B16-BL6 melanoma cells. The amount of endothelin-1 in the culture medium was measured using an enzyme immunoassay. The expression of endothelin-1, kinin B2 receptors, and μ-opioid receptors in B16-BL/6 melanoma cells was determined using immunocytochemistry. Fentanyl citrate inhibited bradykinin-induced endothelin-1 secretion. The inhibitory effect of fentanyl citrate on the secretion of endothelin-1 was attenuated by the μ-opioid receptor antagonist naloxone methiodide. The immunoreactivities of endothelin-1, kinin B2 receptors, and μ-opioid receptors in B16-BL6 melanoma cells were observed. These results suggest that fentanyl citrate regulates bradykinin-induced endothelin-1 secretion through μ-opioid receptors in melanoma cells. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  18. Danish pain specialists' rationales behind the choice of fentanyl transdermal patches and oral transmucosal systems--a delphi study.

    Science.gov (United States)

    Jacobsen, Ramune; Møldrup, Claus; Christrup, Lona

    2009-11-01

    The aim of this study was to describe the rationale behind the choice of fentanyl administration forms among Danish pain specialists. Sixty Danish physicians specializing in pain management were contacted via an Internet survey system to perform a two-phase Delphi survey. Response rates were 45% in the brainstorming and 88% in the rating phases, respectively. Statistical analysis with SPSS for Windows 15.00 included descriptive statistics and factor analysis. The most important rationale to choose fentanyl patches was that patients' clinical condition did not allow them to take analgesia orally, while the main explanations for not choosing a fentanyl patch was a specific chronic pain condition such as nonmalignant or neuropathic pain origin, and price. The foremost rationale behind the choice of oral transmucosal fentanyl citrate (OTFC) were cancer patients' need for the alternative to oral, intravenous or subcutaneous rescue medication, followed by patients' wish and ability to administer pain medication independently. The main reasons for not choosing OTFC were price and the argument that OTFC administration requires much energy and healthy patients' mouth and therefore is inapplicable for terminal pain patients. The study had shown that the rationales behind the choice of administration form with fentanyl reported by a panel of Danish pain specialists partly differed from those overviewed in the literature and those thought to be important while developing fentanyl patches and OTFC.

  19. Extending low-dose epidural analgesia in labour for emergency Caesarean section - a comparison of levobupivacaine with or without fentanyl.

    Science.gov (United States)

    Malhotra, S; Yentis, S M

    2007-07-01

    Women in labour receiving epidural analgesia with 15 ml bupivacaine 0.1% and 2 microg.ml(-1) fentanyl followed by 10-15-ml top-ups as required, who needed Caesarean section, were randomly allocated to receive 20 ml levobupivacaine 0.5% over 3 min with either 75 microg fentanyl (1.5 ml) or 1.5 ml saline. Further top-ups or inhaled or intravenous supplementation were given for breakthrough pain. Time to onset (loss of cold sensation to T4 and touch sensation to T5 bilaterally), quality of analgesia and side-effects were recorded. The study was stopped after 112 patients had been randomly assigned, due to a unit protocol change, from midwife-administered top-ups to patient-controlled epidural analgesia. Data from 51 patients given fentanyl and 54 given saline were available for analysis. There were no significant differences in onset times or supplementation between the groups, but there was more intra-operative nausea/vomiting with fentanyl (53%) than with saline (18%; p = 0.004). We found no advantage of adding fentanyl to epidural levobupivacaine when extending epidural analgesia in women already receiving epidural fentanyl during labour and there was an increased incidence of intra-operative nausea and vomiting. Power analysis suggested the same conclusion even had the study proceeded to completion.

  20. Outbreak of bacteremia due to Burkholderia contaminans linked to intravenous fentanyl from an institutional compounding pharmacy.

    Science.gov (United States)

    Moehring, Rebekah W; Lewis, Sarah S; Isaacs, Pamela J; Schell, Wiley A; Thomann, Wayne R; Althaus, Mary M; Hazen, Kevin C; Dicks, Kristen V; Lipuma, John J; Chen, Luke F; Sexton, Daniel J

    2014-04-01

    IMPORTANCE Many health care facilities compound medications on site to fulfill local demands when customized formulations are needed, national supply is critically low, or costs for manufactured pharmaceuticals are excessive. Small, institutional compounding facilities may perform the same high-risk procedures as large distributors of compounded medications. OBJECTIVES To investigate an outbreak related to contamination of compounded sterile preparations and to determine processes to prevent future outbreaks. DESIGN, SETTING, AND PARTICIPANTS We performed an outbreak investigation of inpatients at Duke University Hospital from August 31 through September 6, 2012. The investigation included a case-control study, compounding facility inspection and environmental sampling, observation of a mock compounding demonstration, and microbiologic and molecular testing of sequestered medication. EXPOSURES Intravenous fentanyl prepared by an institutional compounding pharmacy. MAIN OUTCOMES AND MEASURES Microbiologic and molecular evidence of contamination of a compounded sterile preparation and failure of routine sterility testing. RESULTS Blood cultures of 7 patients during a 7-day period at Duke University Hospital yielded pan-susceptible Burkholderia cepacia complex bacteria. The risk factor common to all patients was receipt of continuous fentanyl infusion prepared by our institutional compounding pharmacy (odds ratio, 11.22; 95% CI, 2.09-∞; P = .01). The outbreak was terminated after sequestration of compounded fentanyl. An intensive evaluation of the compounding facility, its practice, and its procedures was completed. Investigators evaluated the clean room, collected targeted microbiologic samples within the compounding pharmacy environment, and observed a mock demonstration of compounding practice. The B cepacia complex was found in the anteroom sink drain and pH probe calibration fluid from the compounding clean room. Multiple microbiologic analyses of

  1. Comparison of Fentanyl and Morphine in the Prehospital Treatment of Ischemic Type Chest Pain.

    Science.gov (United States)

    Weldon, Erin R; Ariano, Robert E; Grierson, Robert A

    2016-01-01

    In the treatment of acute coronary syndromes, reduction of sympathetic stress and catecholamine release is an important therapeutic goal. One method used to achieve this goal is pain reduction through the systemic administration of analgesia. Historically, morphine has been the analgesic of choice in ischemic cardiac pain. This randomized double-blind controlled trial seeks to prove the utility of fentanyl as an alternate first-line analgesic for ischemic-type chest pain in the prehospital setting. Successive patients who were treated for suspected ischemic chest pain in the emergency medical services system were considered eligible. Once chest pain was confirmed, patients received oxygen, aspirin, and nitroglycerin therapy. If the ischemic-type chest pain continued the patient was randomized in a double-blinded fashion to treatment with either morphine or fentanyl. Pain scale scores, necessity for additional dosing, and rate of adverse events between the groups were assessed every 5 minutes and were compared using t-testing, Fisher's Exact test, or Analysis of Variance (ANOVA) where appropriate. The primary outcome of the study was incidence of hypotension and the secondary outcome was pain reduction as measured by the visual analog score and numeric rating score. A total of 207 patients were randomized with 187 patients included in the final analysis. Of the 187 patients, 99 were in the morphine group and 88 in the fentanyl group. No statistically significant difference between the two groups with respect to hypotension was found (morphine 5.1% vs. fentanyl 0%, p = 0.06). Baseline characteristics, necessity for additional dosing, and other adverse events between the two groups were not statistically different. There were no significant differences between the changes in visual analog scores and numeric rating scale scores for pain between the two groups (p = 0.16 and p = 0.15, respectively). This study supports that fentanyl and morphine are comparable in

  2. Fentanyl supplement expedites the onset time of sensory and motor blocking in interscalene lidocaine anesthesia

    Directory of Open Access Journals (Sweden)

    RS Moharari

    2010-12-01

    Full Text Available Background and the purpose of the study: Opioids are usually used in regional anesthesia, with or without local anesthetics to improve the regional block or postoperative pain control. Since no data are available on fentanyl's effect on the onset time of lidocaine interscalene anesthesia, the purpose of this study was to examine its effect on the onset time of sensory and motor blockade during interscalene anesthesia.  Methods: In a prospective, randomized, double-blind study, ninety patients scheduled for elective shoulder, arm and forearm surgeries under an  interscalene brachial plexus block .They were randomly allocated to receive either 30 ml of  1.5 % lidocaine with 1.5 ml of isotonic saline  (control group, n = 39 or 30 ml of 1.5%  lidocaine with 1.5 ml (75µg of  fentanyl (fentanyl group,n=41. Then the onset time of sensory and motor blockades of the shoulder, arm and forearm were evaluated every 60 sec. The onset time of the sensory and motor blockades was defined as the time between the last injection and the total abolition of the pinprick response and complete paralysis. The duration of sensory blocks were considered as the time interval between the administration of the local anesthetic and the first postoperative pain sensation. Results: Ten patients were excluded because of unsuccessful blockade or unbearable pain during the surgery. The onset time of the sensory block was significantly faster in the fentanyl group (186.54± 62.71sec compared with the control group (289.51± 81.22, P < 0.01. The onset times of the motor block up to complete paralysis in forearm flexion was significantly faster in the fentanyl group (260.61± 119.91sec than the control group (367.08± 162.43sec, P < 0.01 There was no difference in the duration of the sensory block between two groups. Conclusion: Results of the study showed that the combination of 75 µg fentanyl and 1.5% lidocaine solution accelerated the onset of sensory and motor

  3. V̇o2 kinetics associated with moderate-intensity exercise in heart failure: impact of intrathecal fentanyl inhibition of group III/IV locomotor muscle afferents.

    Science.gov (United States)

    Van Iterson, Erik H; Johnson, Bruce D; Joyner, Michael J; Curry, Timothy B; Olson, Thomas P

    2017-07-01

    Heart failure (HF) patients demonstrate impaired pulmonary, circulatory, and nervous system responses to exercise. While HF demonstrates prolonged [time constant (τ)] pulmonary O2 uptake (V̇o2) on-kinetics, contributing to exercise intolerance, it is unknown whether abnormal V̇o2 kinetics couple with ventilatory and circulatory dysfunction secondary to impaired group III/IV afferents in HF. Because lower lumbar intrathecal fentanyl inhibits locomotor muscle afferents, resulting in improved exercise ventilation and hemodynamics, we tested these hypotheses: HF will demonstrate 1) rapid V̇o2 on-kinetics and 2) attenuated steady-state V̇o2 amplitude and O2 deficit (O2def) during exercise with fentanyl versus placebo. On separate visits (randomized), breath-by-breath V̇o2 was measured in HF (ejection fraction: 27 ± 6%, New York Heart Association class I-III) and age- and sex-matched controls (both n = 9, ages: 60 ± 6 vs. 63 ± 8 yr, P = 0.37) during cycling transitions at 65% peak workload (78 ± 24 vs. 115 ± 39 W, P group or condition, optimal phase II (primary component) curve fits reflected a phase I period equal to 35 s (limb-to-lung timing) via single-exponential functions. Condition did not affect steady-state V̇o2, the phase II τ of V̇o2, or O2def within controls (P > 0.05). Without differences in steady-state V̇o2, reduced O2def in fentanyl versus placebo within HF (13 ± 4 vs. 22 ± 15 ml/W, P = 0.04) was accounted for by a rapid phase II τ of V̇o2 in fentanyl versus placebo within HF (45 ± 11 vs. 57 ± 14 s, P = 0.04), respectively. In an integrative manner, these data demonstrate important effects of abnormal locomotor muscle afferents coupled to pulmonary and circulatory dysfunction in determining impaired exercise V̇o2 in HF. Effects of abnormal muscle afferents on impaired exercise V̇o2 and hence exercise intolerance may not be discernable by independently assessing steady-state V̇o2 in HF.NEW & NOTEWORTHY Inhibition of locomotor muscle

  4. Effects of genetic polymorphisms of OPRM1, ABCB1, CYP3A4/5 on postoperative fentanyl consumption in Korean gynecologic patients.

    Science.gov (United States)

    Kim, Kye-Min; Kim, Ho-Sook; Lim, Se Hun; Cheong, Soon Ho; Choi, Eun-Jung; Kang, Hyun; Choi, Hey-Ran; Jeon, Jin-Woo; Yon, Jun Heum; Oh, Minkyung; Shin, Jae-Gook

    2013-05-01

    Fentanyl, a μ-opioid receptor agonist, is a substrate of P-glycoprotein. Its metabolism is catalyzed by CYP3A4 and CYP3A5. The aim of this study was to investigate the association between postoperative fentanyl consumption and genetic polymorphisms of μ-opioid receptor (OPRM1), ABCB1 (gene encoding P-glycoprotein), CYP3A4 and CYP3A5 in Korean patients. 196 female patients scheduled to undergo total abdominal hysterectomy or laparoscopic assisted vaginal hysterectomy under general anesthesia were enrolled in this study. Intravenous patient-controlled analgesia with fentanyl was provided postoperatively. Cumulative fentanyl consumption was measured during the first 48 hours postoperatively. The severity of pain at rest was assessed with the visual analogue scale. OPRM1 118A>G, ABCB1 2677G>A/T, ABCB1 3435C>T, CYP3A4*18 and CYP3A5*3 variant alleles were genotyped. The effects of genetic and non-genetic factors on fentanyl requirements were evaluated with multiple linear regression analysis. The 24-hour cumulative fentanyl doses were significantly associated with pain core, weight and type of surgery (p fentanyl doses were significantly associated with pain score, type of surgery and history of PONV or motion sickness (p fentanyl requirements. In Korean gynecologic patients, no association was found between genetic factors and postoperative fentanyl consumption.

  5. Increases in self-reported fentanyl use among a population entering drug treatment: The need for systematic surveillance of illicitly manufactured opioids.

    Science.gov (United States)

    Cicero, Theodore J; Ellis, Matthew S; Kasper, Zachary A

    2017-08-01

    Recent reports indicate a sharp increase in fentanyl-related overdose deaths across the United States, much of which is likely related to the introduction of cheap, illicitly manufactured fentanyl derivatives. In this study, we sought to estimate the magnitude of illicit fentanyl use from 2012 to 2016 using a national opioid abuse surveillance system. The study program surveyed 10,900 individuals entering substance abuse treatment for opioid use disorder, with participants asked to endorse past month 'use to get high' of fentanyl drugs, stratified by identifiable (i.e., branded) fentanyl formulations or a 'type unknown' drug alleged to contain fentanyl. Total past-month fentanyl-use rose modestly from 2012 to 2016. While use of known fentanyl products remained relatively stable (mean=10.9%; P=0.25), endorsements of 'unknown' fentanyl products nearly doubled from 9% in 2013 to 15.1% by 2016 (Phealth problem requires immediate attention and more systematic efforts to identify and track its abuse. Copyright © 2017. Published by Elsevier B.V.

  6. CLINICAL EVALUATION OF EPIDURAL ADMINISTRATION OF MORPHINE, FENTANYL, METHADONE, LIDOCAINE AND LIDOCAINE WITH EPINEPHRINE IN CATTLE

    Directory of Open Access Journals (Sweden)

    A. Tabatabaei Naeine, A. Rezakhani and J. Fazlinia

    2004-01-01

    Full Text Available The purpose of this study was to determine the analgesic efficacy and clinical effects of morphine, fentanyl, methadone, lidocaine, lidocaine with epinephrine and saline (control when injected epidurally into the caudal epidural space in cattle. Epidural analgesia was achieved in five cattle on five successive occasions at weekly intervals. Analgesia was defined as a lack of response to hemostat pressure and pinprick in the skin of the perineal area and ventral aspect of the tail. The results demonstrated that while epidural lidocaine and lidocaine with epinephrine decreased the response to hemostat and pinprick compared to control, there was no reduction in response after the administration of morphine, methadone or fentanyl. Heart rate, pulse and respiratory rates were not significantly altered by any of the drugs. Neither did the drugs produce any change in the electrocardiogram (ECG of the animals.

  7. Case study and review article: epilepsy-like movements induced by fentanyl analgesia

    Directory of Open Access Journals (Sweden)

    Mahmoud El-Karamany

    2017-01-01

    Full Text Available Epilepsy-like movements are observed immediately after the administration of fentanyl as well as its derivatives. Although the event has no serious outcomes, it is so worrisome that it has garnered the attention of many authors to publish case reports of such events. Despite the presence of cerebral lesions in some cases, epileptic focus cannot be attributed to such lesions. Radiological and electrophysiological studies have failed to reveal abnormal cerebral activity during such events. The reported activity is usually generalized tonic–clonic convulsions. Epileptic convulsive movements were observed with low doses of fentanyl and its derivatives. Previous studies on animals have supported the occurrence of such epileptiform movements in corresponding doses. Idiosyncrasy and narcotic-related muscle rigidity did not satisfactorily explain the seizures. Our case report represents the occurrence of epileptiform movements twice in and an old patient with no cerebral insult. The past history was epileptic activity under control with lamotrigine for last 2 years.

  8. Life-threatening opioid toxicity from a fentanyl patch applied to eczematous skin.

    Science.gov (United States)

    Doris, Mhairi K; Sandilands, Euan A

    2015-04-29

    A 19-year-old man with a history of eczema was admitted to the emergency department following collapsing at home. The paramedics found him unresponsive with poor respiratory effort and a widespread erythematous rash. Anaphylaxis, thought to be secondary to flucloxacillin he had recently been prescribed, was diagnosed. Epinephrine, steroids and antihistamines were administered without clinical improvement. On arrival to hospital, constricted pupils were noted prompting the emergency physicians to consider opiate toxicity. Intravenous naloxone brought about an immediate recovery. His father subsequently disclosed that he had given his son one of his own fentanyl patches to alleviate the distressing symptoms of eczema. Although the patient had removed the patch prior to collapsing, he had suffered life-threatening opioid toxicity likely due to enhanced opiate absorption through eczematous skin. This case highlights the risks associated with fentanyl patches in patients with chronic skin conditions. 2015 BMJ Publishing Group Ltd.

  9. Fentanyl and propofol exposure in the operating room: sensitization hypotheses and further data.

    Science.gov (United States)

    Merlo, Lisa J; Goldberger, Bruce A; Kolodner, Dara; Fitzgerald, Kimberly; Gold, Mark S

    2008-01-01

    Inflated rates of opioid addiction among anesthesiologists may be caused by chronic exposure to low doses of aerosolized anesthetic/analgesic agents in the operating room. Such secondhand exposure produces neurobiological sensitization to the reinforcing effects of these substances, making later addiction more likely. This article extends findings that fentanyl and propofol are detectable in the air of the operating room and demonstrates that fentanyl is also detectable on surfaces in the operating room. Secondhand exposure could, therefore, occur by inhalation and skin absorption. Additionally, data show that many physicians with opiate addiction have a family history of addiction, suggesting genetic vulnerability to the effects of secondhand exposure. Other new data demonstrate that the rates of marijuana and tobacco smoking are much higher among opioid-addicted physicians, suggesting that prior exposure to THC (the psychoactive component of cannabis) or nicotine might increase vulnerability to secondhand effects. Suggestions for reducing secondhand exposure in the operating room are discussed.

  10. Fentanyl pharmacokinetics is not dependent on hepatic uptake by organic anion-transporting polypeptide 1B1 in human beings.

    Science.gov (United States)

    Ziesenitz, Victoria C; König, Sonja K; Mahlke, Nina; Jantos, Ricarda; Skopp, Gisela; Weiss, Johanna; Haefeli, Walter E; Mikus, Gerd

    2013-07-01

    A recent study investigating the pharmacokinetics of fentanyl in Sprague-Dawley rats suggested fentanyl to be a substrate of rat organic anion-transporting polypeptide Oatp. In human beings, the most important OATP for the pharmacokinetics of many drugs is OATP1B1. Therefore, genetic variants of OATP1B1 (SLCO1B1) might modulate fentanyl pharmacokinetics and efficacy in human beings. Sixteen healthy male and female volunteers, homozygous for SLCO1B1*1a (genetic wild-type) (n = 11) or *15 (deficient haplotype carrying the single-nucleotide polymorphisms rs2306283 and rs4149056 and exhibiting altered transport activity; n = 5), were included in this randomized crossover study. The participants received fentanyl (5 μg/kg) intravenously alone or with the OATP inhibitor rifampicin (600 mg single oral dose). The pharmacokinetics of fentanyl and norfentanyl were determined by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). In addition, fentanyl uptake in vitro was evaluated in OATP1B1 overexpressing HEK293 cells and compared to a mock-transfected cell line. In the clinical trial, fentanyl clearance was 18.8 ± 8.2 mL/min. kg in SLCO1B1*1a and 19.5 ± 1.8 mL/min/kg in SLCO1B1*15 carriers and not significantly different between the genotypes. During rifampicin, fentanyl clearance was 15.0 ± 4.4 mL/min/kg in SLCO1B1*1a and 16.7 ± 5.9 mL/min/kg in SLCO1B1*15 carriers (p > 0.5). In addition, in vitro data also indicate that fentanyl is not transported by OATP1B1. In conclusion, our data indicate that OATP1B1 has no impact on fentanyl pharmacokinetics in human beings. © 2013 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.

  11. Chemical stability of admixtures combining ziconotide with fentanyl or sufentanil during simulated intrathecal administration.

    Science.gov (United States)

    Shields, David E; Aclan, Jennifer; Szatkowski, Aaron

    2008-01-01

    Although the U.S. Food and Drug Administration has not approved the combined use of intrathecal medications, practitioners frequently prescribe combination intrathecal therapy for patients who do not experience adequate analgesia with a single intrathecal agent; however, the chemical stability of an analgesic combination may influence the frequency of pump refills necessary to maintain safe and efective pain control. This investigation was performed to evaluate the chemical stability of admixtures containing 25 mcg/mL ziconotide and either 1000 mcg/mL fentanyl citrate or 1000 mcg/mL sufentanil citrate during simulated intrathecal infusion under laboratory conditions at 37 deg C. Admixtures were prepared from commercial ziconotide (25 mcg/mL) and lyophilized powders of the opioid drugs, sparged with nitrogen to remove dissolved oxygen, and stored in implantable intrathecal pumps at 37 deg C. Samples obtained at various intervals over the course of 40 days were assessed for drug concentrations by using high-performance liquid chromatography. The periods of time that the admixtures retained > or = 90% and > or = 80% of the initial concentrations of each drug (i.e., the 90% and 80% stabilities) were determined by using linear regression and 95% confidence intervals. At study end, ziconotide concentrations averaged 87.5% of the initial concentration in the ziconotide/fentanyl admixture and 89.3% of the initial concentration in the ziconotide/sufentanil admixture; opioid concentrations were unchanged. Ziconotide was 90% stable for 26 days and 80% stable for 58 days (extrapolated) when combined with fentanyl; when combined with sufentanil, ziconotide was 90% stable for 33 days and 80% stable for 68 days (extrapolated). The opioids were stable throughout the study. At the concentrations used in this study, ziconotide/fentanyl and ziconotide/sufentanil admixtures were relatively stable.

  12. Discrimination of narcotic drugs on 3H-fentanyl receptor binding.

    Science.gov (United States)

    Leysen, J; Gommeren, W; Laduron, P

    1976-04-01

    Stereospecific opiate receptor binding was measured using specifically labeled fentanyl in the presence of an excess of either dextromoramide or levomoramide, only the former being the analgesic isomer. In a very large series of chemically related drugs, but of different pharmacological activity, it was possible to recognize compounds endowed with a potential morphine-like activity. Attempts were made to localize the opiate receptors within the neuronal cell.

  13. Plasma Beta-Endorphin Levels in Oral Surgery Patients Following Diazepam, Fentanyl or Placebo1

    Science.gov (United States)

    Hargreaves, Kenneth M.

    1984-01-01

    Plasma beta-endorphin, pain and anxiety were measured in patients before, during, and 1 and 3 hours following oral surgery. Diazepam and fentanyl blocked the stress induced increase in plasma beta-endorphin experienced by patients administered placebo. Moreover, intra-operative anxiety and post-operative pain appear to constitute independent and possibly equipotent stimuli for release of pituitary beta-endorphin in humans. PMID:6089614

  14. Comparison of Preanesthetic Sedation after Intranasal Administration of Fentanyle, Ketamin and Midazolam

    Directory of Open Access Journals (Sweden)

    F Javaherforoosh

    2006-07-01

    Full Text Available Introduction & Objective: Induction of anesthesia in children can be a challenge for anesthetist. A stormy induction may increase the personality & behavioral changes. Therefore, it is desirable that they enter the operating room sedated. Many drugs are used for preanesthetic medication and there are many routes for administration. One route of administration is nasal mucous. In this study we compared the effect and side effect of three drugs (midazolam, ketamin and fentanyle after intra nasal administration. Materials & Methods: This is a double blind clinical trial. In this study we selected 60 patients (20 patients for every group A, B or C. We used 3 mg/kg ketamin or 3µg/kg fentanyle or 0.3 mg/kg midazolam by intranasal spray. After administration and in 5, 10 and 15 minutes, we observed the SPO2, PR and RR. After 15 min’s we separated children from parents and brought them to the operating room and controlled the acceptance of separation, depth of sedation with Ramsay score, acceptance of mask and tolerance of IV canulation. The data were then analyzed using K2 and kruskal-wallis test. Results: In our study we found that in SPO2 fentanyle had the highest rate of reduction even though none of the children had SPO2 lower than 90%. There were no differences between drugs in RR. In fentanyle group, we had the lowest rate and in ketamin group the highest rate. Midazolam had the medium rate. The rate of sedation for acceptance of separation from parents had no difference between the groups and all drugs with this dosage were effective for this aim. However, in Ramsay score, acceptance of mask and tolerance of IV canulation, the midazolam was more effective than the others. Conclusion: Intranasal administration of midazolam is a safe route for sedation in children in the pre-anesthetic time.

  15. The Effects of Intrathecal Fentanyl on Sedation Depth and Postoperative Recovery Room Delirium

    Directory of Open Access Journals (Sweden)

    Ozgur Bulent Tuzun

    2015-01-01

    Full Text Available Background/Aim. Intrathecal anaesthesia has been shown to increase sedation level. This study aimed to evaluate the effects of intrathecal applied fentanyl with levobupivacaine on intraoperative sedation and recovery room delirium. Materials and Methods. The study included 68 patients, ASA I–III, 55–85 years. One day preoperatively, the Confusion Assessment Method (CAM and the Mini Mental Status Test (MMST were applied and patients were separated into two groups. In Group L 2.5 mL levobupivacaine and in Group LF 2 mL levobupivacaine and 0.5 mL fentanyl were applied intrathecally. In a supine position, following a propofol IV 1 mg kg−1 bolus to obtain Bispectral Index (BIS of 70–85, propofol infusion was started (1 mg kg−1 st−1. With observation of SpO2, BIS, and the Observer Assessment and Alertness/Sedation Scale (OAA/SS with the haemodynamic values, the total propofol amount was calculated. Evaluations were made of pain severity (VAS, analgesic use, transfusion requirement, and recovery room delirium. Results. In the comparison within the groups, a significant decrease was determined in HR and MAP compared to the initial values (p<0.05. A positive correlation was found between the BIS and OAA/SS values. The amounts of propofol used were similar between the groups. Conclusions. Intrathecal fentanyl and levobupivacaine had the same effect on sedation or BIS and fentanyl did not cause delirium.

  16. Cost-effectiveness analysis of oral fentanyl formulations for breakthrough cancer pain treatment.

    Science.gov (United States)

    Cortesi, Paolo Angelo; D'Angiolella, Lucia Sara; Vellucci, Renato; Allegri, Massimo; Casale, Giuseppe; Favaretti, Carlo; Kheiraoui, Flavia; Cesana, Giancarlo; Mantovani, Lorenzo Giovanni

    2017-01-01

    Breakthrough cancer Pain (BTcP) has a high prevalence in cancer population. Patients with BTcP reported relevant health care costs and poor quality of life. The study assessed the cost-effectiveness of the available Oral Fentanyl Formulations (OFFs) for BTcP in Italy. A decision-analytical model was developed to estimate costs and benefits associated with treatments, from the Italian NHS perspective. Expected reductions in pain intensity per BTcP episodes were translated into, percentage of BTcP reduction, resource use and Quality-Adjusted-Life-Years (QALYs). Relative efficacy, resources used and unit costs data were derived from the literature and validated by clinical experts. Probabilistic and deterministic sensitivity analyses were performed. At base-case analysis, Sublingual Fentanyl Citrate (FCSL) compared to other oral formulations reported a lower patient's cost (€1,960.8) and a higher efficacy (18.7% of BTcP avoided and 0.0507 QALYs gained). The sensitivity analyses confirmed the main results in all tested scenarios, with the highest impact reported by BTcP duration and health care resources consumption parameters. Between OFFs, FCSL is the cost-effective option due to faster reduction of pain intensity. However, new research is needed to better understand the economic and epidemiologic impact of BTcP, and to collect more robust data on economic and quality of life impact of the different fentanyl formulations. Different fentanyl formulations are available to manage BTcP in cancer population. The study is the first that assesses the different impact in terms of cost and effectiveness of OFFs, providing new information to better allocate the resources available to treat BTcP and highlighting the need of better data.

  17. Cardiogenic shock following administration of propofol and fentanyl in a healthy woman: a case report

    OpenAIRE

    Renilla González, Alfredo; Lozano Martinez-Luengas, Iñigo; Secades González, Sandra; Álvarez Pichel, Irene; Álvarez Martinez, Paloma; Santamarta Liébana, Elena; Díaz Molina, Beatriz

    2011-01-01

    Abstract Introduction Cardiogenic shock is very uncommon in healthy people. The differential diagnosis for patients with acute heart failure in previously healthy hearts includes acute myocardial infarction and myocarditis. However, many drugs can also depress myocardial function. Propofol and fentanyl are frequently used during different medical procedures. The cardiovascular depressive effect of both drugs has been well established, but the development of cardiogenic shock is very rare when...

  18. Fatal overdose after ingestion of a transdermal fentanyl patch in two non-human primates

    OpenAIRE

    Deschamps, Jack-Yves; Gaulier, Jean-Michel; Podevin, Guillaume; Cherel, Yan; Ferry, Nicolas; Roux, Françoise

    2012-01-01

     ; Case history and presentation: Two non-human primates (Macaca fascicularis) enrolled in an experimental protocol received a 25 μg hour−1 transdermal fentanyl patch for postoperative analgesia. The following day both animals were clinically normal, but after a new induction of anaesthesia with ketamine, they developed severe and prolonged respiratory distress, profound coma and myosis. Management and follow-up: Attempted reversal with naloxone was ineffective. After several hours of ventila...

  19. Comparison of adding neostigmine and fentanyl to bupivacaine in caudal analgesia in pediatric inguinal herniorrhaphy

    OpenAIRE

    Omid Aghadavoudi; Amir Shafa; Zahra Nowrozi

    2017-01-01

    AbstractObjective: The aim of the present trial was to compare efficacy and adverse effects of neostigmine against fentanyl when used as adjuvant to bupivacaine in caudal anesthesia.Method: A total of 140 children, aged 1-6 year scheduled to elective herniorrhaphy, were enrolled. Exclusion criteria were sacral area infection, history of allergic reactions to local anesthetics, bleeding tendency, neurological or spinal disease and lack of parent consent. Patients were assigned, using permuted ...

  20. EPIDURAL FENTANYL SPEEDS THE ONSET OF SENSORY AND MOTOR BLOCKS DURING EPIDURAL ROPIVACAINE ANAESTHESIA

    OpenAIRE

    A. Mohan Rao; A. Hari Prasad; Vankineni Kuchela Babu

    2016-01-01

    BACKGROUND Different adjuvants are added to local anaesthetic solutions to hasten the onset of sensory and motor block in epidural anaesthesia. OBJECTIVE To study the effect of epidural and intravenous fentanyl on time of onset of sensory and motor blockade in epidural anaesthesia with 0.75% ropivacaine. MATERIALS AND METHODS After obtaining informed consent and permission from hospital scientific and ethical committee 40 patients with ASA grade I and II who are und...

  1. Fatal overdose after ingestion of a transdermal fentanyl patch in two non-human primates

    OpenAIRE

    Deschamps, Jack-Yves; Podevin, Guillaume; Cherel, Yan; Ferry, Nicolas

    2012-01-01

    Case history and presentation: Two non-human primates (Macaca fascicularis) enrolled in an experimental protocol received a 25 μg hour−1 transdermal fentanyl patch for postoperative analgesia. The following day both animals were clinically normal, but after a new induction of anaesthesia with ketamine, they developed severe and prolonged respiratory distress, profound coma and myosis. Management and follow-up: Attempted reversal with naloxone was ineffective. After several hours of ventilatio...

  2. Safety and Efficacy of Oral Transmucosal Fentanyl Citrate for Prehospital Pain Control on the Battlefield

    Science.gov (United States)

    2012-01-01

    for pain relief, which demonstrated the importance of addressing both the patient’s reported pain and desire for pain medica - tions. Singer et al.4...combat experience from which to formulate clinical judgments for using OTFC on the battlefield. Battlefield pain management remains a priority for the...2815. 48. Vasisht N, Gever LN, Tagarro I, Finn AL. Formulation selection and pharmacokinetic comparison of fentanyl buccal soluble film with oral

  3. Bronchoscopic diagnosis of peripheral pulmonary lung cancer employing sedation with fentanyl and midazolam.

    Science.gov (United States)

    Minami, Daisuke; Nakasuka, Takamasa; Ando, Chihiro; Iwamoto Md, Yoshitaka; Sato, Ken; Fujiwara, Keiichi; Shibayama, Takuo; Yonei Md PhD, Toshirou; Sato, Toshio

    2017-09-01

    Sedation with fentanyl and midazolam during bronchoscopic examination is commonly employed by pulmonary physicians in the USA and Europe. We assessed the efficacy of such sedation in the bronchoscopic diagnosis of peripheral lung cancer. We retrospectively evaluated data from 102 patients who underwent transbronchial biopsies (TBB) for diagnosis of peripheral lung cancer. Bronchoscopies with and without fentanyl were performed in 61 (group A) and 41 (group B) patients, respectively. Midazolam was administered to all patients. Medical records were retrieved, and between-group comparisons were made using unpaired Student's t-tests. The mean fentanyl dose was 49.5 μg (range: 10-100 μg), and midazolam doses in groups A and B were 4.29mg (range: 1-14mg) and 5.54mg (range: 1-12mg), respectively. Diagnostic histological specimens were obtained from 75.4% and 65.8% of group A and B patients, respectively (P = 0.30). The diagnostic sensitivities for lung cancer, via at least one of TBB, cytological brushing, or bronchial washing, in groups A and B were 88.5% and 70.4%, respectively (P = 0.035). Moreover, lesion diagnostic sensitivities, via at least one of TBB, cytological brushing, and bronchial washing, in groups A and B were 98.1% and 68.0%, respectively (P = 0.01). Fentanyl and midazolam sedation during bronchoscopy facilitated the diagnosis of peripheral pulmonary lung cancers. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  4. Evaluation of the effect of added fentanyl to hyperbaric bupivacaine for spinal anesthesia

    Directory of Open Access Journals (Sweden)

    Mina Jafari-Javid

    2011-01-01

    Full Text Available Background: Potentiating the effect of the intrathecal local anesthetics by intrathecal injection of opiods for intra-abdominal surgeries is known. The objective of this study is to investigate the pain-relieving effects of intrathecal fentanyl to bupivacaine in elective caesarean surgery.Materials and Method: In a double blind clinical trial 60 patients candidate for elective cesarean section. They were studied in two groups. Cases in the control group received 12.5 mg of bupivacaine and in the study group received 8 mg of bupivacaine and 20 µg fentanyl. The parameters taken into consideration were hemodynamic stability, visceral pain, nausea and vomiting, intraoperative shivering, the amount of intraoperative administered dose of fentanyl and ephedrine and postoperative pain. Results: The average blood pressure changes after 5, 10, 20, 60 minutes were lower in the study group. Shivering and ephedrine dose during operation were lower in study group and statistically significant respectively (p=0.01, p=0.001, respectively. Duration of analgesia after operation increased from (115.5±7.5 min in control group to (138.5±9.9 min in study group, but the quality of analgesia during peritoneal manipulation did not change. Pulse rate and vomiting during operation were not statistically different between two groups.Conclusion: Reduction of local anesthetic dose with adding fentanyl may cause hemodynamic stability, increasing the postoperative pain-free time, decrease shivering and vasopressor consumption in spinal anesthesia and reduction of the amount of blood pressure drop during elective cesarean surgery

  5. The stability of a sulphite-free epidural analgesic solution containing fentanyl, bupivacaine, and adrenaline.

    Science.gov (United States)

    Brustugun, J; Troland, S; Breivik, H

    2013-11-01

    Thoracic epidural infusion analgesia is optimised by using a triple component infusion containing a local anaesthetic, an opioid, and adrenaline. Adrenaline in solution is prone to oxidation, and stabilisers, such as antioxidants (e.g. sulphites) or chelators (edetates), are therefore commonly added. Sulphites may, however, have unwanted effects, especially allergic reactions. The aim of this study was to evaluate the stability of an analgesic infusion solution for epidural administration free of sulphites, containing adrenaline, fentanyl, bupivacaine, and disodium edetate. An epidural infusion solution containing adrenaline 2 μg/ml, fentanyl 2 μg/ml, bupivacaine 1 mg/ml, and disodium edetate 0.18 μg/ml was stored at 2-8°C for 4.5 months. A concentrate 11 times more potent, used for the production of the ready-to-use solution, was stored at 2-8°C for 9 months. Concentrations of the active ingredients were determined, pH was measured throughout the period, the clarity of the solutions was investigated, and the weight of the infusion bags recorded. After 4.5 months at 2-8°C, the infusion solution contained adrenaline 97.5%, bupivacaine 100.9%, and fentanyl 102.6%. The pH stayed between 4.76 and 4.79, the solutions remained clear, and the weight was 99.9% of that found initially. The solution was also stable for 7 days at room temperature. The concentrate was stable (> 90%) for 9 months at 2-8°C. The solution containing adrenaline, fentanyl, and bupivacaine, stabilised with disodium edetate, is stable for several months at 2-8°C, and at least for 7 days at room temperature without the addition of sulphites. © 2013 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  6. Comparison of efficacy of labetalol and fentanyl for attenuating reflex responses to laryngoscopy and intubation.

    Science.gov (United States)

    Meftahuzzaman, S M; Islam, M M; Ireen, S T; Islam, M R; Kabir, H; Rashid, H; Uddin, M Z

    2014-04-01

    Stress response due to laryngoscopy and intubation has been universally recognized phenomenon resulting in increase in heart rate, arterial, intracranial, and intraocular pressure. Various pharmacological approaches have been used to blunt or attenuate such pressure responses. This prospective, randomized, placebo controlled, double blinded study was designed to compare the efficacy of bolus dose of Labetalol and Fentanyl for attenuating reflex responses to laryngoscopy and intubation. Ninety patients with physical status of ASA I and II were scheduled for elective surgery under standard protocol of general anaesthesia, randomly allocated into three groups, consisting of 30 patients in each group, assigned as C (Control), L (Labetalol), and F (Fentanyl). In control group 10ml of 0.9% saline, in Labetalol group 0.25 mg/kg Labetalol and in Fentanyl group 2μgm/kg of Fentanyl were given intravenously at 3 minutes prior to laryngoscopy and intubation. Pulse rate, systolic, diastolic, mean arterial pressure and rate pressure products (RPP) were recorded before and after premedication, after administration of study drugs and at 1, 3, 5, 10 and 15 minutes after intubation. For statistical analysis of data, ANOVA tests were performed for comparison between groups. There were an increase in heart rate, systolic, diastolic, mean arterial pressures and rate pressure product in all the three groups after intubation in comparison to base line value. But the rise was minimum in L and F group as compared to C group which is statistically significant and also minimum in L group as compared to F group. So Labetalol is better agent for attenuation of laryngoscopic and intubation reflex.

  7. Effect of chronic pain on fentanyl self-administration in mice.

    Directory of Open Access Journals (Sweden)

    Carrie L Wade

    Full Text Available The development of opioid addiction in subjects with established chronic pain is an area that is poorly understood. It is critically important to clearly understand the neurobiology associated with propensity toward conversion to addiction under conditions of chronic pain. To pose the question whether the presence of chronic pain influences motivation to self-administer opioids for reward, we applied a combination of rodent models of chronic mechanical hyperalgesia and opioid self-administration. We studied fentanyl self-administration in mice under three conditions that induce chronic mechanical hyperalgesia: inflammation, peripheral nerve injury, and repeated chemotherapeutic injections. Responding for fentanyl was compared among these conditions and their respective standard controls (naïve condition, vehicle injection or sham surgery. Acquisition of fentanyl self-administration behavior was reduced or absent in all three conditions of chronic hyperalgesia relative to control mice with normal sensory thresholds. To control for potential impairment in ability to learn the lever-pressing behavior or perform the associated motor tasks, all three groups were evaluated for acquisition of food-maintained responding. In contrast to the opioid, chronic hyperalgesia did not interfere with the reinforcing effect of food. These studies indicate that the establishment of chronic hyperalgesia is associated with reduced or ablated motivation to seek opioid reward in mice.

  8. Supply-side response to declining heroin purity: fentanyl overdose episode in New Jersey.

    Science.gov (United States)

    Hempstead, Katherine; Yildirim, Emel O

    2014-06-01

    The inelastic price demand observations characteristic of illegal drug markets have led to the conclusion that the burden of a negative supply shock would be completely reflected to consumers. This paper argues that the increasing availability of prescription opioids may threaten heroin sellers' profit margin and force them to find alternative methods to compensate buyers in the event of a supply shock. We investigate the 2006 fentanyl overdose episode in New Jersey and argue that the introduction of non-pharmaceutical fentanyl, its spatial distribution, and the timing of overdose deaths may have been related to trends in heroin purity. Using medical examiner data, as well as data from the Drug Enforcement Administration, Office of Diversion Control on retail sales of prescription opioids in a negative binomial specification, we show that month-to-month fluctuations in heroin purity have a significant effect on fentanyl-related overdoses, particularly in those areas where prescription opioids are highly available. Copyright © 2013 John Wiley & Sons, Ltd.

  9. Bilateral Deep Brain Stimulation of the Subthalamic Nucleus under Sedation with Propofol and Fentanyl.

    Directory of Open Access Journals (Sweden)

    Woong-Woo Lee

    Full Text Available Awakening during deep brain stimulation (DBS surgery may be stressful to patients. The aim of the current study was to evaluate the effect on MER signals and their applicability to subthalmic nucleus (STN DBS surgery for patients with Parkinson's disease (PD under sedation with propofol and fentanyl. Sixteen consecutive patients with PD underwent STN-DBS surgery with propofol and fentanyl. Their MER signals were achieved during the surgery. To identify the microelectrodes positions, the preoperative MRI and postoperative CT were used. Clinical profiles were also collected at the baseline and at 6 months after surgery. All the signals were slightly attenuated and contained only bursting patterns, compared with our previous report. All electrodes were mostly located in the middle one third part of the STN on both sides of the brain in the fused images. Six months later, the patients were improved significantly in the medication-off state and they met with less dyskinesia and less off-duration. Our study revealed that the sedation with propofol and fentanyl was applicable to STN-DBS surgery. There were no significant problems in precise positioning of bilateral electrodes. The surgery also improved significantly clinical outcomes in 6-month follow-up.

  10. Factors in the choice of oral transmucosal fentanyl citrate dose for adult burns dressings.

    Science.gov (United States)

    Shah, H; Smythe, J; Hanafiah, Z; Williams, G J P; Holdcroft, A

    2009-09-01

    Factors that influenced the choice of dose of oral transmucosal fentanyl at the time of burns dressing change were investigated in a prospective study. After Ethics committee approval, data was analysed from 29 consecutive patients who had been recruited and consented for a study of pain associated with burns dressings. Patients had completed an 11-point verbal pain intensity score (VRS) prior to and after the dressing change. Analgesic use during for this period was documented. Doses of 600 to 1200 mcg of transmucosal fentanyl (Actiq) were given based on individual assessment. The pre-dressing VRS (median [range]) in the 15 patients who received 600 mcg was 8 [3-10] and was higher than the VRS of 6 [2-9] in the 800-1200 mcg group. The time since the burn was longer in the low dose group at 7 [1-22] days compared with 5 [0-50] days in the higher dose group. In addition 73% of the low dose group was prescribed opioids regularly prior to the dressing compared with 57% of the high dose group. The choice of a lower transmucosal fentanyl dose was based on prior use of opioids and the age of the burn rather than on the patient's pain intensity.

  11. Complications associated with intravenous midazolam and fentanyl sedation in patients undergoing minor oral surgery.

    Science.gov (United States)

    Saiso, Krittika; Adnonla, Pornnarin; Munsil, Jitpisut; Apipan, Benjamas; Rummasak, Duangdee; Wongsirichat, Natthamet

    2017-09-01

    Anxiety control remains an important concern in dental practice. We evaluated the incidence, nature, and sequelae of complications during and after minor oral surgeries performed under intravenous midazolam and fentanyl sedation using the titration technique. The medical records of patients who had undergone minor oral surgeries under moderate intravenous midazolam and fentanyl sedation at our institution between January 1, 2015 and December 31, 2015 were retrospectively evaluated. Age, sex, body mass index, medical history, American Society of Anesthesiologists (ASA) classification, indications for sedation, amount of sedative used, surgical duration, and recovery time were evaluated for all patients. In total, 107 patients aged 9-84 years were included. ASA class I and class II were observed for 56.1% and 43.9% patients, respectively. Complications associated with sedation occurred in 11 (10.2%) patients. There were no serious adverse events. Oxygen saturation reached 95% during the procedure in six patients; this was successfully managed by stimulating the patients to take a deep breath. Two patients exhibited deep sedation and one exhibited paradoxical excitement. After the procedure, one patient experienced nausea without vomiting and one exhibited a prolonged recovery time. The surgical procedures were completed in all patients. Obesity was found to be significantly associated with sedation-related complications. Our results suggest that complications associated with intravenous midazolam and fentanyl sedation using the titration technique for minor oral surgeries are mostly minor and can be successfully managed with no prolonged sequelae.

  12. Postoperative analgesia in children when using clonidine in addition to fentanyl with bupivacaine given caudally.

    Science.gov (United States)

    Jarraya, Anouar; Elleuch, Sahar; Zouari, Jawhar; Smaoui, Mohamed; Laabidi, Sofiene; Kolsi, Kamel

    2016-01-01

    The aim of the study was to evaluate the efficacy of clonidine in association with fentanyl as an additive to bupivacaine 0.25% given via single shot caudal epidural in pediatric patients for postoperative pain relief. In the present prospective randomized double blind study, 40 children of ASA-I-II aged 1-5 years scheduled for infraumblical surgical procedures were randomly allocated to two groups to receive either bupivacaine 0.25% (1 ml/kg) with fentanyl 1 μg/kg and clonidine 1μg/kg (group I) or bupivacaine 0.25% (1 ml/kg) with fentanyl 1 μg/kg (group II). Caudal block was performed after the induction of general anesthesia. Postoperatively patients were observed for analgesia, sedation, hemodynamic parameters, and side effects or complications. Both the groups were similar with respect to patient and various block characteristics. Heart rate and blood pressure were not different in 2 groups. Significantly prolonged duration of post-operative analgesia was observed in group I (Pfentanyl as additives to bupivacaine in single shot caudal epidural in children may provide better and longer analgesia after infraumblical surgical procedures.

  13. Effect of nitrous oxide on fentanyl consumption in burned patients undergoing dressing change

    Directory of Open Access Journals (Sweden)

    Arthur Halley Barbosa do Vale

    2016-02-01

    Full Text Available BACKGROUND AND OBJECTIVES: Thermal injuries and injured areas management are important causes of pain in burned patients, requiring that these patients are constantly undergoing general anesthesia for dressing change. Nitrous oxide (N2O has analgesic and sedative properties; it is easy to use and widely available. Thus, the aim of this study was to evaluate the analgesic effect of N2O combined with fentanyl in burned patients during dressing change. METHOD: After approval by the institutional Ethics Committee, 15 adult burned patients requiring daily dressing change were evaluated. Patient analgesia was controlled with fentanyl 0.0005% administered by intravenous pump infusion on-demand. Randomly, in one of the days a mixture of 65% N2O in oxygen (O2 was associated via mask, with a flow of 10 L/min (N2O group and on the other day only O2 under the same flow (control group. RESULTS: No significant pain reduction was seen in N2O group compared to control group. VAS score before dressing change was 4.07 and 3.4, respectively, in N2O and control groups. Regarding pain at the end of the dressing, patients in N2O group reported pain severity of 2.8; while the control group reported 2.87. There was no significant difference in fentanyl consumption in both groups. CONCLUSIONS: The association of N2O was not effective in reducing opioid consumption during dressing changes.

  14. Determination of buprenorphine, fentanyl and LSD in whole blood by UPLC-MS-MS.

    Science.gov (United States)

    Berg, Thomas; Jørgenrud, Benedicte; Strand, Dag Helge

    2013-04-01

    A sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method has been developed and validated for the quantification of buprenorphine, fentanyl and lysergic acid diethylamide (LSD) in whole blood. Sample preparation was performed by liquid-liquid extraction (LLE) with methyl tert-butyl ether. UPLC-MS-MS analysis was performed with a mobile phase consisting of ammonium formate (pH 10.2) and methanol. Positive electrospray ionization MS-MS detection was performed with two multiple reaction monitoring transitions for each of the analytes and the deuterium labeled internal standards. Limit of detection values of buprenorphine, fentanyl and LSD were 0.28, 0.044 and 0.0097 ng/mL and limit of quantification values were 0.94, 0.14 and 0.036 ng/mL, respectively. Most phospholipids were removed during LLE. No or only minor matrix effects were observed. The method has been routinely used at the Norwegian Institute of Public Health since September 2011 for qualitative and quantitative detections of buprenorphine, fentanyl and/or LSD in more than 400 whole blood samples with two replicates per sample.

  15. Complications associated with intravenous midazolam and fentanyl sedation in patients undergoing minor oral surgery

    Science.gov (United States)

    2017-01-01

    Background Anxiety control remains an important concern in dental practice. We evaluated the incidence, nature, and sequelae of complications during and after minor oral surgeries performed under intravenous midazolam and fentanyl sedation using the titration technique. Methods The medical records of patients who had undergone minor oral surgeries under moderate intravenous midazolam and fentanyl sedation at our institution between January 1, 2015 and December 31, 2015 were retrospectively evaluated. Age, sex, body mass index, medical history, American Society of Anesthesiologists (ASA) classification, indications for sedation, amount of sedative used, surgical duration, and recovery time were evaluated for all patients. Results In total, 107 patients aged 9–84 years were included. ASA class I and class II were observed for 56.1% and 43.9% patients, respectively. Complications associated with sedation occurred in 11 (10.2%) patients. There were no serious adverse events. Oxygen saturation reached 95% during the procedure in six patients; this was successfully managed by stimulating the patients to take a deep breath. Two patients exhibited deep sedation and one exhibited paradoxical excitement. After the procedure, one patient experienced nausea without vomiting and one exhibited a prolonged recovery time. The surgical procedures were completed in all patients. Obesity was found to be significantly associated with sedation-related complications. Conclusions Our results suggest that complications associated with intravenous midazolam and fentanyl sedation using the titration technique for minor oral surgeries are mostly minor and can be successfully managed with no prolonged sequelae. PMID:29090250

  16. The effectiveness of patient-controlled epidural analgesia with ropivacaine 0.165% with fentanyl 2.0 miroc g/ml or levobupivacaine 0.125% with fentanyl 2.0 micro g/ml as a method of postoperative analgesia after major orthopaedic surgery.

    Science.gov (United States)

    Misiran, Karis Bin; Yahaya, Lenie Suryani Binti

    2013-02-01

    This prospective randomized single-blinded study was conducted to determine whether there were differences in consumption, demand dosing and postoperative analgesia quality between PCEA using ropivacaine and levobupivacaine. Seventy patients with ASA classification I and II aged 18 to 80 years old scheduled for elective total knee replacement or total hip replacement were studied. All patients received CSE and then were randomly allocated to receive either ropivacaine 0.165% (Group A) or levobupivacaine 0.125% (Group B) both added with fentanyl 2.0 mcro g/ml via epidural route. PCEA regime was offered for 48 hours with additional standard orthopaedic practice of oral analgesia (etoricoxib 120 mg OD and paracetamol 1.0 gm QID) on the second postoperative day. Basal infusion of PCEA was at 3.0 ml/hour and discontinued after 24 hours following started of PCEA. The consumption of local anaesthetics used within the first 24 hours (basal + demand) and 48 hours (total basal + total demand) were recorded. The VAS pain score, sedation score, side effects and vital signs (blood pressure, heart rate and respiratory rate) were also recorded every four hours for 48 hours. This study showed that the total volume of drug used was significantly higher in Group A (163.31+/- 29.01 ml) than Group B (142.69 +/- 30.93ml) (phours after surgery was 251.43 +/- 70.02mg and was significantly greater than the mean dose of Group B (178.91 +/-42.33 mg) (pnumbers of PCEA boluses delivered (D) and PCEA attempts (A) were higher in the Group A (22.37 +/-7.32 and 27.66 +/- 9.12) in contrast to Group B (17.63 +/- 7.71 and 24.40 +/- 11.51) but the differences were not statistically significant. The ratio D/A showed significantly higher in Group A (0.83 +/- 0.13) than Group B (0.74 +/- 0.15) (pstudy showed that both PCEA using ropivacaine 0.165% with fentanyl 2.0 micro g/ml and levobupivacaine 0.125% with fentanyl 2.0 micro g/ml provided effective postoperative analgesia within the first 48 hours of

  17. Response surface model predictions of emergence and response to pain in the recovery room: an evaluation of patients emerging from an isoflurane and fentanyl anesthetic

    Science.gov (United States)

    Syroid, Noah D.; Johnson, Ken B.; Pace, Nathan L.; Westenskow, Dwayne R.; Tyler, Diane; Brühschwein, Frederike; Albert, Robert W.; Roalstad, Shelly; Costy-Bennett, Samuel; Egan, Talmage D.

    2009-01-01

    Introduction Sevoflurane - remifentanil interaction models that predict responsiveness and response to painful stimuli have been evaluated in patients undergoing elective surgery. Preliminary evaluations of model predictions were found to be consistent with observations in patients anesthetized with sevoflurane, remifentanil and fentanyl. The present study explored the feasibility of adapting the predictions of sevoflurane-remifentanil interaction models to an isoflurane-fentanyl anesthetic. We hypothesized that model predictions adapted for isoflurane and fentanyl are consistent with observed patient responses and are similar to the predictions observed in our prior work with sevoflurane-remifentanil/fentanyl anesthetics. Methods Twenty-five patients scheduled for elective surgery received a fentanyl-isoflurane anesthetic. Model predictions of unresponsiveness were recorded at emergence and predictions of a response to noxious stimulus were recorded when patients first required analgesics in the recovery room. Model predictions were compared to observations with graphical and temporal analyses. Results were also compared to our prior predictions following a sevoflurane-remifentanil/fentanyl anesthetic. Results While patients were anesthetized, model predictions indicated a high likelihood that patients would be unresponsive (≥ 99%). Following termination of the anesthetic, model predictions of responsiveness well described the actual fraction of patients observed to be responsive during emergence. Half of the patients awoke within 2 minutes of the 50% model predicted probability of unresponsiveness; 70% awoke within 4 minutes. Similarly, predictions of a response to a noxious stimulus were consistent with the number of patients who required fentanyl in the recovery room. Model predictions following an isoflurane-fentanyl anesthetic were similar to model predictions following a sevoflurane-remifentanil/fentanyl anesthetic. Discussion Results confirmed our study

  18. Pain management following myringotomy and tube placement: intranasal dexmedetomidine versus intranasal fentanyl.

    Science.gov (United States)

    Dewhirst, Elisabeth; Fedel, Gina; Raman, Vidya; Rice, Julie; Barry, N'Diris; Jatana, Kris R; Elmaraghy, Charles; Merz, Meredith; Tobias, Joseph D

    2014-07-01

    Despite the brevity of the procedure, bilateral myringotomy and tympanostomy tube placement (BMT) can result in significant postoperative pain and discomfort. As the procedure is frequently performed without intravenous access, non-parenteral routes of administration are frequently used for analgesia. The current study prospectively compares the efficacy of intranasal (IN) dexmedetomidine with IN fentanyl for children undergoing BMT. This prospective, double-blinded, randomized clinical trial included pediatric patients undergoing BMT. The patients were randomized to receive either IN dexmedetomidine (1 μg/kg) or fentanyl (2 μg/kg) after the induction of general anesthesia with sevoflurane. All patients received rectal acetaminophen (40 mg/kg) and the first 50 patients also received premedication with oral midazolam. Postoperative pain and recovery were assessed using pediatric pain and recovery scales, and any adverse effects were monitored for. The study cohort included 100 patients who ranged in age from 1 to 7.7 years and in weight from 8.6 to 37.4 kg. They were divided into 4 groups with 25 patients in each group: (1) midazolam premedication+IN dexmedetomidine; (2) midazolam premedication+IN fentanyl; (3) no premedication+IN dexmedetomidine; and (4) no premedication+IN fentanyl. Pain scores were comparable when comparing groups 2, 3 and 4, but were higher in group 1 (midazolam premedication with IN dexmedetomidine). There was no difference in total time in the post-anesthesia care unit (PACU) or time from arrival in the PACU until hospital discharge between the 4 groups. The heart rate (HR) was significantly lower in group 3 when compared to the other groups at several different times after arrival to the PACU. No clinically significant difference was noted in blood pressure. Following BMT, when no premedication is administered, there was no clinical advantage when comparing IN dexmedetomidine (1 μg/kg) to IN fentanyl (2 μg/kg). The addition of oral

  19. Metabolic Patterns of Fentanyl, Meperidine, Methylphenidate, Tapentadol and Tramadol Observed in Urine, Serum or Plasma.

    Science.gov (United States)

    Wu, Fang; Slawson, Matthew H; Johnson-Davis, Kamisha L

    2017-05-01

    Drug testing is a useful tool to identify drug use or monitor adherence to prescription drugs. The interpretation of drug results can be complicated based on the pattern and proportional concentrations of drugs and/or drug metabolite(s). The purpose of this retrospective study was to detect the positivity rates and metabolic patterns of five prescription drugs, including fentanyl, meperidine, methylphenidate, tapentadol and tramadol. Retrospective data were retrieved from the laboratory information system in a national reference laboratory. Drug testing was performed using four mass spectrometry methods that were validated for clinical use. For urine specimens, the positivity rate was the highest for methylphenidate (62.3%, n = 2,489), followed by tramadol (43.7%, n = 3,483), fentanyl (41.9%, n = 4,657), tapentadol (37.9%, n = 736) and meperidine (8.3%, n = 138). Among positive samples, both parent drug and metabolite(s) was detectable in 94.9% of meperidine samples, 94.5% of tramadol samples, 93.8% of fentanyl samples, 89.9% of methylphenidate and 86.6% of tapentadol samples. For serum or plasma specimens, the positivity rate was the highest for tapentadol (75.0%, n = 39), followed by methylphenidate (74.2%, n = 569), fentanyl (53.6%, n = 113), meperidine (41.9%, n = 18) and tramadol (28.9%, n = 213). Similar metabolic patterns were found in serum or plasma. Of positive results, both parent drug and metabolite(s) were found in 94.7% of fentanyl samples, 83.3% of meperidine samples, 79.6% of methylphenidate samples, 53.8% of tapentadol samples and 44.1% of tramadol samples. Our data demonstrates the metabolic patterns of five drugs from a random urine or serum/plasma collection in patients that have been prescribed these medications. The data presented can be used to guide clinicians in determining drug adherence by assessing the positivity rates of the parent drug and corresponding metabolite(s). © The Author 2017. Published by Oxford University Press. All rights

  20. Chest tube-delivered bupivacaine improves pain and decreases opioid use after thoracoscopy.

    Science.gov (United States)

    Demmy, Todd L; Nwogu, Chukwumere; Solan, Patrick; Yendamuri, Saikrishna; Wilding, Gregory; DeLeon, Oscar

    2009-04-01

    This study compared a simplified method of intrapleural bupivacaine administration with traditional analgesic therapy to decrease postoperative pain and opioid usage in patients after thoracoscopy. Thirty patients who had non-rib-spreading thoracoscopic operations under general anesthesia were prospectively randomized to no local anesthetic infusion (control), intermittent bolus (30 mL every 6 hours), or continuous infusion (5 mL/h). Bupivacaine (0.25%) was delivered through the pleural infusion channel of a specially designed single silicone 28F chest tube. Total intravenous fentanyl patient-controlled analgesia (boluses with basal rate) infused in the first 24 hours postoperatively was the designated primary study end point. Escalations of analgesic therapy, including ketorolac administration, were standardized across all groups. Nurses assessed pain control at onset and every 6 hours by visual analog pain scales (VAPS, 100 mm). VAPS were repeated 10 minutes later to assess any opioid or bupivacaine bolus effects. No study-related adverse events occurred. Compared with controls, pooled VAPS scores and 24-hour fentanyl consumption were significantly lower for the intermittent and continuous administration groups (1753 vs 1180 vs 1177 microg/24 h, respective median; p = 0.04) Early (6-hour) VAPS analgesic responses were more certain for intermittent (10 of 10) and continuous (10 of 10) patients than controls (7 of 10, p = .04). Five continuous patients successfully maintained VAPS scores below 20 mm throughout the study vs 3 intermittent and 2 controls (p = .045). Intermittent or continuous intrapleural bupivacaine infused through the chest tube reliably reduces postoperative pain and 24-hour opioid usage in thoracoscopy patients.

  1. Changes of lidocaine concentration and physiological indices in dogs during anaesthesia with lidocaine and isoflurane combined with ketamine or fentanyl

    Directory of Open Access Journals (Sweden)

    Shi-Xia Zhang

    2016-01-01

    Full Text Available Fentanyl and ketamine are often used as adjuvants in intravenous anaesthesia to prolong analgesia. The aim of this study was to compare changes of the basic physiological variables of intravenous lidocaine administration in combination with ketamine or fentanyl, and to evaluate the impact of addition of fentanyl or ketamine to lidocaine on serum lidocaine concentrations in dogs after intravenous administration. During general anaesthesia, dogs of group L received 2% lidocaine intravenously, dogs of group LF received 2% lidocaine and fentanyl, and dogs of the group LK received 2% lidocaine and ketamine. The heart rate, systolic arterial pressure, diastolic arterial pressure, mean arterial pressure and rectal temperature decreased in all groups, and group LF showed the biggest effect on the basic physiological variables, with the lowest heart rate during the test, significantly decreased rectal temperature, and the most decreased values of arterial pressure. Blood for determination of serum lidocaine concentration was taken before anaesthesia and 5, 30, 60, 90, 120, 150 and 180 min after initial intravenous injection of drugs. Fentanyl and ketamine did not cause significant changes of serum lidocaine concentration in dogs and may be used as adjuvant in intravenous anaesthesia without a significant increase in lidocaine absorption.

  2. Perioperative analgesia after intrathecal fentanyl and morphine or morphine alone for cesarean section: A randomized controlled study.

    Science.gov (United States)

    Weigl, Wojciech; Bieryło, Andrzej; Wielgus, Monika; Krzemień-Wiczyńska, Świetlana; Kołacz, Marcin; Dąbrowski, Michał J

    2017-12-01

    Intrathecal morphine is used in the postoperative management of pain after caesarean section (CS), but might not be optimal for intraoperative analgesia. We hypothesized that intrathecal fentanyl could supplement intraoperative analgesia when added to a local anesthetic and morphine without affecting management of postoperative pain. This prospective, randomized, double-blind, parallel-group study included 60 parturients scheduled for elective CS. Spinal anesthesia consisted of bupivacaine with either morphine 100 μg (M group), or fentanyl 25 μg and morphine 100 μg (FM group). The frequency of intraoperative pain and pethidine consumption in the 24 hours postoperatively was recorded. Fewer patients in the FM group required additional intraoperative analgesia (P fentanyl and morphine may provide better perioperative analgesia than morphine alone in CS and could be useful when the time from anesthesia to skin incision is short. However, an increase in PONV and possible acute spinal opioid tolerance after addition of intrathecal fentanyl warrants further investigation using lower doses of fentanyl.

  3. A randomized, open, parallel group, multicenter trial to investigate analgesic efficacy and safety of a new transdermal fentanyl patch compared to standard opioid treatment in cancer pain

    DEFF Research Database (Denmark)

    Kress, H.G.; Laage, D. Von der; Hoerauf, K.H.

    2008-01-01

    to be pharmacokinetically bioequivalent to the marked fentanyl patch. To determine noninferiority in efficacy in cancer patients and to compare safety, a clinical trial comparing the new fentanyl patch with standard oral or transdermal opioid treatment was planned. The design was an open, parallel group, multicenter trial...

  4. Exposure to time varying magnetic fields associated with magnetic resonance imaging reduces fentanyl-induced analgesia in mice

    Energy Technology Data Exchange (ETDEWEB)

    Teskey, G.C.; Prato, F.S.; Ossenkopp, K.P.; Kavaliers, M.

    1988-01-01

    The effects of exposure to clinical magnetic resonance imaging (MRI) on analgesia induced by the mu opiate agonist, fentanyl, was examined in mice. During the dark period, adult male mice were exposed for 23.2 min to the time-varying (0.6 T/sec) magnetic field (TVMF) component of the MRI procedure. Following this exposure, the analgesic potency of fentanyl citrate (0.1 mg/kg) was determined at 5, 10, 15, and 30 min post-injection, using a thermal test stimulus (hot-plate 50 degrees C). Exposure to the magnetic-field gradients attenuated the fentanyl-induced analgesia in a manner comparable to that previously observed with morphine. These results indicate that the time-varying magnetic fields associated with MRI have significant inhibitory effects on the analgesic effects of specific mu-opiate-directed ligands.

  5. Danish pain specialists' rationales behind the choice of fentanyl transdermal patches and oral transmucosal systems-A Delphi study

    DEFF Research Database (Denmark)

    Jacobsen, Ramune; Møldrup, Claus; Christrup, Lona

    2009-01-01

    ' need for the alternative to oral, intravenous or subcutaneous rescue medication, followed by patients' wish and ability to administer pain medication independently. The main reasons for not choosing OTFC were price and the argument that OTFC administration requires much energy and healthy patients...... not allow them to take analgesia orally, while the main explanations for not choosing a fentanyl patch was a specific chronic pain condition such as nonmalignant or neuropathic pain origin, and price. The foremost rationale behind the choice of oral transmucosal fentanyl citrate (OTFC) were cancer patients......ABSTRACT Objective. The aim of this study was to describe the rationale behind the choice of fentanyl administration forms among Danish pain specialists. Methods. Sixty Danish physicians specializing in pain management were contacted via an Internet survey system to perform a two-phase Delphi...

  6. Follow-up at the corrected age of 24 months of preterm newborns receiving continuous infusion of fentanyl for pain control during mechanical ventilation.

    Science.gov (United States)

    Ancora, Gina; Lago, Paola; Garetti, Elisabetta; Pirelli, Anna; Merazzi, Daniele; Pierantoni, Luca; Ferrari, Fabrizio; Faldella, Giacomo

    2017-05-01

    The neurodevelopmental impact of fentanyl given to preterm newborns for pain control is still unknown. The aim of this study was to assess the neurodevelopmental impact of 2 regimens of fentanyl administration by a prospective follow-up evaluation. In our previous multicenter, double-blind, randomized controlled trial, 131 mechanically ventilated newborns (gestational age ≤32 weeks) were randomized to fentanyl (continuous infusion of fentanyl + open label boluses of fentanyl) or placebo (continuous infusion of placebo + open label boluses of fentanyl). Infant development was evaluated using Griffiths Mental Developmental Scales (Griffiths, 1996) until 24 months of corrected age by trained psychologists who were not aware of the group allocation. 106/131 infants survived at discharge; 3 died after discharge, 25 were lost to follow-up (12 in the fentanyl and 13 in the placebo group). Seventy-eight patients were evaluated at 2 years of corrected age. Children in the fentanyl group, compared with those in the placebo group, obtained significantly lower Griffiths general developmental quotient (mean [SD]: 89.95 [13.64] vs 97.18 [12.72], P = 0.024) together with the scores on the eye-hand coordination (mean [SD]: 89.09 [12.13] vs 99.19 [13.19], P = 0.002) and performance skills (mean [SD]: 79.71 [15.80] vs 90.09 [15.28], P = 0.009) scales. After adjustment for clinical confounders (gestational age, CRIB score, and sex) only eye-hand co-ordination was associated with fentanyl infusion. This study demonstrates that continuous infusion of fentanyl in very preterm infants, given at 1 mcg·kg·h during mechanical ventilation, is associated with a significant decrease in eye and hand co-ordination skills. Longer follow-up is needed to evaluate the impact on future motor, cognitive, and behavioral functions.

  7. Fentanyl Suppresses the Survival of CD4+ T Cells Isolated from Human Umbilical Cord Blood through Inhibition of IKKs-mediated NF-κB Activation.

    Science.gov (United States)

    Ma, K; Ma, P; Lu, H; Liu, S; Cao, Q

    2017-05-01

    The aim of this study was to investigate the effects and the underlying mechanisms of fentanyl anaesthetic on T lymphocytes isolated from human umbilical cord blood in vitro. The percentages of CD4+ , CD8+ and regulatory T (Treg) cells in human umbilical cord blood mononuclear cells (UBMC) treated with fentanyl in vitro were analysed by flow cytometry. The levels of cytokines IFN-γ, IL-2, IL-4 and IL-17 secreted by activated CD4+ T cells were measured by ELISA assays. Expressions of MAPK and NF-κB signalling pathway proteins were determined by Western blotting. Effects of fentanyl on IKK and p65 expression promoter activities were analysed by luciferase assay. Fentanyl decreased the percentages and amounts of CD4+ , CD8+ and Foxp3+ Treg T lymphocyte subsets in UBMCs in a dose-dependent manner. Fentanyl inhibited the proliferation and induced apoptosis of activated CD4+ T cells dose dependently. Fentanyl could not reverse the increase of cell proliferation in activated groups to be equivalent with those in inactivated group. Secretions of IFN-γ, IL-2 and IL-4 cytokines were significantly decreased by moderate to high dose of fentanyl compared with controls. No significant differences were observed in protein expressions of MAPK pathway. In addition, fentanyl suppressed the IKKs-mediated activation of NF-κB. This study demonstrates that fentanyl exerts immunosuppressive effects on T lymphocytes obtained from UBMCs. Thus, the clinical application of fentanyl would not only relieve pain caused by surgery but regulate immune responses post-operation possibly through inhibition of IKKs-mediated NF-κB activation. © 2017 The Foundation for the Scandinavian Journal of Immunology.

  8. Low-dose bupivacaine spinal anaesthesia for percutaneous nephrolithotomy: the suitability and impact of adding intrathecal fentanyl.

    Science.gov (United States)

    Atallah, M M; Shorrab, A A; Abdel Mageed, Y M; Demian, A D

    2006-08-01

    Unilateral spinal anaesthesia has been used for lower limb surgery with a stable cardiovascular state and a short recovery unit stay. We sought to test the suitability of low-dose bupivacaine spinal anaesthesia for percutaneous nephrolithotomy, a procedure hitherto performed under general anaesthesia. Furthermore, we hypothesized that adding intrathecal fentanyl to bupivacaine may improve the quality of anaesthesia. We randomly allocated, through computer-generated randomization, 108 patients subjected to percutaneous nephrolithotomy to receive either 7.5 mg of hyperbaric bupivacaine 5 mg/ml alone or with the addition of 10 microg of fentanyl. Drugs were given at the L(2)-L(3) interspace with the patient in the lateral decubitus position. The patients remained in this position for 10 min, after which the sensory and motor blocks were assessed. Intra-operative analgesic supplementation, when deemed necessary, was achieved with intravenous fentanyl boluses (25 microg). The sensory and motor blocks after intrathecal bupivacaine and bupivacaine-fentanyl were similar. Sensory block, in both groups, reached the fifth and eighth thoracic dermatomes on the operative and non-operative sides, respectively. Deep motor block occurred on the operative side in all patients and in nearly 50% of patients on the non-operative side. The patients in the bupivacaine-fentanyl group required less intra-operative and post-operative analgesics, and both patients and endoscopists were better satisfied. This study demonstrated, for the first time, that intrathecal low-dose bupivacaine and fentanyl offers a reliable neuraxial block for patients subjected to percutaneous nephrolithotomy, with stable haemodynamics, good post-operative analgesia and acceptable patient and endoscopist satisfaction.

  9. Fentanyl and a Novel Synthetic Opioid U-47700 Masquerading as Street "Norco" in Central California: A Case Report.

    Science.gov (United States)

    Armenian, Patil; Olson, Alexander; Anaya, Andres; Kurtz, Alicia; Ruegner, Rawnica; Gerona, Roy R

    2017-01-01

    In 2013 and 2014, more than 700 deaths were attributed to fentanyl and fentanyl analogues in the United States. Of recent concern is the cluster of unintentional fentanyl overdoses because of tablets thought to be "Norco" purchased on the street in Northern California. U-47700 (trans-3,4-dichloro-N-[2-(dimethyl-amino)cyclohexyl]-N-methylbenz-amide) is a nonfentanyl-based synthetic opioid with 7.5 times the binding affinity of morphine to μ-opioid. We report a case of fentanyl and U-47700 intoxication from what was thought to be illicitly purchased Norco. A 41-year-old woman presented to the emergency department (ED) for altered mental status shortly after ingesting 3 beige Norco pills bearing a Watson imprint. She had pinpoint pupils and respiratory depression, which reversed after 0.4 mg naloxone administration intravenously. She had complete recovery and was discharged from the ED after a 4-hour observation period. Serum testing with liquid chromatography-quadrupole time-of-flight mass spectrometry (LC 1260 QTOF/MS 6550; Agilent, Santa Clara, CA) confirmed the presence of the medications the patient reported receiving, and additionally fentanyl (15.2 ng/mL) and U-47700 (7.6 ng/mL). In this case report, street Norco purchased in Central California resulted in altered mental status requiring naloxone reversal because of fentanyl and the novel synthetic opioid U-47700. Because these compounds are not detected by routine urine drug testing and physical examination findings are similar to those of a traditional opioid toxidrome, emergency providers should use the patient's history and other circumstantial details to aid in diagnosis. In cases with suspicion of opioid or opioid analogue cause, we recommend that emergency providers contact their local poison control center, medical toxicologist, or public health department to aid in the investigation. Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

  10. Syndrome surveillance of fentanyl-laced heroin outbreaks: Utilization of EMS, Medical Examiner and Poison Center databases.

    Science.gov (United States)

    Moore, P Quincy; Weber, Joseph; Cina, Steven; Aks, Steven

    2017-11-01

    Describe surveillance data from three existing surveillance systems during an unexpected fentanyl outbreak in a large metropolitan area. We performed a retrospective analysis of three data sets: Chicago Fire Department EMS, Cook County Medical Examiner, and Illinois Poison Center. Each included data from January 1, 2015 through December 31, 2015. EMS data included all EMS responses in Chicago, Illinois, for suspected opioid overdose in which naloxone was administered and EMS personnel documented other criteria indicative of opioid overdose. Medical Examiner data included all deaths in Cook County, Illinois, related to heroin, fentanyl or both. Illinois Poison Center data included all calls in Chicago, Illinois, related to fentanyl, heroin, and other prescription opioids. Descriptive statistics using Microsoft Excel® were used to analyze the data and create figures. We identified a spike in opioid-related EMS responses during an 11-day period from September 30-October 10, 2015. Medical Examiner data showed an increase in both fentanyl and mixed fentanyl/heroin related deaths during the months of September and October, 2015 (375% and 550% above the median, respectively.) Illinois Poison Center data showed no significant increase in heroin, fentanyl, or other opioid-related calls during September and October 2015. Our data suggests that EMS data is an effective real-time surveillance mechanism for changes in the rate of opioid overdoses. Medical Examiner's data was found to be valuable for confirmation of EMS surveillance data and identification of specific intoxicants. Poison Center data did not correlate with EMS or Medical Examiner data. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Comparison of Postoperative Analgesic Effects of Thoracic Epidural Morphine and Fentanyl

    Directory of Open Access Journals (Sweden)

    Gönül Sağıroğlu

    2011-11-01

    Full Text Available Objective: In our study, we aimed to compare epidural morphine and fentanyl analgesia and the side effects in post-thoracotomy pain management. Material and Methods: Forty patients, planned for elective thoracotomy were included. Bupivacain- morphine was administered through an epidural catheter to the patients in Group-M while bupivacain-fentanyl was given in Group-F. Pain assessment was carried out with the Visual Analogue Scale (VAS and VAS-I and VAS-II were assessed in 0, 4, 16 and 24th hour in the postoperative unit. Adverse effects were recorded after the 24th hour. Statistical analyses were performed by using Two-sample independent-t test, Mann Whitney-U test, Wilcoxon-signed ranks test and Pearson chi-squared tests. Results: Although, the VAS-I and VAS-II scores were lower in Group-M than Group-F, the difference was not significant statistically (p>0.05. When other hours were compared with initial states, beginning from the 4th hour, in both groups there was a statistically significant drop in VAS-I and VAS-II scores at all times (p<0.001. Comparing the complications between the groups, in Group-M nausea-vomiting (p<0.015 and bradycardia (p<0.012 were found significantly more frequently than in Group-F. Conclusion: We concluded that, in pain management after thoracic surgery, either morphine or fentanyl may be chosen in thoracal epidural analgesia but, especially in the early postoperative hours, close follow-up is necessary due to the risk of bradycardia development.

  12. Safety and pharmacokinetics of oral cannabidiol when administered concomitantly with intravenous fentanyl in humans.

    Science.gov (United States)

    Manini, Alex F; Yiannoulos, Georgia; Bergamaschi, Mateus M; Hernandez, Stephanie; Olmedo, Ruben; Barnes, Allan J; Winkel, Gary; Sinha, Rajita; Jutras-Aswad, Didier; Huestis, Marilyn A; Hurd, Yasmin L

    2015-01-01

    Cannabidiol (CBD) is hypothesized as a potential treatment for opioid addiction, with safety studies an important first step for medication development. We determined CBD safety and pharmacokinetics when administered concomitantly with a high-potency opioid in healthy subjects. This double-blind, placebo-controlled cross-over study of CBD, coadministered with intravenous fentanyl, was conducted at the Clinical Research Center in Mount Sinai Hospital, a tertiary care medical center in New York City. Participants were healthy volunteers aged 21 to 65 years with prior opioid exposure, regardless of the route. Blood samples were obtained before and after 400 or 800 mg of CBD pretreatment, followed by a single 0.5 (session 1) or 1.0 μg/kg (session 2) of intravenous fentanyl dose. The primary outcome was the Systematic Assessment for Treatment Emergent Events (SAFTEE) to assess safety and adverse effects. CBD peak plasma concentrations, time to reach peak plasma concentrations (tmax), and area under the curve (AUC) were measured. SAFTEE data were similar between groups without respiratory depression or cardiovascular complications during any test session. After low-dose CBD, tmax occurred at 3 and 1.5 hours in sessions 1 and 2, respectively. After high-dose CBD, tmax occurred at 3 and 4 hours in sessions 1 and 2, respectively. There were no significant differences in plasma CBD or cortisol (AUC P = NS) between sessions. Cannabidiol does not exacerbate adverse effects associated with intravenous fentanyl administration. Coadministration of CBD and opioids was safe and well tolerated. These data provide the foundation for future studies examining CBD as a potential treatment for opioid abuse.

  13. Effect of nitrous oxide on fentanyl consumption in burned patients undergoing dressing change.

    Science.gov (United States)

    do Vale, Arthur Halley Barbosa; Videira, Rogério Luiz da Rocha; Gomez, David Souza; Carmona, Maria José Carvalho; Tsuchie, Sara Yume; Flório, Cláudia; Vane, Matheus Fachini; Posso, Irimar de Paula

    2016-01-01

    Thermal injuries and injured areas management are important causes of pain in burned patients, requiring that these patients are constantly undergoing general anesthesia for dressing change. Nitrous oxide (N2O) has analgesic and sedative properties; it is easy to use and widely available. Thus, the aim of this study was to evaluate the analgesic effect of N2O combined with fentanyl in burned patients during dressing change. After approval by the institutional Ethics Committee, 15 adult burned patients requiring daily dressing change were evaluated. Patient analgesia was controlled with fentanyl 0.0005% administered by intravenous pump infusion on-demand. Randomly, in one of the days a mixture of 65% N2O in oxygen (O2) was associated via mask, with a flow of 10 L/min (N2O group) and on the other day only O2 under the same flow (control group). No significant pain reduction was seen in N2O group compared to control group. VAS score before dressing change was 4.07 and 3.4, respectively, in N2O and control groups. Regarding pain at the end of the dressing, patients in N2O group reported pain severity of 2.8; while the control group reported 2.87. There was no significant difference in fentanyl consumption in both groups. The association of N2O was not effective in reducing opioid consumption during dressing changes. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  14. COMPARISON OF DEXMEDETOMIDINE, BUPRENORPHINE AND FENTANYL AS AN ADJUVANT TO BUPIVACAINE DURING SPINAL ANAESTHESIA FOR HEMIARTHROPLASTY

    Directory of Open Access Journals (Sweden)

    Pradeep R

    2016-10-01

    Full Text Available BACKGROUND Opioids such as fentanyl or buprenorphine are being added as adjuvant to local anaesthetic for spinal anaesthesia. Dexmedetomidine, a new α2 agonist is being tried as an adjuvant in the recent times. MATERIALS AND METHODS The patients were randomised into three Groups (n=30 each by closed envelope technique. Patients in Group 1 received 10 µg fentanyl with 15 mg of 0.5% hyperbaric bupivacaine, Group 2 received 15 mg of 0.5% hyperbaric bupivacaine supplemented with 30 µg of buprenorphine and Group 3 received 15 mg of 0.5% hyperbaric bupivacaine plus 5 µg dexmedetomidine intrathecally. The time to reach maximum sensory and motor level, the regression time of the same, any adverse effects were recorded. Data were analysed using chi-square test or Fisher’s exact test for categorical data and analysis of variance for continuous data. A value of P<0.05 was accepted as statistically significant. Settings and Design- The study was conducted in a prospective, randomised and double-blind manner. It included ninety American Society of Anaesthesiologists class I and II patients undergoing hemiarthroplasty under spinal anaesthesia. RESULTS In this study, the patients in dexmedetomidine group showed significantly longer duration of motor block (240±20 mins. and sensory blockade (180±22.2 mins. compared to other groups, which is statistically significant (P=0.0001 and P=0.006, respectively. The time to first request of analgesic postoperatively was also longer (260±30.2 in dexmedetomidine group when compared with other groups (P=0.0001. Haemodynamic parameters were stable and there were no complications in any group. CONCLUSIONS We concluded that intrathecal dexmedetomidine (5 µg with bupivacaine provides significantly longer duration of sensory and motor blockade and longer duration for first request of analgesia in the recovery than intrathecal buprenorphine (30 µg or fentanyl (10 µg with bupivacaine for spinal anaesthesia for

  15. Fentanyl Enhances Hepatotoxicity of Paclitaxel via Inhibition of CYP3A4 and ABCB1 Transport Activity in Mice.

    Directory of Open Access Journals (Sweden)

    Jing-Dun Xie

    Full Text Available Fentanyl, a potent opioid analgesic that is used to treat cancer pain, is commonly administered with paclitaxel in advanced tumors. However, the effect of fentanyl on the hepatotoxicity of paclitaxel and its potential mechanism of action is not well studied. The purpose of this study was to investigate the effect of fentanyl on the hepatotoxicity of paclitaxel and its potential mechanisms of action. Pharmacokinetic parameters of paclitaxel were tested using reversed phase high-performance liquid chromatography (RP-HPLC. Aspartate transaminase (AST, alanine aminotransferase (ALT, and mouse liver histopathology were examined. Moreover, the cytotoxicity of anti-carcinogens was examined using 1-(4, 5-dimethylthiazol-2-yl-3,5-diphenylformazan (MTT, and the intracellular accumulation of doxorubicin and rhodamine 123 was detected by flow cytometry. Furthermore, the expression of ABCB1 and the activity of ABCB1 ATPase and CYP3A4 were also examined. In this study, the co-administration of fentanyl and paclitaxel prolonged the half-life (t1/2 of paclitaxel from 1.455 hours to 2.344 hours and decreased the clearance (CL from 10.997 ml/h to 7.014 ml/h in mice. Fentanyl significantly increased the levels of ALT in mice to 88.2 U/L, which is more than 2-fold higher than the level detected in the control group, and it increased the histological damage in mouse livers. Furthermore, fentanyl enhanced the cytotoxicity of anti-carcinogens that are ABCB1 substrates and increased the accumulation of doxorubicin and rhodamine 123. Additionally, fentanyl stimulated ABCB1 ATPase activity and inhibited CYP3A4 activity in the liver microsomes of mice. Our study indicates that the obvious hepatotoxicity during this co-administration was due to the inhibition of CYP3A4 activity and ABCB1 transport activity. These findings suggested that the accumulation-induced hepatotoxicity of paclitaxel when it is combined with fentanyl should be avoided.

  16. Comparative study between dexmedetomidine and fentanyl for sedation during mechanical ventilation in post-operative paediatric cardiac surgical patients

    OpenAIRE

    S R Prasad; Parimala Prasanna Simha; A M Jagadeesh

    2012-01-01

    Aims and Objectives: To compare the efficacy of sedation and time taken for extubation using dexmedetomidine and fentanyl sedation in post-operative paediatric cardiac surgical patients. Methods: A prospective randomized double-blind study involving 60 children undergoing open heart surgery was conducted. The patients were divided into two groups, each involving 30 patients. One group received fentanyl at 1 μg/kg/h (Group A) and the other received dexmedetomidine at 0.5 μg/kg/h (Group B) for ...

  17. Fentanyl Enhances Hepatotoxicity of Paclitaxel via Inhibition of CYP3A4 and ABCB1 Transport Activity in Mice

    Science.gov (United States)

    Pan, Jia-Hao; Bi, Bing-Tian; Feng, Kun-Yao; Huang, Wan; Zeng, Wei-An

    2015-01-01

    Fentanyl, a potent opioid analgesic that is used to treat cancer pain, is commonly administered with paclitaxel in advanced tumors. However, the effect of fentanyl on the hepatotoxicity of paclitaxel and its potential mechanism of action is not well studied. The purpose of this study was to investigate the effect of fentanyl on the hepatotoxicity of paclitaxel and its potential mechanisms of action. Pharmacokinetic parameters of paclitaxel were tested using reversed phase high-performance liquid chromatography (RP-HPLC). Aspartate transaminase (AST), alanine aminotransferase (ALT), and mouse liver histopathology were examined. Moreover, the cytotoxicity of anti-carcinogens was examined using 1-(4, 5-dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT), and the intracellular accumulation of doxorubicin and rhodamine 123 was detected by flow cytometry. Furthermore, the expression of ABCB1 and the activity of ABCB1 ATPase and CYP3A4 were also examined. In this study, the co-administration of fentanyl and paclitaxel prolonged the half-life (t1/2) of paclitaxel from 1.455 hours to 2.344 hours and decreased the clearance (CL) from 10.997 ml/h to 7.014 ml/h in mice. Fentanyl significantly increased the levels of ALT in mice to 88.2 U/L, which is more than 2-fold higher than the level detected in the control group, and it increased the histological damage in mouse livers. Furthermore, fentanyl enhanced the cytotoxicity of anti-carcinogens that are ABCB1 substrates and increased the accumulation of doxorubicin and rhodamine 123. Additionally, fentanyl stimulated ABCB1 ATPase activity and inhibited CYP3A4 activity in the liver microsomes of mice. Our study indicates that the obvious hepatotoxicity during this co-administration was due to the inhibition of CYP3A4 activity and ABCB1 transport activity. These findings suggested that the accumulation-induced hepatotoxicity of paclitaxel when it is combined with fentanyl should be avoided. PMID:26633878

  18. Comparison of Effect of Intrathecal Sufentanil-Bupivacaine and Fentanyl-Bupivacaine Combination on Postoperative Analgesia

    Directory of Open Access Journals (Sweden)

    Ishwar Singh

    2008-01-01

    Full Text Available Fifty ASA grade I/II patients scheduled for elective lower abdominal, lower limb and urological procedures were divided into two groups of 25 each .The first group (Group S received 2.5 ml of heavy bupivacaine with 0.2. ml sufentanil made up to 3 ml with saline. The second group (Group F received 2.5 ml of heavy bupivacaine with 0.5 ml of fentanyl. From our study it can be concluded that bupivacaine sufentanil combination although had shorter onset of action, but had more side effects especially nausea, vomiting and headache. The time for rescue analgesia in both groups was however similar.

  19. Intrathecal Fentanyl Lidocaine combination for cesarean section: a randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Raji B

    2007-09-01

    Full Text Available Background: Spinal anesthesia can be associated with hemodynamic changes and some other complications. The aim of this study was to evaluate the effect of adding fentanyl to lidocaine on the spinal anesthesia time and its complications for cesarean section.Methods: Sixty pregnant women with gestational age of 37- 42 weeks and ASA physical status I and II undergoing elective cesarean section under spinal anesthesia were enrolled in a randomized double blinded clinical trial. They were randomly allocated to receive spinal anesthesia with lidocaine-normal saline (LS: 75 mg lidocaine 5% with 0.3 ml normal saline lidocaine-fentanyl (LF group (75 mg lidocaine 5% with 50 μg fentanyl. The duration of initiation of sensory block to achieve T4 level, time to return of sensory level to T12, time to first analgesic request, ephedrine requirement, nausea and vomiting during and after the surgery, pruritus, respirator depression, headache and apgar score of the new born  at 1st and 5th minutes were assessed. Results: There was no significant difference between time to achieve T4 level, ephedrine dose, post operative nausea and vomiting (PONV, pruritus and headache in study groups. Time to return of sensory level to T12 was significantly longer in LF group (152.6±14.7 vs. 66.2±11.2 min, P=0.0009. Time to first analgesic request was also longer in LF group (164.2±20.8 vs. 68.1±11.3 min, P=0.0009. The incidence of nausea and vomiting during surgery was significantly more in LF group (20% vs. 0%, P=0.023. No case of respiratory depression was observed in groups. The 1st and 5th minute's apgar score were comparable between groups and were between 7 and 10.Conclusions: Addition of fentanyl to intrathecal lidocaine in patients undergoing elective cesarean section results in increasing of the block duration and time to first analgesic request without significant maternal or neonatal side-effects, without effect on 1st and 5th minutes apgar score

  20. Behavioral effects and receptor binding affinities of fentanyl derivatives in rhesus monkeys.

    Science.gov (United States)

    France, C P; Gerak, L R; Flynn, D; Winger, G D; Medzihradsky, F; Bagley, J R; Brockunier, L L; Woods, J H

    1995-07-01

    These studies examined the opioid receptor binding affinities and behavioral effects of several fentanyl derivatives in rhesus monkeys. OHM3295, OHM3296, OHM3326 and OHM3463 displayed high affinity for mu (IC50 = 7-66 nM) as compared to kappa (IC50 = 263-3255 nM) or delta (IC50 = 480-4500 nM) receptors as measured by their ability to displace [3H](D-Ala2-Me-Phe4,Glyol5)enkephalin, [3H](5,7,8[beta])-N-[2- (1-pyrrolidinyl)1-oxaspiro[4,5]dec-8-yl]benzeneacetamide and [3H](D-Pen2-D-Pen5)enkephalin, respectively. All four compounds maintained i.v. self-administration responding at rates above those maintained by the mu agonist alfentanil. In drug discrimination studies, OHM3463, OHM3326 and OHM3296 substituted completely for nalbuphine whereas OHM3295, and a related compound, mirfentanil, substituted partially for nalbuphine. In morphine-treated monkeys, OHM3295 substituted for naltrexone; in monkeys acutely deprived of morphine, only OHM3463 reversed naltrexone-lever responding. All four compounds had antinociceptive effects, although the extent to which these effects were accompanied by respiratory depression or modified by naltrexone, as well as the interactions between antinociceptive effects of fentanyl derivatives and alfentanil, varied markedly among compounds. Thus, OHM3463 shared effects with mu agonists (e.g., alfentanil) under all conditions; the other three compounds had opioid agonist effects under only a subset of conditions. Moreover, one of these compounds (OHM3295) antagonized the discriminative stimulus and antinociceptive effects of other mu agonists. Collectively, these compounds appear to vary on two dimensions: opioid efficacy and the contribution of nonopioid actions to their antinociceptive effects. Together with results obtained with other fentanyl derivatives (mirfentanil) under similar conditions, results of the current study suggest this chemical class might be especially fertile for the development of novel analgesics that might have reduced

  1. Use of intranasal fentanyl for the relief of pediatric orthopedic trauma pain.

    Science.gov (United States)

    Saunders, Mary; Adelgais, Kathleen; Nelson, Douglas

    2010-11-01

    The objective was to evaluate the use of a single 2 μg/kg dose of intranasal fentanyl as analgesia for painful orthopedic injuries in children presenting to a pediatric emergency department (ED). This was a prospective, nonblinded interventional trial, in a convenience sample of patients 3 to 18 years of age seen in a tertiary care pediatric ED. All had clinically suspected fractures and were treated between July and November 2006. Eligible patients had moderate to severe pain based on initial pain scores using the Wong Baker Faces Scale (WBS) for patients aged 3-8 years or the Visual Analog Scale (VAS) for patients aged 9-18 years. All enrolled patients received fentanyl via intranasal atomization. Pain scores were obtained at baseline and at 10, 20, and 30 minutes after intranasal fentanyl administration. Satisfaction scores were obtained using a 100-mm VAS. Vital signs and adverse events were recorded. Eighty-one patients were enrolled, 28 in the VAS group and 53 in the WBS group. The mean patient age was 8 years. Fracture locations included forearm, 38 (47%); supracondylar, 16 (20%); clavicle, 7 (9%); tibia/fibula, 5 (6%); and other, 15 (18%). In the WBS group, the median pain scores decreased from five faces (interquartile range [IQR] = 4-6) at baseline to three faces (IQR = 2-5) at 10 minutes, two faces (IQR = 1-4) at 20 minutes, and two faces (IQR = 1-3) at 30 minutes. The mean pain score in the VAS group at baseline was 70 mm (95% confidence interval [CI] = 63 to 77 mm). In this group, the pain scores decreased by a mean of 21 mm (95% CI = 14 to 28 mm) at 10 minutes, 25 mm (95% CI = 15 to 34 mm) at 20 minutes, and 27 mm (95% CI = 16 to 37 mm) at 30 minutes. Mean satisfaction scores were 79 mm for providers, 74 mm for parents, and 62 mm for patients. No adverse events were recorded.   Intranasal fentanyl at a dose of 2 μg/kg provides effective analgesia for pediatric ED patients with painful orthopedic trauma within 10 minutes of administration. © 2010

  2. Intrathecal fentanyl abolishes the exaggerated blood pressure response to cycling in hypertensive men

    Science.gov (United States)

    Barbosa, Thales C.; Vianna, Lauro C.; Fernandes, Igor A.; Prodel, Eliza; Rocha, Helena N. M.; Garcia, Vinicius P.; Rocha, Natalia G.; Secher, Niels H.

    2016-01-01

    Key points The increase in blood pressure observed during physical activities is exaggerated in patients with hypertension, exposing them to a higher cardiovascular risk.Neural signals from the skeletal muscles appear to be overactive, resulting in this abnormal response in hypertensive patients.In the present study, we tested whether the attenuation of these neural signals in hypertensive patients could normalize their abnormal increase in blood pressure during physical activity.Attenuation of the neural signals from the leg muscles with intrathecal fentanyl injection reduced the blood pressure of hypertensive men during cycling exercise to a level comparable to that of normotensive men.Skeletal muscle afferent overactivity causes the abnormal cardiovascular response to exercise and was reverted in this experimental model, appearing as potential target for treatment. Abstract Hypertensive patients present an exaggerated increase in blood pressure and an elevated cardiovascular risk during exercise. Although controversial, human studies suggest that group III and IV skeletal muscle afferents might contribute to this abnormal response. In the present study, we investigated whether attenuation of the group III and IV muscle afferent signal of hypertensive men eliminates the exaggerated increase in blood pressure occurring during exercise. Eight hypertensive men performed two sessions of 5 min of cycling exercise at 40 W. Between sessions, the subjects were provided with a lumbar intrathecal injection of fentanyl, a μ‐opioid receptor agonist, aiming to attenuate the central projection of opioid‐sensitive group III and IV muscle afferent nerves. The cardiovascular response to exercise of these subjects was compared with that of six normotensive men. During cycling, the hypertensive group demonstrated an exaggerated increase in blood pressure compared to the normotensive group (mean ± SEM: +17 ± 3 vs. +8 ± 1 mmHg, respectively; P  0.05). Fentanyl

  3. The synthesis and pharmacological evaluation of (±-2,3-seco-fentanyl analogues

    Directory of Open Access Journals (Sweden)

    LJ. DOSEN-MICOVIC

    2004-11-01

    Full Text Available An efficient, five-step synthetic approach to various acyclic 1,3-diamines has been developed and applied to the preparation of a novel class of open-chained fentanyl analogues. The acyclic derivatives 5.1–5.5 (all new compounds were synthesized with the aim of estimating the significance of the piperidine ring for the opioid analgesic activity of anilido-piperidines. The starting b-keto-amide 1.1, prepared by the aminolysis of methyl acetoacetate with methylphenethylamine, (93 % yield, was successively reacted with NaH and BuLi, to form the highly reactive a,g-dienolate anion 1.1a. Regio and chemoselective g-alkylation of the dienolate with various primary and secondary alkyl halides furnished the b-keto-amides 1.2–1.5 (76–91 %. Reductive amination of the keto-amides 1.1–1.5 with aniline and Zn powder in acetic acid, via the enamine intermediates 2.1–2.5, afforded the b-anilino amides 3.1–3.5 (74–85 %. After reductive deoxygenation of the tertiary amide group, using in situ generated diborane, the corresponding 1,3-diamines 4.1–4.5 were obtained (87–97 %. The synthesis of (±-2,3-seco-fentanyls 5.1–5.5 was completed by N-acylation of the diamines 4.1–4.5 with propionyl chloride, followed by precipitation of the monooxalate salts (86–95 %. The parent compound, 2,3-seco-fentanyl 5.1, was found to be a 40 times less potent narcotic analgesic than fentanyl but still 5–6 times more active than morphine in rats, while i-Pr derivative 5.3 was inactive. Apart from the pharmacological significance, the general procedure described herein may afford various functionalized, 1,3-diamines as potential complexing agents and building blocks for the synthesis of aza-crown ethers.

  4. Delivering Science from Big Data

    Science.gov (United States)

    Quinn, Peter Joseph

    2015-08-01

    The SKA will be capable of producing a stream of science data products that are Exa-scale in terms of their storage and processing requirements. This Google-scale enterprise is attracting considerable international interest and excitement from within the industrial and academic communities. In this paper we examine the data flow, storage and processing requirements of a number of key SKA survey science projects to be executed on the baseline SKA1 configuration. Based on a set of conservative assumptions about trends for HPC and storage costs, and the data flow process within the SKA Observatory, it is apparent that survey projects of the scale proposed will potentially drive construction and operations costs beyond the current anticipated SKA1 budget. This implies a sharing of the resources and costs to deliver SKA science between the community and what is contained within the SKA Observatory. A similar situation was apparent to the designers of the LHC more than 10 years ago. We propose that it is time for the SKA project and broader community to consider the effort and process needed to design and implement a distributed science data system that leans on the lessons of other projects and looks to recent developments in Cloud technologies to ensure an affordable, effective and global achievement of science goals.

  5. Role of central and peripheral opiate receptors in the effects of fentanyl on analgesia, ventilation and arterial blood-gas chemistry in conscious rats

    Science.gov (United States)

    Henderson, Fraser; May, Walter J.; Gruber, Ryan B.; Discala, Joseph F.; Puscovic, Veljko; Young, Alex P.; Baby, Santhosh M.; Lewis, Stephen J.

    2015-01-01

    This study determined the effects of the peripherally restricted µ-opiate receptor (µ-OR) antagonist, naloxone methiodide (NLXmi) on fentanyl (25 µg/kg, i.v.)-induced changes in (1) analgesia, (2) arterial blood gas chemistry (ABG) and alveolar-arterial gradient (A-a gradient), and (3) ventilatory parameters, in conscious rats. The fentanyl-induced increase in analgesia was minimally affected by a 1.5 mg/kg of NLXmi but was attenuated by a 5.0 mg/kg dose. Fentanyl decreased arterial blood pH, pO2 and sO2 and increased pCO2 and A-a gradient. These responses were markedly diminished in NLXmi (1.5 mg/kg)-pretreated rats. Fentanyl caused ventilatory depression (e.g., decreases in tidal volume and peak inspiratory flow). Pretreatment with NLXmi (1.5 mg/kg, i.v.) antagonized the fentanyl decrease in tidal volume but minimally affected the other responses. These findings suggest that (1) the analgesia and ventilatory depression caused by fentanyl involve peripheral µ-ORs and (2) NLXmi prevents the fentanyl effects on ABG by blocking the negative actions of the opioid on tidal volume and A-a gradient. PMID:24284037

  6. Delivering flavonoids into solid tumors using nanotechnologies.

    Science.gov (United States)

    Wang, Shengpeng; Zhang, Jinming; Chen, Meiwan; Wang, Yitao

    2013-10-01

    Long-term epidemiological studies have demonstrated that regular ingestion of flavonoids contained in dietary sources is associated with a reduced risk for many chronic diseases including cancer. However, although flavonoids are largely consumed in the diet and high concentrations may exist in the intestine after oral administration, the plasma/tissue concentrations of flavonoids are lower than their effective therapeutic doses due to poor bioavailability, resulting in the limited efficacy of flavonoids in various clinical studies. Therefore, the application of nanotechnology to deliver flavonoids to tumor sites has received considerable attention in recent years. In this review, after a general review of the potential benefits of flavonoids in cancer therapy and several key factors affecting their bioavailability, the current efforts in improving the delivery efficacy of promising candidates that are particularly important in the human diet, namely quercetin, epigallocatechin-3-gallate (EGCG) and genistein were focused on. Finally, the challenges of developing flavonoid delivery systems that improve flavonoid bioavailability and their anticancer therapy potentials were summarized. The design of suitable molecular carriers for flavonoids is an area of research that is in rapid progress. A large number of unheeded promising favonoids are suffering from poor in vivo parameters, their potential benefits deserves further research. Furthermore, more effort should be placed on developing active targeting systems, evaluating the efficacy and toxicity of novel flavonoid delivery systems through small and large scale clinical trials.

  7. Minidose Bupivacaine – Fentanyl Spinal Anesthesia for Cesarean Section In Preeclamptic Parturients

    Directory of Open Access Journals (Sweden)

    N. Fatholahzadeh

    2006-07-01

    Full Text Available Background:Spinal anesthesia for cesarean section is associated with a high incidence of hypotension. The synergism between intrathecal opioids and local anesthetics may make it possible to achieve reliable spinal anesthesia with minimal hypotension using a minidose of local anesthetic. Methods: Forty-four preeclamptic parturients undergoing cesarean section were randomized in two groups of 22 patients. Group A received a spinal anesthetic of bupivacaine 6 mg plus fentanyl 20 µg , and group B received 12 mg bupivacaine. Hypotension was defined as a 30% decrease in systolic and diastolic pressure from baseline. Hypotension was treated with intravenous ephedrine boluses 2.5-5 mg up to maximum 50 mg. Results: All patients had satisfactory anesthesia. Five of 22 patients in group A required ephedrine, a single dose of 5 mg. Seventeen of 22 patients in group B required vasopressor support of blood pressure.The lowest recorded systolic,diastolic and mean blood pressures as fractions of the baseline pressures were 71.2%, 64.5% and 70.3% versus 59.9%, 53.5% and 60.2% respectively for group A versus group B. Conclusion: A “minidose” of 6 mg bupivacaine in combination with 20 µg fentanyl may provide satisfactory spinal anesthesia for cesarean section in the preeclamptic patient. The minidose combination caused dramatically less hypotension than 12 mg bupivacaine and nearly eliminated the need for vasopressor support of blood pressure. 

  8. Restlessness and shivering after naloxone reversal of fentanyl-supplemented anaesthesia.

    Science.gov (United States)

    Tammisto, T; Tigerstedt, I

    1979-02-01

    To study the significance of normalization of ventilatory or thermal homeostasis during naloxone reversal, 95 patients were given naloxone after thiopental-N2O-O2-relaxant anaesthesia supplemented with fentanyl (6 microgram/kg/h). If naloxone 0.16 mg was given to combat postoperative apnoea during hypercapnia (end tidal carbon dioxide concentration (ETco2)8%), minute ventilation and respiratory rate were significantly higher during the first minutes as compared to the normocapnic patients. Shivering occurred in 44% in the hypercapnic group, as compared to about 30% if naloxone was given during normocapnia (ETco2 5%). Postoperative pain and restlessness were significantly increased in the hypercapnic group. During normocapnia, untoward reactions were less frequent (40%) if naloxone was given in smaller increments (0.08 + 0.08 mg) rather than in one dose (0.16 mg) (72%). This was mainly due to nausea (8% compared to 32%). The incidence and severity of shivering showed a positive correlation to the duration of anaesthesia (r = 0.42) and to the total amount of fentanyl (r = 0.32), but not to the actual postoperative oesophageal temperature (r = -0.13). The results indicate that though untoward reactions after naloxone reversal are aggravated by naloxone-induced normalization of deranged homeostatic mechanisms, their aetiology probably should be sought in an acute abstinence syndrome.

  9. Cardiogenic shock following administration of propofol and fentanyl in a healthy woman: a case report

    Directory of Open Access Journals (Sweden)

    Santamarta Liébana Elena

    2011-08-01

    Full Text Available Abstract Introduction Cardiogenic shock is very uncommon in healthy people. The differential diagnosis for patients with acute heart failure in previously healthy hearts includes acute myocardial infarction and myocarditis. However, many drugs can also depress myocardial function. Propofol and fentanyl are frequently used during different medical procedures. The cardiovascular depressive effect of both drugs has been well established, but the development of cardiogenic shock is very rare when these agents are used. Case presentation After a minor surgical intervention, a 32-year-old Caucasian woman with no significant medical history went into sudden hemodynamic deterioration due to acute heart failure. An urgent echocardiogram showed severe biventricular dysfunction and an estimated left ventricular ejection fraction of 20%. Extracorporeal life support and mechanical ventilation were required. Five days later her ventricular function had fully recovered, which allowed the progressive withdrawal of medical treatment. Prior to her hospital discharge, cardiac MRI showed neither edema nor pathological deposits on the delayed contrast enhancement sequences. At her six-month follow-up examination, the patient was asymptomatic and did not require treatment. Conclusion Although there are many causes of cardiogenic shock, the presence of abrupt hemodynamic deterioration and the absence of a clear cause could be related to the use of propofol and fentanyl.

  10. Cardiogenic shock following administration of propofol and fentanyl in a healthy woman: a case report.

    Science.gov (United States)

    Renilla González, Alfredo; Lozano Martinez-Luengas, Iñigo; Secades González, Sandra; Alvarez Pichel, Irene; Alvarez Martinez, Paloma; Santamarta Liébana, Elena; Díaz Molina, Beatriz

    2011-01-01

    Cardiogenic shock is very uncommon in healthy people. The differential diagnosis for patients with acute heart failure in previously healthy hearts includes acute myocardial infarction and myocarditis. However, many drugs can also depress myocardial function. Propofol and fentanyl are frequently used during different medical procedures. The cardiovascular depressive effect of both drugs has been well established, but the development of cardiogenic shock is very rare when these agents are used. After a minor surgical intervention, a 32-year-old Caucasian woman with no significant medical history went into sudden hemodynamic deterioration due to acute heart failure. An urgent echocardiogram showed severe biventricular dysfunction and an estimated left ventricular ejection fraction of 20%. Extracorporeal life support and mechanical ventilation were required. Five days later her ventricular function had fully recovered, which allowed the progressive withdrawal of medical treatment. Prior to her hospital discharge, cardiac MRI showed neither edema nor pathological deposits on the delayed contrast enhancement sequences. At her six-month follow-up examination, the patient was asymptomatic and did not require treatment. Although there are many causes of cardiogenic shock, the presence of abrupt hemodynamic deterioration and the absence of a clear cause could be related to the use of propofol and fentanyl.

  11. Analgesic Effects of Lidocaine and Fentanyl Alone or in Combination Undergoing Ovariohysterectomy in Female Dogs

    Directory of Open Access Journals (Sweden)

    Dezhang Lu1,2, Chenchen Wu1, Yupeng Yin1* and Xinwu Ma1,2*

    2016-11-01

    Full Text Available In this study, the analgesia effects of intravenous injection either of lidocaine, fentanyl, or their combination were compared in dogs undergoing ovariohysterectomy. Forty-eight dogs were randomly assigned into three groups. Anesthesia was induced with 6 mg/kg propofol and maintained with 2% (vaporizer dial setting isoflurane. Animals received lidocaine (4 mg/kg, fentanyl (3 μg/kg, and their combination after 15 minutes of induction. Heart rhythm, respiratory rhythm, blood pressure, rectal temperature, subjective pain scores and arterial blood-gas were measured at same time. Cardiopulmonary variables changed after injection, and some of them had significant differences compared with baselines at the moment of extubation. The maximal subjective pain scores were recorded at three hours after extubation, but rescue analgesic was not required at this study. Though values regarding blood gas changed after intravenous administration of agents, significant differences were not found between groups at any of the time-points. Both drugs and their combination provided adequate analgesia undergoing ovariohysterectomy in dogs. No side effects were observed, no rescue analgesic was required.

  12. Analogosedation during flexible bronchoscopy using a combination of midazolam, propofol and fentanyl - A retrospective analysis.

    Science.gov (United States)

    Müller, Tobias; Thümmel, Kristina; Cornelissen, Christian G; Krüger, Stefan; Dreher, Michael

    2017-01-01

    According to current guidelines flexible bronchoscopy is usually performed under sedation. Previously it has been demonstrated that combined sedation with e. g. the combination of midazolam and propofol or an opioid might have several advantages over sedation with just one sedative drug. However, little is known about the efficacy and safety of combined sedation with midazolam, fentanyl and propofol (MFP) compared to sedation with midazolam and fentanyl (MF) or midazolam and propofol (MP). We carried out a retrospective analysis of bronchoscopies performed under triple (MFP) or double sedation (MF and MP) in an academic hospital. 1392 procedures were analyzed (MFP: n = 824; MF: n = 272; MP: n = 296). In particular, we compared the occurrence of complications and the dosage of administered sedative drugs between the groups. The occurrence of adverse events (MFP vs. MF: odds ratio (OR) 1.116 [95% CI 0.7741 to 1.604]; MFP vs. MP: OR 0.8296 [95% CI 0.5939 to 1.16] and severe adverse events (MFP vs. MF: OR 1.581 [95% CI 0.5594 to 4.336]; MFP vs. MP: OR 3.47 [95% CI 0.908 to 15.15]; all p>0.05) was similar in all groups. The dosage of midazolam was lower in the MFP compared to the MF or MP group (MFP vs. MF: Cohen's d 0.075; MFP vs. MP: Cohen's d 0.225; all ppropofol compared to the MP group (Cohen's d 1.22; ppropofol.

  13. Substance use patterns associated with recent exposure to fentanyl among people who inject drugs in Vancouver, Canada: A cross-sectional urine toxicology screening study.

    Science.gov (United States)

    Hayashi, Kanna; Milloy, M-J; Lysyshyn, Mark; DeBeck, Kora; Nosova, Ekaterina; Wood, Evan; Kerr, Thomas

    2017-12-05

    Vancouver, Canada is experiencing an opioid overdose crisis where fentanyl, a potent, synthetic opioid contaminating the illicit drug supply, has been detected in the majority of fatal overdose cases. Despite its growing presence throughout North America, few studies have characterized exposure to fentanyl among people who use illicit drugs (PWUD). We sought to identify the prevalence and correlates of fentanyl exposure among PWUD in Vancouver. Data were derived from cohort studies of PWUD in Vancouver. In June-October 2016, we administered multi-panel urine drug screens (UDS) to detect recent exposure to fentanyl and eight other substances. Multivariable logistic regression was used to identify substance use patterns associated with recent fentanyl exposure among participants who injected drugs in the past six months (PWID). Among 669 PWUD including 250 (37.4%) females and 452 (67.6%) PWID, 97 (14.5%) tested positive for fentanyl. All these individuals also tested positive for other substances, most commonly for morphine/heroin (89.9%), amphetamine/methamphetamine (75.3%) and cocaine (74.2%). A fentanyl detection rate was significantly higher among PWID (19.7%) compared to non-injection drug users (3.9%) (p<0.001). In multivariable analyses, younger age (adjusted odds ratio [AOR]: 0.96) and testing positive for morphine/heroin (AOR: 6.73), buprenorphine (AOR: 4.25), amphetamine/methamphetamine (AOR: 3.26), cocaine (AOR: 2.92) and cannabis (AOR: 0.52) remained independently associated with fentanyl exposure (all p<0.05). With one in five PWID being exposed to fentanyl, there is an urgent need to design and scale up interventions to reduce overdose risk, including a range of opioid agonist therapies. Copyright © 2017. Published by Elsevier B.V.

  14. Comparison of etomidate in combination with fentanyl or diazepam, with thiopentone as an induction agent for general anaesthesia.

    Science.gov (United States)

    Korttila, K; Tammisto, T; Aromaa, U

    1979-12-01

    In 104 premedicated patients undergoing general surgery, anaesthesia was induced either with etomidate 0.3 mg kg-1 preceded by fentanyl 1.25 or 2.5 microgram kg-1 i.v.or diazepam 0.0625 or 0.125 mg kg-1 i.v., or with thiopentone preceded by fentanyl 1.25 microgram kg-1 i.v. Despite the use of fentanyl or diazepam, the frequency of pain on injection in patients receiving etomidate was between 32% and 53%, being rated as severe in 5-20% of patients. No pain was experienced by patients receiving thiopentone. The frequency of involuntary movement was 15-35% with etomidate and 15% with thiopentone. The frequency of both pain and involuntary muscle movements was least when fentanyl 2.5 microgram kg-1 preceded the administration of etomidate. There was no significant relationship between the pain and muscle movement; three of 10 patients given etomidate into a central vein had such movements.

  15. Remifentanil versus Fentanyl for Assisted Reproductive Technologies:Effect on Hemodynamic Recovery from Anesthesia and Outcome of ART Cycles

    Directory of Open Access Journals (Sweden)

    Mohammad Hossein Jarahzadeh

    2011-01-01

    Full Text Available Background: We conducted this study to compare the outcome of assisted reproductive technology(ART procedures and recovery from anesthesia in women who received opioid analgesia withremifentanil versus fentanyl.Materials and Methods: This double-blind, randomized clinical trial was carried out inthe Yazd Research and Clinical Center for Infertility, Yazd, Iran. We studied 145 womenwho were participants in an ART program. During the first phase of the study, all patientsunderwent induction of anesthesia with thiopental and received analgesia with remifentanilor fentanyl. The primary endpoint was pregnancy rate per transfer. The numbers of oocytescollected, fertilized and cleaved were recorded, as was the number of oocytes transferredand recovery profile. In the second phase of the study, all patients were followed foroutcome of ART cycle.Results: This study suggested that in women undergoing transvaginal ultrasound-guided oocyteretrieval procedures, the likelihood of a successful pregnancy was higher with a remifentanil-basedmonitored anesthesia care (MAC technique than with a fentanyl-based MAC technique. Therecovery from anesthesia was significantly better in the remifentanil group versus fentanyl group.Conclusion: The results of this study suggest that remifentanil in clinical practice is superior tofentanyl (Registeration Number: IRCT201009283468N3.

  16. Prospective study comparing skin impedance with EEG parameters during the induction of anaesthesia with fentanyl and etomidate

    Directory of Open Access Journals (Sweden)

    Winterhalter M

    2010-02-01

    Full Text Available Abstract Objective Sympathetic stimulation leads to a change in electrical skin impedance. So far it is unclear whether this effect can be used to measure the effects of anaesthetics during general anaesthesia. The aim of this prospective study is to determine the electrical skin impedance during induction of anaesthesia for coronary artery bypass surgery with fentanyl and etomidate. Methods The electrical skin impedance was measured with the help of an electro-sympathicograph (ESG. In 47 patients scheduled for elective cardiac surgery, anaesthesia was induced with intravenous fentanyl 10 μg/kg and etomidate 0.3 mg/kg. During induction, the ESG (Electrosympathicograph, BIS (Bispectral IndeX, BP (arterial blood pressure and HR (heart rate values of each patient were recorded every 20 seconds. The observation period from administration of fentanyl to intubation for surgery lasted 4 min. Results The ESG recorded significant changes in the electrical skin impedance after administration of fentanyl and etomidate(p Conclusions The electrical skin impedance measurement may be used to monitor the effects of anesthetics during general anaesthesia.

  17. Concurrent detection of heroin, fentanyl, and xylazine in seven drug-related deaths reported from the Philadelphia Medical Examiner's Office.

    Science.gov (United States)

    Wong, Stella C; Curtis, John A; Wingert, William E

    2008-03-01

    Recreational drugs, such as cocaine and heroin, are often adulterated with other pharmacological agents to either enhance or diminish the drug effects. Between April 21, 2006 and August 8, 2006, the Philadelphia Medical Examiner's Office detected xylazine (a veterinary sedative) and fentanyl (a synthetic opioid) in specimens taken from seven cases. Initial immunoassay screening was performed on urine and blood for fentanyl, opiate, cocaine, phencyclidine (PCP), and benzodiazepines. All tests reported positive were confirmed by gas chromatography-mass spectrometry. All seven xylazine positive cases tested positive for fentanyl and six cases tested positive for 6-acetylmorphine (a metabolite and definitive marker for heroin). The seventh case was positive for morphine and had a history of heroin abuse. Xylazine was present in urine in all seven cases and blood levels were detected in three cases. The blood concentrations ranged from trace to 130 ng/mL. Fentanyl was present in the blood and urine in each case and blood concentrations ranged from 4.7 to 47 ng/mL. Adulteration of illicit drugs has become an epidemic health concern for drug users. Healthcare professionals need to be aware of this issue, so the patients can be treated in an effective, timely manner.

  18. Effects of Fentanyl on Emergence Agitation in Children under Sevoflurane Anesthesia: Meta-Analysis of Randomized Controlled Trials

    Science.gov (United States)

    Xiong, Wei; Zhou, Qin; Yang, Peng; Huang, Xiongqing

    2015-01-01

    Background and Objectives The goal of this meta-analysis study was to assess the effects of fentanyl on emergence agitation (EA) under sevoflurane anesthesia in children. Subjects and Methods We searched electronic databases (PubMed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials) for articles published until December 2014. Randomized controlled trials (RCTs) that assessed the effects of fentanyl and placebo on EA under sevoflurane anesthesia in children that the outcome were the incidence of EA, postoperative pain, emergence time or adverse effects were included in this meta-analysis. Results A total of 16 studies, including 1362 patients (737 patients for the fentanyl group and 625 for the placebo group), were evaluated in final analysis. We found that administration of fentanyl decreased the incidences of EA (RR = 0.37, 95% CI 0.27~0.49, Pfentanyl decreases the incidence of EA under sevoflurane anesthesia in children and postoperative pain, but has a higher incidence of PONV. Considering the inherent limitations of the included studies, more RCTs with extensive follow-up should be performed to validate our findings in the future. PMID:26275039

  19. Differential effect of intravenous S-ketamine and fentanyl on atypical odontalgia and capsaicin-evoked pain

    DEFF Research Database (Denmark)

    Baad-Hansen, Lene; Juhl, Gitte Irene; Jensen, Troels Staehelin

    2007-01-01

    Atypical odontalgia (AO) is an intraoral pain condition of currently unknown mechanisms. In 10 AO patients and 10 matched healthy controls, we examined the effect of intravenous infusion of an N-methyl-D-aspartate (NMDA) receptor antagonist S-ketamine and a mu-opioid agonist fentanyl on spontaneous...

  20. Haplotypes of P2RX7 Gene Polymorphisms are Associated with both Cold Pain Sensitivity and Analgesic Effect of Fentanyl

    National Research Council Canada - National Science Library

    Ide, Soichiro; Nishizawa, Daisuke; Fukuda, Ken-Ichi; Kasai, Shinya; Hasegawa, Junko; Hayashida, Masakazu; Minami, Masabumi; Ikeda, Kazutaka

    2014-01-01

    .... The P2RX7 gene is known to be highly polymorphic. Thus, the present study examined associations between fentanyl sensitivity and polymorphisms in the P2RX7 gene in 355 Japanese patients who underwent painful orofacial cosmetic surgery. Results...

  1. Effect of parecoxib sodium on propofol combined with fentanyl anesthesia effect and postoperative recovery in elderly patients with laparoscopic surgery

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2016-06-01

    Full Text Available Objective: To study the effect of parecoxib sodium on propofol combined with fentanyl anesthesia effect and postoperative recovery in elderly patients with laparoscopic surgery. Methods: A total of 80 cases of elderly patients who received laparoscopic surgery in our hospital from May 2013 to December 2015 were selected for study and randomly divided into observation group who received parecoxib sodium + propofol combined with fentanyl anesthesia and control group who received propofol combined with fentanyl anesthesia, and then pain threshold and serum indicators of two groups were compared. Results: 2 h, 4 h, 6 h, 8 h, 10 h and 12 h after surgery, pain threshold EI50 of observation group was significantly higher than that of control group; serum Glu, PS, histamine, 5-HT, MCP-1, CCR2, JAK2, STAT3, p38MAPK, PX1, Orexin, IRAK1, TRAF6 and FcγRI contents of observation group were significantly lower than those of control group; serum GABA and β-EP contents of observation group were significantly higher than those of control group. Conclusion: Parecoxib sodium has inhibiting effect on the pain perception of propofol combined with fentanyl anesthesia for elderly patients with laparoscopic surgery and can reduce the synthesis of pain neurotransmitters, inflammatory factors and related molecules.

  2. A randomized, open, parallel group, multicenter trial to investigate analgesic efficacy and safety of a new transdermal fentanyl patch compared to standard opioid treatment in cancer pain

    DEFF Research Database (Denmark)

    Kress, Hans G; Von der Laage, Dorothea; Hoerauf, Klaus H

    2008-01-01

    to be pharmacokinetically bioequivalent to the marketed fentanyl patch. To determine noninferiority in efficacy in cancer patients and to compare safety, a clinical trial comparing the new fentanyl patch with standard oral or transdermal opioid treatment was planned. The design was an open, parallel group, multicenter...... trial, in which 220 patients were randomized to receive either the fentanyl patch or standard opioid treatment for 30 days. The primary efficacy variable, pain intensity (PI) on a 0-10-point numerical rating scale, was recorded once daily. The primary endpoint was the relative area under the curve of PI...

  3. Comparative evaluation of femoral nerve block and intravenous fentanyl for positioning during spinal anaesthesia in surgery of femur fracture

    Directory of Open Access Journals (Sweden)

    Ashok Jadon

    2014-01-01

    Full Text Available Background: Spinal anaesthesia is the preferred technique to fix fracture of the femur. Extreme pain does not allow ideal positioning for this procedure. Intravenous fentanyl and femoral nerve block are commonly used techniques to reduce the pain during position for spinal anaesthesia however; results are conflicting regarding superiority of femoral nerve block over intravenous fentanyl. Aims: We conducted this study to compare the analgesic effect provided by femoral nerve block (FNB and intra- venous (IV fentanyl prior to positioning for central neuraxial block in patients undergoing surgery for femur fracture. Patients and Methods: In this randomized prospective study 60 patients scheduled for fracture femur operation under spinal were included. Patients were distributed in two groups through computer generated random numbers table; Femoral nerve block group (FNB and Intravenous fentanyl group (FENT. In FNB group patients received FNB guided by a peripheral nerve stimulator (Stimuplex; B Braun, Melsungen, AG 5 minutes prior to positioning. 20mL, 1.5% lidocaine with adrenaline (1:200,000 was injected incrementally after a negative aspiration test. Patients in the fentanyl group received injection fentanyl 1 μg/kg IV 5 mins prior to positioning. Spinal block was performed and pain scores before and during positioning were recorded. Statistical analysis was done with Sigmaplot version-10 computer software. Student t-test was applied to compare the means and P < 0.05 was taken as significant. Results: VAS during positioning in group FNB: 0.57 ± 0.31 versus FENT 2.53 ± 1.61 (P = 0.0020. Time to perform spinal anesthesia in group FNB: 15.33 ± 1.64 min versus FENT 19.56 ± 3.09 min (P = 0.000049. Quality of patient positioning for spinal anesthesia in group FNB 2.67± 0.606 versus FENT 1.967 ± 0.85 (P = 0.000027. Patient acceptance was less in group FENT (P = 0.000031. Conclusion: Femoral nerve block provides better analgesia, patient

  4. COMBINED SPINAL EPIDURAL ANALGESIA IN LABOUR: COMPARISON OF BUPIVACAINE 1.25 MG WITH FENTANYL AND ROPIVACAINE 2.5 MG WITH FENTANYL INTRATHECAL

    Directory of Open Access Journals (Sweden)

    Prakash T. S. N

    2016-10-01

    with ASA I and ASA II in established labour with cervical dilatation less than 5 cm was selected and randomly allocated into two groups using closed envelope method. Informed written consent was taken from all participants. They were divided into 2 groups of 20 each. Group I received intrathecal Inj. Bupivacaine 1.25 mg and Inj. Fentanyl 20 µg. Group II received intrathecal Inj. Ropivacaine 2.5 mg and Inj. Fentanyl 20 µg for combined spinal epidural. IV line was secured with 18G cannula. Patient was preloaded with 500 mL of Hartmann’s solution. Basal vital parameter like pulse rate, blood pressure, respiration, O2 saturation were recorded. The patient was positioned in a sitting position with the help of an assistant. Under aseptic conditions, the back was prepared with 5% povidone-iodine solution, spirit and area was draped. L3-L4 interspace was identified. Skin was infiltrated with 2 mL of 1% Xylocaine. After infiltration of local anaesthetic by using needle through needle technique 18-gauge Tuohy needle, epidural space was identified with loss of resistance to air technique. Then, a 15 mm (27 G long ‘Whitacre’ spinal needle was introduced through the epidural needle and the correct position of the tip in the intrathecal space was confirmed by observation of free flow of CSF. Patients were allocated randomly to receive intrathecal injection of bupivacaine 1.25 mg (0.5% bupivacaine 0.25 mL with fentanyl 20 µg (Group I n=30 or ropivacaine 2.5 mg/0.2% ropivacaine 1.25 mL with fentanyl 20 µg (Group II, n=30 both made up to total volume of 2 mL with saline. Injection of intrathecal drug was completed in 10 secs., then 20G epidural catheter was threaded through the epidural needle into the epidural space in cephalad direction. The epidural needle was slowly pulled out without disturbing the catheter. About 3 to 5 cm of catheter was left in epidural space. The catheter was well secured with plaster. Patients vitals was recorded every 5, 10, 15, 30, 45, 60, 75, 90

  5. A comparison of intranasal fentanyl spray with oral transmucosal fentanyl citrate for the treatment of breakthrough cancer pain: an open-label, randomised, crossover trial.

    Science.gov (United States)

    Mercadante, S; Radbruch, L; Davies, A; Poulain, P; Sitte, T; Perkins, P; Colberg, T; Camba, M A

    2009-11-01

    The efficacy of intranasal fentanyl spray (INFS) was compared with that of oral transmucosal fentanyl citrate (OTFC) for the relief of cancer-related breakthrough pain (BTP) in an open-label, crossover trial. Adult cancer patients receiving stable background opioid treatment and experiencing BTP episodes were recruited from 44 study centres in seven European countries (Austria, France, Germany, Italy, Poland, Spain and the United Kingdom); of the 196 patients enrolled, 139 were randomised to receive INFS followed by OTFC, or vice versa. Patients were titrated to an effective dose of one agent (50, 100 or 200 microg INFS; 200, 400, 600, 800, 1200 or 1600 microg OTFC) to treat six BTP episodes, then titration and treatment were repeated with the other agent. The primary outcome was patient-recorded time to onset of 'meaningful' pain relief. Secondary outcomes included pain intensity difference (PID) at 10 and 30 minutes (PID(10), PID(30)), sum of PID at 15 and 60 minutes (SPID(0-15), SPID(0-60)), ease of administration, treatment preference and relationship between background opioid dose and effective INFS dose. Additional outcome measures included proportions of episodes with > or =33% and > or =50% pain intensity (PI) reduction, and PID at additional time points. NCT00496392. Among the intention-to-treat population (n = 139), median time to onset of 'meaningful' pain relief was 11 minutes with INFS versus 16 minutes with OTFC; 65.7% of patients attained faster time to 'meaningful' pain-relief onset with INFS (p pain episodes achieved clinically important pain relief (> or =33% and > or =50% PI reduction) up to 30 minutes post-dosing. The proportions of episodes treated with INFS and OTFC achieving a PI reduction of > or =33% at 5 minutes were 25.3% versus 6.8% (p or =50% PI reduction at 5 minutes were 12.8% versus 2.1% (p or =1 AE during the trial. The only AE that occurred in > or =5% of patients in either treatment group was nausea. Among those patients who

  6. The need for fentanyl supplementation of N2O-O2 relaxant anaesthesia in chronic alcoholics.

    Science.gov (United States)

    Tammisto, T; Tigerstedt, I

    1977-01-01

    In order to find out how the need for analgesic supplementation during N2O-O2-relaxant anaesthesia is affected by chronic alcohol consumption, 82 patients with various known alcohol habits were anaesthetized for gastric or biliary surgery. Muscular relaxation was kept constant with the aid of a peripheral neurostimulator, and fentanyl was given in increments of 0.05-0.1 mg for nociceptive symptoms during the anaesthesia. For induction, alcoholics (annual consumption above 151 pure alcohol) needed significantly more thiopental/kg body weight than social drinkers (1--151 annually) or non-alcoholics (less than 11 annually), and excitative symptoms were more frequent in alcoholics. A positive correlation was found between fentanyl supplementation and alcohol consumption (r = 0.41), non-alcoholics requiring on average 3.8 microng/kg/h of fentanyl, as compared with 6.4 microng/kg/h in alcoholics. This correlation was clearer than that found previously under similar conditions by the authors between halothane supplementation and alcohol consumption (r = 0.20). In both studies the correlation was partly due to the higher incidence of gastric surgery among alcoholics, since gastric surgery itself requires more supplementation. An analysis of the different symptoms pointing to the need for fentanyl supplementation revealed that the simultaneous occurrence of several symptoms and the prevalence of motor responses were more common in alcoholics. In one patient halothane had to be used as well. In other patients no special difficulties were observed, and none of the patients reported dreams or recollections. The results suggest that during N2O-O2-relaxant anaesthesia the demand for fentanyl supplementation is increased by about 70% in chronic alcoholics with a mean annual consumption of 311 pure alcohol.

  7. Addition of intrathecal fentanyl or meperidine to lidocaine and epinephrine for spinal anesthesia in elective cesarean delivery.

    Science.gov (United States)

    Farzi, Farnoush; Mirmansouri, Ali; Forghanparast, Kambiz; Heydarzadeh, Abtin; Abdollahzadeh, Mehrsima; Jahanyar Moghadam, Fatemeh

    2014-02-01

    A common and useful approach to pain management is administration of neuraxial opioids. Whether addition of fentanyl or meperidine to lidocaine and epinephrine for spinal anesthesia in elective cesarean delivery has any effects on duration of postoperative pain. This was a clinical trial, conducted on 195 pregnant women candidates for elective cesarean section. All patients were in ASA classes I, and II aged 17-45 years, and were randomly allocated to three groups named as meperidine (P), fentanyl (F), and placebo (S). In the three groups (P, F, and S), 25 mg meperidine, 25 µg fentanyl and 0.5 mL saline with lidocaine and epinephrine were injected into the subarachnoid space for spinal anesthesia, respectively. Perioperative complications and Apgar scores were recorded. Duration of analgesia was measured from the end of operation for 24 hours by using VAS. The first VAS≥4 was recorded as the end of the painless period. Characteristics of sensory and motor block were assessed. Statistical analysis was performed with SPSS software. The mean duration of analgesia with meperidine, fentanyl or placebo were 9.46 ± 0.6, 6.27 ± 0.45, 2.06 ± 0.13 hours, respectively (P < 0.0001). There was significant difference between the group P and the other groups. Patients on meperidine had faster, longer and higher sensory block (P < 0.0001) and faster and longer motor block (P < 0.0001). Frequency of sedation in the group F was more than the others (P < 0.026). There was no difference in Apgar scores between the three groups (P < 0.45). Addition of meperidine or fentanyl to lidocaine and epinephrine solution increases the duration of postoperative analgesia in cesarean section. Meperidine is a recommended adjuvant according to longer duration of analgesia and lower complications.

  8. Effect of Pregnane X Receptor(*)1B genetic polymorphisms on postoperative analgesia with fentanyl in Chinese patients undergoing gynecological surgery.

    Science.gov (United States)

    Yuan, Jing-Jing; Ma, Xiao-Jing; Li, Zhi-Song; Chang, Yan-Zi; Zhang, Wei; Kan, Quan-Cheng; Hou, Jun-Kai; Zhang, Li-Rong

    2016-11-23

    The purpose of the study was to investigate the effects of the pregnane X receptor (PXR)*1B polymorphisms on CYP3A4 enzyme activity and postoperative fentanyl consumption in Chinese patients undergoing gynecological surgery. A total of 287 females of Han ethnicity, aged 20 to 50 years old, ASA I or II, scheduled to abdominal total hysterectomy or myomectomy under general anesthesia were enrolled. The analgesic model used was fentanyl consumption via patient-controlled intravenous analgesia (PCIA) in the post-operative period. Additionally, pain was assessed using a visual analog score (VAS). Pain scores, occurrence of adverse reactions and consumption of fentanyl were recorded during the 24 h postoperative period. The enzyme activity of CYP3A4 was evaluated by measuring the plasma ratio of 1'-hydroxymidazolam to midazolam 1 h after intravenous administration of 0.1 mg/kg midazolam. PXR genotyping was performed by direct DNA sequencing and the PXR (*) 1B haplotype was analyzed via PHASE V.2.1 software. The polymorphism frequency of PXR11156A > C/11193 T > C and 8055C > T were 49.6 and 49.3%, and the rate of PXR (*) 1B haplotype was 48.8% in our study. None of the pain scores, consumption of fentanyl 24 h post-operatively or enzyme activity of CYP3A4, showed differences among different genotypes. PXR11156A > C, PXR11193T > C, PXR8055C > T or the PXR (*) 1B haplotype do not appear to be important factors contributing to CYP3A4 activity and interindividual variations in postoperative fentanyl consumption in Han female patients undergoing gynecological surgery. The DNA samples were obtained since 2007 to 2010 year in our hospital, there was no registration at that time. So this section is not applicable to our research.

  9. Effect of microcurrent skin patch on the epidural fentanyl requirements for post operative pain relief of total hip arthroplasty.

    Science.gov (United States)

    Sarhan, Tarek M; Doghem, Maher A

    2009-10-01

    Major orthopedic surgery that cause considerable pain like total hip arthroplasty, requires good post operative pain management. Microcurrent therapy (MCT) is a new therapy whereby electric current is provided in literally millionth of an ampere. MCT comes as two self adherent active electrode patches linked by a cable Efficacy of MCT in the management of musculoskeletal pain and enhancement of wound healing has been reported. To study the effect of microcurrent therapy (MCT) on the epidural fentanyl requirements and degree of wound healing after total hip arthroplasty. Twenty eight patients undergoing total hip replacement (THR) were randomly allocated into two groups. Group I: had micro current skin patches (two adhesive electrode) attached above the site of operation in addition to the lumbar epidural catheter. Post operative epidural fentanyl infusion with a syringe pump given at a rate ranged between 25 and 75 microgram per hour to keep visual analogue pain score (VAS) less than 3/10. Group II had only continuous epidural infusion with fentanyl at the same range to keep VAS less than 3/10 without MCT. There was statistically significant lower mean epidural fentanyl requirement in Group I (23.24 microgram) when compared to Group II (58.36 microgram). There was 23% incidence of dermatitis in Group I due to application of micro- current skin patch which resolved by treatment. There was statistically significant higher frequency of grade 1 of wound healing in the microcurrent group (41.3 %) when compared to Group II (7.2%). Grade 2 and 3 were more frequent in Group II) CONCLUSION: The microcurrent skin therapy lead to reduction in the requirements of the post operative epidural fentanyl with improvement of degrees of wound healing but with considerable incidence of skin dermatitis after total hip arthroplasty.

  10. Comparison of Dexmedetomidine and Fentanyl as an Adjuvant to Ropivacaine for Postoperative Epidural Analgesia in Pediatric Orthopedic Surgery.

    Science.gov (United States)

    Park, Sang Jun; Shin, Seokyung; Kim, Shin Hyung; Kim, Hyun Woo; Kim, Seung Hyun; Do, Hae Yoon; Choi, Yong Seon

    2017-05-01

    Opioids are commonly used as an epidural adjuvant to local anesthetics, but are associated with potentially serious side effects, such as respiratory depression. The aim of this study was to compare the efficacy and safety of dexmedetomidine with that of fentanyl as an adjuvant to epidural ropivacaine in pediatric orthopedic surgery. This study enrolled 60 children (3-12 years old) scheduled for orthopedic surgery of the lower extremities and lumbar epidural patient-controlled analgesia (PCA). Children received either dexmedetomidine (1 μg/kg) or fentanyl (1 μg/kg) along with 0.2% ropivacaine (0.2 mL/kg) via an epidural catheter at 30 minutes before the end of surgery. Postoperatively, the children were observed for ropivacaine consumption via epidural PCA, postoperative pain intensity, need for rescue analgesics, emergence agitation, and other adverse effects. The mean dose of bolus epidural ropivacaine was significantly lower within the first 6 h after surgery in the dexmedetomidine group, compared with the fentanyl group (0.029±0.030 mg/kg/h vs. 0.053±0.039 mg/kg/h, p=0.012). The median pain score at postoperative 6 h was also lower in the dexmedetomidine group, compared to the fentanyl group [0 (0-1.0) vs. 1.0 (0-3.0), p=0.039]. However, there was no difference in the need for rescue analgesia throughout the study period between groups. The use of dexmedetomidine as an epidural adjuvant had a significantly greater analgesic and local anesthetic-sparing effect, compared to fentanyl, in the early postoperative period in children undergoing major orthopedic lower extremity surgery.

  11. A COMPARATIVE CLINICAL STUDY BETWEEN IV ESMOLOL AND IV FENTANYL ON ATTENUATION OF HAEMODYNAMIC RESPONSES TO LARYNGOSCOPY AND INTUBATION

    Directory of Open Access Journals (Sweden)

    Abu Lais Mustaque

    2016-04-01

    Full Text Available INTRODUCTION Laryngoscopy and intubation is an integral part for providing general anaesthesia to patients undergoing various types of surgery. It also plays an important role in critical care units viz. for providing mechanical ventilation. It is a very essential tool in the hands of anaesthesiologist in maintaining airway. The present study is undertaken to determine and compare the efficacy of single bolus dose of IV esmolol 1 mg/kg and IV fentanyl 2 mcg/kg in attenuating the haemodynamic responses to laryngoscopy and tracheal intubation and to ascertain the effectiveness of esmolol hydrochloride and fentanyl citrate in suppressing sympathetic responses. MATERIAL & METHODS The study was conducted under the Department of Anaesthesiology and Critical Care, Assam Medical College and Hospital, Dibrugarh, during the period July 2013 to June 2014. For this purpose, 150 patients of either sex between 20-50 years of ASA I & II physical status were selected after obtaining informed and written consent and were divided into two groups namely, Group E receiving IV esmolol (1 mg/kg and Group F receiving IV fentanyl (2 mcg/kg. RESULTS Inj. fentanyl 2 mcg/kg IV administered 5 minutes before laryngoscopy and intubation was able to prevent adverse haemodynamic changes better than Inj. esmolol 1 mg/kg IV administered 3 minutes prior to laryngoscopy and intubation during elective surgeries under general anaesthesia. CONCLUSION Hence, from the findings of this study we can conclude that IV bolus dose of fentanyl 2 mcg/kg administered 5 minutes before laryngoscopy and intubation can attenuate the sympathetic response to laryngoscopy and intubation without any side effects of the drug in healthy patients undergoing elective surgeries under general anaesthesia.

  12. The hidden web and the fentanyl problem: Detection of ocfentanil as an adulterant in heroin.

    Science.gov (United States)

    Quintana, Pol; Ventura, Mireia; Grifell, Marc; Palma, Alvaro; Galindo, Liliana; Fornís, Iván; Gil, Cristina; Carbón, Xoán; Caudevilla, Fernando; Farré, Magí; Torrens, Marta

    2017-02-01

    The popularization of anonymous markets such as Silk Road is challenging current drug policy and may provide a new context for old issues, such as adulteration of heroin with fentanyl derivatives. The aims of this paper are to report the presence of ocfentanil, a novel, potent, non-controlled fentanyl analog, in samples sold as heroin in the hidden web, and to summarize the effects reported by users. In 2015, four samples allegedly bought as heroin in cryptomarkets of the hidden web were sent to Energy Control for analysis. Energy Control is a Spanish harm reduction NGO that offers anonymous drug checking with the purpose of adapting counselling to the specific substances present in the drug and monitor the drug market. Identification was performed by GC/MS and LC/MS/MS. We contacted the submitters of the samples and performed an Internet search to retrieve additional information. One sample contained ocfentanil, caffeine and heroin. Three samples contained the aforementioned substances plus paracetamol. Two out of the four contacted users reported distinct short acting, opioid-like effects. No fora discussion could be found about the effects of ocfentanil, neither web pages nor individuals advertising the substance. We report the presence of a new substance detected in the hidden web as an adulterant of heroin, ocfentanil. It has short acting opioid-like effects, roughly the same potency as fentanyl, and can be injected, snorted or smoked. Severe side effects have been associated with its use, including one death. No discussion about this substance could be found in the Internet, which suggests this substance has not been sold as such. Available data about purities of drugs purchased in cryptomarkets suggest that adulteration is not a severe problem and this agrees with users' perceptions. However, this study suggests that adulteration is a real threat not only at the street level, but also for users that buy substances in cryptomarkets, and suggest the need for

  13. Intraoperative "Analgesia Nociception Index"-Guided Fentanyl Administration During Sevoflurane Anesthesia in Lumbar Discectomy and Laminectomy: A Randomized Clinical Trial.

    Science.gov (United States)

    Upton, Henry D; Ludbrook, Guy L; Wing, Andrew; Sleigh, Jamie W

    2017-07-01

    The "Analgesia Nociception Index" (ANI; MetroDoloris Medical Systems, Lille, France) is a proposed noninvasive guide to analgesia derived from an electrocardiogram trace. ANI is scaled from 0 to 100; with previous studies suggesting that values ≥50 can indicate adequate analgesia. This clinical trial was designed to investigate the effect of intraoperative ANI-guided fentanyl administration on postoperative pain, under anesthetic conditions optimized for ANI functioning. Fifty patients aged 18 to 75 years undergoing lumbar discectomy or laminectomy were studied. Participants were randomly allocated to receive intraoperative fentanyl guided either by the anesthesiologist's standard clinical practice (control group) or by maintaining ANI ≥50 with boluses of fentanyl at 5-minute intervals (ANI group). A standardized anesthetic regimen (sevoflurane, rocuronium, and nonopioid analgesia) was utilized for both groups. The primary outcome was Numerical Rating Scale pain scores recorded from 0 to 90 minutes of recovery room stay. Secondary outcomes included those in the recovery room period (total fentanyl administration, nausea, vomiting, shivering, airway obstruction, respiratory depression, sedation, emergence time, and time spent in the recovery room) and in the intraoperative period (total fentanyl administration, intraoperative-predicted fentanyl effect-site concentrations over time [CeFent], the correlation between ANI and predicted CeFent and the incidence of movement). Statistical analysis was performed with 2-tailed Student t tests, χ tests, ordinal logistic generalized estimating equation models, and linear mixed-effects models. Bonferroni corrections for multiple comparisons were made for primary and secondary outcomes. Over the recovery room period (0-90 minutes) Numerical Rating Scale pain scores were on average 1.3 units lower in ANI group compared to the control group (95% confidence interval [CI], -0.4 to 2.4; P= .01). Patients in the ANI group

  14. Incidence and Risk Factors of Postoperative Nausea and Vomiting in Patients with Fentanyl-Based Intravenous Patient-Controlled Analgesia and Single Antiemetic Prophylaxis

    OpenAIRE

    Choi, Jong Bum; Shim, Yon Hee; Lee, Youn-Woo; Lee, Jeong Soo; Choi, Jong-Rim; Chang, Chul Ho

    2014-01-01

    Purpose We evaluated the incidence and risk factors of postoperative nausea and vomiting (PONV) in patients with fentanyl-based intravenous patient-controlled analgesia (IV-PCA) and single antiemetic prophylaxis of 5-hydroxytryptamine type 3 (5 HT3)-receptor antagonist after the general anesthesia. Materials and Methods In this retrospective study, incidence and risk factors for PONV were evaluated with fentanyl IV-PCA during postoperative 48 hours after various surgeries. Results Four hundre...

  15. Relationship between onset of pain relief and patient satisfaction with fentanyl pectin nasal spray for breakthrough pain in cancer.

    Science.gov (United States)

    Torres, Luis M; Revnic, Julia; Knight, Alastair D; Perelman, Michael

    2014-10-01

    Satisfaction with pain relief in patients with breakthrough pain in cancer (BTPc) has typically been assessed by overall efficacy without consideration of the rapidity of that response. To determine the relationship between speed of onset of pain relief and patient satisfaction for treated BTPc episodes overall and for individual treatments. Pooled data from two randomized, double-blinded crossover studies. Patients having 1-4 BTPc episodes per day on ≥60 mg/day oral morphine or equivalent. Episodes treated with fentanyl pectin nasal spray (FPNS; 100-800 μg), immediate-release morphine sulfate (IRMS), or placebo. Pain intensity was measured on an 11-point scale (5-60 minutes posttreatment); satisfaction was measured on a 4-point scale (30 and 60 minutes). The primary analysis assessed the overall relationship of time to onset of pain relief (pain intensity difference [PID]≥1) or time to clinically meaningfully reduction in pain (PID≥2) versus patient satisfaction and overall pain intensity (summed pain intensity difference at 30 [SPID30] and 60 minutes [SPID60]) assessed by analysis of variance (ANOVA). A secondary analysis assessed whether satisfaction was different between treatments using a within-patient comparison. Eight hundred thirty-one FPNS-treated, 368 IRMS-treated, and 200 placebo-treated episodes were analyzed. Overall, within the pool there was a statistically significant relationship between time to onset of pain relief (PID≥1 and PID≥2) and patient satisfaction (both speed of relief and overall) at 30 and 60 minutes (p<0.001); this relationship was also true within individual treatment groups (p<0.01). Similar results were found for overall pain intensity reduction. When treatment groups were compared using within-patient data, FPNS provided earlier onset of pain relief than IRMS or placebo (p<0.05), which translated into better satisfaction at 60 minutes (p<0.01). Earlier onset of pain relief resulted in greater patient satisfaction

  16. Effects of a novel fentanyl derivative on drug discrimination and learning in rhesus monkeys.

    Science.gov (United States)

    Gerak, L R; Moerschbaecher, J M; Bagley, J R; Brockunier, L L; France, C P

    1999-10-01

    Three monkeys discriminated 1.78 mg/kg of mirfentanil while responding under a fixed-ratio 5 schedule of stimulus-shock termination. Two mirfentanil derivatives, OHM3295 and OHM10579, substituted for mirfentanil in all subjects. However, other drugs produced variable effects among monkeys; for example, mu and kappa opioid agonists and clonidine substituted for mirfentanil on some occasions in two monkeys. Cocaine, amphetamine, and ketamine did not substitute in any subject. Opioid antagonists did not attenuate the effects of mirfentanil. In monkeys responding under a repeated acquisition and performance procedure, errors increased only during the acquisition phase at doses of mirfentanil that decreased response rates. Thus, unlike fentanyl, the discriminative stimulus effects of mirfentanil do not appear to be mediated exclusively through opioid receptors. Finally, mirfentanil does not appear to disrupt complex behavioral processes.

  17. Combining rimonabant and fentanyl in a single entity: preparation and pharmacological results

    Science.gov (United States)

    Fernández-Fernández, Cristina; Callado, Luis F; Girón, Rocío; Sánchez, Eva; Erdozain, Amaia M; López-Moreno, José Antonio; Morales, Paula; Rodríguez de Fonseca, Fernando; Fernández-Ruiz, Javier; Goya, Pilar; Meana, J Javier; Martín, M Isabel; Jagerovic, Nadine

    2014-01-01

    Based on numerous pharmacological studies that have revealed an interaction between cannabinoid and opioid systems at the molecular, neurochemical, and behavioral levels, a new series of hybrid molecules has been prepared by coupling the molecular features of two wellknown drugs, ie, rimonabant and fentanyl. The new compounds have been tested for their affinity and functionality regarding CB1 and CB2 cannabinoid and μ opioid receptors. In [35S]-GTPγS (guanosine 5′-O-[gamma-thio]triphosphate) binding assays from the post-mortem human frontal cortex, they proved to be CB1 cannabinoid antagonists and μ opioid antagonists. Interestingly, in vivo, the new compounds exhibited a significant dual antagonist action on the endocannabinoid and opioid systems. PMID:24591816

  18. Intranasal fentanyl for pain management in children: a systematic review of the literature.

    Science.gov (United States)

    Mudd, Shawna

    2011-01-01

    Intranasally administered fentanyl (INF) has been studied as an alternate route of delivery for pain relief in children. The purpose of this systematic review is to evaluate the available research evidence on the use of INF in the pediatric population. A search was conducted of PubMed, ISI, Scopus, Popline, CINAHL, and Embase for research studies evaluating INF in this population (0-18 years of age). The studies were graded on the strength of the evidence and the results reviewed. All of the reviewed studies showed similar or improved pain scores when compared with other opioids and administration methods. No severe adverse outcomes were reported. Current evidence suggests that INF is a safe and effective method of pain management for children in a variety of clinical settings. Copyright © 2011 National Association of Pediatric Nurse Practitioners. Published by Mosby, Inc. All rights reserved.

  19. Propofol and fentanyl sedation for laser treatment of retinopathy of prematurity to avoid intubation.

    Science.gov (United States)

    Piersigilli, Fiammetta; Di Pede, Alessandra; Catena, Gino; Lozzi, Simona; Auriti, Cinzia; Bersani, Iliana; Capolupo, Irma; Lipreri, Anna; Di Ciommo, Vincenzo; Dotta, Andrea; Sgrò, Stefania

    2017-10-03

    Despite the optimization of neonatal assistance, severe retinopathy of prematurity (ROP, stage III-IV) remains a common condition among preterm infants. Laser photocoagulation usually requires general anesthesia and intubation, but extubation can be difficult and these infants often affected by chronic lung disease. We retrospectively evaluated the clinical charts of 13 neonates that were sedated with propofol in association with fentanyl for the laser treatment of ROP. This protocol was introduced in our unit to avoid intubation and minimize side effects of anesthesia and ventilation. Propofol 5% followed by a bolus of fentanyl was administered as sedation during laser therapy to 13 preterm infants, affected by ROP stage III-IV. Propofol was initially infused as a slow bolus of 2-4 mg/kg and then continuously during the entire procedure, at 4 mg/kg/hour, increasing the dosage to 6 mg/kg/hour if sedation was not achieved. A laryngeal mask was placed and patients were ventilated with a flow-inflating resuscitation bag. Thirteen neonates were treated allowing to perform surgery without intubation. Only 4/13 (30.8%) of infants required minimal respiratory support during and/or after surgery. Heart rate after the intervention was higher than that at the beginning while remaining in the range of normal values. Blood pressures before, during and after surgery were similar. No episodes of bradycardia nor hypotension were recorded. Laser treatment was always successful. The good level of anesthesia and analgesia achieved sustains the efficacy of sedation with propofol during laser photocoagulation to avoid intubation and mechanical ventilation during and after the procedure.

  20. Combining rimonabant and fentanyl in a single entity: preparation and pharmacological results

    Directory of Open Access Journals (Sweden)

    Fernández-Fernández C

    2014-02-01

    Full Text Available Cristina Fernández-Fernández,1 Luis F Callado,2 Rocío Girón,3 Eva Sánchez,3 Amaia M Erdozain,2 José Antonio López-Moreno,4 Paula Morales,1 Fernando Rodríguez de Fonseca,5 Javier Fernández-Ruiz,6 Pilar Goya,1 J Javier Meana,2 M Isabel Martín,3 Nadine Jagerovic1 1Instituto de Química Médica, CSIC, Madrid, 2Departamento de Farmacología, Universidad del Pais Vasco, UPV/EHU, CIBERSAM, Leioa, 3Departamento de Farmacología y Nutrición, Ciencias de la Salud, Universidad Rey Juan Carlos, Alcorcón, 4Departamento de Psicobiologia, Universidad Complutense de Madrid, Madrid, 5Laboratorio de Medicina Regenerativa, Hospital Carlos Haya, Fundación IMABIS, Málaga, 6Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, CIBERNED, IRYCIS, Universidad Complutense de Madrid, Madrid, Spain Abstract: Based on numerous pharmacological studies that have revealed an interaction between cannabinoid and opioid systems at the molecular, neurochemical, and behavioral levels, a new series of hybrid molecules has been prepared by coupling the molecular features of two wellknown drugs, ie, rimonabant and fentanyl. The new compounds have been tested for their affinity and functionality regarding CB1 and CB2 cannabinoid and µ opioid receptors. In [35S]-GTPγS (guanosine 5’-O-[gamma-thio]triphosphate binding assays from the post-mortem human frontal cortex, they proved to be CB1 cannabinoid antagonists and µ opioid antagonists. Interestingly, in vivo, the new compounds exhibited a significant dual antagonist action on the endocannabinoid and opioid systems. Keywords: fentanyl, rimonabant, cannabinoid, opioid, behavioral assays

  1. Patient-Controlled Fentanyl Iontophoretic Transdermal System Improved Postoperative Mobility Compared to Intravenous Patient-Controlled Analgesia Morphine: A Pooled Analysis of Randomized, Controlled Trials.

    Science.gov (United States)

    Oliashirazi, Ali; Wilson-Byrne, Timothy; Shuler, Franklin D; Parvizi, Javad

    2017-02-01

    Postoperative pain management protocols that use patient-controlled analgesia (PCA) can hinder mobility due to attached machinery and tubing. Immobility in the postoperative setting can increase complications, length of stay (LOS), and costs. Early and enhanced mobilization can reduce the cost of care while improving patient outcomes. A needle-free, compact, patient-activated, and portable fentanyl iontophoretic transdermal system (fentanyl ITS, IONSYS; The Medicines Company, Parsippany NJ) has been shown to provide comparable efficacy and tolerability to intravenous (IV) PCA morphine that promotes improved mobility. This pooled analysis of 1,882 patients across three randomized, controlled trials compared fentanyl ITS to IV PCA morphine for postoperative pain management. Outcomes of patient mobility were assessed by a validated Patient Ease of Care Questionnaire that was given to patients, patients' nurses, and physical therapists involved in patient care. Safety was assessed via spontaneously reported treatment-emergent adverse events (TEAE). Fentanyl ITS significantly improved overall patient mobility, each mobility subscore (P mobility assessments. TEAEs were generally similar between the two groups. However, more patients reported an opioid-related TEAE with morphine IV PCA than with fentanyl IV PCA (P = 0.003). Due to improved mobility with fentanyl ITS, complications are expected to be less frequent than with IV PCA and epidural PCA. Incorporation of this strategy into postoperative pain management protocols may reduce LOS and total hospital costs. © 2016 World Institute of Pain.

  2. Fentanyl induces autophagy via activation of the ROS/MAPK pathway and reduces the sensitivity of cisplatin in lung cancer cells.

    Science.gov (United States)

    Yao, Jiaqi; Ma, Chi; Gao, Wei; Liang, Jinxiao; Liu, Chang; Yang, Hongfang; Yan, Qiu; Wen, Qingping

    2016-12-01

    Cancer pain is the most common complication of lung carcinoma. Opioid agonist fentanyl is widely used for relieving pain in cancer patients, and cisplatin (DDP)‑based chemotherapy is commonly used for the treatment of advanced lung cancer; these two drugs are always used together in lung carcinoma patients. However, the mechanisms and related biological pathways by which fentanyl influences cisplatin sensitivity are relatively poorly reported. Here, we found that fentanyl reduces the sensitivity of cisplatin in human lung cancer cells and induces autophagy. Fentanyl induced reactive oxygen species (ROS) generation and JNK activation. N-acetyl‑L‑cysteine is a ROS scavenger and antioxidant, and the inhibition of JNK with SP600125 prevented fentanyl‑induced autophagy. We also found that 3-methyladenine (3-MA; an autophagy inhibitor) increased the sensitivity of DDP and weakened the inhibition of fentanyl. In conclusion, fentanyl reduces the sensitivity of cisplatin in lung cancer cells through the ROS-JNK-autophagy pathway, whereas the autophagy inhibitor 3-MA may weaken this effect.

  3. Comparison of the Effects of 3 Methods of Intrathecal Bupivacaine, Bupivacaine-Fentanyl, and Bupivacaine-Fentanyl-Magnesium Sulfate on Sensory Motor Blocks and Postoperative Pain in Patients Undergoing Lumbar Disk Herniation Surgery.

    Science.gov (United States)

    Attari, Moahammad A; Najafabadi, Fereidoun Mortazavi; Talakoob, Reyhanak; Abrishamkar, Saeid; Taravati, Hosein

    2016-01-01

    The aim of this study was to investigate the effects of adding intrathecal (IT) fentanyl and magnesium sulfate (MgSO4) to bupivacaine on sensory motor blocks and postoperative pain in patients undergoing lumbar disk herniation surgery. In a double-blind randomized clinical trial, the patients undergoing lumbar disk herniation surgery were allocated to receive hyperbaric bupivacaine (A), or hyperbaric bupivacaine and fentanyl (B), hyperbaric bupivacaine, fentanyl and MgSO4 (C) IT. Data were collected regarding the onset of sensory block and time to regression to T10, time to complete motor block and full motor recovery, time to first analgesic requirement, postoperative pain score, and analgesic consumption and side effects. Prandomized and assigned to 3 groups (n=35 in each groups). There were no significant differences between groups in regard to time to reach the T10 level of sensory block (P=0.82), time to regression to T10 (P=0.11), and the time to complete motor block (P=0.58). Meanwhile, the time to complete recovery of motor function was significantly longer in group C (116.4±18.4, 126.4±25.5, 130.2±15.7 min, respectively, P=0.016). Time to first analgesic requirement was also significantly longer in group C (3.26±1.12, 5.57±0.92, 6.91±1.27 h, respectively, P<0.001). Total morphine consumption was significantly less in group C (14.3±4.3, 8.3±3.5, 6±3.6 mg, respectively, P<0.001). The severity of pain was significantly less in C group (P<0.001). In patients undergoing lumbar disk herniation surgery, IT MgSO4 in combination with bupivacaine-fentanyl can decrease severity of postoperative pain and analgesic consumption without additional side effect.

  4. Nitrous Oxide 70% for Procedural Analgosedation in a Pediatric Emergency Department With or Without Intranasal Fentanyl?: Analgesic Efficacy and Adverse Events if Combined With Intranasal Fentanyl.

    Science.gov (United States)

    Seiler, Michelle; Landolt, Markus A; Staubli, Georg

    2017-07-03

    Nitrous oxide 70% (N20 70%) is an excellent medication for procedural analgosedation in a pediatric emergency department. However, its analgesic efficacy remains uncertain for painful procedures; therefore, a combination with intranasal fentanyl (INF), an opioid, was suggested. This study aimed at observing and assessing the analgesic efficacy and rate of adverse events using N20 70% with and without INF. Children who received N20 70% in a tertiary children's hospital emergency department from January 1, 2014 to June 30, 2015 were included in this observational study with prospective data collection. Physicians decided individually whether INF was administered. Medical staff documented the child's behavior during the procedure, adverse events, and satisfaction rate. A total of 442 children were included; 206 (46.6%) received INF. Group differences regarding patient behavior were not statistically significant; however, N20 70% application time was longer in the INF group (P = .02). Nausea was the most frequent adverse event with 13.1% in the INF group versus 8.1% without INF. Inadequate procedural analgosedation was documented only in the INF group, affecting 1.8% of all patients (P = .002). In contrast, anxiety was exclusively observed in the group without INF, which was presumably misjudged pain (P = .03); the satisfaction rate in the INF group was 95.6% compared with 98.7% without INF. Because of the study design and limitations, no conclusions about adding INF to N20 70% can be made. Additional research is needed to investigate the effect of combining N20 70% with INF.

  5. Reversal of overdose on fentanyl being illicitly sold as heroin with naloxone nasal spray: A case report.

    Science.gov (United States)

    Fareed, Ayman; Buchanan-Cummings, Ann Marie; Crampton, Kelli; Grant, Angela; Drexler, Karen

    2015-08-01

    This is a case report describing a reversal of fentanyl overdose with naloxone nasal spray. The patient was not aware that he overdosed on fentanyl being sold as heroin. The Veterans Health Administration (VHA) has implemented an initiative to provide education for veterans, their families, friends and significant others about opioid overdose and use of naloxone reversal kits. The Atlanta VA Medical Center adopted this program to reduce the risk of opioid overdose in high risk patients. Over the past year, we provided educational sessions for 63 veterans and their families. We also prescribed 41 naloxone kits. We have received three reports of opioid overdose reversal with use of naloxone kits prescribed by the Atlanta VA Medical Center. The authors recommend that public health administrators and policy makers advocate for the implementation of these programs to reduce the rising number of overdose death in the United States and worldwide. © American Academy of Addiction Psychiatry.

  6. Dose sparing of induction dose of propofol by fentanyl and butorphanol: A comparison based on entropy analysis

    Directory of Open Access Journals (Sweden)

    Jasleen Kaur

    2013-01-01

    Full Text Available Background: The induction dose of propofol is reduced with concomitant use of opioids as a result of a possible synergistic action. Aim and Objectives: The present study compared the effect of fentanyl and two doses of butorphanol pre-treatment on the induction dose of propofol, with specific emphasis on entropy. Methods: Three groups of 40 patients each, of the American Society of Anaesthesiologistsphysical status I and II, were randomized to receive fentanyl 2 μg/kg (Group F, butorphanol 20 μg/kg (Group B 20 or 40 μg/kg (Group B 40 as pre-treatment. Five minutes later, the degree of sedation was assessed by the observer′s assessment of alertness scale (OAA/S. Induction of anesthesia was done with propofol (30 mg/10 s till the loss of response to verbal commands. Thereafter, rocuronium 1 mg/kg was administered and endotracheal intubation was performed 2 min later. OAA/S, propofol induction dose, heart rate, blood pressure, oxygen saturation and entropy (response and state were compared in the three groups. Statistical Analysis: Data was analyzed using ANOVA test with posthoc significance, Kruskal-Wallis test, Chi-square test and Fischer exact test. A P<0.05 was considered as significant. Results: The induction dose of propofol (mg/kg was observed to be 1.1±0.50 in Group F, 1.05±0.35 in Group B 20 and 1.18±0.41 in Group B40. Induction with propofol occurred at higher entropy values on pre-treatment with both fentanyl as well as butorphanol. Hemodynamic variables were comparable in all the three groups. Conclusion: Butorphanol 20 μg/kg and 40 μg/kg reduce the induction requirement of propofol, comparable to that of fentanyl 2 μg/kg, and confer hemodynamic stability at induction and intubation.

  7. Innate Immune Signalling Genetics of Pain, Cognitive Dysfunction and Sickness Symptoms in Cancer Pain Patients Treated with Transdermal Fentanyl

    Science.gov (United States)

    Barratt, Daniel T.; Klepstad, Pål; Dale, Ola; Kaasa, Stein; Somogyi, Andrew A.

    2015-01-01

    Common adverse symptoms of cancer and chemotherapy are a major health burden; chief among these is pain, with opioids including transdermal fentanyl the mainstay of treatment. Innate immune activation has been implicated generally in pain, opioid analgesia, cognitive dysfunction, and sickness type symptoms reported by cancer patients. We aimed to determine if genetic polymorphisms in neuroimmune activation pathways alter the serum fentanyl concentration-response relationships for pain control, cognitive dysfunction, and other adverse symptoms, in cancer pain patients. Cancer pain patients (468) receiving transdermal fentanyl were genotyped for 31 single nucleotide polymorphisms in 19 genes: CASP1, BDNF, CRP, LY96, IL6, IL1B, TGFB1, TNF, IL10, IL2, TLR2, TLR4, MYD88, IL6R, OPRM1, ARRB2, COMT, STAT6 and ABCB1. Lasso and backward stepwise generalised linear regression were used to identify non-genetic and genetic predictors, respectively, of pain control (average Brief Pain Inventory fentanyl concentrations did not predict between-patient variability in these outcomes, nor did genetic factors predict pain control, sickness response or opioid adverse event complaint. Carriers of the MYD88 rs6853 variant were half as likely to have cognitive dysfunction (11/111) than wild-type patients (69/325), with a relative risk of 0.45 (95% CI: 0.27 to 0.76) when accounting for major non-genetic predictors (age, Karnofsky functional score). This supports the involvement of innate immune signalling in cognitive dysfunction, and identifies MyD88 signalling pathways as a potential focus for predicting and reducing the burden of cognitive dysfunction in cancer pain patients. PMID:26332828

  8. Innate Immune Signalling Genetics of Pain, Cognitive Dysfunction and Sickness Symptoms in Cancer Pain Patients Treated with Transdermal Fentanyl.

    Directory of Open Access Journals (Sweden)

    Daniel T Barratt

    Full Text Available Common adverse symptoms of cancer and chemotherapy are a major health burden; chief among these is pain, with opioids including transdermal fentanyl the mainstay of treatment. Innate immune activation has been implicated generally in pain, opioid analgesia, cognitive dysfunction, and sickness type symptoms reported by cancer patients. We aimed to determine if genetic polymorphisms in neuroimmune activation pathways alter the serum fentanyl concentration-response relationships for pain control, cognitive dysfunction, and other adverse symptoms, in cancer pain patients. Cancer pain patients (468 receiving transdermal fentanyl were genotyped for 31 single nucleotide polymorphisms in 19 genes: CASP1, BDNF, CRP, LY96, IL6, IL1B, TGFB1, TNF, IL10, IL2, TLR2, TLR4, MYD88, IL6R, OPRM1, ARRB2, COMT, STAT6 and ABCB1. Lasso and backward stepwise generalised linear regression were used to identify non-genetic and genetic predictors, respectively, of pain control (average Brief Pain Inventory < 4, cognitive dysfunction (Mini-Mental State Examination ≤ 23, sickness response and opioid adverse event complaint. Serum fentanyl concentrations did not predict between-patient variability in these outcomes, nor did genetic factors predict pain control, sickness response or opioid adverse event complaint. Carriers of the MYD88 rs6853 variant were half as likely to have cognitive dysfunction (11/111 than wild-type patients (69/325, with a relative risk of 0.45 (95% CI: 0.27 to 0.76 when accounting for major non-genetic predictors (age, Karnofsky functional score. This supports the involvement of innate immune signalling in cognitive dysfunction, and identifies MyD88 signalling pathways as a potential focus for predicting and reducing the burden of cognitive dysfunction in cancer pain patients.

  9. Location of the hydrophobic pocket in the binding site of fentanyl analogs in the m-opioid receptor

    Directory of Open Access Journals (Sweden)

    LJILJANA DOSEN–MICOVIC

    2007-07-01

    Full Text Available Fentanyl is a highly potent and clinically widely used narcotic analgesic. The synthesis of its analogs remains a challenge in an attempt to develop highly se­lective m-opioid receptor agonists with specific pharmacological properties. In this paper, the use of flexible molecular docking of several specific fentanyl analogs to the m-opioid receptor model, in order to test the hypothesis that the hydrophobic po­cket accommodates alkyl groups at position 3 of the fentanyl skeleton, is descri­bed. The stereoisomers of the following compounds were studied: cis- and trans-3-me­thylfentanyl, 3,3-dimethylfentanyl, cis- and trans-3-ethylfentanyl, cis- and trans-3-propylfentanyl, cis-3-isopropylfentanyl and cis-3-benzylfentanyl. The opti­mal position and orientation of these fentanyl analogs in the binding pocket of the m-receptor, explaining their enantiospecific potency, were determined. It was found that the 3-alkyl group of cis-3R,4S and trans-3S,4S stereoisomers of all the active compounds occupies the hydrophobic pocket between TM5, TM6 and TM7, made up of the amino acids Trp318 (TM7, Ile322 (TM7, Ile301 (TM6 and Phe237 (TM5. However, the fact that this hydrophobic pocket can also accommodate the bulky 3-alkyl substituents of the two inactive compounds: cis-3-isopro­pylfentanyl, and cis-3-benzylfentanyl, indicates that this hydrophobic pocket in the employed receptor model is probably too large.

  10. Fentanyl pectin nasal spray for painful mucositis in head and neck cancers during intensity-modulated radiation therapy with or without chemotherapy.

    Science.gov (United States)

    Mazzola, R; Ricchetti, F; Fiorentino, A; Giaj-Levra, N; Fersino, S; Tebano, U; Albanese, S; Gori, S; Alongi, F

    2017-05-01

    The aim of the current analysis was to evaluate the effectiveness and tolerability of rapid onset opioid in a cohort of head and neck cancer (HNC) patients affected by painful mucositis influencing swallowing function during RT ± ChT with definitive or adjuvant intent. A retrospective analysis was conduct on HNC patients during RT ± ChT that received fentanyl pectin na sal spray (FPNS) for incidental BTP due to painful mucositis 13 min before the main meals. The period of observation has been 90 days starting from the beginning of RT ± ChT. Forty HNC patients with incidental BTP due to painful mucositis treated with FPNS were analyzed. The mean NRS of untreated episodes of BTP was 5.73 ± 1.54 decreasing to 2.25 ± 2.45 with FPNS (median dose 100 mcg). During the pain treatment, the number of meals increased from 2.08 ± 0.35 to 2.868 ± 0.4 (p = 0.000), and the BMI remained stable (from 25.086 ± 3.292 to 25.034 ± 3.090; p = 0.448). The 94.9% of patients was satisfied or very satisfied for the rapidity of the effect, and 97.4% for the easiness and convenience in the use. FPNS showed an acceptable safety activity profile in predictable BTP due to painful mucositis in HNC patients during RT ± ChT. FPNS was also effective in reducing the mucositis sequelae and allowing the completion of RT scheduled scheme. Moreover, patients declared satisfaction in terms of ease of use.

  11. A comparative study of efficacy of esmolol and fentanyl for pressure attenuation during laryngoscopy and endotracheal intubation

    Directory of Open Access Journals (Sweden)

    Shobhana Gupta

    2011-01-01

    Full Text Available Objective: To compare the effectiveness of single bolus dose of esmolol or fentanyl in attenuating the hemodynamic responses during laryngoscopy and endotracheal intubation. Methods: Ninety adult ASA I and ASA II patients were included in the study who underwent elective surgical procedures. Patients were divided into three groups. Group C (control receiving 10 ml normal saline, group E (esmolol receiving bolus dose of esmolol 2 mg/kg and group F (fentanyl receiving bolus dose of fentanyl 2 μg/kg intravenously slowly. Study drug was injected 3 min before induction of anesthesia. Heart rate, systemic arterial pressure and ECG were recorded as baseline and after administration of study drug at intubation and 15 min thereafter. Results: Reading of heart rate, blood pressure and rate pressure product were compared with baseline and among each group. The rise in heart rate was minimal in esmolol group and was highly significant. Also the rate pressure product at the time of intubation was minimal and was statistically significant rate 15 min thereafter in group E. Conclusion: Esmolol 2 mg/kg as a bolus done proved to be effective in attenuating rises in heart rate following laryngoscopy and intubation while the rise in blood pressure was suppressed but not abolished by bolus dose of esmolol.

  12. Comparing ‘remifentanil-propofol’ and ‘fentanyl-propofol’ in patients undergoing craniotomy for supratentorial space-occupying lesions

    Directory of Open Access Journals (Sweden)

    S Yousef Zadeghan

    2012-12-01

    Full Text Available Background: Control of intracranial pressure (ICP before, during and after neurosurgical operations is crucially important. Therefore, trying different methods and drug combinations to attain this goal is an ongoing effort in anesthesiology. In this study we compared two combinations of a narcotic agent with propofol in neurosurgical operations to control intracranial pressure.Methods: In this prospective randomized double-blind clinical trial, we enrolled 34 patients with supratentorial brain tumors who were candidates for craniotomy in Alzahra Hospital in Isfahan, Iran from April 2008 to April 2009. The patients were randomly divided into two groups of 17, in whom the first and the second group, respectively, received a combination of "propofol and fentanyl" and a combination of "propofol and remifentanyl" as maintenance of anesthesia. The hemodynamic status, ICP during the surgery, and post-surgical complications in recovery unit were observed for and registered in a questionnaire.Results: Hemodynamic status was similar in both groups and they did not differ in recovery complications except for pain which was more prevalent in remifentanil group (P<0.03. Although the patients in fentanyl group better responded to the drug for lowering ICP than remifentanyl group, but the difference was not statistically significant.Conclusion: There is no difference between these two anesthetic agent combinations and both could be useful in the anesthesia of neurosurgical operations. However combination of propofol and fentanyl seem to be superior because of more pain relief and a smoother recovery period.  

  13. [Efficacy of a fentanyl citrate buccal tablet for esophageal cancer pain management in a patient unable to take oral medication].

    Science.gov (United States)

    Fujimura, Yoshinori; Nakahara, Osamu; Ohshima, Shigeki; Baba, Hideo

    2015-04-01

    We report a case ofa 60-year old male esophageal cancer patient who was unable to take oral medication, but was successfully treated using a fentanyl citrate buccal tablet. The patient survived a suicide attempt as a youth in which he ingested poison, but was left with a stricture of the esophagus. It became difficult for him to take nutrition orally, and he underwent an esophageal bypass operation, although he still required frequent endoscopic esophageal dilation. He subsequently presented with an anastomotic stenosis due to anastomotic leakage, and oral intake became completely impossible. The onset of esophageal cancer presented as corrosive esophagitis. We used oxycodone hydrochloride to treat a sharp pain resulting from cataplectic cancer in the jejunal tube, but this provided only limited pain relief. We therefore used a fentanyl citrate oral mucosa absorption preparation with a rescue agent, which did provide effective pain relief. Thus a fentanyl citrate buccal tablet could effectively relief pain in cancer patients who are unable to receive oral medication.

  14. Low-dose epidural top up for emergency caesarean delivery: a randomised comparison of levobupivacaine versus lidocaine/epinephrine/fentanyl.

    Science.gov (United States)

    Balaji, P; Dhillon, P; Russell, I F

    2009-10-01

    Levobupivacaine has a greater safety margin for cardiotoxicity than bupivacaine; consequently it has been recommended as the agent of choice for extending low-dose epidural analgesia for emergency caesarean section. We wished to compare the onset of levobupivacaine with that of a 2% lidocaine/epinephrine/fentanyl mixture. In a prospective, single blind study, we compared the speed of onset and efficacy of 20 mL of plain 0.5% levobupivacaine with 2% lidocaine/epinephrine 100 mug/fentanyl 100 mug for extending a previous low-dose labour epidural for emergency caesarean section in 100 patients. The median [interquartile range] onset time for block of the T7 dermatome to touch from the end of the top up for 2% lidocaine /epinephrine/fentanyl mixture and levobupivacaine was 10 [8, 13] vs. 15 [10, 20] min respectively (Plevobupivacaine (median 145 s [120, 200] vs. 60 s [44, 60] Plevobupivacaine: 15 [15, 19] vs. 18 [13.8, 22.4] min (Panaesthesia was not required for inadequate blocks but additional local anaesthetic or intraoperative analgesic supplements were needed more frequently in the levobupivacaine group: 9% vs. 29%, (Plevobupivacaine 20 mL.

  15. Differential effect of intravenous S-ketamine and fentanyl on atypical odontalgia and capsaicin-evoked pain.

    Science.gov (United States)

    Baad-Hansen, Lene; Juhl, Gitte Irene; Jensen, Troels Staehelin; Brandsborg, Birgitte; Svensson, Peter

    2007-05-01

    Atypical odontalgia (AO) is an intraoral pain condition of currently unknown mechanisms. In 10 AO patients and 10 matched healthy controls, we examined the effect of intravenous infusion of an N-methyl-D-aspartate (NMDA) receptor antagonist S-ketamine and a mu-opioid agonist fentanyl on spontaneous AO pain and on an acute intraoral nociceptive input evoked by topical application of capsaicin. The drugs were administered in a randomized, placebo-controlled, cross-over manner. Furthermore, measures of intraoral sensitivity to mechanical and thermal quantitative sensory testing (QST) including temporal summation were compared between groups and sides. Both drugs failed to produce an analgesic effect on spontaneous AO pain, but fentanyl effectively reduced capsaicin-evoked pain. AO patients showed increased sensitivity to capsaicin and heat pain, but no significant differences in cold and mechanical sensitivity compared with healthy controls. No side-to-side differences in QST measures were found in AO patients. The present study demonstrates that AO is unlikely to be primarily due to a persistent afferent barrage from the peripheral region. Furthermore, in contrast to studies on various neuropathic pain conditions, fentanyl and S-ketamine in the present doses failed to attenuate AO pain.

  16. Comparison of the Effects of Fentanyl and Midazolam as a Premedication in Children Undergoing Inguinal Hernial Surgery

    Directory of Open Access Journals (Sweden)

    MH Abdollahi

    2011-04-01

    Full Text Available Introduction: Premedication with midazolam can occasionally result in increased pediatric anxiety. In this study, we compared the effects of intravenous midazolam and fentanyl as pediatric premedication in children posted for inguinal hernia surgery. Methods: In this double blind randomized clinical trial study, sixty pediatric patients were randomly allocated to two study groups. Anesthesia was similar in both groups. Sedation score by Richmond agitation sedation scale was repeatedly measured on arrival to the preoperative part of the operating room, during drug administration, separation of the child from parent for transfer to the operating room, induction of anesthesia, time of transfer to the recovery room and discharge from the recovery room. Post-operative nausea and vomiting was also recorded. The collected data was analyzed with SPSS 15 and P value<0.05 was considered meaningful. Results: Baseline characteristics of the two study groups were similar. Mean RASS at separation of patients from parents; the time between the study drug administrations till separation from parents, induction of anesthesia and end of operation and need for additional drug during separation was significantly lower in the midazolam group. Opioid need in the fentanyl group was higher. Other findings were similar in the two groups. Conclusion: Use of fentanyl instead of midazolam as a premedication is not a priority in children posted for surgery.

  17. Comparison of the Effects of Intrathecal Fentanyl and Intrathecal Morphine on Pain in Elective Total Knee Replacement Surgery

    Directory of Open Access Journals (Sweden)

    Refika Kılıçkaya

    2016-01-01

    Full Text Available Objective. Total knee replacement is one of the most painful orthopedic surgical procedures. In this study, our goal was to compare the intraoperative and postoperative hemodynamic effects, the side effects, the effect on the duration of pain start, the 24-hour VAS, and the amount of additional analgesia used, of the fentanyl and morphine we added to the local anesthetic in the spinal anesthesia we administered in cases of elective knee replacement. Materials and Methods. After obtaining the approval of the Erciyes University Medical Faculty Clinical Drug Trials Ethics Committee, as well as the verbal and written consent of the patients, we included 50 patients in our prospective, randomized study. Results. In our study, the morphine group (Group M had lower pain scores in the 2nd, 6th, 12th, and 24th hours compared to the fentanyl group (Group F. When additional analgesic requirements were compared, it was found that in the 2nd, 6th, and 24th hours fewer Group M patients needed more analgesics than did Group F patients. Conclusion. The fentanyl group also had lower first analgesic requirement times than did the morphine group. In terms of nausea and vomiting, there was no statistically significant difference between the two groups.

  18. Naloxone reversal of an overdose of a novel, long-acting transdermal fentanyl solution in laboratory Beagles.

    Science.gov (United States)

    Freise, K J; Newbound, G C; Tudan, C; Clark, T P

    2012-08-01

    Opioid overdose in dogs is manifested by clinical signs such as excessive sedation, bradycardia, and hypothermia. The ability of two different intramuscular (i.m.) naloxone reversal regimens to reverse the opioid-induced effects of a fivefold overdose of long-acting transdermal fentanyl solution was evaluated in dogs. Twenty-four healthy Beagles were administered a single 13 mg/kg dose (fivefold overdose) of transdermal fentanyl solution and randomized to two naloxone reversal regimen treatment groups, hourly administration for 8 h of 40 (n = 8) or 160 μg/kg i.m. (n = 16). All dogs were sedated and had reduced body temperatures and heart rates (HRs) prior to naloxone administration. Both dosage regimens significantly reduced sedation (P naloxone regimen resulted in a nearly threefold lower odds of sedation than that of the 40 μg/kg i.m. naloxone regimen (P naloxone significantly increased the mean body temperatures and HR (P naloxone dosage regimens. The opioid-induced effects of an overdose of transdermal fentanyl solution can be safely and effectively reversed by either 40 or 160 μg/kg i.m. naloxone administered at hourly intervals. © 2012 Blackwell Publishing Ltd.

  19. Delay Efficient Method for Delivering IPTV Services

    National Research Council Canada - National Science Library

    Sangamesh; Shilpa. K. Gowda

    2014-01-01

    Internet Protocol Television (IPTV) is a system through which Internet television services are delivered using the architecture and networking methods of the Internet Protocol Suite over a packet-switched network infrastructure, e.g...

  20. Evaluation of the brain anaesthesia response monitor during anaesthesia for cardiac surgery: a double-blind, randomised controlled trial using two doses of fentanyl.

    Science.gov (United States)

    Shoushtarian, Mehrnaz; McGlade, Desmond P; Delacretaz, Louis J; Liley, David T J

    2016-12-01

    The brain anaesthesia response (BAR) monitor uses a method of EEG analysis, based on a model of brain electrical activity, to monitor the cerebral response to anaesthetic and sedative agents via two indices, composite cortical state (CCS) and cortical input (CI). It was hypothesised that CCS would respond to the hypnotic component of anaesthesia and CI would differentiate between two groups of patients receiving different doses of fentanyl. Twenty-five patients scheduled to undergo elective first-time coronary artery bypass graft surgery were randomised to receive a total fentanyl dose of either 12 μg/kg (fentanyl low dose, FLD) or 24 μg/kg (fentanyl moderate dose, FMD), both administered in two divided doses. Propofol was used for anaesthesia induction and pancuronium for intraoperative paralysis. Hemodynamic management was protocolised using vasoactive drugs. BIS, CCS and CI were simultaneously recorded. Response of the indices (CI, CCS and BIS) to propofol and their differences between the two groups at specific points from anaesthesia induction through to aortic cannulation were investigated. Following propofol induction, CCS and BIS but not CI showed a significant reduction. Following the first dose of fentanyl, CI, CCS and BIS decreased in both groups. Following the second dose of fentanyl, there was a significant reduction in CI in the FLD group but not the FMD group, with no significant change found for BIS or CCS in either group. The BAR monitor demonstrates the potential to monitor the level of hypnosis following anaesthesia induction with propofol via the CCS index and to facilitate the titration of fentanyl as a component of balanced anaesthesia via the CI index.

  1. Long non-coding RNA MALAT1 functions as a mediator in cardioprotective effects of fentanyl in myocardial ischemia-reperfusion injury.

    Science.gov (United States)

    Zhao, Zhi-Hui; Hao, Wei; Meng, Qing-Tao; Du, Xiao-Bing; Lei, Shao-Qing; Xia, Zhong-Yuan

    2017-01-01

    Long non-coding (lncRNA) MALAT1 can be increased by hypoxia or ischemic limbs. Also, downregulation of MALAT1 contributes to reduction of cardiomyocyte apoptosis. However, the functional involvement of MALAT1 in myocardial ischemia-reperfusion (I/R) injury has not been defined. This study investigated the functional involvement of lncRNA-MALAT1 in cardioprotective effects of fentanyl. HL-1, a cardiac muscle cell line from the AT-1 mouse atrial cardiomyocyte tumor lineage was pre-treated with fentanyl and generated cell model of hypoxia-reoxygenation (H/R). Relative expression of MALAT1, miR-145, and Bnip3 mRNA in cells was determined by quantitative real-time PCR. Cardiomyocyte H/R injury was indicated by lactate dehydrogenase (LDH) release and cell apoptosis. The results showed that fentanyl abrogates expression of responsive gene for H/R and induces downregulation of MALAT1 and Bnip3 and upregulation of miR-145. We found that miR-145/Bnip3 pathway was negatively regulated by MALAT1 in H/R-HL-1 cell with or without fentanyl treatment. Moreover, both MALAT1 overexpression and miR-145 knockdown reverse cardioprotective effects of fentanyl, as indicated by increase in LDH release and cell apoptosis. The reversal effect of MALAT1 for fentanyl is confirmed in cardiac ischemia/reperfusion (I/R) mice. In summary, lncRNA-MALAT1 is sensitive to H/R injury and abrogates cardioprotective effects of Fentanyl by negatively regulating miR-145/Bnip3 pathway. © 2016 International Federation for Cell Biology.

  2. Transdermal buprenorphine and fentanyl patches in cancer pain: a network systematic review

    Directory of Open Access Journals (Sweden)

    Ahn JS

    2017-08-01

    Full Text Available Jin Seok Ahn,1 Johnson Lin,2 Setsuro Ogawa,3 Chen Yuan,4 Tony O’Brien,5,6 Brian HC Le,7 Andrea M Bothwell,8 Hanlim Moon,9 Yacine Hadjiat,9 Abhijith Ganapathi9 1Division of Hematology and Oncology, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea; 2Division of Hematology and Oncology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan, Republic of China; 3Department of Anesthesiology, Nihon University School of Medicine, Tokyo, Japan; 4Department of Oncology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 5Marymount University Hospital and Hospice, 6Cork University Hospital, College of Medicine and Health, University College Cork, Cork, Ireland; 7Department of Palliative Care, Royal Melbourne Hospital, Parkville, VIC, Australia; 8In Vivo Communications (Asia, 9Mundipharma Pte Ltd, Singapore, Singapore Abstract: Treatment of cancer pain is generally based on the three-step World Health Organization (WHO pain relief ladder, which utilizes a sequential approach with drugs of increasing potency. Goals of pain management include optimization of analgesia, optimization of activities of daily living, minimization of adverse effects, and avoidance of aberrant drug taking. In addition, it is recommended that analgesic regimens are individualized and simplified to help ensure patient compliance and should provide the least invasive, easiest, and safest route of opioid administration to ensure adequate analgesia. Buprenorphine and fentanyl are two opioids available for the relief of moderate-to-severe cancer pain. Available clinical data regarding the transdermal (TD formulations of these opioids and the extent to which they fulfill the recommendations mentioned earlier are systematically reviewed, with the aim of providing additional information for oncologists and pain specialists regarding their comparative use. Due to lack of

  3. Randomized Controlled Feasibility Trial of Intranasal Ketamine Compared to Intranasal Fentanyl for Analgesia in Children with Suspected Extremity Fractures.

    Science.gov (United States)

    Reynolds, Stacy L; Bryant, Kathleen K; Studnek, Jonathan R; Hogg, Melanie; Dunn, Connell; Templin, Megan A; Moore, Charity G; Young, James R; Walker, Katherine Rivera; Runyon, Michael S

    2017-12-01

    We compared the tolerability and efficacy of intranasal subdissociative ketamine to intranasal fentanyl for analgesia of children with acute traumatic pain and investigated the feasibility of a larger noninferiority trial that could investigate the potential opioid-sparing effects of intranasal ketamine. This randomized controlled trial compared 1 mg/kg intranasal ketamine to 1.5 μg/kg intranasal fentanyl in children 4 to 17 years old with acute pain from suspected isolated extremity fractures presenting to an urban Level II pediatric trauma center from December 2015 to November 2016. Patients, parents, treating physicians, and outcome assessors were blinded to group allocation. The primary outcome, a tolerability measure, was the frequency of cumulative side effects and adverse events within 60 minutes of drug administration. The secondary outcomes included the difference in mean pain score reduction at 20 minutes, the proportion of patients achieving a clinically significant reduction in pain in 20 minutes, total dose of opioid pain medication in morphine equivalents/kg/hour (excluding study drug) required during the emergency department (ED) stay, and the feasibility of enrolling children presenting to the ED in acute pain into a randomized trial conducted under U.S. regulations. All patients were monitored until 6 hours after their last dose of study drug or until admission to the hospital ward or operating room. Of 629 patients screened, 87 received the study drug and 82 had complete data for the primary outcome (41 patients in each group). The median (interquartile range) age was 8 (6-11) years and 62% were male. Baseline pain scores were similar among patients randomized to receive ketamine (73 ± 26) and fentanyl (69 ± 26; mean difference [95% CI] = 4 [-7 to 15]). The cumulative number of side effects was 2.2 times higher in the ketamine group, but there were no serious adverse events and no patients in either group required intervention. The most

  4. Fentanyl iontophoretic transdermal system versus morphine intravenous patient-controlled analgesia for pain management following gynecological surgery: a meta-analysis of randomized, controlled trials.

    Science.gov (United States)

    Saffer, Craig S; Minkowitz, Harold S; Ding, Li; Danesi, Hassan; Jones, James B

    2015-09-01

    To compare the efficacy and safety of patient-controlled fentanyl iontophoretic transdermal system (ITS) with morphine intravenous (i.v.) patient-controlled analgesia (PCA) for pain management following gynecological surgery. Two-open-label, multicenter, randomized, active-controlled, parallel-group studies (n = 1142) were conducted that compared fentanyl ITS with morphine iv. PCA for postoperative pain. The subgroup of gynecological surgery patients from each trial was utilized for this meta-analysis (n = 604). Of these patients, 295 received fentanyl ITS (40 μg/dose) and 309 received morphine i.v. PCA (1 mg/dose) for up to 72 h. Efficacy measures included the patient global assessment (PGA) and the investigator global assessment (IGA) of the method of pain control. Gynecological surgery patients (n = 604) included in this meta-analysis had a mean age of 45 years, were predominantly Caucasian (65%) and had a mean body mass index of 29 mg/kg2. There were statistically significantly more patients treated with fentanyl ITS and more investigators who rated their pain control method as 'excellent' on the PGA at 24 h (49.3 vs 37.4%, respectively; p = 0.0029) and IGA at the last assessment (59.5 vs. 38.0%, respectively; p fentanyl ITS than morphine iv. PCA as a method of pain control.

  5. [Opioid combination of transdermal fentanyl and oral oxycodone for pain in a patient with giant-cell tumor of the sacrum].

    Science.gov (United States)

    Yoshitake, Atsushi; Yamamoto, Tatsuo; Susaki, Sachiko; Abe, Eiji

    2014-02-01

    We describe successful pain control in a patient suffering from severe pain, using an opioid combination of transdermal fentanyl and oral oxycodone. A woman in her 40s with a giant-cell tumor of the sacrum suffered from refractory 4-5/5 pain on the Wong-Baker faces pain rating scale in her sacrum, feet and legs. Despite administration of fentanyl (2,520 microg day(-1)), she could not sleep in the supine position due to pain and dysesthesia. We gradually changed her medication from transdermal fentanyl to oral oxycodone. However, the patient complained of constant drowsiness after the complete switch to oral oxycodone (120 mg x day(-1)). Hence, we reduced the oral oxycodone dose and began a combination of transdermal fentanyl and oral oxycodone in addition to increasing doses of pregabalin. With the combination of transdermal fentanyl (25 microg x hr(-1)) and oral oxycodone (60 mg x day(-1)) her pain decreased to 1-3/5 on the faces pain rating scale. Our experience suggests that an opioid combination may provide favorable pain control in patients with severe pain, while minimizing the side effects of each drug.

  6. Effects of addition of ketamine, fentanyl and saline with Propofol induction on hemodynamics and laryngeal mask airway insertion conditions in oral clonidine premedicated children.

    Science.gov (United States)

    Ghatak, Tanmoy; Singh, Dinesh; Kapoor, Rajni; Bogra, Jaishree

    2012-04-01

    The aim of this double-blind, prospective, randomized, controlled study was to compare the effect of addition of ketamine; fentanyl and saline with propofol anesthesia on hemodynamic profile and laryngeal mask airway (LMA) insertion conditions in oral clonidine premedicated children. 180 children (age 2 - 10 years) were at first given oral clonidine (4 μg/kg) 90 minutes before operation, and then were randomly allocated to receive either ketamine 0.5 mg/kg (n=60), fentanyl 1 μg/kg (n=60) or 0.9% normal saline (n=60) before induction with propofol 3.0 mg/kg. Insertion of LMA was performed within 1 minute of injection of propofol. Heart rate and mean blood pressure were noted 1 min before induction (baseline), immediately after induction, before and after insertion of LMA for up to 3 min. Following LMA insertion, 6 subjective end points were noted-mouth opening, coughing, swallowing, patient's movement, laryngospasm, and ease of an insertion. LMA insertion summed score was prepared depending upon these variables. LMA insertion summed score was nearly similar in ketamine and fentanyl group, which were significantly better than saline group (P120 secs.) was higher in fentanyl group compared to ketamine and saline group. Even in oral clonidine premedicated children, addition of ketamine with propofol provides hemodynamic stability and comparable conditions for LMA insertion like fentanyl propofol with significantly less prolonged apnea.

  7. Effects of addition of ketamine, fentanyl and saline with Propofol induction on hemodynamics and laryngeal mask airway insertion conditions in oral clonidine premedicated children

    Directory of Open Access Journals (Sweden)

    Tanmoy Ghatak

    2012-01-01

    Full Text Available Background: The aim of this double-blind, prospective, randomized, controlled study was to compare the effect of addition of ketamine; fentanyl and saline with propofol anesthesia on hemodynamic profile and laryngeal mask airway (LMA insertion conditions in oral clonidine premedicated children. Methods: 180 children (age 2 - 10 years were at first given oral clonidine (4 μg/kg 90 minutes before operation, and then were randomly allocated to receive either ketamine 0.5 mg/kg (n=60, fentanyl 1 μg/kg (n=60 or 0.9% normal saline (n=60 before induction with propofol 3.0 mg/kg. Insertion of LMA was performed within 1 minute of injection of propofol. Heart rate and mean blood pressure were noted 1 min before induction (baseline, immediately after induction, before and after insertion of LMA for up to 3 min. Following LMA insertion, 6 subjective end points were noted-mouth opening, coughing, swallowing, patient′s movement, laryngospasm, and ease of an insertion. LMA insertion summed score was prepared depending upon these variables. Results: LMA insertion summed score was nearly similar in ketamine and fentanyl group, which were significantly better than saline group (P120 secs. was higher in fentanyl group compared to ketamine and saline group. Conclusion: Even in oral clonidine premedicated children, addition of ketamine with propofol provides hemodynamic stability and comparable conditions for LMA insertion like fentanyl propofol with significantly less prolonged apnea.

  8. Pre-emptive analgesia using intravenous fentanyl plus low-dose ketamine for radical prostatectomy under general anesthesia does not produce short-term or long-term reductions in pain or analgesic use.

    NARCIS (Netherlands)

    Katz, J.; Schmid, R.L.; Snijdelaar, D.G.; Coderre, T.J.; McCartney, C.J.; Wowk, A.

    2004-01-01

    The aim of the study was to evaluate post-operative pain and analgesic use after pre-operative or post-incisional i.v. fentanyl plus low dose i.v. ketamine vs. a standard treatment receiving i.v. fentanyl but not ketamine. Men undergoing radical prostatectomy under general anesthesia were randomly

  9. The use of sublingual fentanyl for breakthrough pain by using doses proportional to opioid basal regimen.

    Science.gov (United States)

    Mercadante, Sebastiano; Prestia, Giovanna; Casuccio, Alessandra

    2013-11-01

    The aim of this study was to prospectively assess the efficacy and safety of sublingual fentanyl (SLF) in doses proportional to opioid doses used for background analgesia for the treatment of BTP of cancer patients. A sample of patients admitted to an acute palliative care unit, presenting breakthrough pain (BTP) episodes and receiving stable doses of opioids for background pain was selected to assess the efficacy and safety of SLF used in doses proportional to the basal opioid regimen used for the management of BTP. For each patient, data from four consecutive episodes were collected. For each episode, nurses collected changes in pain intensity and adverse effects when pain got severe (T0), and 5, 10, and 15 minutes after SLF was given (T15). Seventy patients were recruited for the study. The mean age was 61.7 (±11.5). Forty-one patients were males. A total of 173 episodes of BTP were recorded (mean 2.5 episodes/patient). In 19 events, documentation regarding changes in pain intensity was incomplete. Of the 154 evaluable episodes, 143 were successfully treated (92%). Mean doses of SLF were 637 µg (SD 786), and 51 patients (72.8%) received SLF doses ≥800 µg. When compared to younger adult patients, older patients received significantly lower doses of SLF (p opioid regimen. Pain intensity significantly decreased at T5, 10 and T15 (p opioid regimen for the management of BTP is safe and effective in clinical practice.

  10. Isotopic fractionation of fentanyl and its deuterated analogues by capillary gas chromatography

    Energy Technology Data Exchange (ETDEWEB)

    Sera, Shoji; Goromaru, Tsuyoshi [Fukuyama Univ., Hiroshima (Japan)

    1997-12-01

    Isotopic fractionation of fentanyl (FT) and its deuterated analogues by gas chromatography using capillary columns (CBP1 and CBP5) has been investigated. Seven kinds of analogues were labeled with 5 to 19 deuterium atoms at the anilino, propionyl and/or phenylethyl group of FT. The retention times of deuterated FT in CBP1 and CBP5 columns are inversely proportional to the number of labeled deuterium atoms in the molecule. The difference in free enegy changes ({Delta}{Delta}G) had a linear relationship with the number of labeled deuterium atoms, except for labeling at anilino and phenylethyl group. The contribution of a deuterium atom to the {Delta}{Delta}G value was estimated to be 1.13 cal/mol in CBP1 and 1.40 cal/mol in CBP5, respectively. While, its contribution in the propiony group was 2.84 cal/mol in CBP1 and 2.48 cal/mol in CBP5, respectively. An important factor in separation by GC may differences in interactions between the stationary phase of the column with the three dimensional protrusive moiety in the molecule. (author)

  11. Quantification of fentanyl in serum by isotope dilution analysis using capillary gas chromatography

    Energy Technology Data Exchange (ETDEWEB)

    Sera, Shoji; Goromaru, Tsuyoshi [Fukuyama Univ., Hiroshima (Japan); Sameshima, Teruko; Kawasaki, Koichi; Oda, Toshiyuki

    1998-06-01

    The quantitative determination of fentanyl (FT) in serum was examined by isotope dilution analysis using a capillary gas chromatograph equipped with a surface ionization detector. The separation of FT and its deuterated analogue, FT-{sup 2}H{sub 19}, was achieved within 15 min a column temperature of 260degC by using a 25 m column. Measurement of the samples prepared by the addition of a known amount of FT in the range of 0.2 to 40 ng/ml with 20 ng/ml of FT-{sup 2}H{sub 19} to human control serum allowed observation of a linear relationship between the peak area ratio and the added amount ratio. The correlation coefficient obtained by regression analysis was 0.999. The advantage of the present isotope dilution method was demonstrated by comparison with other FT analogues which substituted a propionyl group with an acetyl group or a phenethyl group with a benzyl group as the internal standard. The present method was used to determine the serum level of FT in surgical patients after i.v. administration. No endogenous compounds and concomitant drugs interfered with the detection of FT or FT-{sup 2}H{sub 19}. This method was considered to be useful for the pharmacokinetic study of FT in patients. (author)

  12. [Breakthrough pain treatment with sublingual fentanyl in patients with chronic cutaneous ulcers].

    Science.gov (United States)

    Domingo-Triadó, V; López Alarcón, M D; Villegas Estévez, F; Alba Moratillas, C; Massa Domínguez, B; Palomares Payá, F; Mínguez Martí, A; Debón Vicent, L

    2014-10-01

    The aim of the study was to assess the efficacy and safety of opioids in the management of pain in those patients with chronic cutaneous ulcers and breakthrough/incidental pain. An open-label, multicentre, prospective, uncontrolled study was conducted in the pain and ulcer units of 5 hospitals across the Comunidad Valenciana. Eligibility criteria were baseline pain 4 in the visual analogue scale or breakthrough procedural pain 4. Exclusion criteria were cognitive impairment, opioid intolerance, or patient refusal to provide informed consent. The protocol scheduled 5 controls: baseline (enrolment), 15 days, one month, 2 months, and 3 months. The main outcome measure of the study was the visual analogue scale score during rest, movement and procedures. Opioids were administered for release of the baseline pain, and sublingual fentanyl for breakthrough pain. A total of 32 patients (86.5%) completed the study. Baseline pain achieved a mean improvement of 3.6 visual analogue scale points (SD 2.3), movement pain improved by 3.9 points (SD 2.5) and procedural pain improved by 4.5 points (SD 2.8), and the mean pain intensity improvement was statistically significant from the first control and at all controls thereafter (PDolor. Published by Elsevier España. All rights reserved.

  13. A COMPARATIVE STUDY OF PREEMPTIVE USE OF 0.2% ROPIVACAINE AND 0.125% BUPIVACAINE ALONG WITH FENTANYL AND FENTANYL INCREMENTS TO PROVIDE POSTOPERATIVE EPIDURAL ANALGESIA UP TO 24 HOURS

    Directory of Open Access Journals (Sweden)

    Chiranji Lal Khedia

    2016-06-01

    Full Text Available BACKGROUND AND OBJECTIVES The present study was carried out to compare duration of analgesia, haemodynamic changes (Systolic and Diastolic Blood Pressure, Pulse Rate, Respiratory Rate, total incremental doses of epidural fentanyl required to maintain VAS 3 up to 24 hours in each group and total required incremental fentanyl doses were compared between both the groups. Once the data were collected from all the patients, they were compared using, chi-square test, two sample t-test. The p-value was calculated and P <0.05 was considered statistically significant. RESULTS The duration of analgesia was more with Group BF (245+17.58 min. than Group RF (217.6+22.41 min., thus it is concluded that difference in duration of analgesia was statistically significant between the groups (P<0.05. In this study, it was noticed that patients of Group RF required much more incremental doses of epidural fentanyl (218+31.88 μg to maintain VAS<3 up to 24 hours than group BF (170+32.27 μg, and difference was statistically significant (P<0.05. Haemodynamic parameters like SBP, DBP, HR and RR were comparable in both the groups. Hypotension and bradycardia were noted in two patients of group BF. CONCLUSION Duration of analgesia was longer and comparatively better in group BF and less incremental doses were required to maintain VAS <3 up to 24 hours as compared to group RF, but haemodynamic stability was more in group RF as compared to group BF.

  14. Is International Accounting Education Delivering Pedagogical Value?

    Science.gov (United States)

    Patel, Chris; Millanta, Brian; Tweedie, Dale

    2016-01-01

    This paper examines whether universities are delivering pedagogical value to international accounting students commensurate with the costs of studying abroad. The paper uses survey and interview methods to explore the extent to which Chinese Learners (CLs) in an Australian postgraduate accounting subject have distinct learning needs. The paper…

  15. Delivering best care in war and peace.

    Science.gov (United States)

    Moore, Alison

    2014-06-24

    Col Alan Finnegan, the fi rst Ministry of Defence professor of nursing, is driving forward research into preparing nurses for deployment and ensuring they deliver the best care possible in war and peace. Research topics range from the role of autonomous practitioners to the effects on soldiers of injuries to their genitalia.

  16. Delivering Online Examinations: A Case Study

    Directory of Open Access Journals (Sweden)

    John MESSING

    2004-07-01

    Full Text Available Delivering Online Examinations: A Case Study Jason HOWARTH John MESSING Irfan ALTAS Charles Sturt University Wagga Wagga-AUSTRALIA ABSTRACT This paper represents a brief case study of delivering online examinations to a worldwide audience. These examinations are delivered in partnership with a commercial online testing company as part of the Industry Master’s degree at Charles Sturt University (CSU. The Industry Master’s degree is an academic program for students currently employed in the IT industry. Using Internet Based Testing (IBT, these students are examined in test centres throughout the world. This offers many benefits. For example, students have the freedom of sitting exams at any time during a designated interval. Computer-based testing also provides instructors with valuable feedback through test statistics and student comments. In this paper, we document CSU’s use of the IBT system, including how tests are built and delivered, and how both human and statistical feedback is used to evaluate and enhance the testing process.

  17. Rapid Prototyping

    Science.gov (United States)

    1999-01-01

    Javelin, a Lone Peak Engineering Inc. Company has introduced the SteamRoller(TM) System as a commercial product. The system was designed by Javelin during a Phase II NASA funded small commercial product. The purpose of the invention was to allow automated-feed of flexible ceramic tapes to the Laminated Object Manufacturing rapid prototyping equipment. The ceramic material that Javelin was working with during the Phase II project is silicon nitride. This engineered ceramic material is of interest for space-based component.

  18. Modulations of NeuroD activity contribute to the differential effects of morphine and fentanyl on dendritic spine stability

    Science.gov (United States)

    Hui, Zheng; Zeng, Yan; Chu, Ji; Kam, Angel YuetFang; Loh, Horace H.; Law, Ping-Yee

    2010-01-01

    The cellular level of neurogenic differentiation 1 (NeuroD) is modulated differentially by μ-opioid receptor agonists: fentanyl increases NeuroD level by reducing the amount of miR-190, an inhibitor of NeuroD expression, whereas morphine does not alter NeuroD level. In the current study, NeuroD activity was demonstrated to be also under agonist-dependent regulation. After three-day treatment, morphine and fentanyl decreased the activity of the Ca2+/calmodulin-dependent protein kinase II α (CaMKIIα), which phosphorylates and activates NeuroD. Because NeuroD activity is determined by both the CaMKIIα activity and the cellular NeuroD level, the overall NeuroD activity was reduced by morphine, but maintained during fentanyl treatment. The differential effects of agonists on NeuroD activity were further confirmed by measuring the mRNA levels of four NeuroD downstream targets: doublecortin, Notch1, NeuroD4 and Roundabout 1. Decreased dendritic spine stability and μ-opioid receptor signaling capability were also observed when NeuroD activity was attenuated by miR-190 overexpression or treatment with KN93, a CaMKIIα inhibitor. The decrease could be rescued by NeuroD overexpression which restored NeuroD activity to the basal level. Furthermore, elevating NeuroD activity attenuated the morphine-induced decrease in dendritic spine stability. Therefore, by regulating NeuroD activity, μ-opioid receptor agonists modulate the stability of dendritic spines. PMID:20554861

  19. EFFECTS OF PREANESTHETIC SINGLE DOSE INTRAVENOUS DEXMEDETOMIDINE VERSUS FENTANYL ON HEMODYNAMIC RESPONSE TO ENDOTRACHEAL INTUBATION-A CLINICAL COMPARATIVE STUDY

    Directory of Open Access Journals (Sweden)

    Chandita

    2015-12-01

    Full Text Available INTRODUCTION Many pharmacological agents have been evaluated in regards to their efficacy of blunting the adverse cardiovascular response to laryngoscopy and tracheal intubation. The aim of this study was to evaluate the efficacy of dexmedetomidine compared to fentanyl in blunting the haemodynamic response to laryngoscopy and intubation. METHOD Sixty patients were randomly allocated into two groups (30 patients in each group. The group D received intravenously 1 µgm/kg dexmedetomidine infusion and group F received 2µgm/kg fentanyl infusion. The study drugs were prepared in an identical looking container and were infused fifteen minutes prior to induction of anaesthesia. The study drugs were infused over a period of ten minutes and all the patients underwent a similar anaesthetics technique. Heart rate (HR and blood pressure (systolic, diastolic and mean blood pressure were noted at baseline, at the end of infusion of the study drugs, after induction of anaesthesia, immediately after laryngoscopy and intubation and at 1, 3, 5, 7 and 10 minutes after laryngoscopy and intubation. RESULTS HR significantly decreased in the group D when compared to group F immediately after study drug infusion and there was statistically significant reduction in heart rate for up to 5 min after intubation in both the groups. Although HR increased after intubation in both the groups, the magnitude was lower in the group D. In both the groups, laryngoscopy and intubation led to an increase in systolic, diastolic and mean arterial pressure; the magnitude was lower in the group D. CONCLUSION Dexmeditomidine (1µ/kg attenuates these untoward responses of laryngoscopy and intubation more effectively than fentanyl (2 µ/kg when administered as bolus dose in the pre-induction period of general anaesthesia.

  20. Intravenous Dexmedetomidine Infusion Compared with that of Fentanyl in Patients Undergoing Arthroscopic Shoulder Surgery under General Anesthesia.

    Science.gov (United States)

    Abdel Hamid, Mona Hossam Eldin

    2017-01-01

    Anesthesia for arthroscopic shoulder surgery is challenging due to the need for oligaemic surgical field as well as a good postoperative recovery profile. The present study was prospective, randomized to evaluate the efficacy of dexmdetomidine infusion compared to that of fentanyl in patients undergoing arthroscopic shoulder surgery under general anesthesia. A total of 60 patients aged from thirty to fifty years, American Society of Anesthesiologists Class I/II of either sex for arthroscopic shoulder surgery, were included. The patients were divided into two groups of 30 patients each. Group I received dexmedetomidine loading 1 μg/kg over 10 min followed by maintenance 0.5 μg/kg/h and Group II Fentanyl loading 1 μg/kg followed by maintenance 0.5 μg/kg/h. Hemodynamic readings (Heart rate HR, and mean arterial blood pressure MAP) were recorded after the start of the study drug infusion (T1), after intubation (T2), then every 15 minutes till the end of surgery (T15, T30, T45, T60, T75, T90). In the PACU, MAP, and HR were recorded on arrival, after 30 min, 1 hr, and 2 hrs (R0, R30, R1 hr, R2 hr) Postoperative analgesia was assessed by visual analogue scale (VAS), Modified Observers's Assessment of Alertness and Sedation OAA/S was recorded on arrival to PACU. This study showed that in the dexmedatomidine group there was statistically significant decrease of MAP and HR after drug infusion up to two hours in the recovery period, more sedation, better control of pain and surgeon satisfaction. Iv infusion of dexamedatomidine may be an attractive option during arthroscopic shoulder surgery as it provided a better hypotensive anesthesia by lowering MAP and HR which leads to better surgical field and surgeon satisfaction than iv infusion fentanyl along with a better postoperative VAS.

  1. Intramuscular Fentanyl and Ketorolac Associated with Superior Pain Control After Pediatric Bilateral Myringotomy and Tube Placement Surgery: A Retrospective Cohort Study.

    Science.gov (United States)

    Stricker, Paul A; Muhly, Wallis T; Jantzen, Ellen C; Li, Yue; Jawad, Abbas F; Long, Alexander S; Polansky, Marcia; Cook-Sather, Scott D

    2017-01-01

    Bilateral myringotomy and pressure equalization tube insertion (BMT) is the most common surgery in children. Multiple anesthetic techniques for BMT have been proposed, but that which reliably promotes ideal recovery remains unclear. We sought to assess associations between anesthetic regimens that included single-agent (fentanyl or ketorolac) or dual-agent (fentanyl and ketorolac) analgesic therapy and the primary outcome of maximal postanesthesia care unit (PACU) pain score. Secondary outcomes included in-hospital rescue analgesic administration, recovery time, and emesis incidence. Principal analysis was conducted on a retrospective cohort of 3669 children aged 6 months to fentanyl and/or ketorolac. Routine anesthetic care included preoperative oral midazolam, general anesthesia via a mask maintained with sevoflurane and N2O or air in O2, and intramuscular analgesic administration. Multivariable analyses were performed examining relationships between analgesic regimen with the following outcomes: maximum PACU Face, Legs, Activity, Cry, and Consolability (FLACC) score = 0 or 7 to 10, oxycodone administration, and time to discharge readiness. Demographic variables, midazolam exposure, and location (main hospital vs ambulatory surgery center) were included in the multivariable analyses as potential confounders. Associations with postoperative vomiting were studied separately in 2725 children from a subsequent, nonoverlapping 12-month period using similar inclusion criteria. Fentanyl and ketorolac dose-response relationships were evaluated for selected outcome variables. Maximum FLACC = 0, maximum FLACC score of 7 to 10, and oxycodone rescue were most strongly associated with dual-agent therapy versus single-agent ketorolac: odds ratios 4.89 (95% confidence interval [CI], 4.04-5.93), 0.13 (95% CI, 0.10-0.16), and 0.11 (98.3% CI, 0.09-0.14), respectively, P fentanyl (≥1.5 µg/kg) and ketorolac (≥0.75 mg/kg), 90% had no demonstrable pain, agitation, or distress

  2. Increased Hyperalgesia and Proinflammatory Cytokines in the Spinal Cord and Dorsal Root Ganglion After Surgery and/or Fentanyl Administration in Rats.

    Science.gov (United States)

    Chang, Lu; Ye, Fang; Luo, Quehua; Tao, Yuanxiang; Shu, Haihua

    2018-01-01

    Perioperative fentanyl has been reported to induce hyperalgesia and increase postoperative pain. In this study, we tried to investigate behavioral hyperalgesia, the expression of proinflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and the activation of microglia in the spinal cord and dorsal root ganglion (DRG) in a rat model of surgical plantar incision with or without perioperative fentanyl. Four groups of rats (n = 32 for each group) were subcutaneously injected with fentanyl at 60 μg/kg or normal saline for 4 times with 15-minute intervals. Plantar incisions were made to rats in 2 groups after the second drug injection. Mechanical and thermal nociceptive thresholds were assessed by the tail pressure test and paw withdrawal test on the day before, at 1, 2, 3, 4 hours, and on the days 1-7 after drug injection. The lumbar spinal cord, bilateral DRG, and cerebrospinal fluid of 4 rats in each group were collected to measure IL-1β, IL-6, and TNF-α on the day before, at the fourth hour, and on the days 1, 3, 5, and 7 after drug injection. The lumbar spinal cord and bilateral DRG were removed to detect the ionized calcium-binding adapter molecule 1 on the day before and on the days 1 and 7 after drug injection. Rats injected with normal saline only demonstrated no significant mechanical or thermal hyperalgesia or any increases of IL-1β, IL-6, and TNF-α in the spinal cord or DRG. However, injection of fentanyl induced analgesia within as early as 4 hours and a significant delayed tail mechanical and bilateral plantar thermal hyperalgesia after injections lasting for 2 days, while surgical plantar incision induced a significant mechanical and thermal hyperalgesia lasting for 1-4 days. The combination of fentanyl and incision further aggravated the hyperalgesia and prolonged the duration of hyperalgesia. The fentanyl or surgical incision upregulated the expression of IL-1β, IL-6, and TNF-α in the

  3. Evaluating the Implementation Barriers of an Intranasal Fentanyl Pain Pathway for Pediatric Long-Bone Fractures.

    Science.gov (United States)

    Arnautovic, Tamara; Sommese, Kathryn; Mullan, Paul C; Frazier, Steven Barron; Vazifedan, Turaj; Ramirez, Dana Erikson

    2017-12-01

    This study aimed to assess physician comfort, knowledge, and implementation barriers regarding the use of intranasal fentanyl (INF) for pain management in patients with long-bone fractures in a pediatric emergency department (ED) with an INF pain pathway. A retrospective chart review was conducted of patients, 3 to 21 years old, in our ED with an International Classification of Diseases-9th Revision code for a long-bone fracture from September 1, 2013, to August 31, 2015. Patients were divided into 4 groups: (1) received INF on the pathway appropriately; (2) "missed opportunities" to receive INF, defined as either INF was ordered and then subsequently canceled (for pain ratings, ≥6/10), or INF was ordered, cancelled, and intravenous (IV) morphine given, or INF was not ordered and a peripheral IV line was placed to give IV morphine as first-line medication; (3) peripheral IV established upon ED arrival; (4) no pain medication required. Additionally, a survey regarding practice habits for pain management was completed to evaluate physician barriers to utilization of the pathway. A total of 1374 patients met the inclusion criteria. Missed opportunities were identified 41% of the time. Neither younger patient age nor more years of physician experience in the ED were associated with increased rates of missed opportunities. The survey (95% response rate) revealed greater comfort with and preference for IV morphine over INF. The high rate of missed opportunities, despite the implementation of an INF pain pathway, indicates the need for further exploration of the barriers to utilization of the INF pain pathway.

  4. Rebamipide delivered by brushite cement enhances osteoblast and macrophage proliferation.

    Directory of Open Access Journals (Sweden)

    Michael Pujari-Palmer

    Full Text Available Many of the bioactive agents capable of stimulating osseous regeneration, such as bone morphogenetic protein-2 (BMP-2 or prostaglandin E2 (PGE2, are limited by rapid degradation, a short bioactive half-life at the target site in vivo, or are prohibitively expensive to obtain in large quantities. Rebamipide, an amino acid modified hydroxylquinoline, can alter the expression of key mediators of bone anabolism, cyclo-oxygenase 2 (COX-2, BMP-2 and vascular endothelial growth factor (VEGF, in diverse cell types such as mucosal and endothelial cells or chondrocytes. The present study investigates whether Rebamipide enhances proliferation and differentiation of osteoblasts when delivered from brushite cement. The reactive oxygen species (ROS quenching ability of Rebampide was tested in macrophages as a measure of bioactivity following drug release incubation times, up to 14 days. Rebamipide release from brushite occurs via non-fickian diffusion, with a rapid linear release of 9.70% ± 0.37% of drug per day for the first 5 days, and an average of 0.5%-1% per day thereafter for 30 days. Rebamipide slows the initial and final cement setting time by up to 3 and 1 minute, respectively, but does not significantly reduce the mechanical strength below 4% (weight percentage. Pre-osteoblast proliferation increases by 24% upon exposure to 0.4 uM Rebamipide, and by up to 73% when Rebamipide is delivered via brushite cement. Low doses of Rebamipide do not adversely affect peak alkaline phosphatase activity in differentiating pre-osteoblasts. Rebamipide weakly stimulates proliferation in macrophages at low concentrations (118 ± 7.4% at 1 uM, and quenches ROS by 40-60%. This is the first investigation of Rebamipide in osteoblasts.

  5. The effect of variable-dose diazepam on dreaming and emergence phenomena in 400 cases of ketamine-fentanyl anaesthesia.

    Science.gov (United States)

    Grace, R F

    2003-09-01

    This randomised double-blind field study compared 400 anaesthetics using diazepam (0, 0.025, 0.5, 0.1, 0.175 mg.kg-1) with ketamine (1 mg.kg-1) and fentanyl (1 microg.kg-1) in Melanesian patients. Dreams were very common and generally positive in nature. A minimum of 0.1 mg.kg-1 of diazepam was needed to significantly reduce dreaming when compared with water (67.5% vs. 94.6%; p dreamers than in non-dreamers. All groups had high rate-pressure products but this was highest when diazepam was not used. Higher diazepam doses significantly reduced the increase in blood pressure and heart rate at 3 and 6 min postketamine. When used with ketamine and fentanyl, 0.1 mg.kg-1 of diazepam has favourable psychic and cardiovascular effects. Lower diazepam doses generally had little effect whereas larger doses did not enhance the benefits further.

  6. Study on the effects of six intravenous anesthetic agents on regional ventricular function in dogs (thiopental, etomidate, propofol, fentanyl, sufentanil, alfentanil)

    NARCIS (Netherlands)

    de Hert, S. G.

    1991-01-01

    This study evaluates the effects of 30 min increasing doses infusions of six intravenous anesthetic agents (thiopental, etomidate, propofol, fentanyl, sufentanil and alfentanil) on regional ventricular function in a normal and an acute ischemic heart segment in dogs. Part 1 discusses the methodology

  7. Remifentanil/midazolam versus fentanyl/midazolam for analgesia and sedation of mechanically ventilated neonates and young infants: a randomized controlled trial.

    Science.gov (United States)

    Welzing, Lars; Oberthuer, Andre; Junghaenel, Shino; Harnischmacher, Urs; Stützer, Hartmut; Roth, Bernhard

    2012-06-01

    Common opioids for analgesia and sedation of mechanically ventilated infants may tend to accumulate and cause prolonged sedation with an unpredictable extubation time. Remifentanil is a promising option due to its unique pharmacokinetic properties, which seem to be valid in adults as well as in infants. In this double-blind, randomized, controlled trial mechanically ventilated neonates and young infants (sedation regimen with low dose midazolam. The primary endpoint of the trial was the extubation time following discontinuation of the opioid infusion. Secondary endpoints included efficacy and safety aspects. Between November 2006 and March 2010, we screened 431 mechanically ventilated infants for eligibility. The intention to treat group included 23 infants who were assigned to receive either remifentanil (n = 11) or fentanyl (n = 12). Although this was designed as a pilot study, median extubation time was significantly shorter in the remifentanil group (80.0 min, IQR = 15.0-165.0) compared to the fentanyl group (782.5 min, IQR = 250.8-1,875.0) (p = 0.005). Remifentanil and fentanyl provided comparable efficacy with more than two-thirds of the measurements indicating optimal analgesia and sedation (66.4 and 70.2 %, respectively; p = 0.743). Overall, both groups had good hemodynamic stability and a comparably low incidence of adverse events. As neonates and young infants have a decreased metabolism of common opioids like fentanyl and are more prone to respiratory depression, remifentanil could be the ideal opioid for analgesia and sedation of mechanically ventilated infants.

  8. Intrathecal Fentanyl for Labour Analgesia in a Patient with Severe Mitral Stenosis and Atrial Fibrillation in Advanced Stage of Labour-Case Report

    OpenAIRE

    Vaijayanti Nitin Gadre

    2013-01-01

    Labour is an intensely painful experience and puts considerable physiological stress on the circulation. A case of rheumatic valvular heart disease with severe mitral stenosis in atrial fibrillation is discussed here in which analgesia with intrathecal fentanyl proved beneficial given during the advanced first stage of labour.

  9. Quantifying the interaction of rocuronium (Org 9426) with etomidate, fentanyl, midazolam, propofol, thiopental, and isoflurane using closed-loop feedback control of rocuronium infusion.

    Science.gov (United States)

    Olkkola, K T; Tammisto, T

    1994-04-01

    The present study was designed to evaluate the interactions of rocuronium with etomidate, fentanyl, midazolam, propofol, thiopental, and isoflurane using closed-loop feedback control of infusion of rocuronium. Sixty patients were randomly assigned to one of six sequences where anesthesia was maintained with etomidate, fentanyl, midazolam, propofol, or thiopental and nitrous oxide, or with isoflurane and nitrous oxide. The possible interaction of rocuronium with the anesthetics was quantified by determining the asymptotic steady-state rate of infusion (Iss) of rocuronium necessary to produce a constant 90% neuromuscular block. This was accomplished by applying nonlinear curve fitting to data on the cumulative dose requirement during the initial 90-min period after bolus administration of rocuronium. Patient characteristics and controller performance, i.e., the ability of the controller to maintain the neuromuscular block constant at the set-point, did not differ significantly between the groups. Iss values calculated per lean body mass were 0.64 +/- 0.22, 0.60 +/- 0.15, 0.61 +/- 0.21, 0.67 +/- 0.31, 0.63 +/- 0.15, and 0.39 +/- 0.17 mg.kg-1.h-1 in the etomidate, fentanyl, midazolam, propofol, thiopental, and isoflurane groups, respectively. The isoflurane group had a lower steady-state rate of infusion of rocuronium than the other five groups (P < 0.05). Compared to intravenous anesthetics, etomidate, fentanyl, midazolam, propofol, or thiopental, isoflurane reduced the infusion requirement of rocuronium by 35%-40%.

  10. Comparison of the analgesic properties of transdermally administered fentanyl and intramuscularly administered buprenorphine during and following experimental orthopedic surgery in sheep.

    Science.gov (United States)

    Ahern, Benjamin J; Soma, Lawrance R; Boston, Raymond C; Schaer, Thomas P

    2009-03-01

    To evaluate the analgesic properties of transdermally administered fentanyl and IM administered buprenorphine in sheep undergoing unilateral tibial osteotomy. 20 mature sheep. Fentanyl patches (n = 15 sheep) or placebo patches (5 sheep) were applied 12 hours before sheep underwent general anesthesia and a unilateral tibial osteotomy. Buprenorphine was administered to the placebo group every 6 hours commencing at time of induction. Signs of pain were assessed every 12 hours after surgery by 2 independent observers unaware of treatment groups. There were no differences in preoperative and intraoperative physiologic data between the 2 groups. Sheep treated with fentanyl required less preoperative administration of diazepam for sedation and had significantly lower postoperative pain scores, compared with those treated with buprenorphine. No complications associated with the antebrachium at the site of patch application were detected. Under the conditions of this study, transdermally administered fentanyl was a superior option to IM administered buprenorphine for alleviation of postoperative orthopedic pain in sheep. This information can be used to assist clinicians in the development of a rational analgesic regimen for research and clinical patients.

  11. Notes on the use of Azaperone and Fentanyl in the immobilization of the Bontebok (Damaliscus Dorcas Dorcas in the Bontebok National Park

    Directory of Open Access Journals (Sweden)

    G. F Barkhuizen

    1972-01-01

    Full Text Available The use of Azaperone and Fentanyl in the immobiliza- tion of the bontebok (Damaliscus dorcas dorcas is briefly discussed, and the resulting reactions of the animals to the drugs noted. Measurements of body and horn values are also given for 14 male individuals.

  12. Report of Increasing Overdose Deaths that include Acetyl Fentanyl in Multiple Counties of the Southwestern Region of the Commonwealth of Pennsylvania in 2015-2016.

    Science.gov (United States)

    Dwyer, Jessica B; Janssen, Jennifer; Luckasevic, Todd M; Williams, Karl E

    2018-01-01

    Acetyl fentanyl is a Schedule I controlled synthetic opioid that is becoming an increasingly detected "designer drug." Routine drug screening procedures in local forensic toxicology laboratories identified a total of 41 overdose deaths associated with acetyl fentanyl within multiple counties of the southwestern region of the state of Pennsylvania. The range, median, mean, and standard deviation of blood acetyl fentanyl concentrations for these 41 cases were 0.13-2100 ng/mL, 11 ng/mL, 169.3 ng/mL, and 405.3 ng/mL, respectively. Thirty-six individuals (88%) had a confirmed history of substance abuse, and all but one case (96%) were ruled multiple drug toxicities. This report characterizes this localized trend of overdose deaths associated with acetyl fentanyl and provides further evidence supporting an alarmingly concentrated opiate and opioid epidemic of both traditional and novel drugs within this region of the United States. © 2017 American Academy of Forensic Sciences.

  13. Intrathecal Fentanyl for Labour Analgesia in a Patient with Severe Mitral Stenosis and Atrial Fibrillation in Advanced Stage of Labour-Case Report

    Directory of Open Access Journals (Sweden)

    Vaijayanti Nitin Gadre

    2013-12-01

    Full Text Available Labour is an intensely painful experience and puts considerable physiological stress on the circulation. A case of rheumatic valvular heart disease with severe mitral stenosis in atrial fibrillation is discussed here in which analgesia with intrathecal fentanyl proved beneficial given during the advanced first stage of labour.

  14. A randomized controlled trial of fentanyl in the pre-emptive treatment of pain associated with turning in patients under mechanical ventilation: research protocol.

    Science.gov (United States)

    Robleda, Gemma; Roche-Campo, Ferran; Urrútia, Gerard; Navarro, Marta; Sendra, Maria-Àngels; Castillo, Ana; Rodríguez-Arias, Ainhoa; Juanes-Borrejo, Elena; Gich, Ignasi; Mancebo, Jordi; Baños, Josep-E

    2015-02-01

    To compare the effectiveness and safety of fentanyl with placebo as pre-emptive treatment for pain associated with turning in patients in intensive care units. Turning is frequently a painful procedure in this setting. Pre-emptive administration of supplementary analgesia may help decrease this pain. However, medical literature on pre-emptive analgesia in these patients is scarce. A randomized, double-blind, controlled clinical trial. This study will assess the benefits and risks of pre-emptive analgesia with fentanyl compared with placebo on turning-associated pain. Eighty patients will be recruited from among those older than 18 years and needing mechanical ventilation for at least 24 hours. Pain intensity will be assessed using the Behavioral Pain Scale. Primary outcome will be pain intensity between the baseline and 30 minutes after turning, measured by the area under the curve of the pain scale scores. Secondary outcomes will be the usefulness of physiological parameters and the Bispectral Index to measure pain and the safety of pre-emptive fentanyl in turning. The study protocol was approved in February 2011. If pre-emptive fentanyl is more effective than placebo and reasonably safe, the results of the current study may change nursing attitude in managing turning in critically ill patients. As a consequence, pain may be decreased during this nursing procedure. © 2014 John Wiley & Sons Ltd.

  15. Further Evaluation of Delta Opioid Agonists as Candidate Adjuncts to Mu Opioid Analgesics: A Comparison of Interactions between Fentanyl and either Ketamine or the Delta Agonist SNC162 in Rhesus Monkeys

    Science.gov (United States)

    Banks, Matthew L.; Folk, John E.; Rice, Kenner C.; Negus, S. Stevens

    2010-01-01

    Mu-opioid receptor agonists such as fentanyl are effective analgesics, but their clinical use is limited by untoward effects. Adjunct medications may improve the effectiveness and/or safety of opioid analgesics. This study compared interactions between fentanyl and either the noncompetitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine or the delta-opioid receptor agonist SNC162 [(+)-4-[(alphaR)-alpha-[(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-phenyl)methyl]-N,N-diethylbenzamide] in two behavioral assays in rhesus monkeys. An assay of thermal nociception evaluated tail-withdrawal latencies from water heated to 50 and 54°C. An assay of schedule-controlled responding evaluated response rates maintained under a fixed-ratio 30 schedule of food presentation. Effects of each drug alone and of three mixtures of ketamine +fentanyl (22:1, 65:1, 195:1 ketamine/fentanyl) or SNC162+fentanyl (59:1, 176:1, 528:1 SNC162/fentanyl) were evaluated in each assay. All drugs and mixtures dose-dependently decreased rates of food-maintained responding, and drug proportions in the mixtures were based on relative potencies in this assay. Ketamine and SNC162 were inactive in the assay of thermal antinociception, but fentanyl and all mixtures produced dose-dependent antinociception. Drug interactions were evaluated using dose-addition and dose-ratio analysis. Dose-addition analysis revealed that interactions for all ketamine/fentanyl mixtures were additive in both assays. SNC162/fentanyl interactions were usually additive, but one mixture (176:1) produced synergistic antinociception at 50°C. Dose-ratio analysis indicated that ketamine failed to improve the relative potency of fentanyl to produce antinociception vs. rate suppression, whereas two SNC162/fentanyl mixtures (59:1 and 176:1) increased the relative potency of fentanyl to produce antinociception. These results suggest that delta agonists may produce more selective enhancement than ketamine of mu

  16. Poor adhesion of fentanyl transdermal patches may mimic end-of-dosage failure after 48 hours and prompt early patch replacement in hospitalized cancer pain patients

    Directory of Open Access Journals (Sweden)

    Arnet I

    2016-11-01

    Full Text Available Isabelle Arnet,1 Sabrina Schacher,1 Eva Balmer,2 Dieter Koeberle,2 Kurt E Hersberger1 1Department of Pharmaceutical Sciences, Pharmaceutical Care Research Group, University of Basel, 2Palliative Care Unit, Division of Oncology/Haematology, St Claraspital, Basel, Switzerland Context: Renewal of fentanyl transdermal patch (transdermal therapeutic system [TTS] should occur every 3 days (72 hours according to manufacturer’s guidelines. Some studies mentioned patients reporting end-of-dose failure, and thus, some authors recommend shortening the interval of application to 2 days (48 hours. However, reasons for early replacement are mostly unknown. Objectives: The objectives of this study were to assess the prevalence of early replacement of fentanyl TTS in a cancer center in Basel, Switzerland, and to assess the reasons for early replacement in stationary patients. Methods: We retrieved all fentanyl TTS administered in a cancer center in Basel, Switzerland, between November 11, 2011, and January 31, 2015, from the electronic medical database. Results: A total of 739 patients (mean age 71.4±11.5 years, 55% women were administered 2,250 fentanyl TTS (dosage 6–500 µg/hour. Most replacements occurred after 72 hours (61.6% and a few after 48 hours (7.4%. Patients with early replacement after 48 hours were significantly younger (63.8 years versus 71.5 years, p<0.001 and obtained higher mean dosages of fentanyl TTS (89 µg/hour versus 44.1 µg/hour, p<0.001 and rescue medication (calculated as oral morphine equivalent in milligrams: 185.1 mg versus 39.6 mg during the first 24 hours after replacement, p<0.001. No pharmacological rationale for early replacement was observed. According to 57 physicians, nurses, and pharmacists, the most often reasons for early TTS replacement were end-of-dosage pain (41.4% and poor adhesion (31.4%. Conclusion: In the absence of any physiological, pharmacological, or environmental reasons recorded in the

  17. Delivering IT and eBusiness value

    CERN Document Server

    Willcocks, Leslie

    2001-01-01

    Delivering Business Value from IT' is focused on the evaluation issue in IT and how IT evaluation can proceed across the life-cycle of any IT investment and be linked positively to improving business performance. .Chapters 1,2 and 3 detail an approach to IT evaluation whilst chapters 4 and 5 build on these by showing two distinctive approaches to linking IT to business performance. The remaining three chapters deal with a range of evaluation issues emerging as important - specifically Internet evaluation, Y2K and beyond, EMU, quality outsourcing, infrastructure, role of benchmarking, and cost

  18. Post-operative pain and analgesic requirements after paravertebral block for mastectomy: A randomized controlled trial of different concentrations of bupivacaine and fentanyl

    Directory of Open Access Journals (Sweden)

    V Bhuvaneswari

    2012-01-01

    Full Text Available Background: Paravertebral block (PVB is useful for post-operative analgesia after breast surgery. Bupivacaine is used for PVB at higher concentrations (0.5%, which may lead to systemic toxicity after absorption. Therefore, we proposed to evaluate the efficacy of lower concentrations of bupivacaine with and without fentanyl for thoracic PVB in patients undergoing surgery for carcinoma breast. Methods: Forty-eight patients scheduled for surgery for breast cancer were enrolled in this prospective, randomized, double-blinded, placebo-controlled trial and were allocated to one of four groups: 0.25% bupivacaine with epinephrine 5 mcg/ ml, 0.25% bupivacaine + epinephrine 5 mcg/ ml with 2 mcg/ml fentanyl, 0.5% bupivacaine + epinephrine 5 mcg/ml or isotonic saline. PVB was performed and 0.3 ml/kg of the test drug was administered before induction of general anaesthesia. The primary outcome assessed was post-operative analgesic requirement for a period of 24 h. Secondary outcome measures were post-operative pain scores at rest and on movement of the arm, latency to first opioid, post-operative nausea and vomiting, quality of sleep, ability to move arm and patient satisfaction. Results: The patient characteristics and anaesthetic technique were comparable among the groups. The rescue analgesic consumption as well as cumulative pain scores at rest and on movement were significantly less in 0.25% bupivacaine+epinephrine with fentanyl and 0.5% bupivacaine+epinephrine groups (P<0.05. The average duration of analgesia was found to be 18 h after either 0.25% bupivacaine with epinephrine+fentanyl or 0.5% bupivacaine with epinephrine. Conclusions: Lower concentrations of bupivacaine can be combined with fentanyl to achieve analgesic efficacy similar to bupivacaine at higher concentrations, decreasing the risk of toxicity in PVB.

  19. Comparison of the effects of ketamine-midazolam with those of fentanyl-midazolam on cortical somatosensory evoked potentials during major spine surgery.

    Science.gov (United States)

    Langeron, O; Lille, F; Zerhouni, O; Orliaguet, G; Saillant, G; Riou, B; Coriat, P

    1997-06-01

    Cortical somatosensory evoked potentials (CSEP) allow monitoring of spinal cord function during surgery. Ketamine has been shown to enhance CSEP amplitude, but there is no previous study comparing its effects with those of other anaesthetic regimens. Therefore, we have compared the effects of ketamine with those of fentanyl, both combined with midazolam, on CSEP monitoring during major spine surgery. Twenty patients with normal preoperative CSEP were allocated randomly to a ketamine or fentanyl group. Anaesthesia was induced with ketamine 3 mg kg-1 or fentanyl 6 micrograms kg-1 i.v., and midazolam 0.3 mg kg-1 i.v in both groups, and maintained with continuous i.v infusion of ketamine 2 mg kg-1 h-1 or fentanyl 3 micrograms kg-1 h-1, combined in both groups with midazolam 0.15 mg kg-1 h-1 and 60% nitrous oxide in oxygen. CSEP were elicited by tibial posterior nerve stimulation and measured P1 and N1 latencies, and P1-N1 amplitude, CSEP were recorded before and after induction, at 15 min, 1 and 2 h after induction, during skin closure and after removal of nitrous oxide. Both groups were comparable in characteristics, duration of surgery, mean arterial pressure and temperature. CSEP latencies were not significantly affected in either group. CSEP amplitude decreased significantly over time in the fentanyl group (from mean 2.02 (SEM 0.41) to 0.95 (0.17) microV, P obtaining the first voluntary postoperative motor response was significantly greater in the ketamine group (170 (54) vs 55 (17) min, P obtain reliable CSEP during major spine surgery, and there were no significant difference between these two anaesthetic regimens for CSEP monitoring, but a longer delay for voluntary postoperative motor assessment was observed in the ketamine group.

  20. Stability of fentanyl 5 microg/mL diluted with 0.9% sodium chloride injection and stored in polypropylene syringes.

    Science.gov (United States)

    McCluskey, Susan V; Graner, Kevin K; Kemp, Jesse; Aloumanis, Vasileios; Ben, Michel; Kupiec, Thomas; Vu, Nicole

    2009-05-01

    The stability of fentanyl 5 microg/mL in 0.9% sodium chloride solution packaged in polypropylene syringes was studied. Samples of fentanyl 5 microg (as the citrate) per milliliter in 0.9% sodium chloride injection were prepared and assessed for chemical stability using a validated, stability-indicating high- performance liquid chromatographic (HPLC) assay. A total of 12 syringe samples were submitted for chemical stability testing by HPLC. The syringes were protected from light and stored in controlled ambient conditions (23-27 degrees C and 55-65% relative humidity) in an environmental chamber. Three samples were tested initially and at each 30-day interval. Each syringe sample was tested with two determinations, using the average of the determinations for the assay result. Samples were assessed for pH and inspected for color and visible particulate matter. Stability was defined as the retention of 90-110% of the initial drug concentration at 30, 60, and 90 days. Fentanyl citrate injection maintained the appearance of a clear, colorless solution, with mean +/- S.D. pH values ranging from 4.13 +/- 0.01 to 4.52 +/- 0.02 throughout the study period. Recovery of fentanyl ranged from 99.86% +/- 0.29% to 102.74% +/- 1.60% of the initial concentration, with no detectable changes in the chromatographic profiles of all tested samples. Fentanyl 5 microg (as the citrate) per milliliter in 0.9% sodium chloride injection, packaged in polypropylene syringes and stored protected from light, was stable for at least 90 days in controlled ambient conditions.

  1. Effect of Fentanyl with Lidocaine on Hemodynamical Stability of Patients with History of Hypertension in TURP Surgery: A Double Blind Controlled Clinical Trial

    Directory of Open Access Journals (Sweden)

    M. Saheban Maleki

    2016-09-01

    Full Text Available Aims: Some severe hemodynamic changes are known as problems due to 5% lidocaine spinal anesthesia at the elderly. Such changes, also, may lead to the cardio-vascular or renal problems. The aim of this study was to compare between the hemodynamic changes in two spinal-cord anesthesia methods with 5% lidocaine (the current method and with low 5% lidocaine dose with 50μg fentanyl in the elderly patients with a systemic blood-pressure increase history in the transurethral resection of the prostate (TURP. Materials & Methods: In the two-blinded clinical trial, 148 patients aged more than 50 years with benign prostate hypertrophy, who had referred to 15th of Khordad Hospital of Gonabad for TURP between 2011 and 2012, were studied. The subjects, selected via simple random sampling method, were randomly divided into two groups (n=74 per group. The first and the second groups underwent spinal-cord anesthesia with the administrations of 5% lidocaine (2cc; 100mg and 5% lidocaine (1cc; 50mg + fentanyl (1cc; 50μg, respectively. Blood-pressure and heart-rate were recorded immediately after the anesthesia and at every 5 minutes. Data was analyzed by SPSS 21 software using independent T and Fisher’s exact tests. Findings: Mean reductions in the systolic and the diastolic blood-pressures (p<0.001 and mean reduction in the heart-rate (p=0.009 in lidocaine+fentanyl group were significantly lower than lidocaine group. In lidocaine group, ephedrine and atropine administrations were required in 26 and 19 patients, respectively. Nevertheless, no administration either of ephedrine or of atropine was required in lidocaine + fentanyl group (p<0.001. Conclusion: Without any hemodynamic instability, low lidocaine dose (50mg with fentanyl (50μg may result in sufficient anesthesia and no-pain in the elderly patients with a history of controlled high-pressure, who undergo TURP.

  2. Fentanyl Patches to Supplement Ultrasound-Guided Nerve Blocks for Improving Pain Control After Foot and Ankle Surgery: A Prospective Study.

    Science.gov (United States)

    Song, Jae-Hwang; Kang, Chan; Hwang, Deuk-Soo; Hwang, Jung-Mo; Shin, Byung-Kon

    2016-01-01

    The analgesic effects of preoperative ultrasound-guided nerve blocks wear off after about 12 hours, leaving some patients in substantial pain. Transdermal fentanyl concentrations peak at 12 to 24 hours after application and maintain this concentration for approximately 72 hours. We sought to determine whether combining the use of a transdermal fentanyl patch with either a sciatic or femoral-sciatic nerve block would improve pain control in patients undergoing foot and/or ankle surgery. Consecutive patients in the no-patch control group (n = 104) were enrolled from July 2011 to October 2011, and those in the treatment group (n = 232) were enrolled from November 2011 to May 2012 and received a transdermal patch (4.125 mg/7.5 cm(2) releasing 25 μg of fentanyl per hour) applied to their chest postoperatively. Pain was assessed using a visual analog scale at 6, 12, 24, and 48 hours after surgery. The primary outcome measure was the number of requests for additional postoperative pain medication. Additional postoperative analgesia was requested by 49 of the 104 control patients (47.1%) and 63 of the 232 treated patients (27.1%; p = .002). The mean pain scores were also lower in the treatment group, with a statistically significant difference (p fentanyl patch combined with an ultrasound-guided nerve block required less supplemental analgesia to maintain adequate pain control than did those receiving a nerve block alone. In conclusion, a fentanyl patch is a useful adjunct to an ultrasound-guided nerve block in foot and ankle surgery. Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  3. Efficacy and safety of sublingual fentanyl orally disintegrating tablet at doses determined from oral morphine rescue doses in the treatment of breakthrough cancer pain.

    Science.gov (United States)

    Shimoyama, Naohito; Gomyo, Ikuo; Teramoto, Osamu; Kojima, Keisuke; Higuchi, Hitomi; Yukitoshi, Nobuyuki; Ohta, Eri; Shimoyama, Megumi

    2015-02-01

    A randomized, crossover, double-blinded placebo-controlled and non-blinded active drug-controlled, comparative clinical trial was conducted to evaluate the efficacy and safety of sublingual fentanyl tablet. Subjects were patients treated with strong opioids at fixed intervals for chronic cancer pain and with oral morphine as rescue medication for breakthrough pain. Sublingual fentanyl was administered at doses that were 1/25th (high dose) and 1/50th (low dose) of the dose of rescue morphine and was compared with placebo and oral morphine. The primary endpoint was pain intensity difference at 30 min after administration. (Clinical Trials Government; NCT00684632). Fifty-one patients were enrolled in the investigation. Their mean pain intensity in visual analog scale before rescue medication prior to the investigation was 60.96 (16.44, standard deviation) mm. Compared with placebo, the low and high doses of sublingual fentanyl showed significant analgesic effects (least squares mean difference, 4.54 and 8.49 mm; P = 0.014, P pain and with oral morphine at doses up to 20 mg as rescue medication were investigated. The doses of sublingual fentanyl to treat breakthrough pain were determined from rescue morphine doses by use of conversion ratios. In these patients, administration of sublingual fentanyl at doses determined by a conversion ratio of 1/50 was effective and safe. Further studies are needed to validate the use of this conversion method. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Randomized double-blind comparison of ketamine-propofol and fentanyl-propofol for the insertion of laryngeal mask airway in children.

    Science.gov (United States)

    Singh, Ranju; Arora, Madhur; Vajifdar, Homay

    2011-01-01

    Till date, different combinations of adjuncts with induction agents have been tried for Laryngeal Mask Airway (LMA) insertion; yet, the ideal combination that provides the best insertion conditions with minimal side effects has not been identified, particularly in children. PATIENTS #ENTITYSTARTX00026; Hundred paediatric ASA grade I and II patients, aged 3-12 years, were randomly allocated to receive intravenously either fentanyl 2μg kg(-1) (Group F, n=50) or ketamine 0.5 mg kg(-1) (Group K, n=50), before induction of anaesthesia with propofol 3.5 mg kg(-1). Arterial blood pressure and heart rate were measured before induction (baseline), immediately before induction, immediately before LMA insertion, and at 1, 3 and 5 minutes after LMA insertion. Following LMA insertion, the following six subjective endpoints were graded by a blinded anaesthetist using ordinal scales graded 1 to 3: mouth opening, gagging, swallowing, head and limb movements, laryngospasm and resistance to insertion. Duration and incidence of apnoea was also recorded. The incidence of resistance to mouth opening, resistance to LMA insertion and incidence of swallowing was not statistically significant between the two groups. Coughing/ gagging was seen in 8% patients in group K as compared to 28% patients in group K. Limb/ head movements were observed in 64% patients in the fentanyl group and in 76% patients in the ketamine group. Laryngospasm was not seen in any patient in either group. Incidence of apnoea was 80% in the fentanyl group and 50% in the ketamine group. The heart rate, systolic blood pressure, diastolic blood pressure and mean arterial pressure were consistently higher in the ketamine group as compared to the fentanyl group. The combination of fentanyl (2μg kg-1) and propofol (3.5mg kg-1) provides better conditions for LMA insertion in children than a combination of ketamine (0.5 mg kg-1) and propofol (3.5mg kg-1).

  5. Randomized double-blind comparison of ketamine-propofol and fentanyl-propofol for the insertion of laryngeal mask airway in children

    Directory of Open Access Journals (Sweden)

    Ranju Singh

    2011-01-01

    Full Text Available Background: Till date, different combinations of adjuncts with induction agents have been tried for Laryngeal Mask Airway (LMA insertion; yet, the ideal combination that provides the best insertion conditions with minimal side effects has not been identified, particularly in children. Patients & Methods: Hundred paediatric ASA grade I and II patients, aged 3-12 years, were randomly allocated to receive intravenously either fentanyl 2μg kg -1 (Group F, n=50 or ketamine 0.5 mg kg -1 (Group K, n=50, before induction of anaesthesia with propofol 3.5 mg kg -1 . Arterial blood pressure and heart rate were measured before induction (baseline, immediately before induction, immediately before LMA insertion, and at 1, 3 and 5 minutes after LMA insertion. Following LMA insertion, the following six subjective endpoints were graded by a blinded anaesthetist using ordinal scales graded 1 to 3: mouth opening, gagging, swallowing, head and limb movements, laryngospasm and resistance to insertion. Duration and incidence of apnoea was also recorded. Results: The incidence of resistance to mouth opening, resistance to LMA insertion and incidence of swallowing was not statistically significant between the two groups. Coughing/ gagging was seen in 8% patients in group K as compared to 28% patients in group K. Limb/ head movements were observed in 64% patients in the fentanyl group and in 76% patients in the ketamine group. Laryngospasm was not seen in any patient in either group. Incidence of apnoea was 80% in the fentanyl group and 50% in the ketamine group. The heart rate, systolic blood pressure, diastolic blood pressure and mean arterial pressure were consistently higher in the ketamine group as compared to the fentanyl group. Conclusion: The combination of fentanyl (2μg kg-1 and propofol (3.5mg kg-1 provides better conditions for LMA insertion in children than a combination of ketamine (0.5 mg kg-1 and propofol (3.5mg kg-1.

  6. Attenuation of the hemodynamic response to laryngoscopy and tracheal intubation with fentanyl, lignocaine nebulization, and a combination of both: A randomized controlled trial.

    Science.gov (United States)

    Kumar, Abhyuday; Seth, Anita; Prakash, Smita; Deganwa, Mangilal; Gogia, Anoop Raj

    2016-01-01

    The present study was undertaken to compare and evaluate the efficacy of intravenous (IV) fentanyl and lignocaine airway nebulization and a combination of both in attenuating the hemodynamic response to laryngoscopy and tracheal intubation. Ninety-six patients of either sex aged between 18 and 65 years of age, belonging to the American Society of Anesthesiologists (ASA) health status Classes I and II, undergoing elective surgery requiring general anesthesia with endotracheal intubation were included in the study. Patients were randomly divided into three groups. Group F received IV fentanyl 2 μg/kg, Group L received nebulization with 3 mg/kg of 4% lignocaine, and Group FL received both nebulization with 3 mg/kg of 4% lignocaine and IV fentanyl 2 μg/kg before intubation. Hemodynamic parameters were noted before and immediately after induction, 1 min after intubation, and every minute after intubation for 10 min. Hemodynamic response to laryngoscopy and intubation was not completely abolished in any of the groups. Nebulized lignocaine was least effective in attenuating hemodynamic response to intubation, and hemodynamic parameters were significantly high after intubation as compared to other groups. Fentanyl alone or in combination with nebulized lignocaine was most effective, and Group F and Group FL were comparable. The maximum increase in mean blood pressure after intubation from baseline in Groups F, L, and FL was 7.4%, 14.6%, and 5.4%, respectively. In our study, IV fentanyl 2 μg/kg administered 5 min before induction was found to be the most effective in attenuating the hemodynamic response. There was no advantage to the use of nebulized lignocaine in attenuating the hemodynamic response to laryngoscopy and intubation.

  7. DESIGNS MATTER: Delivering Information Sources for Tourism

    Directory of Open Access Journals (Sweden)

    Margie A. Nolasco

    2016-11-01

    Full Text Available Tourism has benefits not just for travelers, but also to the local economy. Since, Bicol Region has natural and cultural attractions; it is a potential travel destination in the country. Technology in delivering information sources played vital role for the success of the tourism industry in the Region. This allows travel enthusiasts to get more information about various tourist attractions. This paper analyzes the effectiveness of delivering information sources such as web advertisement and desktop publishing for tourist promotion in the Bicol Region. Specifically, it determined the status of tourism, and identified common forms of promotions for tourism development. The study adopted mixed method of research. This method was utilized to confirm and validate findings. Interviews and focus group discussions were used to gather data from the respondents of the selected Local Government Units, Department of Tourism, Travel Agencies and Hotel Agents in the Region. Based on the findings, of the total foreign visitors in the country, only 9.14% visited Bicol Region in 2014. That is why, domestic tourist showed high percentage against foreign visitors with 25.7%. Brochures with EZ maps as most commonly used desktop publishing materials and websites and social media for web advertisement. Thus, there is a need to reevaluate promotional activities by the DOT and other agencies. Adoption suggestive features for creative desktop publishing materials and web services should be considered to increase tourist visitors in the Region.

  8. Fatty acids are rapidly delivered to and extracted from membranes by methyl-β-cyclodextrin

    OpenAIRE

    Brunaldi, Kellen; Huang, Nasi; Hamilton, James A.

    2010-01-01

    We performed detailed biophysical studies of transfer of long-chain fatty acids (FAs) from methyl-β-CD (MBCD) to model membranes (egg-PC vesicles) and cells and the extraction of FA from membranes by MBCD. We used i) fluorescein phosphatidylethanolamine to detect transfer of FA anions arriving in the outer membrane leaflet; ii) entrapped pH dyes to measure pH changes after FA diffusion (flip-flop) across the lipid bilayer; and iii) soluble fluorescent-labeled FA binding protein to measure the...

  9. Preoperative epidural administration of lidocaine-methadone or lidocaine-fentanyl in female dogs undergoing elective ovariohysterectomy

    Directory of Open Access Journals (Sweden)

    Kalyne Danielly Silva de Oliveira

    2017-06-01

    Full Text Available We compared the analgesia and cardiopulmonary changes induced by epidural methadone or fentanyl in combination with lidocaine in female dogs undergoing elective ovariohysterectomy and anesthetized with propofol. Eighteen female dogs were randomly assigned to two groups and given either methadone (0.3 mg kg?¹ + 2% lidocaine without vasoconstrictor (LM or fentanyl (5 µg kg?¹ + 2% lidocaine without vasoconstrictor (LF. The drugs were administered epidurally in a volume of 0.25 ml kg?¹. Heart rate (HR, respiratory rate (RR, rectal temperature (RT, systolic blood pressure (SBP, and blood glucose levels were recorded before and 15 minutes after premedication (T0 and T1; 15 minutes after epidural administration (T2; five minutes after dermotomy (T3; five minutes after clamping of the ovarian pedicle (T4; five minutes and 1, 3, 6, 12, 18, and 24 hours (T5, T6, T7, T8, T9, T10, and T11, respectively after surgery. The number of additional propofol injections and total propofol dose (mg kg?¹ were recorded. Analgesia was assessed using a numerical descriptive scale. SBP and HR were similar in both groups, but hypotension was detected in animals from both groups at different times. Respiratory rate decreased significantly at T6 in the LF group and was lower than in the LM group. Hypothermia was observed in animals from both groups, but RT was significantly lower than baseline values only at T4 in the LM group. Blood glucose levels increased significantly only in the LF group at T4, T7, and T8. All animals in the LF group and eight animals in the LM group required additional propofol injections at T4, but no significant differences were detected in the number of propofol injections and total propofol dose between the LF (3 ± 1 injections, 7.5 ± 4.5 mg kg?¹ and LM (2 ± 2 injections, 4.5 ± 3.4 mg kg?¹ groups. The latency period, anesthetic period, and the duration of surgery were similar in both groups. No animals required rescue analgesia. The

  10. Forest conservation delivers highly variable coral reef conservation outcomes.

    Science.gov (United States)

    Klein, Carissa J; Jupiter, Stacy D; Selig, Elizabeth R; Watts, Matthew E; Halpern, Benjamin S; Kamal, Muhammad; Roelfsema, Chris; Possingham, Hugh P

    2012-06-01

    Coral reefs are threatened by human activities on both the land (e.g., deforestation) and the sea (e.g., overfishing). Most conservation planning for coral reefs focuses on removing threats in the sea, neglecting management actions on the land. A more integrated approach to coral reef conservation, inclusive of land-sea connections, requires an understanding of how and where terrestrial conservation actions influence reefs. We address this by developing a land-sea planning approach to inform fine-scale spatial management decisions and test it in Fiji. Our aim is to determine where the protection of forest can deliver the greatest return on investment for coral reef ecosystems. To assess the benefits of conservation to coral reefs, we estimate their relative condition as influenced by watershed-based pollution and fishing. We calculate the cost-effectiveness of protecting forest and find that investments deliver rapidly diminishing returns for improvements to relative reef condition. For example, protecting 2% of forest in one area is almost 500 times more beneficial than protecting 2% in another area, making prioritization essential. For the scenarios evaluated, relative coral reef condition could be improved by 8-58% if all remnant forest in Fiji were protected rather than deforested. Finally, we determine the priority of each coral reef for implementing a marine protected area when all remnant forest is protected for conservation. The general results will support decisions made by the Fiji Protected Area Committee as they establish a national protected area network that aims to protect 20% of the land and 30% of the inshore waters by 2020. Although challenges remain, we can inform conservation decisions around the globe by tackling the complex issues relevant to integrated land-sea planning.

  11. Comparison of bupivacaine alone and in combination with fentanyl or pethidine for bilateral infraorbital nerve block for postoperative analgesia in paediatric patients for cleft lip repair: A prospective randomized double blind study

    Directory of Open Access Journals (Sweden)

    Rajesh S Mane

    2011-01-01

    Conclusion: Thus we conclude that addition of fentanyl or pethidine to bupivacaine for Bilateral Intraoral Infraorbital Nerve Block prolong the duration of analgesia with no complications and can be used safely in paediatric patients.

  12. Combining Technologies to Deliver Distance Education

    Directory of Open Access Journals (Sweden)

    Vicki Freeman

    1999-01-01

    Full Text Available In 1997 a Health Resources and Services Administration (HRSA grant was awarded to the Department of Clinical Laboratory Sciences (CLS at The University of Texas Medical Branch - Galveston (UTMB for support of the Laboratory Education and Advancement Project (LEAP. The project entailed three primary objectives, targeting laboratory practitioners in rural and medically underserved areas of Texas for delivering a bachelor's degree, laboratory-intensive course of study via distance education. Several delivery mechanisms were utilized and evaluated for their effectiveness and friendliness to both the faculty and students. The authors discuss and describe the mechanisms utilized for delivery of courses, the advantages and disadvantages encountered with each mechanism, and subjective evaluation of the effectiveness of the courses. Also discussed are the lessons learned and plans for future development.

  13. Intranasal formulations: promising strategy to deliver vaccines.

    Science.gov (United States)

    Riese, Peggy; Sakthivel, Priya; Trittel, Stephanie; Guzmán, Carlos A

    2014-10-01

    The emergence of new diseases and the lack of efficient vaccines against numerous non-treatable pathogens require the development of novel vaccination strategies. To date, only a few mucosal vaccines have been approved for humans. This was in part due to i) the use of live attenuated vaccines, which are not suitable for certain groups of individuals, ii) safety concerns derived from implementation in humans of some mucosal vaccines, iii) the poor stability, absorption and immunogenicity of antigens delivered by the mucosal route and iv) the limited number of available technologies to overcome the bottlenecks associated with mucosal antigen delivery. Recent advances make feasible the development of efficacious mucosal vaccines with adequate safety profile. Thus, currently intranasal vaccines represent an attractive and valid alternative to conventional vaccines. The present review is focused on the potentials and limitations of market-approved intranasal vaccines and promising candidates undergoing clinical investigations. Furthermore, emerging strategies to overcome main bottlenecks including efficient breaching of the mucosal barrier and safety concerns by implementation of new adjuvants and delivery systems are discussed. The rational design of intranasal vaccines requires an in-depth understanding of the anatomic, physicochemical and barrier properties of the nasal mucosa, as well as the molecular mechanisms governing the activation of the local innate and adaptive immune system. This would provide the critical knowledge to establish effective approaches to deliver vaccine antigens across the mucosal barrier, supporting the stimulation of a long-lasting protective response at both mucosal and systemic levels. Current developments in the area of adjuvants, nanotechnologies and mucosal immunology, together with the identification of surface receptors that can be exploited for cell targeting and manipulating their physiological properties, will become instrumental

  14. EVALUATION OF EFFECT OF EPIDURAL ADMINISTRATION OF FENTANYL ADDED TO BUPIVACAINE, ON POST - OPERATIVE ANALGESIA, IN GYNAECOLOGICAL SURGICAL PATIENTS

    Directory of Open Access Journals (Sweden)

    Balasubramanyam

    2015-04-01

    Full Text Available Post - operative pain, which is most stressful, is receiving more attention recently. Almost each surgical procedure is associated with post - operative pain and severity depends on site and nature of surgery . 1 since the newer narcotic analgesics are no more effective as analgesics than the old; and various traditional modes of administration are associated with significant complications role of Epidural administration of Narcotic drugs has come into vogue . 2 Despite the availability of many techniques to reduce postoperative pain, the search is on for a safe, simple and readily available procedure to lessen the post - operative pain. In this study we are trying to assess the effect of Epidural administration of Fentanyl added to Bupivacaine in Gynaecological surgical patients, studying its efficacy and duration of post - operative analgesia, which is likely to reduce the complications associated with narcotic usage and effective post - operative analgesia

  15. The fentanyl/etomidate-anaesthetised beagle (FEAB) dog: a versatile in vivo model in cardiovascular safety research.

    Science.gov (United States)

    Van Deuren, Bruno; Van Ammel, Karel; Somers, Yves; Cools, Frank; Straetemans, Roel; van der Linde, Henk J; Gallacher, David J

    2009-01-01

    The purpose of conducting cardiovascular safety pharmacology studies is to investigate the pharmacological profiles of new molecular entities (NMEs) and provide data that can be used for optimization of a possible new drug, and help make a selection of NMEs for clinical development. An anaesthetised dog preparation has been used for more than two decades by our department to measure multiple cardiovascular and respiratory parameters and to evaluate different scientific models, leading to more in-depth evaluation of drug-induced cardiovascular effects. An anaesthetic regime developed in house (induction with lofentanil, scopolamine and succinylcholine, and maintenance with fentanyl and etomidate) gives us a preparation free of pain and stress, with minimal effects on the cardiovascular system. This anaesthetic regime had minimal influences on circulating catecholamine levels, on the baroreflex sensitivity, and on all measured basal parameters compared to conscious dogs. All parameters were stable for at least 3 h, with acceptable tolerance intervals, evaluated over 99 safety studies with 3 vehicle treatments (saline, 10% and 20% hydroxypropyl-beta-cyclodextrin). This translates into a highly sensitive model for detecting possible drug-induced effects of NMEs with different mechanisms of action such as: Ca-, Na-, I(Kr)-, I(Ks)-channel blockers, K- and Ca-channel activators, alpha1- and beta-agonists, and muscarinic antagonists. Fentanyl in combination with etomidate is a successful anaesthetic regime in humans [Stockham, R.J., Stanley, T.H., Pace, N.L., King, K., Groen, F. & Gillmor, S.T. (1987). Induction of anaesthesia with fentanyl or fentanyl plus etomidate in high-risk patients. Journal of Cardiothoracic Anesthesia. 1(1), 19-23.]. In the anaesthetised dog, QT correction factors (Van de Water correction and body temperature correction) and risk factors (total, short-term and long-term instability) have been evaluated, using this regime [Van de Water, A., Verheyen

  16. A marked decrease in heart rate variability associated with junctional rhythm during anesthesia with sevoflurane and fentanyl.

    Science.gov (United States)

    Fujiwara, Y; Asakura, Y; Shibata, Y; Nishiwaki, K; Komatsu, T

    2006-04-01

    Heart rate variability (HRV) was investigated using a new technique for time series analysis combining the maximum entropy method and non-linear least squares method -- the 'MemCalc method' -- in patients undergoing general anesthesia with sevoflurane and fentanyl for elective surgery. As the occurrence of junctional rhythm coincided with the measurement of these variables in two patients, we successfully evaluated the entropy, low (LF) and high (HF) frequency component of the HRV during junctional rhythm and found that the occurrence of junctional rhythm is associated with marked decreases in the entropy, LF and HF of HRV. When evaluating autonomic control of the heart using HRV analysis, the decrease in HRV caused by the occurrence of junctional rhythm must be taken into account.

  17. Effects of Fentanyl-lidocaine-propofol and Dexmedetomidine-lidocaine-propofol on Tracheal Intubation Without Use of Muscle Relaxants

    Directory of Open Access Journals (Sweden)

    Volkan Hancı

    2010-05-01

    Full Text Available The aim of this study was to compare the effects of fentanyl or dexmedetomidine when used in combination with propofol and lidocaine for tracheal intubation without using muscle relaxants. Sixty patients with American Society of Anesthesiologists stage I risk were randomized to receive 1 mg/kg dexmedetomidine (Group D, n = 30 or 2 mg/kg fentanyl (Group F, n = 30, both in combination with 1.5 mg/kg lidocaine and 3 mg/kg propofol. The requirement for intubation was determined based on mask ventilation capability, jaw motility, position of the vocal cords and the patient's response to intubation and inflation of the endotracheal tube cuff. Systolic arterial pressure, mean arterial pressure, heart rate and peripheral oxygen saturation values were also recorded. Rate pressure products were calculated. Jaw relaxation, position of the vocal cords and patient's response to intubation and inflation of the endotracheal tube cuff were significantly better in Group D than in Group F (p < 0.05. The intubation conditions were significantly more satisfactory in Group D than in Group F (p = 0.01. Heart rate was significantly lower in Group D than in Group F after the administration of the study drugs and intubation (p < 0.05. Mean arterial pressure was significantly lower in Group F than in Group D after propofol injection and at 3 and 5 minutes after intubation (p < 0.05. After intubation, the rate pressure product values were significantly lower in Group D than in Group F (p < 0.05. We conclude that endotracheal intubation was better with the dexmedetomidine–lidocaine–propofol combination than with the fentanyl–lidocaine–propofol combination. However, side effects such as bradycardia should be considered when using dexmedetomidine.

  18. Adding fentanyl to etomidate fails to reduce painful recall of external direct current cardioversion in adults: a randomised trial.

    Science.gov (United States)

    Souvatzis, Xenia; Kalogridaki, Marina; Mavrakis, Hercules E; Kanoupakis, Emmanouel M; Marouli, Diamantina; Vardas, Panos; Askitopoulou, Helen

    2015-01-01

    External electrical cardioversion under hypnotics, even when combined with opioids, has been consistently described as distressing or painful. The main objective of the present study was to determine if adding an opioid to a hypnotic, in comparison to the same hypnotic alone, would decrease the incidence of unpleasant or painful recall during anaesthesia for external electrical cardioversion. This was a single-centre, prospective, randomised, double-blinded clinical trial that took place from September 2011 to March 2012. Fifty-two adult patients with persistent atrial fibrillation, scheduled for external direct current cardioversion, were enrolled. Exclusion criteria were age >80 years, previous cardiac surgery, implanted pacemaker or defibrillator, and haemodynamic instability. Patients received intravenously either (group EF) fentanyl 50 g and after 60 s etomidate 0.1 mg/kg, or (group E) only etomidate 0.1 mg/kg. If the patients did not lose their eyelid reflex, repeated doses of etomidate 4 mg were given. Cardioversion was attempted with an extracardiac biphasic electrical shock from 200 to 300 J, at most three times. The primary endpoint was recall of something unpleasant or painful. Secondary outcome measures were predictors of the requirement for repeat doses of etomidate, and the number of shocks needed. Fifty-one patients (35 male, 16 female), aged 62.1 ± 10.2 years, completed the study. There were no differences between group EF and group E regarding recall (unpleasant recall 0 vs. 2 patients, p=0.235; painful recall 1 vs. 0 patients, p=0.510). The administration of etomidate alone was a significant predictor for subsequent repeated doses of etomidate (p=0.049, odds ratio 4.312, 95% confidence interval 1.007-18.460). The number of shocks needed to restore sinus rhythm did not differ between the groups (p=0.846). In the present study, the addition of fentanyl to etomidate did not diminish distressing or painful experience during anaesthesia for external

  19. A predictive pharmacokinetic/pharmacodynamic model of fentanyl for analgesia/sedation in neonates based on a semi-physiologic approach.

    Science.gov (United States)

    Encinas, Esther; Calvo, Rosario; Lukas, John C; Vozmediano, Valvanera; Rodriguez, Monica; Suarez, Elena

    2013-06-01

    Fentanyl is a synthetic opioid commonly used as an anesthetic and also increasingly popular as a sedative agent in neonates. Initial dosage regimens in this population are often empirically derived from adults on a body weight basis. However, ontogenic maturation processes related to drug disposition are not necessarily always body weight correlates. We developed a predictive pharmacokinetic/pharmacodynamic model that includes growth and maturation physiologic changes for fentanyl in neonatal care. Key pharmacokinetic variables and principles (protein binding, clearance, distribution) as related to fentanyl pharmacokinetic/pharmacodynamic behavior in adults (tricompartmental model) and to neonatal physiologic data (organ weights and blood flows, body composition, renal and hepatic function, etc.) were used to guide the building of a semi-physiologic ontogenic model. The model applies to a normal-term neonate without any other intervention. Then, extension to a pharmacokinetic/pharmacodynamic link model for fentanyl was made. The final model was evaluated by predicting the time course of plasma concentrations and the effect of a standard regimen of 10.5 μg/kg over a 1-h period followed by 1.5 μg/kg/h for 48 h. Hepatic clearance was linked to ontogeny of unbound fraction and of α1-acid glycoprotein. All parameters were reduced in the neonate compared to adults but in a differing proportion due to qualitative changes in physiology that are analyzed and accounted for. Systemic clearance (CLS), volume of the central compartment (V1) and steady-state volume of distribution predicted by the model were 0.028 L/min, 1.26 L, and 22.04 L, respectively. Weight-corrected parameters generally decreased in adults compared with neonates, but differentially, e.g., CLS = 0.0093 versus 0.0088 L/min/kg, while V1 = 0.42 versus 0.18 L/kg (neonates vs. adults). Under such complexity a pharmacokinetic/pharmacodynamic model is the appropriate method for rational efficacy targeting

  20. Intrathecal fentanyl blockade of afferent neural feedback from skeletal muscle during exercise in heart failure patients: Influence on circulatory power and pulmonary vascular capacitance.

    Science.gov (United States)

    Van Iterson, Erik H; Snyder, Eric M; Joyner, Michael J; Johnson, Bruce D; Olson, Thomas P

    2015-12-15

    Secondary pulmonary hypertension is common in heart failure (HF) patients. We hypothesized that inhibition of feedback from locomotor muscle group III/IV neurons contributes to reduced pulmonary vascular pressures independent of changes in cardiac function during exercise in HF. 9 HF patients (ages, 60 ± 2; EF, 26.7 ± 1.9%; New York Heart Association classes, I-III) and 9 age/gender matched controls (ages, 63 ± 2) completed five-minutes of constant-load cycling (65% Workloadpeak) with intrathecal fentanyl or placebo on randomized separate days. Mean arterial pressure (MAP), heart rate (HR), end-tidal partial pressure of CO2 (PETCO2), and oxygen consumption (VO2) were measured at rest and exercise. Non-invasive surrogates for cardiac power (circulatory power, CircP=VO2 × MAP), stroke volume (oxygen pulse, O2pulse=VO2/HR), and pulmonary arterial pressure (GXCAP=O2pulse × PETCO2) were calculated. At rest and end-exercise, differences between fentanyl versus placebo were not significant for CircP in HF or controls. Differences between fentanyl versus placebo for GXCAP were not significant at rest in HF or controls. At end-exercise, GXCAP was significantly higher with fentanyl versus placebo in HF (691 ± 59 versus 549 ± 38 mL/beat × mmHg), but not controls (536 ± 59 versus 474 ± 43 mL/beat × mmHg). Slopes (rest to end-exercise) for GXCAP were significantly higher with fentanyl versus placebo in HF (95.1 ± 9.8 versus 71.6 ± 6.0 mL/beat × mmHg), but not controls (74.3 ± 9.5 versus 60.8 ± 6.5 mL/beat × mmHg). CircP slopes did not differ between fentanyl versus placebo in HF or controls (p>0.05). We conclude that feedback from locomotor muscle group III/IV neurons may evoke increases in pulmonary vascular pressures independent of changes in cardiac function during exercise in HF. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.