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.

Two placebo-controlled, randomized withdrawal studies to evaluate the fentanyl 1 day patch in opioid-naïve patients with chronic pain.

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Arai, Tsutomu; Kashimoto, Yuji; Ukyo, Yoshifumi; Tominaga, Yushin; Imanaka, Keiichiro

2015-12-01

To evaluate the efficacy and safety of fentanyl 1 day patch in opioid-naïve patients with non-cancer chronic pain insufficiently relieved by non-opioid analgesics. Two phase III placebo-controlled, double-blind, group-comparison, randomized withdrawal studies were conducted in patients with osteoarthritis and/or low back pain (N01 study) and post-herpetic neuralgia, complex regional pain syndrome, or chronic postoperative pain (N02) in Japan. Both studies consisted of period I (10-29 days of titration, fentanyl 12.5-50.0 µg/h) and period II (12 weeks double-blind). N01, NCT01008618; N02, NCT01008553 MAIN OUTCOME MEASURES: The primary endpoint was the number of days until study discontinuation due to insufficient pain relief in period II, and secondary endpoints included pain scored on visual analog scale (VAS), subject's overall assessment, the number of rescue dose, brief pain inventory short form score, score on short-form 36-item health survey version 2.0, physician's overall assessment, and assessment of adverse events. Of the 218 (N01) and 258 (N02) subjects who entered period I, 150 and 163 subjects entered period II, respectively. In the N01 study, the between-group difference was significant in the VAS score (95% CI: 7.3 [1.1, 13.5] mm, P = 0.0215) but not in the primary endpoint (P = 0.0846, log-rank test). In the N02 study, both primary efficacy (P = 0.0003) and VAS (8.7 [2.4, 15.0] mm, P = 0.0071) results showed that fentanyl was more effective than placebo. The major adverse events were nervous system and gastrointestinal disorders typically associated with opioid analgesic use. The incidence of adverse events in the fentanyl group was 68.5% to 85.7%. Although the primary efficacy results showed significant effects of fentanyl in the N02 but not the N01 study, overall results showed that fentanyl 1 day patch is effective and well tolerated.

Comparison of an Additional Transdermal Fentanyl Patch Compared to Intravenous NSAID and Opioid Analgesics within 24 Hours of an Uterine Artery Embolization for Myoma and Adenomyosis

Energy Technology Data Exchange (ETDEWEB)

Song, Suk Yun; Kang, Byung Chul; Rho, Kyung Min [Dept. of Radiology, Mokdong Hospital, Ewha Womans University School of Medicine, Seoul (Korea, Republic of)

2011-05-15

To evaluate the effectiveness of an additional transdermal fentanyl patch compared to intravenous analgesics in pain control during the 24-hour period following uterine artery embolization (UAE) for myoma and adenomyosis. Between September 2009 and August 2010, 42 patients underwent UAE for myoma or adenomyosis. Of these, 21 received an intravenous opioid (pethidine) and a nonsteroidal anti-inflammatory drug (group A), and 21 received an additional transdermal fentanyl patch (group B). Pain perception levels were established verbally on a 0-10 scale during the 24-hour period following UAE. Differences in pain trends, mean dose of intravenous pethidine, and adverse effects were compared between the two groups. Pain perception was most severe at 6 hours after UAE and the mean pain level of group B at that time was 6.3 {+-} 0.7, which was significantly lower than that of group A, 8.2 {+-} 0.7 (p<0.05). The mean dose of intravenous pethidine was 114.3 {+-} 59.5 mg in group A and 90.5 {+-} 49.0 mg in group B, while the incidence of nausea was 67% in group A and 77% in group B. In both cases, the differences were not significantly different (p>0.05), and no evidence of respiratory distress was demonstrated. The addition of a transdermal fentanyl patch to intravenous analgesics is effective in reducing post-embolization pain during the 24-hour period after UAE.

Plasma Concentrations of Fentanyl Achieved With Transdermal Application in Chickens

NARCIS (Netherlands)

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

2017-01-01

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

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).

Effects of smoking and body mass index on the exposure of fentanyl in patients with cancer.

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Kuip, Evelien J M; Oldenmenger, Wendy H; Thijs-Visser, Martine F; de Bruijn, Peter; Oosten, Astrid W; Oomen-de Hoop, Esther; Koolen, Stijn L W; Van der Rijt, Carin C D; Mathijssen, Ron H J

2018-01-01

The transdermal fentanyl patch is widely used to treat cancer-related pain despite its wide inter- and intrapatient variability in pharmacokinetics. The aim of this study was to investigate whether smoking and body size (i.e. body mass index) influence fentanyl exposure in patients with cancer. These are factors that typically change during treatment and disease trajectories. We performed an explorative cohort study in patients with cancer using transdermal fentanyl patches (Durogesic®), by taking a blood sample for pharmacokinetic analysis one day after applying a patch in patients with a stable fentanyl dose. A total of 88 patients were evaluable. Although no statistically significant difference was found, the plasma concentrations of non-smokers was 28% (95% CI [-14%; +89-%]) higher than those of smokers normalizing for a dose of 25μg/min. Patients with a low BMI ( 25 kg/m2). A wider variation in fentanyl plasma concentrations was found in this study than anticipated. Due to this variation, studies in larger patient cohorts are needed to further investigate the effect of smoking on plasma concentration of fentanyl and thereby clarify the clinical significance of our findings.

Pharmacokinetics of a Transdermal Fentanyl Solution in Suffolk Sheep (Ovis aries).

Science.gov (United States)

Jen, Kimberly Y; Dyson, Melissa C; Lester, Patrick A; Nemzek, Jean A

2017-09-01

Sheep used as surgical models require appropriate pain management, and the commonly used transdermal fentanyl patches require a long predosing period to achieve adequate plasma concentrations. The aim of this study was to assess the pharmacokinetic parameters of an FDA-approved transdermal fentanyl solution (TFS) that has yet to be tested in sheep. In this study, we compared TFS at 2.7 mg/kg (n = 2), 1.7 mg/kg (n = 3), and 0.5 mg/kg (n = 3) with the control fentanyl patch at 2 μg/kg/h (n = 1); both products were applied topically to the intrascapular region. Plasma concentrations showed significant interanimal variability. Severe adverse effects occurred at both 2.7 and 1.7 mg/kg TFS and mild to moderate adverse effects were noted at 0.5 mg/kg. At all 3 doses, TFS had greater maximal concentration, clearance rate, and volume of distribution; shorter time to maximal concentration; and similar half-lives to those of the patch. In addition, we validated the use of a commercial human fentanyl ELISA kit, which positively correlated with the liquid chromatography-mass spectroscopy data, but absolute values did not match. Overall, at all 3 dosages tested (0.5, 1.7, and 2.7 mg/kg), TFS delivered fentanyl plasma concentrations that exceeded the minimal effective concentration; however, adverse effects were noted at all 3 dosages. Caution and further study are required before the use of TFS in sheep can be recommended fully.

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.

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.

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.

Multicenter clinical study for evaluation of efficacy and safety of transdermal fentanyl matrix patch in treatment of moderate to severe cancer pain in 474 chinese cancer patients.

Science.gov (United States)

Zhu, Yu-Lin; Song, Guo-Hong; Liu, Duan-Qi; Zhang, Xi; Liu, Kui-Feng; Zang, Ai-Hua; Cheng, Ying; Cao, Guo-Chun; Liang, Jun; Ma, Xue-Zhen; Ding, Xin; Wang, Bin; Li, Wei-Lian; Hu, Zuo-Wei; Feng, Gang; Huang, Jiang-Jin; Zheng, Xiao; Jiao, Shun-Chang; Wu, Rong; Ren, Jun

2011-12-01

Although a new matrix formulation fentanyl has been used throughout the world for cancer pain management, few data about its efficacy and clinical outcomes associated with its use in Chinese patients have been obtained. This study aimed to assess the efficacy and safety of the new system in Chinese patients with moderate to severe cancer pain. A total of 474 patients with moderate to severe cancer pain were enrolled in this study and were treated with the new transdermal fentanyl matrix patch (TDF) up to 2 weeks. All the patients were asked to record pain intensity, side effects, quality of life (QOL), adherence and global satisfaction. The initial dose of fentanyl was 25 μg/h titrated with opioid or according to National Comprehensive Cancer Network (NCCN) guidelines. Transdermal fentanyl was changed every three days. After 2 weeks. The mean pain intensity of the 459 evaluated patients decreased significantly from 5.63±1.26 to 2.03±1.46 (P<0.0001). The total remission rate was 91.29%, of which moderate remission rate 53.16%, obvious remission rate 25.49% and complete remission rate 12.64%. The rate of adverse events was 33.75%, 18.78% of which were moderate and 3.80% were severe. The most frequent adverse events were constipation and nausea. No fatal events were observed. The quality of life was remarkably improved after the treatment (P<0.0001). The new TDF is effective and safe in treating patients with moderate to severe cancer pain, and can significantly improve the quality of life.

TongueToSpeech (TTS): Wearable wireless assistive device for augmented speech.

Science.gov (United States)

Marjanovic, Nicholas; Piccinini, Giacomo; Kerr, Kevin; Esmailbeigi, Hananeh

2017-07-01

Speech is an important aspect of human communication; individuals with speech impairment are unable to communicate vocally in real time. Our team has developed the TongueToSpeech (TTS) device with the goal of augmenting speech communication for the vocally impaired. The proposed device is a wearable wireless assistive device that incorporates a capacitive touch keyboard interface embedded inside a discrete retainer. This device connects to a computer, tablet or a smartphone via Bluetooth connection. The developed TTS application converts text typed by the tongue into audible speech. Our studies have concluded that an 8-contact point configuration between the tongue and the TTS device would yield the best user precision and speed performance. On average using the TTS device inside the oral cavity takes 2.5 times longer than the pointer finger using a T9 (Text on 9 keys) keyboard configuration to type the same phrase. In conclusion, we have developed a discrete noninvasive wearable device that allows the vocally impaired individuals to communicate in real time.

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.

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

PATIENTS' KNOWLEDGE OF MEDICAL PATCHES IN HUNGARY.

Science.gov (United States)

Somogyi, Orsolya; Zelko, Romana

2016-11-01

Transdermal therapy with medical patches is a simple possibility in home medication. As the correct use of patches has a decisive impact from the point of its modulator effect.A questionnaire survey was developed to explore level of patients' knowledge of the correct use of transdermal patches. A survey was administered in thirteen Hungarian community pharmacies from October of 2012 to May of 2015. Most of the participants, men and women over 18 years of age (n = 233), used major analgesic patches (fentanyl); the remainder were given nitroglycerin, NSAID analgesics patches during the survey. For the hypothesis testing it was assumed that men were more likely to use a razor for skin depilation before patch application than women as their denser pelage hinders patch adhesion. The hypothesis testing showed no significant gender difference in razor use (X² = 0.201; p = 0.654). Pharmacists should direct patients to avoid using soap for skin cleansing before patch application because only 22 percent of the participants always avoided its use. Since only 9 tests were flawless from 233 completed questionnaires. Many patients do not understand how to correctly apply a transdermal dosage patch. Pharmacists should teach their correct application based on results.

Enhacements to the TTS-502 time transfer system

Science.gov (United States)

Vandierendonck, A. J.; Hua, Q. D.

1985-04-01

Two years ago STI introduced an affordable, relatively compact time transfer system on the market -- the TTS-502, and described that system at the 1981 PTTI conference. Over the past few months, that system has been improved, and new features have been added. In addition, new options have been made available to further enhance the capabilities of the system. These enhancements include the addition of a positioning algorithm and new options providing a corrected 5 MHz output that is phase coherent with the 1 pps output, and providing an internal Rubidium Oscillator. The Positioning Algorithm was developed because not all time transfer users had the luxury of the Defense Mapping Agency's (DMA) services for determining their position in WGS-72 coordinates. The enhanced TTS-502 determines the GPS position anywhere in the world, independent of how many GPS satellites are concurrently visible. However, convergence time to a solution is inversely proportional to the number of satellites concurrently visible and the quality of frequency standard used in conjunction with the TTS-502. Real World solution results will be presented for a variety of cases and satellite scheduling scenarios. Typically, positioning accuracies were achieved better than 5 to 10 meters r.s.s. using the C/A code only at Sunnyvale, California.

COMPARATIVE STUDY OF EPIDURAL FENTANYL AND FENTANYL PLUS MAGNESIUM SULPHATE FOR POSTOPERATIVE ANALGESIA

Directory of Open Access Journals (Sweden)

Shiva

2015-11-01

Full Text Available AIMS AND OBJECTIVES Magnesium has antinociceptive effects in animal and human models of pain. It is found that the addition of Magnesium sulphate to postoperative Epidural infusion of Fentanyl may decrease the need for Fentanyl. We undertook a study to compare the duration of postoperative analgesia after Epidural Fentanyl and Epidural Fentanyl plus Magnesium sulphate administered postoperatively, along with side effects. MATERIALS AND METHODS 50 patients undergoing elective lower limb and abdominal surgeries were randomized into one of the two groups with 25 patients in each group. Combined Spinal Epidural Anaesthesia was used for all patients. Spinal anaesthesia with 2.5 cc of 0.5% Hyperbaric Bupivacaine was given. When sensory blockade regressed to L1, patients were given either 50 µg of Fentanyl (diluted to 6cc with normal saline, Group F or 50 µg of Fentanyl plus 50 mg Magnesium sulphate (diluted to 6cc with normal saline, Group FM. Parameters like blood pressure, pulse rate, respiratory rate and oxygen saturation were monitored, and other side effects were noted. Data were analysed by using Student t test and Chi-square/ Fisher Exact tests. RESULTS There was significant difference in duration of analgesia between Group F (107 min and Group FM (143 min. Hemodynamic parameters were stable in both the groups with minimal side effects. CONCLUSION Co-administration of Magnesium sulphate with Fentanyl for postoperative Epidural analgesia results in prolongation of Fentanyl analgesia without significant side-effects.

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.

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

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...

TTS-Polttopuu - cost calculation model for fuelwood

International Nuclear Information System (INIS)

Naett, H.; Ryynaenen, S.

1998-01-01

The TTS-Institutes's Forestry Department has developed a computer based costcalculation model, 'TTS-Polttopuu', for the calculation of unit costs and resource needs in the harvesting systems for wood chips and split firewood. The model enables to determine the productivity and device cost per operating hour by each working stage of the harvesting system. The calculation model also enables the user to find out how changes in the productivity and cost bases of different harvesting chains influence the unit cost of the whole system. The harvesting chain includes the cutting of delimbed and non-delimbed fuelwood, forest haulage, road transportation chipping and chopping of longwood at storage. This individually operating software was originally developed to serve research needs, but it also serves the needs of the forestry and agricultural education, training and extension as well as individual firewood producers. The system requirements for this cost calculation model are at least 486-level processor with the Windows 95/98 -operating system, 16 MB of memory (RAM) and 5 MB of available hard-disk. This development work was carried out in conjunction with the nation-wide BIOENERGY Research Programme. (orig.)

TTS-Polttopuu - cost calculation model for fuelwood

International Nuclear Information System (INIS)

Naett, H.; Ryynaenen, S.

1999-01-01

The TTS-Institutes's Forestry Department has developed a computer based cost-calculation model, 'TTS-Polttopuu', for the calculation of unit costs and resource needs in the harvesting systems for wood chips and split firewood. The model enables to determine the productivity and device cost per operating hour by each working stage of the harvesting system. The calculation model also enables the user to find out how changes in the productivity and cost bases of different harvesting chains influence the unit cost of the whole system. The harvesting chain includes the cutting of delimbed and non-delimbed fuelwood, forest haulage, road transportation, chipping and chopping of longwood at storage. This individually operating software was originally developed to serve research needs, but it also serves the needs of the forestry and agricultural education, training and extension as well as individual firewood producers. The system requirements for this cost calculation model are at least 486- level processor with the Windows 95/98 -operating system, 16 MB of memory (RAM) and 5 MB of available hard-disk. This development work was carried out in conjunction with the nation-wide BIOENERGY-research programme. (orig.)

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.

Isoflurane minimum alveolar concentration reduction by fentanyl.

Science.gov (United States)

McEwan, A I; Smith, C; Dyar, O; Goodman, D; Smith, L R; Glass, P S

1993-05-01

Isoflurane is commonly combined with fentanyl during anesthesia. Because of hysteresis between plasma and effect site, bolus administration of fentanyl does not accurately describe the interaction between these drugs. The purpose of this study was to determine the MAC reduction of isoflurane by fentanyl when both drugs had reached steady biophase concentrations. Seventy-seven patients were randomly allocated to receive either no fentanyl or fentanyl at several predetermined plasma concentrations. Fentanyl was administered using a computer-assisted continuous infusion device. Patients were also randomly allocated to receive a predetermined steady state end-tidal concentration of isoflurane. Blood samples for fentanyl concentration were taken at 10 min after initiation of the infusion and before and immediately after skin incision. A minimum of 20 min was allowed between the start of the fentanyl infusion and skin incision. The reduction in the MAC of isoflurane by the measured fentanyl concentration was calculated using a maximum likelihood solution to a logistic regression model. There was an initial steep reduction in the MAC of isoflurane by fentanyl, with 3 ng/ml resulting in a 63% MAC reduction. A ceiling effect was observed with 10 ng/ml providing only a further 19% reduction in MAC. A 50% decrease in MAC was produced by a fentanyl concentration of 1.67 ng/ml. Defining the MAC reduction of isoflurane by all the opioids allows their more rational administration with inhalational anesthetics and provides a comparison of their relative anesthetic potencies.

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

Fentanyl

Science.gov (United States)

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

A sensitive radioimmunoassay for fentanyl

International Nuclear Information System (INIS)

Michiels, M.; Hendriks, R.; Heykants, J.

1977-01-01

Antiserum to fentanyl was obtained in rabbits repeatedly injected with carboxyfentanyl conjugated to bovine serum albumin. Using the antiserum, a highly sensitive radioimmunoassay has been developed, based on the dextran-coated charcoal method. It proved possible to assay the drug directly in plasma, in amounts as small as 30 picogram in 0.5 ml. The antibody was highly specific for fentanyl and no cross-reaction was observed with its major metabolites. This sensitive and specific radioimmunoassay method was employed to determine fentanyl in plasma from six volunteers after an intravenous bolus of 0.2 mg, and in plasma from dogs treated both intravenously and subcutaneously with 0.02 mg/kg. The plasma level of fentanyl could be followed for up to 6 h after a therapeutic dose in dogs and man. (orig.) [de

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.

Two Fatal Intoxications Involving Butyryl Fentanyl

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

2016-01-01

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. PMID:27339481

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. ...

Consumption of three strong opioids (morphine, oxycodone and fentanyl) in seven European countries during seven years (2003-2009).

Science.gov (United States)

Hudec, R; Tisonova, J; Foltan, V; Kristova, V

2013-01-01

The aim was to analyse the consumption of selected strong opioid analgesics during a seven-year period of 2003-2009 in order to compare Slovak consumption with that in six other European countries and to determine our position. Drug consumption data from the State Institute for Drug Control in Slovak Republic were used. As to the data from other countries, annual health statistics published on websites were used in comparison. Obviously the consumption of one of studied opioid drugs with transdermal aplication route, particularly fentanyl, tended to increase in all countries during the observed period. Oxycodone tends to yield a rapid increase in consumption as well. As opposed to the latter drugs, the consumption of morphine was decreasing throughout the observed period. The consumption of these drugs in Slovakia remains low (except for that of fentanyl). Our analysis confirmed a clear shift from oral to transdermal therapy as well as usage of newer drugs. Drug consumption data are a relatively new source of information for health research. Our analysis showed increasing trends in fentanyl (patch opioid) consumption in all compared countries as well as an increasing consumption of oxycodone and decreasing consumption of morphine (Fig. 3, Ref. 17).

TTS-Driven Synthetic Behaviour-Generation Model for Artificial Bodies

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Izidor Mlakar

2013-10-01

Full Text Available Visual perception, speech perception and the understanding of perceived information are linked through complex mental processes. Gestures, as part of visual perception and synchronized with verbal information, are a key concept of human social interaction. Even when there is no physical contact (e.g., a phone conversation, humans still tend to express meaning through movement. Embodied conversational agents (ECAs, as well as humanoid robots, are visual recreations of humans and are thus expected to be able to perform similar behaviour in communication. The behaviour generation system proposed in this paper is able to specify expressive behaviour strongly resembling natural movement performed within social interaction. The system is TTS-driven and fused with the time-and-space efficient TTS-engine, called ‘PLATTOS’. Visual content and content presentation is formulated based on several linguistic features that are extrapolated from arbitrary input text sequences and prosodic features (e.g., pitch, intonation, stress, emphasis, etc., as predicted by several verbal modules in the system. According to the evaluation results, when using the proposed system the synchronized co-verbal behaviour can be recreated with a very high-degree of naturalness, either by ECAs or humanoid robots alike.

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...

Time profiles and pulse structure of bright, long gamma-ray bursts using BATSE TTS data

International Nuclear Information System (INIS)

Lee, A.; Bloom, E.; Scargle, J.

1996-04-01

The time profiles of many gamma-ray bursts observed by BATSE consist of distinct pulses, which offer the possibility of characterizing the temporal structure of these bursts using a relatively small set of pulse-shape parameters. This pulse analysis has previously been performed on some bright, long bursts using binned data, and on some short bursts using BATSE Time-Tagged Event (TTE) data. The BATSE Time- to-Spill (TTS) burst data records the times required to accumulate a fixed number of photons, giving variable time resolution. The spill times recorded in the TTS data behave as a gamma distribution. We have developed an interactive pulse-fitting program using the pulse model of Norris et al. and a maximum-likelihood fitting algorithm to the gamma distribution of the spill times. We then used this program to analyze a number of bright, long bursts for which TTS data is available. We present statistical information on the attributes of pulses comprising these bursts

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.

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

The Effectiveness of Transdermal Opioid in the Management Multiple Rib Fractures: Randomized Clinical Trial

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Okan Solak

2013-09-01

Full Text Available Background: The most commonly observed pathology in chest traumas is rib fracture, and the most important clinical symptom is severe pain. Aims: To investigate the effectiveness of intramuscular opioid (IMO, intravenous patient-controlled analgesia (IVPCA and the Fentanyl transdermal therapeutic system (TTS in the management of rib fracture pain. Study Design: Prospective randomized clinical trial. Methods: In our prospective and randomised study, we included 45 patients with a diagnosis of multiple rib fractures. There were three groups and intercostal nerve blockage (ICB in the first day and oral paracetamol for five days was administered to each group as standard. In Group IMO (n=15, 4x40 mg pethidine HCl was administered to the patients, while in Group IVPCA (n=15 this was 5 µg/mL continuous intravenous fentanyl and was 50 µg fentanyl TTS in Group TTS (n=15. The demographics, injury data and vital signs of the patients were recorded. Pain was scored using Visual Analogue Scale (VAS. The pain during lying down (VASl and mobilisation (VASm was detected. Results: There were no differences between the three groups regarding age, sex, the trauma pattern, the number and distribution of costal fracture localisations, the presence of additional pathology, complications, thoracal catheter and the duration of thoracal catheter. No significant difference between the groups regarding systolic and diastolic arterial tension, number of breaths and beats in a minute was observed (p>0.05. We observed an improvement in the mean VAS score after treatment in all three groups. The mean VASl score significantly decreased after treatment in each group (p0.05. Conclusion: In the analgesia of patients with multiple rib fractures, TTS administration with ICB showed similar effectiveness with IVPCA administration with ICB. In the management of pain due to multiple rib fractures, TTS administration is a safe, non-invasive and effective procedure.

The effectiveness of transdermal opioid in the management multiple rib fractures: randomized clinical trial.

Science.gov (United States)

Solak, Okan; Oz, Gürhan; Kokulu, Serdar; Solak, Ozlem; Doğan, Gökçen; Esme, Hıdır; Ocalan, Kubilay; Baki, Elif Doğan

2013-09-01

The most commonly observed pathology in chest traumas is rib fracture, and the most important clinical symptom is severe pain. To investigate the effectiveness of intramuscular opioid (IMO), intravenous patient-controlled analgesia (IVPCA) and the Fentanyl transdermal therapeutic system (TTS) in the management of rib fracture pain. Prospective randomized clinical trial. In our prospective and randomised study, we included 45 patients with a diagnosis of multiple rib fractures. There were three groups and intercostal nerve blockage (ICB) in the first day and oral paracetamol for five days was administered to each group as standard. In Group IMO (n=15), 4×40 mg pethidine HCl was administered to the patients, while in Group IVPCA (n=15) this was 5 μg/mL continuous intravenous fentanyl and was 50 μg fentanyl TTS in Group TTS (n=15). The demographics, injury data and vital signs of the patients were recorded. Pain was scored using Visual Analogue Scale (VAS). The pain during lying down (VASl) and mobilisation (VASm) was detected. There were no differences between the three groups regarding age, sex, the trauma pattern, the number and distribution of costal fracture localisations, the presence of additional pathology, complications, thoracal catheter and the duration of thoracal catheter. No significant difference between the groups regarding systolic and diastolic arterial tension, number of breaths and beats in a minute was observed (p>0.05). We observed an improvement in the mean VAS score after treatment in all three groups. The mean VASl score significantly decreased after treatment in each group (p0.05). In the analgesia of patients with multiple rib fractures, TTS administration with ICB showed similar effectiveness with IVPCA administration with ICB. In the management of pain due to multiple rib fractures, TTS administration is a safe, non-invasive and effective procedure.

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.

A retrospective study on the influence of nutritional status on pain management in cancer patients using the transdermal fentanyl patch.

Science.gov (United States)

Takahashi, Hiroaki; Chiba, Takeshi; Tairabune, Tomohiko; Kimura, Yusuke; Wakabayashi, Go; Takahashi, Katsuo; Kudo, Kenzo

2014-01-01

It is unknown whether nutritional status influences pain intensity in cancer patients receiving a transdermal fentanyl patch (FP). This study aimed to determine whether nutritional status is associated with pain intensity and to evaluate the influence of changes in nutritional status on pain intensity in cancer patients receiving transdermal FP treatment. We included 92 patients receiving transdermal FP treatment for the first time with switching from oxycodone. The patients were classified into low- and normal-nutrition groups based on their nutritional status, which was assessed according to the Nutrition Risk Screening 2002 (NRS 2002) parameters. The pain intensity of each patient was evaluated by a numeric rating scale (11-point scale from 0 to 10). NRS 2002 score and pain intensity were obtained on day 3 after the FP was applied to the skin. Pain intensities were significantly higher among patients in the low-nutrition group than among patients in the normal-nutrition group. NRS 2002 scores showed a significant positive correlation with the pain intensities. In 52 of 92 patients, who were evaluated using the NRS 2002 score and pain intensity on day 30 after FP application, the changes in NRS 2002 scores were significantly related to changes in pain intensities (odds ratio, 30.0; 95% confidence interval, 4.48-200.97; p=0.0005). These results suggest that an increase in the NRS 2002 score is a risk factor for an increase in pain intensity in cancer patients receiving FP treatment. Malnutrition may lead to poor pain management in cancer patients receiving FP treatment.

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.

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.

The first Malay language storytelling text-to-speech (TTS) corpus for ...

African Journals Online (AJOL)

speech annotations are described in detail in accordance to baseline work. The stories were recorded in two speaking styles that are neutral and storytelling speaking style. The first. Malay language storytelling corpus is not only necessary for the development of a storytelling text-to-speech (TTS) synthesis. It is also ...

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.

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.

COMPARISON OF INTRAMUSCULAR FENTANYL-MIDAZOLAM, FENTANYL-MIDAZOLAM-KETAMINE, AND KETAMINE-MEDETOMIDINE FOR IMMOBILIZATION OF JAPANESE MACAQUES ( MACACA FUSCATA).

Science.gov (United States)

Ølberg, Rolf-Arne; Sinclair, Melissa; Barker, Ian K; Crawshaw, Graham

2018-03-01

The combination of fentanyl and midazolam is commonly used as a sedative in humans. The objective of this study was to evaluate the sedative properties and physiological effects of fentanyl-midazolam and fentanyl-midazolam-ketamine compared with medetomidine-ketamine given intramuscularly in Japanese macaques ( Macaca fuscata). In a randomized crossover design, eight Japanese macaques were hand-injected with either 30 μg/kg fentanyl + 0.3 mg/kg midazolam (FM), 15 μg/kg fentanyl + 0.3 mg/kg midazolam + 5.0 mg/kg ketamine (FMK), or 0.05 mg/kg medetomidine + 5.0 mg/kg ketamine (MedK). Heart rate; indirect systolic, mean, and diastolic arterial pressure; respiratory rate; blood gas concentrations; rectal temperature; and duration of immobilization were recorded. Mixed linear models were used to evaluate the effects of drug treatment on all continuous variables, with a significance level of P < 0.05. Only three of seven animals receiving FM were successfully immobilized. All eight animals in both the FMK and MedK treatment groups had a rapid, smooth induction and were successfully immobilized. Both FMK and MedK treatments resulted in significant hypoxia and the animals required supplemental oxygen via face mask. The mean duration of FMK immobilization was 42 ± 10 min, significantly shorter than the 65 ± 14 min for the animals receiving MedK. Immobilization with MedK resulted in significantly lower heart rates, and significantly higher arterial pressure compared with FMK. Hypoventilation was significantly more pronounced in FMK-treated animals compared with MedK treatments. Immobilization with FMK resulted in a gradual, slow recovery whereas MedK-treated animals woke up more rapidly. Fentanyl-midazolam alone is not a useful sedative in Japanese macaques. A combination of fentanyl and midazolam with ketamine can be used as an alternative to medetomidine-ketamine in this species.

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.

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

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.

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

International Nuclear Information System (INIS)

Watts, V.W.; Caplan, Y.H.

1990-01-01

The Coat-A-Count solid phase 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 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 125 I RIA was compared to GC/MS quantifications of fentanyl in 35 positive and 20 negative case urine specimens

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

Evidence of "hidden hearing loss" following noise exposures that produce robust TTS and ABR wave-I amplitude reductions.

Science.gov (United States)

Lobarinas, Edward; Spankovich, Christopher; Le Prell, Colleen G

2017-06-01

In animals, noise exposures that produce robust temporary threshold shifts (TTS) can produce immediate damage to afferent synapses and long-term degeneration of low spontaneous rate auditory nerve fibers. This synaptopathic damage has been shown to correlate with reduced auditory brainstem response (ABR) wave-I amplitudes at suprathreshold levels. The perceptual consequences of this "synaptopathy" remain unknown but have been suggested to include compromised hearing performance in competing background noise. Here, we used a modified startle inhibition paradigm to evaluate whether noise exposures that produce robust TTS and ABR wave-I reduction but not permanent threshold shift (PTS) reduced hearing-in-noise performance. Animals exposed to 109 dB SPL octave band noise showed TTS >30 dB 24-h post noise and modest but persistent ABR wave-I reduction 2 weeks post noise despite full recovery of ABR thresholds. Hearing-in-noise performance was negatively affected by the noise exposure. However, the effect was observed only at the poorest signal to noise ratio and was frequency specific. Although TTS >30 dB 24-h post noise was a predictor of functional deficits, there was no relationship between the degree of ABR wave-I reduction and degree of functional impairment. Copyright © 2016 Elsevier B.V. All rights reserved.

Pharmacokinetics and safety of fentanyl sublingual spray and fentanyl citrate intravenous: a single ascending dose study in opioid-naïve healthy volunteers.

Science.gov (United States)

Rauck, Richard; Oh, D Alexander; Parikh, Neha; Koch, Christian; Singla, Neil; Yu, Jin; Nalamachu, Srinivas; Vetticaden, Santosh

2017-11-01

Fentanyl sublingual spray offers rapid pain relief in opioid-tolerant cancer patients, and may be useful in acute or post-operative pain. Both opioid-naïve and non-tolerant patients are likely to receive opioids in these settings. Understanding the relationship between systemic exposure of fentanyl sublingual spray and effects on respiratory function in opioid-naïve or non-tolerant populations is important to ensure patient safety. This study evaluated single-dose fentanyl sublingual spray in opioid-naïve participants. Participants were randomized to receive single-dose fentanyl sublingual spray (100, 200, 400, 600, 800 mcg) or fentanyl citrate IV in one of five cohorts. Dosing occurred following a 10-h fast, with fasting continuing for 4 h post-dose. Dose proportionality was assessed using analysis of variance and linear regression techniques. PK assessments and safety monitoring were performed through 24 h post-dose. Safety assessments, including adverse event (AE) monitoring, occurred from dosing through Day 7. Fifty participants (19-53 years) received fentanyl sublingual spray or fentanyl citrate IV. Mean maximum plasma concentrations were reached between 0.27-0.60 h post-dose for fentanyl sublingual spray. Peak (C max ) and total (AUC 0- t , AUC 0-∞ ) fentanyl exposures increased in a linear, but more than dose-proportional manner, with higher doses. The most common AEs were somnolence, nausea, and vomiting. All AEs were mild or moderate in severity. Doses at 400, 600, and 800 mcg were associated with nausea and vomiting, requiring pharmacologic intervention. Hypoxia episodes requiring nasal cannula oxygenation were observed with 600mcg and 800mcg doses. Overall, single-dose fentanyl sublingual spray (100-800 mcg) was generally well tolerated, with greater incidences of AEs (e.g. nausea, vomiting, hypoxia) at higher doses. Doses up to 200 mcg may be safely administered to healthy opioid-naïve individuals with routine monitoring; doses

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.

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).

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.

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

International Nuclear Information System (INIS)

Alburges, M.E.

1988-01-01

The assay is based on the competition of these drugs with [ 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 [ 3 H]fentanyl for the opioid receptor, but other morphine-like compounds were relatively weak displacers of [ 3 H]fentanyl. Many other commonly abused drugs do not compete with [ 3 H]fentanyl for the opioid receptors. Urine samples from animals injected with fentanyl, (±)-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

Fentanyl Sublingual Spray

Science.gov (United States)

... medication, and who are tolerant (used to the effects of the medication) to narcotic pain medications. Fentanyl ... medications for seizures such as carbamazepine (Tegretol, Teril), oxcarbazepine (Trileptal), and phenytoin (Dilantin, Phenytek); modafinil (Provigil); nalbuphine; ...

Fentanyl Nasal Spray

Science.gov (United States)

... medication, and who are tolerant (used to the effects of the medication) to narcotic pain medications. Fentanyl ... Afrin, Neo-Synephrine, Vicks Sinex, others); nevirapine (Viramune); oxcarbazepine (Trileptal); pentazocine (Talwin); phenytoin (Dilantin, Phenytek); pioglitazone (Actos, ...

A novel prosodic-information synthesizer based on recurrent fuzzy neural network for the Chinese TTS system.

Science.gov (United States)

Lin, Chin-Teng; Wu, Rui-Cheng; Chang, Jyh-Yeong; Liang, Sheng-Fu

2004-02-01

In this paper, a new technique for the Chinese text-to-speech (TTS) system is proposed. Our major effort focuses on the prosodic information generation. New methodologies for constructing fuzzy rules in a prosodic model simulating human's pronouncing rules are developed. The proposed Recurrent Fuzzy Neural Network (RFNN) is a multilayer recurrent neural network (RNN) which integrates a Self-cOnstructing Neural Fuzzy Inference Network (SONFIN) into a recurrent connectionist structure. The RFNN can be functionally divided into two parts. The first part adopts the SONFIN as a prosodic model to explore the relationship between high-level linguistic features and prosodic information based on fuzzy inference rules. As compared to conventional neural networks, the SONFIN can always construct itself with an economic network size in high learning speed. The second part employs a five-layer network to generate all prosodic parameters by directly using the prosodic fuzzy rules inferred from the first part as well as other important features of syllables. The TTS system combined with the proposed method can behave not only sandhi rules but also the other prosodic phenomena existing in the traditional TTS systems. Moreover, the proposed scheme can even find out some new rules about prosodic phrase structure. The performance of the proposed RFNN-based prosodic model is verified by imbedding it into a Chinese TTS system with a Chinese monosyllable database based on the time-domain pitch synchronous overlap add (TD-PSOLA) method. Our experimental results show that the proposed RFNN can generate proper prosodic parameters including pitch means, pitch shapes, maximum energy levels, syllable duration, and pause duration. Some synthetic sounds are online available for demonstration.

Heroin and fentanyl overdoses in Kentucky: Epidemiology and surveillance.

Science.gov (United States)

Slavova, Svetla; Costich, Julia F; Bunn, Terry L; Luu, Huong; Singleton, Michael; Hargrove, Sarah L; Triplett, Jeremy S; Quesinberry, Dana; Ralston, William; Ingram, Van

2017-08-01

The study aims to describe recent changes in Kentucky's drug overdose trends related to increased heroin and fentanyl involvement, and to discuss future directions for improved drug overdose surveillance. The study used multiple data sources (death certificates, postmortem toxicology results, emergency department [ED] records, law enforcement drug submissions, and prescription drug monitoring records) to describe temporal, geographic, and demographic changes in drug overdoses in Kentucky. Fentanyl- and heroin-related overdose death rates increased across all age groups from years 2011 to 2015 with the highest rates consistently among 25-34-year-olds. The majority of the heroin and fentanyl overdose decedents had histories of substantial exposures to legally acquired prescription opioids. Law enforcement drug submission data were strongly correlated with drug overdose ED and mortality data. The 2016 crude rate of heroin-related overdose ED visits was 104/100,000, a 68% increase from 2015 (62/100,000). More fentanyl-related overdose deaths were reported between October, 2015, and September, 2016, than ED visits, in striking contrast with the observed ratio of >10 to 1 heroin-related overdose ED visits to deaths. Many fatal fentanyl overdoses were associated with heroin adulterated with fentanyl; fentanyl and other synthetic drugs. In order to inform coordinated public health and safety responses, drug overdose surveillance must move from a reactive to a proactive mode, utilizing the infrastructure for electronic health records. Copyright © 2017 Elsevier B.V. All rights reserved.

Pharmacokinetics and safety of fentanyl sublingual spray and fentanyl citrate intravenous: a multiple ascending dose study in opioid-naïve healthy volunteers.

Science.gov (United States)

Rauck, Richard L; Oh, D Alexander; Singla, Neil; Koch, Christian; Parikh, Neha; Nalamachu, Srinivas; Wilson, Daniel; Yu, Jin; Vetticaden, Santosh

2017-11-01

Fentanyl sublingual spray, with its rapid onset for pain relief, may be efficacious in the management of acute or post-operative pain. Because patients in these settings may be opioid-naïve, the study was conducted to determine the safety, tolerability, and pharmacokinetics of multiple dose administration of fentanyl sublingual spray in an opioid-naïve population. Fentanyl sublingual spray (100 mcg, 200 mcg, and 400 mcg) and fentanyl citrate intravenous (IV; 50 mcg) were administered every 0.5, 1.0, 2.0, and 4.0 h for up to three doses per cohort in opioid-naïve subjects (ClinicalTrials.gov identifier: NCT02641340). Eight subjects in each cohort were randomly assigned (six subjects received fentanyl sublingual spray; two subjects received fentanyl citrate IV). Pharmacokinetic and safety-related pharmacodynamic assessments were performed through 24 h post-first dose. Safety assessments were collected through Day 7. Ninety-six opioid-naïve subjects, aged 20-55 years, with a body mass index of 18.7-31.5 kg/m 2 , participated in the study. Multiple doses of fentanyl sublingual spray (100, 200, and 400 mcg) were generally well tolerated. Hypoxia, observed in the 200-mcg and 400-mcg dose groups, increased with increasing doses and higher dosing frequency, but was readily managed by nasal cannula oxygenation. Overall, nausea increased with increasing doses, and ∼52.6% (10 out of 19) cases of nausea that occurred at the highest dose of 400 mcg were treated with concomitant medication. Overall, the reported adverse events were consistent with the known safety profile of fentanyl. Fentanyl sublingual spray (100 mcg, 200 mg, and 400 mcg) administered every 0.5, 1, 2, and 4 h was generally well tolerated in an opioid-naïve population. The results suggest that doses of 200 mcg or lower may be safe for use in an opioid-naïve population.

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

The effect of inhalant anesthetic and body temperature on peri-anesthetic serum concentrations of transdermally administered fentanyl in dogs.

Science.gov (United States)

Pettifer, Glenn R; Hosgood, Giselle

2004-04-01

To determine whether moderate hypothermia during anesthesia significantly affects the serum concentration of transdermally delivered fentanyl and whether halothane or isoflurane affect these concentrations. Randomized cross-over experimental trial. Six mature, healthy Beagles (three males, three females) weighing 10.6 +/- 0.43 kg. A 50-microg hour(-1) fentanyl patch was applied 36 hours prior to anesthesia. Anesthesia was induced at time 0 (t = 0). Each dog received four treatments: isoflurane + normothermia (ISO-NORM), isoflurane + hypothermia (ISO-HYPO), halothane + normothermia (HAL-NORM), and halothane + hypothermia (HAL-HYPO). Dogs were intubated and maintained at 1.5 times MAC. Animals in the hypothermia treatments were cooled to 35 degrees C during anesthesia. Serum fentanyl analysis was performed at -36, -24, -12, 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 18, and 26 hours. Direct arterial blood pressures and arterial blood gases were monitored. The mean body temperatures (+/-SEM) during the anesthetic period for the four treatments were: ISO-NORM = 37.7 +/- 0.07 degrees C, ISO-HYPO = 35.8 +/- 0.1 degrees C, HAL-NORM = 37.7 +/- 0.06 degrees C, and HAL-HYPO = 35.8 +/- 0.13 degrees C. The mean (+/-SEM) serum fentanyl concentrations (SFC) for both hypothermia treatments were significantly lower than baseline concentrations at t = 1 hour and persisted for the duration of anesthesia for the ISO-HYPO treatment but only from t = 1 to 2 hours for the HAL-HYPO treatment. Serum fentanyl concentrations returned to baseline within one hour of the end of anesthesia, regardless of body temperature. There were no significant differences between treatments for systolic or diastolic blood pressure but mean blood pressures were higher during normothermia versus hypothermia during the last hour of anesthesia. Hypothermia during inhalation anesthesia produced a significant reduction in SFC using transdermal administration and was more protracted with isoflurane

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...... patients (1.3%) and hypotension observed in 71 patients (3.0%). CONCLUSION: Intravenous fentanyl caused clinically meaningful pain reduction in most patients and was safe in the hands of ambulance personnel. Many patients had moderate to severe pain at hospital arrival. As the protocol allowed higher doses...

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

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.

Digital music exposure reliably induces temporary threshold shift (TTS) in normal hearing human subjects

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Le Prell, C. G.; Dell, S.; Hensley, B.; Hall, J. W.; Campbell, K. C. M.; Antonelli, P. J.; Green, G. E.; Miller, J. M.; Guire, K.

2012-01-01

Objectives One of the challenges for evaluating new otoprotective agents for potential benefit in human populations is availability of an established clinical paradigm with real world relevance. These studies were explicitly designed to develop a real-world digital music exposure that reliably induces temporary threshold shift (TTS) in normal hearing human subjects. Design Thirty-three subjects participated in studies that measured effects of digital music player use on hearing. Subjects selected either rock or pop music, which was then presented at 93–95 (n=10), 98–100 (n=11), or 100–102 (n=12) dBA in-ear exposure level for a period of four hours. Audiograms and distortion product otoacoustic emissions (DPOAEs) were measured prior to and after music exposure. Post-music tests were initiated 15 min, 1 hr 15 min, 2 hr 15 min, and 3 hr 15 min after the exposure ended. Additional tests were conducted the following day and one week later. Results Changes in thresholds after the lowest level exposure were difficult to distinguish from test-retest variability; however, TTS was reliably detected after higher levels of sound exposure. Changes in audiometric thresholds had a “notch” configuration, with the largest changes observed at 4 kHz (mean=6.3±3.9dB; range=0–13 dB). Recovery was largely complete within the first 4 hours post-exposure, and all subjects showed complete recovery of both thresholds and DPOAE measures when tested 1-week post-exposure. Conclusions These data provide insight into the variability of TTS induced by music player use in a healthy, normal-hearing, young adult population, with music playlist, level, and duration carefully controlled. These data confirm the likelihood of temporary changes in auditory function following digital music player use. Such data are essential for the development of a human clinical trial protocol that provides a highly powered design for evaluating novel therapeutics in human clinical trials. Care must be

Pheniramine Maleate is more effective than Lidocaine on Fentanyl Induced Cough.

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Ozmen, Ozgur; Kara, Duygu; Karaman, Emine Uzlas; Karakoc, Fatma; Karakaya, Muhammet Ahmet; Arslan, Zakir

2016-01-01

Fentanyl is frequently used during anesthesia induction. The use of fentanyl can cause cough through different mechanisms. Here, we aimed to investigate effects of pheniramine maleate (PM), an antihistaminic agent, and compare it with lidocaine on fentanyl induced cough. This is a randomized double-blind prospective clinical study of ASA I-II, 120 patients scheduled for elective abdominal surgery. Patients were administered drugs intravenously and randomly allocated into three groups: Group C (2 ml 0.9 % normal saline), Group L (1mg/kg lidocaine), and Group F (PM 45.5 mg). 90 seconds after administration, 2µ/kg fentanyl was applied in three seconds to all patients. Severity of cough (mild: 1-2, moderate: 3-5, severe> 5), time of the cough and vital parameters were recorded 90 seconds after fentanyl injection. Eight patients (25%) in Group C had fentanyl induced cough whereas three patients (7.5%) in Group L and one patient (2.5%) in Group F experienced this phenomenon. There was statistically significant difference between Group F and Group C (p0.05). Pheniramine Maleate 45.5 mg is better that placebo and as effective as lidocaine to prevent fentanyl induced cough.

Neurotoxic effects of levobupivacaine and fentanyl on rat spinal cord

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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.

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

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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

The effect of titrated fentanyl on suppressed cough reflex in healthy adult volunteers.

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Kelly, H E; Shaw, G M; Brett, C N; Greenwood, F M; Huckabee, M L

2016-05-01

Cough suppression is part of the pharmacodynamic profile of opioids. We investigated the impact of clinical doses of fentanyl on suppressing the cough reflex. Thirteen volunteers received 2 μg.kg(-1) of fentanyl in a divided administration protocol. Three minutes after each administration and at 10 min intervals during washout, suppressed cough reflex testing with nebulised citric acid was performed and compared with fentanyl effect-site concentration. Mean (SD) citric acid concentration provoking cough increased from 0.5 (0.28) mol.l(-1) at baseline to 1.2 (0.50) mol.l(-1) after 2 μg.kg(-1) of fentanyl (p = 0.01). Mean (SD) fentanyl effect-site concentration after the final dose of fentanyl was 1.89 (0.05) ng.ml(-1) . A strong positive correlation was found between suppressed cough reflex thresholds and fentanyl effect-site concentrations during both fentanyl administration and washout phases of the study (r(2) = 0.79, p = 0.01). The mean (SD) length of time for return of suppressed cough response was 44.6 (18.8) min. Clinically relevant doses of fentanyl produced cough reflex suppression in healthy volunteers. © 2016 The Association of Anaesthetists of Great Britain and Ireland.

[Low-dose hypobaric spinal anesthesia for anorectal surgery in jackknife position: levobupivacaine-fentanyl compared to lidocaine-fentanyl].

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de Santiago, J; Santos-Yglesias, J; Girón, J; Jiménez, A; Errando, C L

2010-11-01

To compare the percentage of patients who were able to bypass the postoperative intensive care recovery unit after selective spinal anesthesia with lidocaine-fentanyl versus levobupivacaine-fentanyl for anorectal surgery in jackknife position. Randomized double-blind clinical trial comparing 2 groups of 30 patients classified ASA 1-2. One group received 18 mg of 0.6% lidocaine plus 10 microg of fentanyl while the other group received 3 mg of 0.1% levobupivacaine plus 10 microg of fentanyl. Intraoperative variables were time of start of surgery, maximum extension of sensory blockade, requirement for rescue analgesics, and hemodynamic events. The level of sensory blockade was recorded at 5, 10, and 15 minutes after the start of surgery and at the end of the procedure. The degrees of postoperative motor blockade and proprioception were recorded, as were the results of the Romberg test and whether or not the patient was able to bypass the postoperative recovery unit. Also noted were times of start of ambulation and discharge, complications, and postoperative satisfaction. Intraoperative variables did not differ significantly between groups, and all patients in both groups bypassed the postoperative recovery unit. Times until walking and discharge home, complications, and overall satisfaction after surgery were similar in the 2 groups. Both spinal anesthetic solutions provide effective, selective anesthesia and are associated with similar rates of recovery care unit bypass after anorectal surgery in jackknife position.

Drug withdrawal symptoms in children after continuous infusions of fentanyl.

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French, J P; Nocera, M

1994-04-01

The purpose of this research was to determine the extent to which critically ill infants exhibited signs and symptoms of narcotic withdrawal after receiving continuous infusions of fentanyl. The convenience sample consisted of 12 pediatric intensive care unit (PICU) patients under 25 months of age who received fentanyl infusions for at least 24 hours. Drug withdrawal symptoms were monitored using the Neonatal Abstinence Score Tool (NAST), which assigns a score to each behavior indicative of withdrawal. A score of 8 or greater indicates Neonatal Abstinence Syndrome (NAS). Scoring began 4 hours after discontinuation of fentanyl and was conducted once per hour for 8 hours. Six subjects had a NAST score exceeding 8; these infants frequently exhibited tremors with or without stimulation, increased muscle tone, insomnia, and increased respiratory rate and effort. There were significant correlations between fentanyl dosage and NAST score (r = .76, p observation protocol and a possible weaning regimen after fentanyl is discontinued.

Administration order of midazolam/fentanyl for moderate dental sedation.

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Lobb, Douglas; Clarke, Alix; Lai, Hollis

2018-02-01

The purpose of this study is to investigate the effects of administration order when a sedative drug (midazolam) and an opioid analgesic drug (fentanyl) is applied for moderate intravenous (IV) sedation in dentistry. A retrospective chart review was conducted in one dental clinic during its transition from a midazolam-first to a fentanyl-first protocol for dental procedures requiring moderate IV sedation. Physiological parameters, drug administration times, patient recovery times, drug dosages, and patient recall and satisfaction were investigated for differences. A total of 76 charts (40 midazolam-first and 36 fentanyl-first administrations), were used in the analysis. Administering midazolam first resulted in an average 4.38 min (52%) decrease in administration times (P 0.05). Oxygen saturation levels did not drop below 90% for either group; however, 5 cases in the fentanyl-first group fell to between 90% and 92%, compared with 0 cases in the midazolam-first group. The administration order of fentanyl and midazolam may have different effects on patients and the sedation procedure. Findings from this study should be used to facilitate discussion among dental practitioners and to guide additional research investigating this topic.

Development of TTS Engine for Indian Accent using Modified HMM Algorithm

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Sasanko Sekhar Gantayat

2018-03-01

Full Text Available A text-to-speech (TTS system converts normal language text into speech. An intelligent text-to-speech program allows people with visual impairments or reading disabilities, to listen to written works on a home computer. Many computer operating systems and day to day software applications like Adobe Reader have included text-to-speech systems. This paper is presented to show that how HMM can be used as a tool to convert text to speech.

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

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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.

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

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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

Hypobaric bupivacaine spinal anesthesia for cystoscopic intervention: the impact of adding fentanyl.

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Atallah, Mohamed M; Helal, Mostafa A; Shorrab, Ahmed A

2003-10-01

Addition of fentanyl to hyperbaric bupivacaine spinal anesthesia prolonged the duration of sensory block. This study seeks to test the hypothesis that adding fentanyl to small dose hypobaric spinal anesthesia will improve intraoperative patients and surgeon satisfaction without delay in recovery. Patients (n = 80) subjected to minor cystoscopic surgery were randomly assigned to have spinal anesthesia with either 5 mg bupivacaine 0.1% or 5 mg bupivacaine 0.1% mixed with 20 micrograms fentanyl. The main outcome measures included intraoperative patient and endoscopist satisfaction, sedative/analgesic supplementation, postoperative side effects and time to ambulation. Patients in the bupivacaine group needed more analgesic supplementation. Analgesia was more adequate in the bupivacaine-fentanyl group. Pruritus was the main side effect in the bupivacaine fentanyl group. Ambulation and discharge of patients were nearly the same in both groups. Spinal anesthesia with small dose (5 mg) hypobaric (0.1%) bupivacaine mixed with fentanyl (20 micrograms) produced adequate anesthesia for short cystoscopic procedures with minimal side effects and without delay in ambulation.

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

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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 (MAC NM ) in dogs. ANIMALS 6 adult Beagles. PROCEDURES Dogs were anesthetized with sevoflurane in oxygen 3 times (1-week intervals). Baseline MAC NM (MAC NM-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 MAC NM (MAC NM-T ) was initiated 90 minutes after start of the CRI. Venous blood samples were collected at the time of each treatment MAC NM measurement for determination of plasma concentrations of fentanyl and lidocaine. RESULTS Mean ± SEM overall MAC NM-B for the 3 treatments was 2.70 ± 0.27 vol%. The MAC NM decreased from MAC NM-B to MAC NM-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 MAC NM of sevoflurane in dogs.

Changes in blood glucose level during and after light sedations using propofol-fentanyl and midazolam-fentanyl in diabetic patients who underwent cataract surgery.

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Khalighinejad, Pooyan; Rahimi, Mojtaba; Naghibi, Khosro; Niknam, Negar

2015-01-01

Surgeries may trigger the stress response which leads to changes in blood glucose level, and studies suggest that different sedation and anesthesia methods have different effects on blood glucose level. The aim of this study was to investigate changes of blood glucose levels in diabetic patients and compare them in two sedation methods of propofol + fentanyl and midazolam + fentanyl. Totally, 80 diabetic candidates for cataract surgery who had all the inclusion criteria, underwent cataract surgery using two methods of propofol (1 mg/kg/h) + fentanyl (2 μg/kg) (Group P) and midazolam (0.03 mg/kg) + fentanyl (2 μg/kg) (Group M) for light sedation. In the end, 70 patients (Group P n = 35 and Group M n = 35) remained in the study. Patients' blood glucose levels, vital signs, and hemodynamic data were assessed 30 min prior to the surgery, each 15 min during surgery and at the end of surgery. Hemodynamic parameters did not have a statistically significant difference between the two groups mean blood glucose level in Group M was 149.15 mg/dl and in Group P was 149.2 mg/dl, and based on repeated measures analysis of variance test, significant differences were not observed between the two groups (P = 0.99). T-test showed no significant differences in the blood glucose level at any time of the study between the two groups. Light sedation methods of propofol + fentanyl and midazolam + fentanyl did not have any differences in alteration of blood glucose level.

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

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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.

Fatalities Involving Carfentanil and Furanyl Fentanyl: Two Case Reports.

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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.

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

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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.

Supraspinally-administered agmatine attenuates the development of oral fentanyl self-administration

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Wade, Carrie L.; Schuster, Daniel J.; Domingo, Kristine M.; Kitto, Kelley F.; Fairbanks, Carolyn A.

2009-01-01

The decarboxylation product of arginine, agmatine, has effectively reduced or prevented opioid-induced tolerance and dependence when given either systemically (intraperitoneally or subcutaneously) or centrally (intrathecally or intracerebroventricularly). Systemically administered agmatine also reduces the escalation phase of intravenous fentanyl self-administration in rats. The present study assessed whether centrally (intracerebroventricular, i.c.v.) delivered agmatine could prevent the development of fentanyl self-administration in mice. Mice were trained to respond under a fixed-ratio 1 (FR1) schedule for either fentanyl (0.7 μg/70 μl, p.o.) or food reinforcement. Agmatine (10 nmol/5 μl), injected i.c.v. 12-14h before the first session and every other evening (12-14h before session) for 2 weeks, completely attenuated oral fentanyl self-administration (but not food-maintained responding) compared to saline-injected controls. When agmatine was administered after fentanyl self-administration had been established (day 8) it had no attenuating effects on bar pressing. This dose of agmatine does not decrease locomotor activity as assessed by rotarod. The present findings significantly extend the previous observation that agmatine prevents opioid-maintained behavior to a chronic model of oral fentanyl self-administration as well as identifying a supraspinal site of action for agmatine inhibition of drug addiction. PMID:18495108

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

International Nuclear Information System (INIS)

Bagley, J.R.; Wilhelm, J.A.

1992-01-01

The synthesis of [ 14 C]-fentanyl, the radiolabelled congener of the potent opioid analgesic chosen for utilization in drug disposition studies, is described. [ 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- 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 [ 14 C]-fentanyl with the radiolabel in the aniline benzene ring. (author)

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

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Oosten, Astrid W; Abrantes, João A; Jönsson, Siv; de Bruijn, Peter; Kuip, Evelien J M; Falcão, Amílcar; van der Rijt, Carin C D; Mathijssen, Ron H J

2016-04-01

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 pharmacokinetics of subcutaneous and transdermal fentanyl. Furthermore, we evaluated rotations from the subcutaneous to the transdermal route. Fifty-two patients treated with subcutaneous and/or transdermal fentanyl for moderate to severe cancer-related pain participated. A population pharmacokinetic model was developed and evaluated using non-linear mixed-effects modelling. For rotations from subcutaneous to transdermal fentanyl, a 1:1 dose conversion ratio was used while the subcutaneous infusion was continued for 12 h (with a 50 % tapering after 6 h). A 6-h scheme with 50 % tapering after 3 h was simulated using the final model. A one-compartment model with first-order elimination and separate first-order absorption processes for each route adequately described the data. The estimated apparent clearance of fentanyl was 49.6 L/h; the absorption rate constant for subcutaneous and transdermal fentanyl was 0.0358 and 0.0135 h(-1), respectively. Moderate to large inter-individual and inter-occasion variability was found. Around rotation from subcutaneous to transdermal fentanyl, measured and simulated plasma fentanyl concentrations rose and increasing side effects were observed. We describe the pharmacokinetics of subcutaneous and transdermal fentanyl in one patient cohort and report several findings that are relevant for clinical practice. Further research is warranted to study the optimal scheme for rotations from the subcutaneous to the transdermal route.

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.

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

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

International Nuclear Information System (INIS)

Schuettler, J.; White, P.F.

1984-01-01

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

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.

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.

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...

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

Due to its non-invasive mode of administration, intranasal (IN) application of drugs may be a valuable alternative to non-invasive pain management. With characteristics that appear to be ideal for IN application, IN fentanyl may have a place in the out-of-hospital treatment and the paediatric...... 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...... database, and Cumulative Index to Nursing and Allied Health Literature. Reports were considered for inclusion if they were double-blinded randomized controlled trials (RCTs) of IN fentanyl in the treatment of acute pain. Thirty-two RCTs were identified, and 16 were included in the final analysis...

Labour analgesia with intrathecal fentanyl decreases maternal stress.

Science.gov (United States)

Cascio, M; Pygon, B; Bernett, C; Ramanathan, S

1997-06-01

Lumbar epidural analgesia (LEA) decreases maternal stress as measured by maternal circulating plasma catecholamine concentrations. Intrathecal fentanyl (ITF) provides effective labour analgesia but its effect on maternal epinephrine (Epi) and norepinephrine (NE) concentrations is not known. This study assesses whether ITF reduces maternal stress in the same manner as conventional LEA. Twenty-four healthy women in active labour received either 25 micrograms ITF (n = 12) or epidural lidocaine 1.5% (n = 12) for analgesia. Venous blood samples were collected before anaesthesia and at five minute intervals for 30 min following anaesthesia for the measurement of plasma Epi and NE by high performance liquid chromatography. Maternal blood pressure (BP), heart rate (HR), visual analog scores (VAS) to pain and pruritus were recorded at the same time. Both ITF and LEA decreased pain VAS scores, maternal BP, and plasma Epi concentrations with only minimal effects on plasma NE concentrations. Intrathecal fentanyl (ITF) and LEA reduced plasma epi to a similar extent, with ITF reducing the levels slightly faster than LEA. Intrathecal fentanyl(ITF) and LEA reduced plasma Epi concentrations by 52% and 51%, respectively (P value < 0.01). We conclude that ITF is as effective as LEA in producing pain relief in the labouring patient. Intrathecal Fentanyl (ITF) is also capable of reducing maternal plasma epinephrine concentration, thus avoiding the possibly deleterious side effects of excess amounts of this catecholamine during labour.

Intrathecal isobaric ropivacaine-fentanyl versus intrathecal isobaric bupivacaine-fentanyl for labor analgesia: A controlled comparative double-blinded study

Directory of Open Access Journals (Sweden)

Meenoti Pramod Potdar

2014-01-01

Full Text Available Context: Neuraxial analgesia and walking epidural is the popular method of practicing labor analgesia. The combination of local anesthetic and opioid is advantageous as it prolongs the duration of labor analgesia. Ropivacaine is the newer local anesthetic agent having lesser motor effects and toxic effects hence would be preferred for labor analgesia. Aims: The primary objective of the study was to assess the duration of analgesia of the intrathecal drug. The secondary objective was the assessment of onset, fixation of analgesia, motor weakness, ambulation, sedation, incidence of side-effects, maternal, and neonatal outcomes. Settings and Design: This is prospective, randomized, controlled, double-blinded, study of 120 patients consenting for labor analgesia. Subjects and Methods: A total of 120 primiparas with a singleton pregnancy in active labor who were given combined spinal epidural (CSE were included in the study. These patients were randomly allocated to three groups of 40 each and received CSE. Group F-received 25 μcg fentanyl intrathecally. Group BF-received 25 μcg fentanyl with 2.5 mg isobaric bupivacaine intrathecally. Group RF-received 25 μcg fentanyl with 2.5 mg isobaric ropivacaine intrathecally. Statistical Analysis Used: Correlations among different measurements were assessed using Pearson′s correlation coefficients, P <0.05 was considered to be statistically significant. Results: The three groups show comparable demographic data and obstetric parameters. The duration of spinal analgesia was significantly greater with Group RF 106.63 ± 17.99 min and Group BF 111.75 ± 23.58 min than the control Group F which was 60 ± 10.39 min with P = 0.001, but were comparable for Group BF and RF. The secondary outcome was comparable in all the three groups. Conclusions: The addition of bupivacaine or ropivacaine to fentanyl intrathecally increased duration and quality of analgesia, did not affect ambulation and bearing down. The

Use of intranasal fentanyl in children undergoing myringotomy and tube placement during halothane and sevoflurane anesthesia.

Science.gov (United States)

Galinkin, J L; Fazi, L M; Cuy, R M; Chiavacci, R M; Kurth, C D; Shah, U K; Jacobs, I N; Watcha, M F

2000-12-01

Many children are restless, disoriented, and inconsolable immediately after bilateral myringotomy and tympanosotomy tube placement (BMT). Rapid emergence from sevoflurane anesthesia and postoperative pain may increase emergence agitation. The authors first determined serum fentanyl concentrations in a two-phase study of intranasal fentanyl. The second phase was a prospective, placebo-controlled, double-blind study to determine the efficacy of intranasal fentanyl in reducing emergence agitation after sevoflurane or halothane anesthesia. In phase 1, 26 children with American Society of Anesthesiologists (ASA) physical status I or II who were scheduled for BMT received intranasal fentanyl, 2 microg/kg, during a standardized anesthetic. Serum fentanyl concentrations in blood samples drawn at emergence and at postanesthesia care unit (PACU) discharge were determined by radioimmunoassay. In phase 2, 265 children with ASA physical status I or II were randomized to receive sevoflurane or halothane anesthesia along with either intranasal fentanyl (2 microg/kg) or saline. Postoperative agitation, Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) scores, and satisfaction of PACU nurses and parents with the anesthetic technique were evaluated. In phase 1, the mean fentanyl concentrations at 10 +/- 4 min (mean +/- SD) and 34 +/- 9 min after administering intranasal fentanyl were 0.80 +/- 0.28 and 0.64 +/- 0.25 ng/ml, respectively. In phase 2, the incidence of severe agitation, highest CHEOPS scores, and heart rate in the PACU were decreased with intranasal fentanyl. There were no differences between sevoflurane and halothane in these measures and in times to hospital discharge. The incidence of postoperative vomiting, hypoxemia, and slow respiratory rates were not increased with fentanyl. Serum fentanyl concentrations after intranasal administration exceed the minimum effective steady state concentration for analgesia in adults. The use of intranasal fentanyl during

Two Different Epidural Analgesic Combinations: Morphine vs. Fentanyl/Bupivacaine or Fentanyl/Ropivacaine and Their Post Operative Effects

National Research Council Canada - National Science Library

Pearce, Tori

2001-01-01

.... This study's purpose was to compare one institutions postoperative epidural opioid/local anesthetic protocol, currently fentanyl with bupivacaine or ropivacaine and compare it to the previously used morphine...

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

Inhibition of protein kinase A and GIRK channel reverses fentanyl-induced respiratory depression.

Science.gov (United States)

Liang, Xiaonan; Yong, Zheng; Su, Ruibin

2018-06-11

Opioid-induced respiratory depression is a major obstacle to improving the clinical management of moderate to severe chronic pain. Opioids inhibit neuronal activity via various pathways, including calcium channels, adenylyl cyclase, and potassium channels. Currently, the underlying molecular pathway of opioid-induced respiratory depression is only partially understood. This study aimed to investigate the mechanisms of opioid-induced respiratory depression in vivo by examining the effects of different pharmacological agents on fentanyl-induced respiratory depression. Respiratory parameters were detected using whole body plethysmography in conscious rats. We show that pre-treatment with the protein kinase A (PKA) inhibitor H89 reversed the fentanyl-related effects on respiratory rate, inspiratory time, and expiratory time. Pre-treatment with the G protein-gated inwardly rectifying potassium (GIRK) channel blocker Tertiapin-Q dose-dependently reversed the fentanyl-related effects on respiratory rate and inspiratory time. A phosphodiesterase 4 (PDE4) inhibitor and cyclic adenosine monophosphate (cAMP) analogs did not affect fentanyl-induced respiratory depression. These findings suggest that PKA and GIRK may be involved in fentanyl-induced respiratory depression and could represent useful therapeutic targets for the treatment of fentanyl-induced ventilatory depression. Copyright © 2018 Elsevier B.V. All rights reserved.

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).

Functionality Effect of Pressure Sensitive Adhesives on In Vitro Drug Release Behavior of Fentanyl Drug in an Adhesive Patch

Directory of Open Access Journals (Sweden)

S.M. Taghizadeh

2009-12-01

Full Text Available Some formulations of drug in adhesive transdermal drug delivery systems (TDDSs( with different functional and non-functional acrylic pressure sensitive adhesives PSAs( were prepared. For this purpose fentanyl was used as a drug component. The effects of PSAs type on skin permeation and in vitro drug release from devices were evaluated using hydrodynamically well-characterized Chien permeation system fitted with excised rat abdominal skin. The adhesion properties of devices (peel strength and tack values( were obtained. It was found that TDDS with –COOH functional PSA had the lowest steady state flux. Drug release was followed by Higuchi's kinetic model. Adhesion properties of the samples were improved by addition of functional PSA in the formulations.

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

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.

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

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

2018-03-01

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 < 0.001) and various pharmaceutical substances (P = 0.002-0.027), third party reports indicated more recent heroin use among illicit 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.

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

76 FR 19997 - Determination That FENTORA (Fentanyl Citrate) Buccal Tablet, 300 Micrograms, Was Not Withdrawn...

Science.gov (United States)

2011-04-11

...] Determination That FENTORA (Fentanyl Citrate) Buccal Tablet, 300 Micrograms, Was Not Withdrawn From Sale for... Food and Drug Administration (FDA) has determined that FENTORA (fentanyl citrate) buccal tablet, 300... allow FDA to approve abbreviated new drug applications (ANDAs) for fentanyl citrate buccal tablet, 300...

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

Subcutaneous Fentanyl Administration: A Novel Approach for Pain Management in a Rural and Suburban Prehospital Setting.

Science.gov (United States)

Lebon, Johann; Fournier, Francis; Bégin, François; Hebert, Denise; Fleet, Richard; Foldes-Busque, Guilaume; Tanguay, Alain

2016-01-01

To determine the feasibility, safety, and effectiveness of the subcutaneous route of fentanyl administration by Basic Life Support-Emergency Medical Technicians (BLS-EMT) in a rural and suburban region, with the support of an online pain management medical control center. Retrospective study of patients who received subcutaneous fentanyl and were transported by BLS-EMT to the emergency department (ED) of an academic hospital between July 1, 2013 and January 1, 2014, inclusively. Fentanyl orders were obtained from emergency physicians via an online medical control (OLMC) center. Effectiveness was defined by changes in pain scores 15 minutes, 30 minutes, and 45+ minutes after initial fentanyl administration. Safety was evaluated by measuring vital signs, Ramsay sedation scores, and adverse events subsequent to fentanyl administration. Feasibility was defined as successful fentanyl administration by BLS-EMT. SPSS-20 was used for descriptive statistics, and independent t-tests and Mann-Whitney U tests were used to determine inter- and intra-group differences based on transport time. Two hundred and eighty-eight patients (288; 14 to 93 years old) with pain scores ≥7 were eligible for the study. Of the 284 (98.6%) who successfully received subcutaneous fentanyl, 35 had missing records or data, and 249 (86.5%) were included in analyses. Average pain score pre-fentanyl was 8.9 ± 1.1. Patients fentanyl than those ≥70 years old (1.4 ± 0.3 vs, 0.8 ± 0.2 mcg/kg, p fentanyl administration and the proportion of patients achieving pain relief increased significantly (p 3 (n = 1; 0.4%). Prehospital subcutaneous fentanyl administration by BLS-EMT with the support of an OLMC center is a safe and feasible approach to pain relief in prehospital settings, and is not associated with major adverse events. Effectiveness, subsequent to subcutaneous fentanyl administration is characterized by a decrease in pain over the course of transport to ED. Further studies are needed to

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.

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

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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.

Subeffective doses of dexketoprofen trometamol enhance the potency and duration of fentanyl antinociception

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Gaitán, Gema; Herrero, Juan F

2002-01-01

The combination of classic non-steroidal antiinflammatory drugs (NSAIDs) with opiates induces more analgesia than the summed effect of each drug given separately. No studies have been performed using new generation NSAIDs and fentanyl nor on the duration of this effect. We have studied the analgesic effect of fentanyl alone and after the administration of subeffective doses of dexketoprofen trometamol in rat nociceptive responses. The responses were evoked by noxious mechanical stimulation and were recorded as single motor units in male Wistar rats anaesthetized with α-chloralose. The effective dose 50 (ED50) observed with fentanyl was 22.4±1.5 μg kg−1 and full recovery was apparent 20 min later. The administration of a total dose of 40 μg kg−1 of dexketoprofen trometamol did not induce any significant effect on the nociceptive responses. In the presence of dexketoprofen trometamol, the ED50 for fentanyl was 5 fold lower than before: 3.8±1.1 μg kg−1 and no significant recovery was observed 45 min later. The opioid antagonist naloxone (200 μg kg−1) did not reverse the effect, although in control experiments the same dose was able to prevent any action of fentanyl given alone. We conclude that the combination of fentanyl and subeffective doses of dexketoprofen trometamol induces a more potent and longer lasting analgesic effect than that observed with fentanyl alone, and that this is not an opioid mediated action. PMID:11815374

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

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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...

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

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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 secondhand smokers was lower than that in smokers in the PACU and at 24 h (P secondhand smokers than in nonsmokers (P effects such as nausea, vomiting, and dizziness (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.

[Understanding Oral and Nasal Mucosal Absorption of Fentanyl, and Rectal Absorption of Buprenorphine].

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Shimoyama, Naohito; Shimoyama, Megumi; Kubota, Yukino; Kato, Yoko

2015-11-01

One of the key issues in the treatment of pain is to choose the appropriate route and dosage form of analgesics for each individual patient in pain. New drug forms of fentanyl absorbed by oral or nasal mucosa, and buprenorphine absorbed by rectal mucosa are described in this chapter. Only lipophilic opioids such as fentanyl and buprenorphine can be absorbed via the mucosa of oral or nasal cavity of the human body. The T max of rapid onset opioids (ROO) such as fentanyl buccal or sublingual tablets is the fastest among various dosage forms of opioid analgesics. However, such rapid increase in plasma concentration of fentanyl by ROO formulations may cause the risk of respiratory depression. Safe ways to use ROO analgesics are described.

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

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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 phy...

Association between UGT2B7 gene polymorphisms and fentanyl sensitivity in patients undergoing painful orthognathic surgery

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Muraoka, Wataru; Nishizawa, Daisuke; Fukuda, Kenichi; Kasai, Shinya; Hasegawa, Junko; Wajima, Koichi; Nakagawa, Taneaki

2016-01-01

Background Fentanyl is often used instead of morphine for the treatment of pain because it has fewer side effects. The metabolism of morphine by glucuronidation is known to be influenced by polymorphisms of the UGT2B7 gene. Some metabolic products of fentanyl are reportedly metabolized by glucuronate conjugation. The genes that are involved in the metabolic pathway of fentanyl may also influence fentanyl sensitivity. We analyzed associations between fentanyl sensitivity and polymorphisms of the UGT2B7 gene to clarify the hereditary determinants of individual differences in fentanyl sensitivity. Results This study examined whether single-nucleotide polymorphisms (SNPs) of the UGT2B7 gene affect cold pain sensitivity and the analgesic effects of fentanyl, evaluated by a standardized pain test and fentanyl requirements in healthy Japanese subjects who underwent uniform surgical procedures. The rs7439366 SNP of UGT2B7 is reportedly associated with the metabolism and analgesic effects of morphine. We found that this SNP is also associated with the analgesic effects of fentanyl in the cold pressor-induced pain test. It suggested that the C allele of the rs7439366 SNP may enhance analgesic efficacy. Two SNPs of UGT2B7, rs4587017 and rs1002849, were also found to be novel SNPs that may influence the analgesic effects of fentanyl in the cold pressor-induced pain test. Conclusions Fentanyl sensitivity for cold pressor-induced pain was associated with the rs7439366, rs4587017, and rs1002849 SNPs of the UGT2B7 gene. Our findings may provide valuable information for achieving satisfactory pain control and open to new avenues for personalized pain treatment. PMID:28256933

Analysis of fentanyl in urine by DLLME-GC-MS.

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Gardner, Michael A; Sampsel, Sheena; Jenkins, Werner W; Owens, Janel E

2015-03-01

Fentanyl is a synthetic narcotic anesthetic ∼80-100 times more potent than morphine. Owing to the potential for its abuse, the drug may be included in a forensic toxicology work-up, which requires fast, precise and accurate measurements. Here, the stability of fentanyl was assessed when stored at three different temperatures (-20, 4 and 25°C) in synthetic urine. Stability at those three temperatures was demonstrated over 12 weeks upon analysis by gas chromatography-mass spectrometry with a deuterated internal standard (fentanyl-D5) utilizing three different extraction techniques: liquid-liquid extraction (LLE), solid-phase extraction and dispersed liquid-liquid microextraction (DLLME). The DLLME method was then optimized before use in the analysis of fentanyl in urine samples obtained from autopsy cases at the El Paso County Coroner's Office. Accuracy of the DLLME method was assessed by completing spike and recovery studies at three different fortification levels (10, 100 and 250 ng/mL) with excellent recovery (89.9-102.6%). The excellent comparability between DLLME and LLE is demonstrated (Bland-Altman difference plot with a mean difference of 4.9 ng/mL) and the use of this methodology in the analysis of forensically relevant samples is discussed. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effects of fentanyl on isoflurane minimum alveolar concentration in New Zealand White rabbits (Oryctolagus cuniculus).

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Barter, Linda S; Hawkins, Michelle G; Pypendop, Bruno H

2015-02-01

To determine effects of increasing plasma fentanyl concentrations on the minimum alveolar concentration (MAC) of isoflurane in rabbits. 6 adult female New Zealand White rabbits (Oryctolagus cuniculus). Rabbits were anesthetized with isoflurane in oxygen; ventilation was controlled and body temperature maintained between 38.5° and 39.5°C. Fentanyl was administered IV by use of a computer-controlled infusion system to achieve 6 target plasma concentrations. Isoflurane MAC was determined in duplicate by use of the bracketing technique with a supramaximal electrical stimulus. Blood samples were collected for measurement of plasma fentanyl concentration at each MAC determination. The MAC values were analyzed with a repeated-measures ANOVA followed by Holm-Sidak pairwise comparisons. Mean ± SD plasma fentanyl concentrations were 0 ± 0 ng/mL (baseline), 1.2 ± 0.1 ng/mL, 2.2 ± 0.3 ng/mL, 4.4 ± 0.4 ng/mL, 9.2 ± 0.4 ng/mL, 17.5 ± 2.6 ng/mL, and 36.8 ± 2.4 ng/mL. Corresponding mean values for isoflurane MAC were 1.92 ± 0.16%, 1.80 ± 0.16%, 1.60 ± 0.23%, 1.46 ± 0.22%, 1.12 ± 0.19%, 0.89 ± 0.14%, and 0.70 ± 0.15%, respectively. Isoflurane MAC for plasma fentanyl concentrations ≥ 2.2 ng/mL differed significantly from the baseline value. In 3 rabbits, excessive spontaneous movement prevented MAC determination at the highest plasma fentanyl concentration. Fentanyl reduced isoflurane MAC by approximately 60% in New Zealand White rabbits. Further studies will be needed to investigate the cardiorespiratory effects of isoflurane and fentanyl combinations in rabbits; however, fentanyl may prove to be a useful adjunct to inhalation anesthesia in this species.

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

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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.

Exposure to fentanyl-contaminated heroin and overdose risk among illicit opioid users in Rhode Island: A mixed methods study.

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Carroll, Jennifer J; Marshall, Brandon D L; Rich, Josiah D; Green, Traci C

2017-08-01

Illicit fentanyl use has become wide spread in the US, causing high rates of overdose deaths among people who use drugs. This study describes patterns and perceptions of fentanyl exposure among opioid users in Rhode Island. A mixed methods study was conducted via questionnaire with a convenience sample of 149 individuals using illicit opioids or misusing prescription opioids in Rhode Island between January and November 2016. Of these, 121 knew of fentanyl and reported known or suspected exposure to fentanyl in the past year. Semi-structured interviews were conducted with the first 47 participants. Study participants were predominantly male (64%) and white (61%). Demographic variables were similar across sample strata. Heroin was the most frequently reported drug of choice (72%). Self-reported exposure to illicit fentanyl in the past year was common (50.4%, n=61). In multivariate models, regular (at least weekly) heroin use was independently associated with known or suspected fentanyl exposure in the past year (adjusted prevalence ratio (APR)=4.07, 95% CI: 1.24-13.3, p=0.020). In interviews, users described fentanyl as unpleasant, potentially deadly, and to be avoided. Participants reporting fentanyl exposure routinely experienced or encountered non-fatal overdose. Heroin users reported limited ability to identify fentanyl in their drugs. Harm reduction strategies used to protect themselves from fentanyl exposure and overdose, included test hits, seeking prescription opioids in lieu of heroin, and seeking treatment with combination buprenorphine/naloxone. Participants were often unsuccessful in accessing structured treatment programs. Among illicit opioid users in Rhode Island, known or suspected fentanyl exposure is common, yet demand for fentanyl is low. Fentanyl-contaminated drugs are generating user interest in effective risk mitigation strategies, including treatment. Responses to the fentanyl epidemic should be informed by the perceptions and experiences of

Efficacy of tramadol versus fentanyl for postoperative analgesia in neonates.

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Alencar, Ana Julia Couto; Sanudo, Adriana; Sampaio, Virginia Maria Ramos; Góis, Rôsicler Pereira; Benevides, Fernando Antônio Barbosa; Guinsburg, Ruth

2012-01-01

To assess, in newborn infants submitted to surgical procedures, the efficacy of two opioids-fentanyl and tramadol-regarding time to extubate, time to achieve 100 ml/kg of enteral feeding and pain in the first 72 h after surgery. Controlled, blind, randomised clinical trial. Neonatal intensive care unit. 160 newborn infants up to 28 days of life requiring major or minor surgeries. Patients were randomised to receive analgesia with fentanyl (1-2 μg/kg/h intravenously) or tramadol (0.1-0.2 mg/kg/h intravenously) in the first 72 h of the postoperative period, stratified by surgical size and by patient's gender. Pain assessed by validated neonatal scales (Crying, Requires oxygen, Increased vital signs, Expression and Sleepless Scale and the Neonatal Facial Coding System), time until extubation and time to reach 100 ml/kg enteral feeding. Statistical analysis included repeated measures analysis of variance adjusted for confounding variables and Kaplan-Meier curve adjusted by a Cox model of proportional risks. Neonatal characteristics were (mean±SD) birth weight of 2924±702 g, gestational age of 37.6±2.2 weeks and age at surgery of 199±63 h. The main indication of surgery was gastrointestinal malformation (85 newborns; 53%). Neonates who received fentanyl or tramadol were similar regarding time until extubation, time to reach 100 ml/kg of enteral feeding and pain scores in the first 72 h after surgery. Tramadol was as effective as fentanyl for postoperative pain relief in neonates but does not appear to offer advantages over fentanyl regarding the duration of mechanical ventilation and time to reach full enteral feeding. Trial registration NCT00713726.

Fentanyl versus magnesium sulphate as adjuvant to peribulbar anesthesia in cataract surgery

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Mohamed M. Abu Elyazed

2017-04-01

Conclusions: Addition of fentanyl (2 μg/ml or magnesium sulphate (50 mg to peribulbar block in patients undergoing cataract surgery equally prolongs the duration of postoperative analgesia. In addition to this effect, fentanyl fastens the onset lid and globe akinesia and provides better akinesia score.

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

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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.

Pragmatic pharmacology: population pharmacokinetic analysis of fentanyl using remnant samples from children after cardiac surgery

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Van Driest, Sara L.; Marshall, Matthew D.; Hachey, Brian; Beck, Cole; Crum, Kim; Owen, Jill; Smith, Andrew H.; Kannankeril, Prince J.; Woodworth, Alison; Caprioli, Richard M.

2016-01-01

Aims One barrier contributing to the lack of pharmacokinetic (PK) data in paediatric populations is the need for serial sampling. Analysis of clinically obtained specimens and data may overcome this barrier. To add evidence for the feasibility of this approach, we sought to determine PK parameters for fentanyl in children after cardiac surgery using specimens and data generated in the course of clinical care, without collecting additional blood samples. Methods We measured fentanyl concentrations in plasma from leftover clinically‐obtained specimens in 130 paediatric cardiac surgery patients and successfully generated a PK dataset using drug dosing data extracted from electronic medical records. Using a population PK approach, we estimated PK parameters for this population, assessed model goodness‐of‐fit and internal model validation, and performed subset data analyses. Through simulation studies, we compared predicted fentanyl concentrations using model‐driven weight‐adjusted per kg vs. fixed per kg fentanyl dosing. Results Fentanyl clearance for a 6.4 kg child, the median weight in our cohort, is 5.7 l h–1 (2.2–9.2 l h–1), similar to values found in prior formal PK studies. Model assessment and subset analyses indicated the model adequately fit the data. Of the covariates studied, only weight significantly impacted fentanyl kinetics, but substantial inter‐individual variability remained. In simulation studies, model‐driven weight‐adjusted per kg fentanyl dosing led to more consistent therapeutic fentanyl concentrations than fixed per kg dosing. Conclusions We show here that population PK modelling using sparse remnant samples and electronic medical records data provides a powerful tool for assessment of drug kinetics and generation of individualized dosing regimens. PMID:26861166

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

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

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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/m 2 (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 AUC 0-∞ 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).

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

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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

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

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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 (Pfentanyl use shows that recent increases in fentanyl use seem to be due almost entirely to 'unknown' fentanyl presumed to be illicitly manufactured. Given that it is difficult to assess the extent to which fentanyl may have been substituted for another drug (i.e., oxycodone, alprazolam, etc.) or was used as a heroin admixture, our data likely represent an underestimation of the full magnitude of illicit fentanyl abuse. As such, this growing public health problem requires immediate attention and more systematic efforts to identify and track its abuse. Copyright © 2017. Published by Elsevier B.V.

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

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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

Effect of fentanyl on 125I-β-CIT uptake in mice brain

International Nuclear Information System (INIS)

Liu Xingdang; Lin Xiangtong

2003-01-01

Objective: To investigate the effect of fentanyl on 125 I-2β-carbomethoxy-3β-(4-iodophenyl) tropane ( 125 I-β-CIT) uptake in mice brain. Methods: 1) KM mice groups of five were given different doses of fentanyl, and 10 min or 1 h later were given a dose of 125 I-β-CIT. 2)Two groups of animals were killed at 2 h after injection of 125 I-β-CIT. 3)One group of animals were killed at 1 h after injection of 125 I-β-CIT. Results: 1)In the striatum, frontal cortex, hippocampus, brain stem, cerebellum and whole brain, a dose-dependent increase in uptake (%ID/g or %ID) of 125 I-β-CIT was detected at the fentanyl doses ranging from 125 to 300 μg/kg, and the uptakes of hippocampus and cerebellum were higher than that of the controls. There was a great difference in the value of %ID/g or %ID between the group treated with 250 μg/kg fentanyl and the control group; while at the doses from 12.5 to 100 μg/kg, a dose-dependent decrease in uptake in the same regions was observed and all the uptake levels were lower (hippocampus: except 62.5 and 12.5 μg/kg groups; brain stem: except 62.5 μg/kg group) than that of the controls. 2)The uptakes of 125 I-β-CIT in the striatum, frontal cortex, hippocampus, brain stem, cerebellum and whole brain in the groups injected with 125 I-β-CIT 10 min after fentanyl treatment were higher than that in the groups injected with 125 I-β-CIT 1 h after fentanyl treatment. 3)The binding of 125 I-β-CIT in the striatum, frontal cortex, hippocampus, brain stem, cerebellum and whole brain in the groups killed at 1 h after injection of 125 I-β-CIT was higher than that in the control group, but without significant difference. Conclusion: Fentanyl may have different effects on 125 I-β-CIT at various time points and doses

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

Clinical efficacy of dexmedetomidine in the diminution of fentanyl dosage in pediatric cardiac surgery.

Science.gov (United States)

Sun, Yingying; Ye, Hongwu; Xia, Yin; Li, Yuanhai; Yuan, Xianren; Wang, Xing

2017-06-01

This study aims to explore the clinical efficacy of dexmedetomidine (DEX) in the diminution of fentanyl dosage in pediatric cardiac surgery based on some clinical and biochemical parameters. Fifty pediatric patients (American Society of Anesthesiologists II), 1-6 years old, were randomly allocated into two groups: group F (control group), in which patients received normal saline and high dosage of fentanyl (30 μg/kg), and group D, in which patients were given DEX and low dosage of fentanyl (15 μg/kg). Some hemodynamic and clinical parameters of the two groups were recorded. Furthermore, stress hormone (serum cortisol, norepinephrine, blood glucose) levels and cytokine (interleukin 6, tumor necrosis factor alpha) levels in the two groups were compared with each other. Stress hormone levels, cytokine levels, hemodynamic parameters and the consumption of sevoflurane did not differ between the two groups. Meanwhile, the extubation time was significantly shorter in Group D than F (Pfentanyl supplemented with DEX almost had the same anesthesia effects and inflammation extent compared with high dose of fentanyl, which suggested that infusion DEX might decrease fentanyl consumption in pediatric cardiac surgery.

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...

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

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....

Intravenous ketamine is as effective as midazolam/fentanyl for procedural sedation and analgesia in the emergency department.

Science.gov (United States)

Jamal, S M; Fathil, S M; Nidzwani, M M; Ismail, A K; Yatim, F M

2011-08-01

The study compared the effectiveness of ketamine and midazolam/fentanyl as procedural sedation and analgesia agents for reduction of fractures and dislocated joints. Forty-one adult patients were enrolled by convenience sampling. They were randomized to receive ketamine or midazolam/fentanyl. Depth of sedation, pain score, procedural outcome and memory of the procedure were documented. The ketamine group had deeper sedation, but there was no statistical difference in other variables between the two groups. Three patients in the midazolam/fentanyl group had oxygen desaturation. More adverse effects were associated with ketamine. Intravenous ketamine is as effective as midazolam/fentanyl for procedural sedation.

Stress, Predictability, and Oral Fentanyl Self-Administration in Female and Male Rats

Science.gov (United States)

1995-03-09

naloxone. When dissolved in water, fentanyl hydrochloride (Hel) is less bitter-tasting than morphine and it is readily self- administered by rats...and for assessment of the biochemical effects of the stressor. Drugs Fentanyl- hydrochloride (HCI) (NIDA, Baltimore, MD), in a concentration of 50...responses despite lower opioid SA, treatment for men might focus on pharmacologic replacement therapies, such as methadone maintenance programs. The

Fentanyl and Other Synthetic Opioids Drug Overdose Deaths

Science.gov (United States)

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

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

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.

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.

Intrathecal fentanyl abolishes the exaggerated blood pressure response to cycling in hypertensive men

DEFF Research Database (Denmark)

Barbosa, Thales C; Vianna, Lauro C; Fernandes, Igor A

2016-01-01

. 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 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 inhibited the blood pressure response to exercise...

Withdrawal syndrome associated with cessation of fentanyl and midazolam in pediatrics

OpenAIRE

Bicudo, J.n. [UNIFESP; Souza, N. de [UNIFESP; Mângia, C.m.f. [UNIFESP; Carvalho, Werther Brunow de [UNIFESP

1999-01-01

PURPOSE: To determine the incidence of abstinence syndrome in children interned in the Pediatric Intensive Care Unit (PICU) in fentanyl use and midazolam METHODS: Evaluation of 36 children interned in PICU of the Hospital São Paulo - Federal University of São Paulo, in the period from March to September 1997, with age varying from 5 days to 22 months (22 masc: 14 fem) who used fentanyl use and midazolam for more than 24 hours. Used the Escore Neonatal of Abstinence adapted by Finnegan determi...

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.

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.

The fentanyl concentration required for immobility under propofol anesthesia is reduced by pre-treatment with flurbiprofen axetil.

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Kodaka, Mitsuharu; Tsukakoshi, Mikiko; Miyao, Hideki; Tsuzaki, Koichi; Ichikawa, Junko; Komori, Makiko

2013-12-01

We hypothesized that nonsteroidal anti-inflammatory drugs decrease the plasma fentanyl concentration required to produce immobility in 50% of patients in response to skin incision (Cp50incision) compared with placebo under target-controlled infusion (TCI) propofol anesthesia. Sixty-two unpremedicated patients scheduled to undergo gynecologic laparoscopy were randomly assigned to receive placebo (control group) or flurbiprofen axetil 1 mg·kg(-1) (flurbiprofen group) preoperatively. General anesthesia was induced with fentanyl and propofol, and intubation was performed after succinylcholine 1 mg·kg(-1). Propofol was administered via a target-controlled infusion (TCI) system (Diprifusor™) set at an effect-site concentration of 5 μg·mL(-1). Fentanyl was given by a TCI system using the STANPUMP software (Schafer model). The concentration for the first patient was set at 3 ng·mL(-1) and modified in each group according to the up-down method. Skin incision was performed after more than ten minutes equilibration time. Serum fentanyl concentration, bispectral index (BIS), and hemodynamic parameters were measured two minutes before and after skin incision. The Cp50incision of fentanyl was derived from the mean of the crossovers (i.e., the serum fentanyl concentrations of successive participants who responded and those who did not or vice versa). Ten and 11 independent crossover pairs were collected in the control and flurbiprofen groups, respectively, representing 42 of 62 enrolled patients. The mean (SD) fentanyl Cp50incision was less in the flurbiprofen group [0.84 (0.63) ng·mL(-1)] than in the control group [1.65 (1.15) ng·mL(-1)]; P = 0.007; however, there were no differences in BIS, blood pressure, or heart rate, between groups. Preoperative flurbiprofen axetil decreased the Cp50incision of fentanyl by 49% during propofol anesthesia without changing the BIS or hemodynamic variables.

Fentanyl Ameliorates Severe Acute Pancreatitis-Induced Myocardial Injury in Rats by Regulating NF-κB Signaling Pathway.

Science.gov (United States)

Wang, Yayun; Chen, Manhua

2017-07-06

BACKGROUND Acute pancreatitis (AP) is a sudden inflammation of the pancreas. It results in multiple, severe complications, and 15-20% of patients develop severe acute pancreatitis (SAP) with mortality as high as 30%. Consequently, it is imperative to develop an effective therapy for SAP. MATERIAL AND METHODS We used 30 adult male Sprague Dawley (SD) rats. Rats were randomly divided into 3 groups - sham, SAP, and fentanyl+SAP - with 10 rats in each group. An automatic biochemical analyzer was used to analyze the concentration of creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH). Terminal-deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) assay was applied to assess the cell apoptosis rate. Pathological changes in pancreas/heart were detected with hematoxylin and eosin (HE) staining. Western immunoblot assay was used to analyze protein levels of interleukin (IL)-1β, IL-6, and IκB. RESULTS Fentanyl pre-treatment inhibits SAP-induced elevation of CK-MB/LDH concentrations in serum. Compared with the sham group, SAP generates a higher brown/yellow staining rate, which is abated by fentanyl. In the pancreas, SAP generated more serious interstitial edema/hemorrhage and fat necrosis than in the sham group, which are attenuated by fentanyl. Likewise, compared to the sham group, SAP generates swelled/disordered myocardial fibers and congested blood vessels in myocardium, which are ameliorated by fentanyl. In the sham group, there was little IL-1β/IL-6, and fentanyl significantly inhibited SAP-induced up-regulation of IL-1β/IL-6 levels. Compared with the sham group, SAP significantly reduced IκB level, which was rescued by fentanyl. CONCLUSIONS Fentanyl effectively alleviates SAP-induced pancreas and heart injuries through regulating the nuclear factor-κB (NF-κB) signaling pathway.

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

Design and functionality of a smart fentanyl iontophoretic transdermal system for the treatment of moderate-to-severe postoperative pain.

Science.gov (United States)

Joshi, Nitin; Lemke, John; Danesi, Hassan

2016-04-01

Fentanyl iontophoretic transdermal system (ITS) is a patient-controlled analgesia system used for the management of acute postoperative pain. The first-generation fentanyl ITS was an integrated one-piece system; however, corrosion that could limit reliability was detected in a small number of systems. A second-generation fentanyl ITS was designed to separate the hydrogels in the Drug Unit from the electronic circuit of the Controller during manufacture and storage, removing the primary cause of corrosion and thereby improving reliability. No evidence of corrosion has been observed in over 10,000 systems tested in real-time aging studies for the second generation fentanyl ITS. The second generation fentanyl ITS design features combine to ensure safe operation of the system with high reliability.

An epidemic of illicit fentanyl deaths in Cook County, Illinois: September 2005 through April 2007.

Science.gov (United States)

Denton, J Scott; Donoghue, Edmund R; McReynolds, Jennifer; Kalelkar, Mitra B

2008-03-01

Between September 2005 and April 2007, 350 fentanyl intoxication deaths were investigated and certified by the Cook County Medical Examiners Office. Investigations revealed that the majority of these fatalities were by intravenous injection of a white powder followed by a rapid collapse. The fentanyl was clandestinely produced in a lab in Toluca, Mexico and sold by the Mickey Cobra street gang. The term "Drop Dead" was coined for this "tainted heroin." Postmortem samples were screened by ELISA and confirmed by standard GC-MS methods. Fentanyl fatalities peaked at 47 per month in May and June 2006. Fifty-two percent were single fentanyl intoxications, with the remainder accompanied by either cocaine, morphine from heroin, or alcohol. This epidemic stressed the limited resources of the toxicology laboratory and autopsy service of the Medical Examiners Office. The clandestine lab was terminated, distributing gang members and leaders arrested, and the epidemic ceased in April 2007.

Intrathecal tramadol versus intrathecal fentanyl for visceral pain ...

African Journals Online (AJOL)

2013-10-29

Oct 29, 2013 ... Nigerian Journal of Clinical Practice • May-Jun 2014 • Vol 17 • Issue 3. Original ... intrathecal fentanyl and a normal saline placebo‑controlled protocol for ..... pain experienced by pregnant women during Caesarean section.

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

Isoflurane minimum alveolar concentration sparing effects of fentanyl in the dog.

Science.gov (United States)

Williamson, Allan J; Soares, Joao H N; Pavlisko, Noah D; McAlister Council-Troche, Robert; Henao-Guerrero, Natalia

2017-07-01

To characterize the isoflurane-sparing effects of a high and a low dose of fentanyl in dogs, and its effects on mean arterial pressure (MAP) and heart rate (HR). Prospective, randomized crossover trial. Eight healthy male Beagle dogs weighing 12.1 ± 1.6 kg [mean ± standard deviation (SD)] and approximate age 1 year. Dogs were anesthetized using isoflurane and minimum alveolar concentration (MAC) was determined in duplicate by the bracketing method using an electrical stimulus on the tarsus. Animals were administered fentanyl: low dose (33 μg kg -1 loading dose, 0.2 μg kg -1  minute -1 ) or high dose (102 μg kg -1 loading dose, 0.8 μg kg -1  minute -1 ) and MAC was re-determined (MAC ISO-F ). Blood was collected for analysis of plasma fentanyl concentrations before administration and after MAC ISO-F determination. All values are presented as mean ± SD. Isoflurane MAC (MAC ISO ) was 1.30 ± 0.23% in the low dose treatment, which significantly decreased to 0.75 ± 0.22% (average MAC reduction 42.3 ± 9.4%). MAC ISO was 1.30 ± 0.18% in the high dose treatment, which significantly decreased to 0.30 ± 0.11% (average MAC reduction 76.9 ± 7.4%). Mean fentanyl plasma concentrations were 6.2 and 29.5 ng mL -1 for low and high dose treatments, respectively. MAP increased significantly only in the high dose treatment (from 81 ± 8 to 92 ± 9 mmHg). HR decreased significantly in both treatments from 108 ± 25 to 61 ± 14 beats minute -1 with the low dose and from 95 ± 14 to 42 ± 4 beats minute -1 with the high dose. Fentanyl administration resulted in a dose-dependent isoflurane MAC-sparing effect with bradycardia at both doses and an increase in MAP only at high dose. Further evaluation is needed to determine the effects of fentanyl on the overall cardiovascular function. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All

Synergism between fentanyl and tramadol in tonic inflammatory pain: the orofacial formalin test.

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Miranda, Hugo F; Noriega, Viviana; Zepeda, Ramiro J; Sierralta, Fernando; Prieto, Juan C

2012-06-01

Opioids have been used for long time to management of pain, the coadministration of two opioids may induce synergism. The present study was conducted to determine the antinociceptive interaction between the dual mechanism of action of tramadol compared to the main of fentanyl antinociception in the orofacial formalin which represents a model of persistent cutaneous nociception in the region innervated by the trigeminal nerve. The i.p. administration of tramadol and fentanyl induced a dose-dependent antinociception with an ED(50) of 2.97 ± 0.32 mg/kg for phase I and 1.79 ± 0.30 mg/kg for phase II and 0.062 ± 0.0040 mg/kg in phase I and 0.041 ± 0.0039 mg/kg in phase II, respectively. The coadministration of fentanyl with tramadol induced synergism in both phases of the test with an interaction index of 0.343 and 0.163 for phase I and phase II, respectively. This finding could be explained by the more complex pharmacology of tramadol compared to fentanyl.

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

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 B 2 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 B 2 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.

Plasma concentrations of fentanyl with subcutaneous infusion in palliative care patients.

OpenAIRE

Miller, R S; Peterson, G M; Abbott, F; Maddocks, I; Parker, D; McLean, S

1995-01-01

1. Plasma concentrations of fentanyl were measured by g.c. in 20 patients (median age: 75 years and range: 54-86 years; eight females) in palliative care receiving the drug by continuous s.c. infusion (median rate: 1200 micrograms day-1 and range: 100-5000 micrograms day-1). 2. The infusion rate was significantly related to the duration of therapy (Spearman rho = 0.56, P < 0.05). The total steady-state plasma concentrations of fentanyl ranged between 0.1 and 9 ng ml-1, with a median of 1 ng m...

Knee strength retention and analgesia with continuous perineural fentanyl infusion after total knee replacement: randomized controlled trial.

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Mangar, Devanand; Karlnoski, Rachel A; Sprenker, Collin J; Downes, Katheryne L; Taffe, Narrene; Wainwright, Robert; Gustke, Kenneth; Bernasek, Thomas L; Camporesi, Enrico

2014-04-01

Despite providing adequate pain relief, a femoral nerve block can induce postoperative muscle weakness after total knee arthoplasty (TKA). Fentanyl has been shown to have peripheral effects but has not been used as a perineural infusate alone after TKA. Sixty patients scheduled for TKA were randomized to one of three blinded groups: a continuous 24 h infusion of either fentanyl 3 μg/ml, ropivacaine 0.1%, or 0.9% normal saline through a femoral nerve sheath catheter at 10 ml/h. The main outcome was maximum voluntary isometric contraction (MVIC) in the quadriceps femoris (knee extension), measured by a handheld dynamometer (Nm/kg). Other variables assessed were preoperative and postoperative visual analog scale (VAS) scores, hamstrings MVIC (knee flexion), active range of motion of the operative knee, distance ambulated, incidence of knee buckling, supplemental morphine usage, postoperative side effects, and serum fentanyl levels. Quadriceps MVIC values were significantly greater in the fentanyl group compared to the group that received ropivacaine (median values, 0.08 vs. 0.03 Nm/kg; p = 0.028). The incidence of postoperative knee buckling upon ambulation was higher in the ropivacaine group compared to the fentanyl group, although not statistically significant (40% vs. 15 %, respectively; p = 0.077). VAS scores while ambulating were not significantly different between the fentanyl group and the ropivacaine group (p = 0.270). Postoperative morphine consumption, nausea and vomiting, and resting VAS scores were similar among the three groups. A continuous perineural infusion of fentanyl produced greater strength retention than ropivacaine post-TKA.

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

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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.

Pain Levels Within 24 Hours After UFE: A Comparison of Morphine and Fentanyl Patient-Controlled Analgesia

International Nuclear Information System (INIS)

Kim, Hyun S.; Czuczman, Gregory J.; Nicholson, Wanda K.; Pham, Luu D.; Richman, Jeffrey M.

2008-01-01

The purpose of this study was to assess the presence and severity of pain levels during 24 h after uterine fibroid embolization (UFE) for symptomatic leiomyomata and compare the effectiveness and adverse effects of morphine patient-controlled analgesia (PCA) versus fentanyl PCA. We carried out a prospective, nonrandomized study of 200 consecutive women who received UFE and morphine or fentanyl PCA after UFE. Pain perception levels were obtained on a 0-10 scale for the 24-h period after UFE. Linear regression methods were used to determine pain trends and differences in pain trends between two groups and the association between pain scores and patient covariates. One hundred eighty-five patients (92.5%) reported greater-than-baseline pain after UFE, and 198 patients (99%) required IV opioid PCA. One hundred thirty-six patients (68.0%) developed nausea during the 24-h period. Seventy-two patients (36%) received morphine PCA and 128 (64%) received fentanyl PCA, without demographic differences. The mean dose of morphine used was 33.8 ± 26.7 mg, while the mean dose of fentanyl was 698.7 ± 537.4 μg. Using this regimen, patients who received morphine PCA had significantly lower pain levels than those who received fentanyl PCA (p < 0.0001). We conclude that patients develop pain requiring IV opioid PCA within 24 h after UFE. Morphine PCA is more effective in reducing post-uterine artery embolization pain than fentanyl PCA. Nausea is a significant adverse effect from opioid PCA.

Fentanyl induces autophagy via activation of the ROS/MAPK pathway and reduces the sensitivity of cisplatin in lung cancer cells.

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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.

Fentanyl and heroin contained in seized illicit drugs and overdose-related deaths in British Columbia, Canada: An observational analysis.

Science.gov (United States)

Baldwin, Nicholas; Gray, Roger; Goel, Anirudh; Wood, Evan; Buxton, Jane A; Rieb, Launette Marie

2018-04-01

Due to the alarming rise in opioid-related overdose deaths, a public health emergency was declared in British Columbia (BC). In this study, we examined the relationship between illicit fentanyl and heroin found in seized drugs and illicit overdose deaths in BC. An observational cross-sectional survey was conducted using BC data from Health Canada's Drug Analysis Service, which analyzes drug samples seized by law enforcement agencies, and non-intentional illicit overdoses from the BC Coroner's Service, from 2000 to 2016. Initial scatter plots and subsequent multivariate regression analysis were performed to describe the potential relationship between seized illicit fentanyl samples and overdose deaths and to determine if this differed from seized heroin and overdose deaths. Fentanyl samples were analyzed for other drug content. Fentanyl is increasingly being found combined with other opioid and non-opioid illicit drugs. Strong positive relationships were found between the number of seized fentanyl samples and total overdose deaths (R2 = 0.97) as well as between seized fentanyl and fentanyl-detected overdose deaths (R2 = 0.99). A positive association was found between the number of seized heroin samples and total overdose deaths (R2 = 0.78). This research contributes to the expanding body of evidence implicating illicit fentanyl use (often combined with heroin or other substances) in overdose deaths in BC. Policy makers and healthcare providers are urged to implement drug treatment and harm reduction strategies for people at risk of overdose associated with current trends in illicit opioid use. Copyright © 2018 Elsevier B.V. All rights reserved.

COMPARATIVE STUDY OF EFFECT OF INTRAVENOUS MAGNESIUM SULPHATE AND INTRAVENOUS FENTANYL IN ATTENUATING THE HAEMODYNAMIC RESPONSES TO LARYNGOSCOPY AND INTUBATION

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Patta

2016-07-01

Full Text Available AIM To compare the haemodynamic response to laryngoscopy and intubation with intravenous MgSO4 and intravenous fentanyl. METHODS Fifty adult patients were divided into two groups randomly into group M and group F. Patients of group M received 30 mg/kg body weight of IV MgSO4 and group F received IV fentanyl 1.5 µg/kg 5 minutes before intubation. RESULTS IV Fentanyl showed greater degree of haemodynamic stability i.e. rise in heart rate, mean arterial pressure during laryngoscopy and intubation compared to IV MgSO4. IV fentanyl showed side effects like respiratory depression, nausea and vomiting. CONCLUSION IV fentanyl is a better drug in controlling haemodynamic response to laryngoscopy and intubation.

The median effective concentration (EC50) of propofol with different doses of fentanyl during colonoscopy in elderly patients.

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Li, Shiyang; Yu, Fang; Zhu, Huichen; Yang, Yuting; Yang, Liqun; Lian, Jianfeng

2016-04-21

Propofol and fentanyl are the most widely administered anesthesia maintaining drugs during colonoscopy. In this study, we determined the median effective concentration (EC50) of propofol required for colonoscopy in elderly patients, and the purpose of this study was to describe the pharmacodynamic interaction between fentanyl and propofol when used in combination for colonoscopy in elderly patients. Ninety elderly patients scheduled for colonoscopy were allocated into three groups in a randomized, double-blinded manner as below, F0.5 group (0.5 μg.kg(-1) fentanyl), F1.0 group (1.0 μg.kg(-1) fentanyl) and saline control group. Anaesthesia was achieved by target-controlled infusion of propofol (Marsh model, with an initial plasma concentration of 2.0 μg.ml(-1)) and fentanyl. Colonoscopy was started 3 min after the injection of fentanyl. The EC50 of propofol for colonoscopy with different doses of fentanyl was measured by using an up-and-down sequential method with an adjacent concentration gradient at 0.5 μg.ml(-1) to inhibit purposeful movements. Anaesthesia associated adverse events and recovery characters were also recorded. The EC50 of propofol for colonoscopy in elderly patients were 2.75 μg.ml(-1) (95% CI, 2.50-3.02 μg.ml(-1)) in F0.5 group, 2.05 μg.ml(-1) (95% CI, 1.98-2.13 μg.ml(-1)) in F1.0 group and 3.08 μg.ml(-1) (95% CI, 2.78-3.42 μg.ml(-1)) in control group respectively (P fentanyl up to 1.0 μg.kg(-1) reduces the propofol EC50 required for elderly patients undergoing colonoscopy, and there was no significant difference in anaesthesia associated adverse events but prolonged awake and discharge time. Chinese Clinical Trial Registry ChiCTR15006368. Date of registration: May 3, 2015.

Intrathecal tramadol versus intrathecal fentanyl for visceral pain ...

African Journals Online (AJOL)

Intrathecal tramadol versus intrathecal fentanyl for visceral pain control during bupivacaine subarachnoid block for open appendicectomy. ... Visual analog scale scores and frequency of subjective symptoms among patients in the three groups formed the primary outcome measure of this study. Results: Effective ...

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.

Plasma concentrations of fentanyl with subcutaneous infusion in palliative care patients.

Science.gov (United States)

Miller, R S; Peterson, G M; Abbott, F; Maddocks, I; Parker, D; McLean, S

1995-12-01

1. Plasma concentrations of fentanyl were measured by g.c. in 20 patients (median age: 75 years and range: 54-86 years; eight females) in palliative care receiving the drug by continuous s.c. infusion (median rate: 1200 micrograms day-1 and range: 100-5000 micrograms day-1). 2. The infusion rate was significantly related to the duration of therapy (Spearman rho = 0.56, P Infusion rates and both total and unbound plasma concentrations of fentanyl were correlated (Spearman rho = 0.92, P infusion in the palliative care setting, which necessitates careful titration of dosage according to individual clinical response.

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....

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.

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 ...

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

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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.

The interaction of fentanyl on the Cp50 of propofol for loss of consciousness and skin incision.

Science.gov (United States)

Smith, C; McEwan, A I; Jhaveri, R; Wilkinson, M; Goodman, D; Smith, L R; Canada, A T; Glass, P S

1994-10-01

We have previously demonstrated that the minimum alveolar concentration of isoflurane at 1 atm that is required to prevent movement in 50% of patients or animals exposed to a maximal noxious stimulus is markedly reduced by increasing fentanyl concentrations. Total intravenous anesthesia with propofol is increasing in popularity, yet the propofol concentrations required for total intravenous anesthesia or the interaction between propofol and fentanyl have not yet been defined. Propofol and fentanyl were administered via computer-assisted continuous infusion to provide pseudo-steady-state concentrations and allow equilibration between plasma-blood concentration and their biophase concentration. For the induction of anesthesia patients were randomly allocated to receive propofol only or propofol plus fentanyl 0.2, 0.8, 1.5, 3.0, and 4.5 ng/ml. In each group patients were randomized to target propofol concentrations of 1.5-10 micrograms/ml. At 7 and 10 min arterial blood samples were taken for subsequent measurement of propofol and fentanyl concentrations. At 10 min loss of consciousness was assessed by the patients' ability to respond to a simple verbal command. Thereafter a new target concentration of propofol was entered to ensure loss of consciousness, and succinylcholine was administered to facilitate tracheal intubation. Patients were rerandomized to a new target concentration of propofol (1-19 micrograms/ml) until skin incision. Before skin incision and 1 min after skin incision, arterial blood samples were again obtained for subsequent measurement of fentanyl and propofol concentrations. At skin incision and for 1 min the patient was observed for purposeful movement. Only samples in which the pre- and poststimulus drug concentrations were within 35% of each other were included. The propofol blood concentration at which 50% or 95% of patients did not respond to verbal command (Cp50s and Cp95s, respectively) and to skin incision (Cp50i and Cp95i, respectively

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

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

Energy Technology Data Exchange (ETDEWEB)

Hwang, Dahren; 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.

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

International Nuclear Information System (INIS)

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

1986-01-01

Three fluorinated derivatives of fentanyl, fluorofentanyl (3), keto-fluorofentanyl (5), and fluorofentanol (6), were synthesized and their abilities to compete with 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 [ 3 H]naltrexone for binding sites in rat brain membranes. Both fentayl and 6 exhibited a similar high ''sodium ratio'' (quotient of the IC 50 's against [ 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 [ 18 F]-6 was developed and the tissue distribution of [ 18 F]-6 in mice was determined 5, 60, and 120 minutes after intravenous injection. The use of this general route to 18 F-labeled derivatives of fentanyl for studies of the opiate receptor using positron emission tomography is planned. (author)

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

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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.

Postoperative analgesia in children when using clonidine or fentanyl with ropivacaine given caudally

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Usha Shukla

2011-01-01

Full Text Available Background: The aim of the study was to compare the efficacy of clonidine and fentanyl as an additive to ropivacaine given via single shot caudal epidural in pediatric patients for postoperative pain relief. Materials and Methods: In the present double blind study, 90 children of ASA-I-II aged 3-8 years scheduled for infraumblical surgical procedures were randomly allocated to two groups to receive either ropivacaine 0.25% 1 ml/kg+clonidine 2 μg/kg (group I or ropivacaine 0.25% 1 μl/kg+fentanyl 1 μg/kg (group II. Caudal block was performed after the induction of general anesthesia. Postoperatively patients were observed for analgesia, sedation, hemodynamics, and side effects/complications. Results: Both the groups were similar with respect to patient and various block characteristics. The analgesic properties and hemodynamics were also comparable in both groups (P > 0.05. Side effects such as respiratory depression, vomiting bradycardia were significantly less in group I than group II (P < 0.05 ensuing more patient comfort. Conclusions: The analgesic properties of clonidine and fentanyl as additives to ropivacaine in single shot caudal epidural in children are comparable but clonidine offers a more favorable side effect profile. The use of clonidine as additive to ropivacaine in caudal epidural is superior choice to fentanyl because of lack of unwanted side effects and increased patient comfort.

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.

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. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

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.

Fentanyl increases dopamine release in rat nucleus accumbens: involvement of mesolimbic mu- and delta-2-opioid receptors

NARCIS (Netherlands)

Yoshida, Y.; Koide, S.; Hirose, N.; Takada, K.; Tomiyama, K; Koshikawa, N.; Cools, A.R.

1999-01-01

The effects of the u-receptor agonist fentanyl on extracellular levels of dopamine in rat nucleus accumbens were studied in awake animals by in vivo brain microdialysis. Fentanyl dosedependently increased the levels of dopamine when given intravenously (ug/kg) or via a microdialysis probe placed

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.

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

Comparison of efficacy of bupivacaine and fentanyl with bupivacaine and sufentanil for epidural labor analgesia

Directory of Open Access Journals (Sweden)

Kalra Sumit

2010-01-01

Full Text Available Objectives: A study to compare the efficacy between fentanyl and sufentanil combined with low concentration (0.0625% of bupivacaine for epidural labor analgesia in laboring women. Materials and Methods: Fifty full term parturients received an initial bolus dose of a 10 ml solution containing 0.125% bupivacaine. The patients were randomly divided into two: group F received 0.0625% bupivacaine with 2.5 mcg/ml fentanyl and group S received 0.0625% bupivacaine with 0.25 mcg/ml sufentanil. Verbal analogue pain scores, need of supplementary/rescue boluses dose of bupivacaine consumed, mode of delivery, maternal satisfaction, and neonatal Apgar scores were recorded. No significant difference was observed between both groups. Results: Both the groups provided equivalent labor analgesia and maternal satisfaction. The chances of cesarean delivery were also not increased in any group. No difference in the cephalad extent of sensory analgesia, motor block or neonatal Apgar score were observed. Although mean pain scores throughout the labor and delivery were similar in both groups, more patients in fentanyl group required supplementary boluses though not statistically significant. Conclusion: We conclude that both 0.0625% bupivacaine-fentanyl (2.5 μg/ml and 0.0625% bupivacaine-sufentanil (0.25 μg/ml were equally effective by continuous epidural infusion in providing labor analgesia with hemodynamic stability achieving equivalent maternal satisfaction without serious maternal or fetal side effects. We found that sufentanil was 10 times more potent than fentanyl as an analgesic for continuous epidural labor analgesia.

Effect of fentanyl on the induction dose and minimum infusion rate of propofol preventing movement in dogs.

Science.gov (United States)

Davis, Carrie A; Seddighi, Reza; Cox, Sherry K; Sun, Xiaocun; Egger, Christine M; Doherty, Thomas J

2017-07-01

To determine the effect of fentanyl on the induction dose of propofol and minimum infusion rate required to prevent movement in response to noxious stimulation (MIR NM ) in dogs. Crossover experimental design. Six healthy, adult intact male Beagle dogs, mean±standard deviation 12.6±0.4 kg. Dogs were administered 0.9% saline (treatment P), fentanyl (5 μg kg -1 ) (treatment PLDF) or fentanyl (10 μg kg -1 ) (treatment PHDF) intravenously over 5 minutes. Five minutes later, anesthesia was induced with propofol (2 mg kg -1 , followed by 1 mg kg -1 every 15 seconds to achieve intubation) and maintained for 90 minutes by constant rate infusions (CRIs) of propofol alone or with fentanyl: P, propofol (0.5 mg kg -1  minute -1 ); PLDF, propofol (0.35 mg kg -1  minute -1 ) and fentanyl (0.1 μg kg -1  minute -1 ); PHDF, propofol (0.3 mg kg -1  minute -1 ) and fentanyl (0.2 μg kg -1  minute -1 ). Propofol CRI was increased or decreased based on the response to stimulation (50 V, 50 Hz, 10 mA), with 20 minutes between adjustments. Data were analyzed using a mixed-model anova and presented as mean±standard error. ropofol induction doses were 6.16±0.31, 3.67±0.21 and 3.33±0.42 mg kg -1 for P, PLDF and PHDF, respectively. Doses for PLDF and PHDF were significantly decreased from P (pFentanyl, at the doses studied, caused statistically significant and clinically important decreases in the propofol induction dose and MIR NM . Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

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.

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.

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

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

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

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.

Stability of Fentanyl Citrate, Hydromorphone Hydrochloride, Ketamine Hydrochloride, Midazolam, Morphine Sulfate, and Pentobarbital Sodium in Polypropylene Syringes

OpenAIRE

Anderson, Collin; MacKay, Mark

2015-01-01

Purpose: Determine the stability of fentanyl 10 mcg/mL in 0.9% sodium chloride, fentanyl 10 mcg/mL in 5% dextrose, fentanyl 50 mcg/mL, hydromorphone 100 mcg/mL in 0.9% sodium chloride, ketamine 10 mg/mL, midazolam 0.4 mg/mL in 5% dextrose, midazolam 5 mg/mL, morphine 1 mg/mL in 0.9% sodium chloride, morphine 1 mg/mL in 5% dextrose, and pentobarbital 50 mg/mL when stored as single drug entities at room temperature in polypropylene syringes. Methods: Four 5 mL samples of each drug and concentra...

The effect of nitrous oxide in comparison to oxygen combined with fentanyl on the hospitalization time and pain reduction in renal colic patients at emergency department

Directory of Open Access Journals (Sweden)

Omid Ahmadi

2018-01-01

Full Text Available Background: Renal colic is a painful medical emergency, needs urgent intervention to reduce pain. Nonsteroidal anti-inflammatory drugs, opioids, and entonox are pain-relieving agents. This study was aimed to compare fentanyl + entonox (nitrous oxide + O2 versus fentanyl + oxygen. Materials and Methods: One hundred and twenty patients with acute renal colic presenting to the emergency department were enrolled. First, 50 μg fentanyl was infused for all patients. Then, patients divided into two groups receiving masks of entonox and oxygen, respectively. Quantitative measurement of pain was performed by visual analog scale, before the intervention, after 3, 5, 10, and 30 min of that. If the pain was not relieved after 30 min, 50 μg fentanyl was infused. If the pain was still continued, ketorolac and ketamine were used. Hospitalization duration and severity of pain at specified times were compared between patients in two groups. Results: The mean (standard deviation time of hospitalization was 211 (59 and 236 (61 min in fentanyl + entonox and fentanyl + O2 groups, respectively (P = 0.024. The decrease in pain severity after 10 and 30 min in fentanyl + entonox group were significantly greater than fentanyl + O2 group (P = 0.002 and 0.001, respectively. Mean (standard error of needed time for renal colic pain to get better was 11.27 (1.23 and 20.47 (1.71 min in fentanyl + entonox and fentanyl + O2 groups, respectively (P < 0.001. Proportion of patients relief from pain in fentanyl + entonox in the second, third, and fourth measurements were significantly more than fentanyl + O2 group (P = 0.036, P < 0.001, and P < 0.001, respectively. Conclusion: Entonox is more effective to decrease the duration of hospitalization and reduction of pain than O2 in renal colic patients.

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...

Effect of Fentanyl Nasal Packing Treatment on Patients With Acute Postoperative Pain After Nasal Operation: A Randomized Double-Blind Controlled Trial.

Science.gov (United States)

Kim, Kwan-Sub; Yeo, Nam-Kyung; Kim, Seong-Su; Park, Woong-Sub; Kwak, Su-Hyun; Cho, Sang-Hyeon; Sung, Gyu-Wan; Kim, Hae-Sook; Yi, Sang-Wook; Cho, Hae Jun

2018-05-01

Nasal packing is an option for bleeding control after endoscopic sinus surgery and septoplasty. Although new packing materials have been developed, patients still suffer from pain and require additional analgesics treatments. In this study, a prospective, randomized, and double-blind controlled trial was designed to evaluate the effect of fentanyl-soaked packing on pain after endoscopic sinus surgery and septoplasty. One hundred fifty-two patients who underwent nasal surgeries due to chronic rhinosinusitis or nasal septal deviation were enrolled in this study. At the end of operation, 50 mcg fentanyl-soaked biodegradable synthetic polyurethane foams packing Nasopore or Merocel were applied to a group of 79 patients, and saline-soaked ones were applied to another group of 73 patients. To evaluate the influence of fentanyl on postoperative nasal pain, patients' conditions were assessed via means of Numeric Rating Scale, patient satisfaction, and Ramsay Sedation Scale. In addition, symptoms of headache or sore throat and any signs of cardiopulmonary-relevant indicators were monitored. The fentanyl group had significantly decreased Numeric Rating Scale and increased patient satisfaction in every operation type for the majority of postoperative time periods ( P fentanyl group showed a higher score on Ramsay Sedation Scale than the control group ( P .05). Fentanyl group showed significantly reduced postoperative pain without serious adverse effects. We suggest that topical fentanyl application to nasal packs can be a useful method to reduce pain during the early postoperative period after endoscopic sinus surgery and septoplasty.

A series of forensic toxicology and drug seizure cases involving illicit fentanyl alone and in combination with heroin, cocaine or heroin and cocaine.

Science.gov (United States)

Marinetti, Laureen J; Ehlers, Brooke J

2014-10-01

The Montgomery County Coroner's Office Toxicology Section and the Miami Valley Regional Crime Lab (MVRCL) Drug Chemistry Section have been receiving case work in drug seizures, death cases and human performance cases involving products marketed as heroin or as illicit fentanyl. Upon analysis by the Drug Chemistry Section, these products were found to contain various drug(s) including illicit fentanyl only, illicit fentanyl and heroin, illicit fentanyl and cocaine and illicit fentanyl, heroin and cocaine. Both the Chemistry and Toxicology Sections began seeing these combinations starting in late October 2013. The percentage of the combinations encountered by the MVRCL as well as the physical appearance of the product, and the results of presumptive screening tests will be discussed. The demographics of the users and the results of toxicology and autopsy findings on the decedents will also be discussed. According to regional drug task force undercover agents, there is evidence that some of the products are being sold as illicit fentanyl and not just as a heroin product. Also, there is no evidence to support that the fentanyl source is being diverted from pharmaceutical grade fentanyl. The chemistry section currently has over 109 confirmed cases, and the toxicology section currently has 81 confirmed drug deaths, 8 driving under the influence of drugs and 1 suicidal hanging. Both sections are continuing to see these cases at the present time. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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 endotoxin-induced sepsis had an infusion rate of 2.2 mg/kg/hr (S.D. 0.5) for propofol and 12 microg/kg/hr (S.D. 2) for fentanyl, whereas...

A quality improvement project to reduce the intraoperative use of single-dose fentanyl vials across multiple patients in a pediatric institution.

Science.gov (United States)

Buck, David; Subramanyam, Rajeev; Varughese, Anna

2016-01-01

The use of a single-dose vial across multiple patients presents a risk to sterility and is against CDC guidelines. We initiated a quality improvement (QI) project to reduce the intraoperative use of single-dose vials of fentanyl across multiple patients at Cincinnati Children's Hospital Medical Center (CCHMC). The initial step of the improvement project was the development of a Key Driver Diagram. The diagram has the SMART aim of the project, key drivers inherent to the process we are trying to improve, and specific interventions targeting the key drivers. The number of patients each week receiving an IV dose of fentanyl, from a vial previously accessed for another patient was tracked in a high turnover operating room (OR). The improvement model used was based on the concept of building Plan-Do-Study-Act (PDSA) cycles. Tests of change included provider education, provision of an increased number of fentanyl vials, alternate wasting processes, and provision of single-use fentanyl syringes by the pharmacy. Prior to initiation of this project, it was common for a single fentanyl vial to be accessed for multiple patients. Our data showed an average percentage of failures of just over 50%. During the end of the project, after 7 months, the mean percentage failures had dropped to 5%. Preparation of 20 mcg single-use fentanyl syringes by pharmacy, combined with education of providers on appropriate use, was successful in reducing failures to below our goal of 25%. Appropriately sized fentanyl syringes prepared by pharmacy, education on correct use of single-dose vials, and reminders in the OR, reduced the percentage of patients receiving a dose of fentanyl from a vial previously accessed for another patient in a high-volume otolaryngology room. © 2015 John Wiley & Sons Ltd.

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

International Nuclear Information System (INIS)

Delgado-Guay, Marvin Omar

2010-01-01

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

Image quality assessment based on inter-patch and intra-patch similarity.

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Fei Zhou

Full Text Available In this paper, we propose a full-reference (FR image quality assessment (IQA scheme, which evaluates image fidelity from two aspects: the inter-patch similarity and the intra-patch similarity. The scheme is performed in a patch-wise fashion so that a quality map can be obtained. On one hand, we investigate the disparity between one image patch and its adjacent ones. This disparity is visually described by an inter-patch feature, where the hybrid effect of luminance masking and contrast masking is taken into account. The inter-patch similarity is further measured by modifying the normalized correlation coefficient (NCC. On the other hand, we also attach importance to the impact of image contents within one patch on the IQA problem. For the intra-patch feature, we consider image curvature as an important complement of image gradient. According to local image contents, the intra-patch similarity is measured by adaptively comparing image curvature and gradient. Besides, a nonlinear integration of the inter-patch and intra-patch similarity is presented to obtain an overall score of image quality. The experiments conducted on six publicly available image databases show that our scheme achieves better performance in comparison with several state-of-the-art schemes.

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

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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

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

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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.

Safety of a Brief Emergency Department Observation Protocol for Patients With Presumed Fentanyl Overdose.

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Scheuermeyer, Frank X; DeWitt, Christopher; Christenson, Jim; Grunau, Brian; Kestler, Andrew; Grafstein, Eric; Buxton, Jane; Barbic, David; Milanovic, Stefan; Torkjari, Reza; Sahota, Indy; Innes, Grant

2018-03-09

Fentanyl overdoses are increasing and few data guide emergency department (ED) management. We evaluate the safety of an ED protocol for patients with presumed fentanyl overdose. At an urban ED, we used administrative data and explicit chart review to identify and describe consecutive patients with uncomplicated presumed fentanyl overdose (no concurrent acute medical issues) from September to December 2016. We linked regional ED and provincial vital statistics databases to ascertain admissions, revisits, and mortality. Primary outcome was a composite of admission and death within 24 hours. Other outcomes included treatment with additional ED naloxone, development of a new medical issue while in the ED, and length of stay. A prespecified subgroup analysis assessed low-risk patients with normal triage vital signs. There were 1,009 uncomplicated presumed fentanyl overdose, mainly by injection. Median age was 34 years, 85% were men, and 82% received out-of-hospital naloxone. One patient was hospitalized and one discharged patient died within 24 hours (combined outcome 0.2%; 95% confidence interval [CI] 0.04% to 0.8%). Sixteen patients received additional ED naloxone (1.6%; 95% CI 1.0% to 2.6%), none developed a new medical issue (0%; 95% CI 0% to 0.5%), and median length of stay was 173 minutes (interquartile range 101 to 267). For 752 low-risk patients, no patients were admitted or developed a new issue, and one died postdischarge; 3 (0.4%; 95% CI 0.01% to 1.3%) received ED naloxone. In our cohort of ED patients with uncomplicated presumed fentanyl overdose-typically after injection-deterioration, admission, mortality, and postdischarge complications appear low; the majority can be discharged after brief observation. Patients with normal triage vital signs are unlikely to require ED naloxone. Copyright © 2018 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Use of Fentanyl Iontophoretic Transdermal System (ITS) (IONSYS®) in the Management of Patients with Acute Postoperative Pain: A Case Series.

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Poplawski, Steven; Johnson, Matthew; Philips, Philip; Eberhart, Leopold H J; Koch, Tilo; Itri, Loretta M

2016-12-01

Fentanyl iontophoretic transdermal system (ITS) [IONSYS ® , The Medicines Company, Parsippany, NJ, USA] is a needle-free, patient-controlled, postoperative opioid pain management treatment. It is indicated for the short-term management of acute postoperative pain in adults requiring opioid analgesia in the hospital. The safety and effectiveness of fentanyl ITS for acute postoperative pain management has been demonstrated in a range of surgery and patient types studied in seven phase 3 trials (three placebo-controlled trials and four active-comparator trials). The majority of the patients in the phase 3 trials had undergone either abdominal/pelvic, orthopedic, or thoracic surgery. Consistent with the prescribing information, physicians in clinical practice may treat patients with this system following any type of surgery including those that may not have been included in the phase 3 trials. The purpose of this case series is to illustrate how fentanyl ITS is being utilized for postoperative pain management in real-world clinical practice following a variety of surgeries and in current pain management protocols that may have evolved since the completion of the phase 3 program. There are seven cases from three clinical centers described within this case series, each using fentanyl ITS according to the prescribing information. The surgery types included are bariatric (N = 3), prostate (N = 2), colorectal (N = 1), and perirectal abscess drainage (N = 1). A systematic review of each patient chart was conducted via a standardized retrospective assessment by the clinicians who managed each patient. Additionally, each healthcare professional was interviewed regarding their overall experience and key learnings using fentanyl ITS. Overall, fentanyl ITS was effective and well tolerated in these case reports in current-day clinical practice settings. These case studies are informative about fentanyl ITS use shortly after product approval and set the stage for

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

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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.

Effects of Fentanyl on Emergence Agitation in Children under Sevoflurane Anesthesia: Meta-Analysis of Randomized Controlled Trials

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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

Comparative evaluation of femoral nerve block and intravenous fentanyl for positioning during spinal anaesthesia in surgery of femur fracture

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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

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

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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

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

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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

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...

Exposure to time varying magnetic fields associated with magnetic resonance imaging reduces fentanyl-induced analgesia in mice

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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.

Intraoperative "Analgesia Nociception Index"-Guided Fentanyl Administration During Sevoflurane Anesthesia in Lumbar Discectomy and Laminectomy: A Randomized Clinical Trial.

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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

Genome-wide association study identifies polymorphisms associated with the analgesic effect of fentanyl in the preoperative cold pressor-induced pain test

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Kaori Takahashi

2018-03-01

Full Text Available Opioid analgesics are widely used for the treatment of moderate to severe pain. The analgesic effects of opioids are well known to vary among individuals. The present study focused on the genetic factors that are associated with interindividual differences in pain and opioid sensitivity. We conducted a multistage genome-wide association study in subjects who were scheduled to undergo mandibular sagittal split ramus osteotomy and were not medicated until they received fentanyl for the induction of anesthesia. We preoperatively conducted the cold pressor-induced pain test before and after fentanyl administration. The rs13093031 and rs12633508 single-nucleotide polymorphisms (SNPs near the LOC728432 gene region and rs6961071 SNP in the tcag7.1213 gene region were significantly associated with the analgesic effect of fentanyl, based on differences in pain perception latency before and after fentanyl administration. The associations of these three SNPs that were identified in our exploratory study have not been previously reported. The two polymorphic loci (rs13093031 and rs12633508 were shown to be in strong linkage disequilibrium. Subjects with the G/G genotype of the rs13093031 and rs6961071 SNPs presented lower fentanyl-induced analgesia. Our findings provide a basis for investigating genetics-based analgesic sensitivity and personalized pain control. Keywords: Opioid sensitivity, Analgesia, Fentanyl, Polymorphism, GWAS

Coevolution of patch-type dependent emigration and patch-type dependent immigration.

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Weigang, Helene C

2017-08-07

The three phases of dispersal - emigration, transfer and immigration - are affecting each other and the former and latter decisions may depend on patch types. Despite the inevitable fact of the complexity of the dispersal process, patch-type dependencies of dispersal decisions modelled as emigration and immigration are usually missing in theoretical dispersal models. Here, I investigate the coevolution of patch-type dependent emigration and patch-type dependent immigration in an extended Hamilton-May model. The dispersing population inhabits a landscape structured into many patches of two types and disperses during a continuous-time season. The trait under consideration is a four dimensional vector consisting of two values for emigration probability from the patches and two values for immigration probability into the patches of each type. Using the adaptive dynamics approach I show that four qualitatively different dispersal strategies may evolve in different parameter regions, including a counterintuitive strategy, where patches of one type are fully dispersed from (emigration probability is one) but individuals nevertheless always immigrate into them during the dispersal season (immigration probability is one). I present examples of evolutionary branching in a wide parameter range, when the patches with high local death rate during the dispersal season guarantee a high expected disperser output. I find that two dispersal strategies can coexist after evolutionary branching: a strategy with full immigration only into the patches with high expected disperser output coexists with a strategy that immigrates into any patch. Stochastic simulations agree with the numerical predictions. Since evolutionary branching is also found when immigration evolves alone, the present study is adding coevolutionary constraints on the emigration traits and hence finds that the coevolution of a higher dimensional trait sometimes hinders evolutionary diversification. Copyright © 2017

The synthesis and pharmacological evaluation of (±-2,3-seco-fentanyl analogues

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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.

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

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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 (Pbupivacaine in single shot caudal epidural in children may provide better and longer analgesia after infraumblical surgical procedures.

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

International Nuclear Information System (INIS)

Shankaran, Harish; Adeshina, Femi; Teeguarden, Justin G.

2013-01-01

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 50 human datasets. • Model predictions are in good agreement with the available pharmacokinetic data. • The model can be used for extrapolating across routes, doses and exposure durations. • We illustrate how the model can be used for developing Provisional Advisory Levels

Fentanyl and a Novel Synthetic Opioid U-47700 Masquerading as Street "Norco" in Central California: A Case Report.

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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.

Comparison of Postoperative Analgesic Effects of Thoracic Epidural Morphine and Fentanyl

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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.

Fentanyl activates hypoxia-inducible factor 1 in neuronal SH-SY5Y cells and mice under non-hypoxic conditions in a μ-opioid receptor-dependent manner.

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Daijo, Hiroki; Kai, Shinichi; Tanaka, Tomoharu; Wakamatsu, Takuhiko; Kishimoto, Shun; Suzuki, Kengo; Harada, Hiroshi; Takabuchi, Satoshi; Adachi, Takehiko; Fukuda, Kazuhiko; Hirota, Kiichi

2011-09-30

Hypoxia-inducible factor 1 (HIF-1) is the main transcription factor responsible for hypoxia-induced gene expression. Perioperative drugs including anesthetics have been reported to affect HIF-1 activity. However, the effect of fentanyl on HIF-1 activity is not well documented. In this study, we investigated the effect of fentanyl and other opioids on HIF-1 activity in human SH-SY5Y neuroblastoma cells, hepatoma Hep3B cells, lung adenocarcinoma A549 cells and mice. Cells were exposed to fentanyl, and HIF-1 protein expression was examined by Western blot analysis using anti-HIF-1α and β antibodies. HIF-1-dependent gene expression was investigated by semi-quantitative real-time reverse transcriptase (RT)-PCR (qRT-PCR) and luciferase assay. Furthermore, fentanyl was administered intraperitoneally and HIF-1-dependent gene expression was investigated by qRT-PCR in the brains and kidneys of mice. A 10-μM concentration of fentanyl and other opioids, including 1 μM morphine and 4 μM remifentanil, induced HIF-1α protein expression and HIF-1 target gene expression in an opioid receptor-dependent manner in SH-SY5Y cells with activity peaking at 24h. Fentanyl did not augment HIF-1α expression during hypoxia-induced induction. HIF-1α stabilization assays and experiments with cycloheximide revealed that fentanyl increased translation from HIF-1α mRNA but did not stabilize the HIF-1α protein. Furthermore, fentanyl induced HIF-1 target gene expression in the brains of mice but not in their kidneys in a naloxone-sensitive manner. In this report, we describe for the first time that fentanyl, both in vitro and in vivo, induces HIF-1 activation under non-hypoxic conditions, leading to increases in expression of genes associated with adaptation to hypoxia. Copyright © 2011 Elsevier B.V. All rights reserved.

Combination effect of low dose fentanyl and propofol on emergence agitation in children following sevoflurane anesthesia

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Bakhamees, Hassan S; Mercan, Arzu; ElHalafawy, Yasser M

2009-01-01

To investigate the combination effect of low dose fentanyl and subhypnotic dose of propofol on emergence agitation in children receiving sevoflurane for adenotonsillectomy procedure.After ethical approval, a prospective, randomized, clinical study was performed in Saad Specialist Hospital, Al-Khobar, Kingdom of Saudi Arabia in 2007-2008. One hundred and twenty children in physical status of I according to the American Society of Anesthesiologists, aged 2-6 years, scheduled for adentonsillectomy under general anesthesia were allocated into 3 groups randomly. Anesthesia was induced and maintained by sevoflurane in all groups. Children received 0.1 ml.kg-1 normal saline at the end of surgery in group C (n=40), 1.5 mcg.kg-1 fentanyl during induction, and 0.1 ml.kg-1 normal saline at the end of surgery in group F (n=40), and 1.5 mcg.kg-1 fentanyl during induction and 1 mg.kg-1 propofol at the end of surgery in group FP (n=40). Postoperative agitation was recorded, if any, for the first postoperative hour.Three groups were comparable with regard to demographic data. Twenty-one patients (53%) in the control group, 14 patients (35%) in group F and 7 (18%) patients in group FP experienced postoperative agitation.The combination of low dose fentanyl before surgery and propofol at the end of surgery decreases the incidence and level of emergence agitation in children after adenotonsillectomy procedure under sevoflurane anesthesia. (author)

Investigation of the potentiation of the analgesic effects of fentanyl by ketamine in humans: a double-blinded, randomised, placebo controlled, crossover study of experimental pain[ISRCTN83088383

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Nadeson Raymond

2005-04-01

Full Text Available Abstract Background Despite preclinical evidence suggesting a synergistic interaction between ketamine and opioids promoting analgesia, several clinical trials have not identified dosing regimens capable of eliciting a benefit in the co-administration of ketamine with opioids. Methods Ten healthy volunteers participated in a double blinded, randomised, placebo controlled, crossover laboratory study in order to determine whether a low dose of ketamine potentiated the antinociceptive effect of fentanyl without causing an increase in sedative effects. A battery of tests was used to assess both nociception and sedation including electrical current, pressure, thermal stimuli, psychometric tests, and both subjective and objective scores of sedation. Target controlled infusions of the study drugs were used. Ketamine and fentanyl were administered alone and in combination in a double-blinded randomised crossover design. Saline was used as the control, and propofol was used to validate the tests of sedation. Cardiovascular and respiratory parameters were also assessed. Results The electrical current pain threshold dose response curve of fentanyl combined with ketamine was markedly steeper than the dose response curve of fentanyl alone. While a ketamine serum concentration of 30 ng/ml did not result in a change in electrical pain threshold when administered alone, when it was added to fentanyl, the combination resulted in greater increase in pain threshold than that of fentanyl administered alone. When nociception was assessed using heat and pressure stimuli, ketamine did not potentiate the anti-nociceptive effect of fentanyl. There was no difference between the sedative effect of fentanyl and fentanyl in combination with ketamine as assessed by both subjective and objective measures of sedation. Cardiovascular and respiratory parameters were unaffected by the study drugs at the doses given. Conclusion A serum concentration of ketamine that did not alter

Comparison of Dexmedetomidine and Fentanyl as an Adjuvant to Ropivacaine for Postoperative Epidural Analgesia in Pediatric Orthopedic Surgery.

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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. © Copyright: Yonsei University College of Medicine 2017

[Assessment of the use of racemic ketamine and its S(+) isomer, associated or not with low doses of fentanyl, in balneotherapy for major burn patients].

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Cantinho, Fernando Antônio de Freitas; Silva, Antonio Carlos Pereira da

2009-01-01

The care of the wounds of major burn patients triggers severe painful stimuli. The objective of this study was to assess the safety and efficacy of different drug combinations in anesthesia for balneotherapy. After approval by the Ethics Commission, 200 procedures of balneotherapy in 87 major burn adult patients were evaluated. Midazolam was used in all cases. The vials of ketamine were numbered and, therefore, at the time of the use, one did not know whether racemic or S(+)ketamine was being used. Each morning it was decided by drawing lots whether fentanyl would be used or not in the procedures of that day. Patients were included in one of four groups: ISO/sf (S(+) isomer without fentanyl), ISO/cf (S(+) isomer with fentanyl), RAC/sf (racemic ketamine without fentanyl), and RAC/cf (racemic ketamine with fentanyl). The initial doses proposed were as follows: midazolam, 0.06 mg.kg-1; ketamine, 1.0 to 1.1 mg.kg-1; and fentanyl, 0.8 (1/4)g.kg1-1; additional doses were administered as needed. Only one patient recalled the pain of balneotherapy. In the group that received S(+)ketamine, the use of fentanyl did not bring additional advantages; however, when associated with racemic ketamine, fentanyl reduced the total dose and the number of ketamine boluses. The extension of body surface burned was the main determinant of the severity of post-procedure pain. Reduced pain severity was the main factor considered by patients when grading their satisfaction with the anesthesia. The four different drug combinations proved to be safe and guaranteed the absence of pain during balneotherapy. Characteristics not directly related to the anesthetics proved to be more important in the incidence of post-procedure pain, which was the main factor considered by major burn patient to define their satisfaction with the anesthesia used.

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

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2013-07-24

... for an NADA from Nexcyon Pharmaceuticals, Inc. to Elanco Animal Health, A Division of Eli Lilly & Co..., NADA 141-337 for RECUVYRA (fentanyl) Transdermal Solution to Elanco Animal Health, A Division of Eli Lilly & Co., Lilly Corporate Center, [[Page 44433

Physico-chemical stability of butorphanol-tramadol and butorphanol-fentanyl patient-controlled analgesia infusion solutions over 168 hours.

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Chen, Fuchao; Fang, Baoxia; Li, Peng; Zhu, Xuesong; Zhou, Benhong

2014-08-01

This study was to investigate the physical and chemical compatibility of butorphanol with tramadol or fentanyl in 0.9% sodium chloride injections for patient controlled analgesia administration. The solutions were prepared in polyvinyl chloride (PVC) infusion bags and stored without protected from light exposure at room temperature (25 degrees C) or refrigerated (4 degrees C). Over a period of 168 hours, stabilities were determined by visual inspection, pH measurement, and high-pressure liquid chromatography (HPLC) assay of drug concentrations. At both temperatures, admixtures of butorphanol-tramadol and butorphanol-fentanyl were clear in appearance, and no color change or precipitation was observed during the study period. The maximum losses obtained were lower than 5% for the three drugs after 168 hours of storage. The results indicate that, at ambient or refrigerated storage conditions, the drug mixtures of butorphanol-tramadol and butorphanol-fentanyl in 0.9% sodium chloride injections were physically and chemically stable for at least 168 hours when stored in PVC syringes.

Fault-patch stress-transfer efficiency in presence of sub-patch geometric complexity

KAUST Repository

Zielke, Olaf

2015-04-01

It is well known that faults are not planar surfaces. Instead they exhibit self-similar or self-affine properties that span a wide range of spatial (sub-micrometer to tens-of-kilometer). This geometric fault roughness has a distinct impact on amount and distribution of stresses/strains induced in the medium and on other portions of the fault. However, when numerically simulated (for example in multi-cycle EQ rupture simulations or Coulomb failure stress calculations) this roughness is largely ignored: individual fault patches --the incremental elements that build the fault surface in the respective computer models-- are planar and fault roughness at this and lower spatial scales is not considered. As a result, the fault-patch stress-transfer efficiency may be systematically too large in those numerical simulations with respect to the "actual" efficiency level. Here, we investigate the effect of sub-patch geometric complexity on fault-patch stress-transfer efficiency. For that, we sub-divide a fault patch (e.g., 1x1km) into a large number of sub-patches (e.g., 20x20m) and determine amount of induced stresses at selected positions around that patch for different levels and realizations of fault roughness. For each fault roughness level, we compute mean and standard deviation of the induced stresses, enabling us to compute the coefficient of variation. We normalize those values with stresses from the corresponding single (planar) fault patch, providing scaling factors and their variability for stress transfer efficiency. Given a certain fault roughness that is assumed for a fault, this work provides the means to implement the sub-patch fault roughness into investigations based on fault-patch interaction schemes.

The effect of small dose bupivacaine-fentanyl in spinal anesthesia on hemodynamic nausea and vomiting in cesarean section

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Seyedhejazi, M.; Madarek, E.

2007-01-01

To compare the hemodynamic, nausea and vomiting with small dose bupivacaine-fentanyl spinal anesthetic versus a conventional dose of spinal bupivacaine in parturients undergoing cesarean section. Forty patients aged 17-35 years old which underwent cesarean section were randomized into two groups. Group-A received spinal anesthesia with 8 mg of bupivacaine and 10 microg fentanyl, group B received 12 mg bupivacaine. The mean dose of ephedrine needed was 4mg in group A and 11.75 mg in group B (P=0.006). The mean ratio of lowest systolic pressure to baseline systolic pressure was 0.75 for group A and 0.65 for group B (P=0.04). Nausea and vomiting was observed in 10% of group A versus 20% in group B. Small dose of bupivacaine and fentanyl provides good spinal anesthesia for cesarean section with less hypotension, nausea and vomiting. (author)

Optimal dose of rocuronium bromide undergoing adenotonsillectomy under 5% sevoflurane with fentanyl.

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Huh, Hyub; Park, Jeong Jun; Kim, Ji Yeong; Kim, Tae Hoon; Yoon, Seung Zhoo; Shin, Hye Won; Lee, Hye-Won; Lim, Hye-Ja; Cho, Jang Eun

2017-10-01

Adenotonsillectomy is a short surgical procedure under general anaesthesia in children. An ideal muscle relaxant for adenotonsillectomy would create an intense neuromuscular block while having a quick recovery time without postoperative morbidity. We compared the effect of different doses of rocuronium for the tracheal intubation in children under 5% sevoflurane and fentanyl. 75 children (aged 3-10 years, ASA I) scheduled for adenotonsillectomy were enrolled. Anaesthesia was induced with propofol 2.5 mg/kg, followed by fentanyl 2 μg/kg. After mask ventilation with 5 vol% sevoflurane in 100% oxygen for 2 min, 2 ml of study drug was administered intravenously, i.e., either normal saline (S Group) or one of two doses (0.15 or 0.3 mg/kg) of rocuronium. We assessed conditions during tracheal intubation and also recorded the surgical condition, the time from discontinuation of sevoflurane to extubation and PAED scale, pain scores in PACU. Rocuronium groups (96% and 100%, respectively; P rocuronium (80%) treatment clearly resulted in excellent intubating conditions compared with the 0.15 mg/kg group (44%; p = 0.028). There was no significant difference in the time to extubation and surgical condition, and in the postoperative measures of emergence delirium, pain, and recovery time among the three groups. A dose of 0.3 mg/kg rocuronium may provide optimal intubating conditions without delayed recovery in 5% sevoflurane anaesthesia with fentanyl in children undergoing adenotonsillectomy. NCT02467595. Copyright © 2017 Elsevier B.V. All rights reserved.

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

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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.

A COMPARATIVE CLINICAL STUDY BETWEEN IV ESMOLOL AND IV FENTANYL ON ATTENUATION OF HAEMODYNAMIC RESPONSES TO LARYNGOSCOPY AND INTUBATION

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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.

Butorphanol suppresses fentanyl-induced cough during general anesthesia induction

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Cheng, Xiao-Yan; Lun, Xiao-Qin; Li, Hong-Bo; Zhang, Zhi-Jie

2016-01-01

Abstract Fentanyl-induced cough (FIC) is unwanted in the patients requiring stable induction of general anesthesia. This study was designed to evaluate the suppressive effects of butorphanol pretreatment on the incidence and severity of FIC during the induction of general anesthesia. A total of 315 patients of American Society of Anesthesiologists physical status I and II, scheduled for elective surgery under general anesthesia were randomized into 3 equally sized groups (n = 0105). Two minut...

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

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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.

Comparison of IV dexketoprofen trometamol, fentanyl, and paracetamol in the treatment of renal colic in the ED: A randomized controlled trial.

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Al, Behcet; Sunar, Mehmet Mustafa; Zengin, Suat; Sabak, Mustafa; Bogan, Mustafa; Can, Basri; Kul, Seval; Murat Oktay, M; Eren, Sevki Hakan

2018-04-01

In this study, we aimed to compare the analgesic efficacy of intravenous dexketoprofen trometamol, fentanyl, and paracetamol in patients presenting to the emergency department with renal colic. Data obtained from the emergency departments of Gaziantep University's Hospital for Research and Practice along with two other state hospitals in Gaziantep, Turkey between January 2016 and January 2017 was used for this study. A total of three hundred patients (n=300), who presented to the ER with complaints most common to renal colic whose diagnoses were subsequently confirmed with Computerized Tomography were included in the study. Patients' pain scores were recorded using the Visual Analogue Scale, at admission (immediately before drug administration), then at the 15th, and 30th minutes. SPSS 22.0 software package was used for analysis. pdexketoprofen trometamol was statistically more effective than paracetamol and fentanyl. There was no statistically significant difference between fentanyl and paracetamol. The need for additional analgesia in the group receiving dexketoprofen trometamol was found to be lower. Dexketoprofen trometamol was statistically superior to the other two agents in achieving full analgesia at the end of the thirty-minute period. Fentanyl was found to be statistically significant in achieving moderate analgesia. As a Non-steroidal antiinflammatory drug dexketoprofen trometamol is superior to paracetamol and fentanyl in achieving analgesia and reducing the need for additional drugs for the treatment of renal colic. Copyright © 2017 Elsevier Inc. All rights reserved.

Efficacy of magnesium sulphate and/or fentanyl as adjuvants to intrathecal low-dose bupivacaine in parturients undergoing elective caesarean section

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Shelly Rana

2017-01-01

Full Text Available Background and Aim: Recent developments in the field of intrathecal adjuvants have led to accelerated functional recovery with adequate postoperative analgesia following caesarean section. Encouraging results have been obtained with the use of intrathecal magnesium with or without fentanyl in parturients. This study was conceived to evaluate the effects of adding magnesium sulphate and/or fentanyl to low-dose intrathecal bupivacaine in parturients undergoing caesarean section under subarachnoid block (SAB. Materials and Methods: Ninety, American Society of Anesthesiologists I or II, parturients for the elective caesarean section were enrolled in this prospective randomized, double-blind study. The parturients were randomly assigned to three groups. In Group M, parturients received 8.5 mg (1.7 mL hyperbaric bupivacaine 0.5% with 50 mg (0.1 mL magnesium sulphate and 0.4 mL normal saline. Group F received 8.5 mg hyperbaric bupivacaine 0.5% with 20 μg (0.4 mL fentanyl and 0.1 mL of normal saline and Group MF parturients received 8.5 mg hyperbaric bupivacaine 0.5% with 20 μg fentanyl added to 50 mg magnesium sulphate. Results: Parturients in the group MF were pain free for longest period (273.70 ± 49.30 min as compared to group M (252.67 ± 40.76 min and group F (239.80 ± 38.45 mins [gp MF vs F and, gp M vs F (P = 0.00]. The total doses of rescue analgesics were least in group MF (2.43 ± 0.56 and maximum in group F (3.30 ± 0.63, with comparable neonatal outcomes in three groups. Conclusion: Our data supports synergistic action of intrathecal magnesium sulphate to fentanyl, and it is concluded that on addition of intrathecal magnesium sulphate and fentanyl to low-dose bupivacaine as adjuvant in subarachnoid block, results in prolonged duration of postoperative analgesia with lesser pain scores and lesser dose of rescue analgesia with better haemodynamic stability.

Increased Hyperalgesia and Proinflammatory Cytokines in the Spinal Cord and Dorsal Root Ganglion After Surgery and/or Fentanyl Administration in Rats.

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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

Anaesthetic effects of alfaxalone administered intraperitoneally alone or combined with dexmedetomidine and fentanyl in the rat.

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Arenillas, Mario; Gomez de Segura, Ignacio A

2018-01-01

Alfaxalone is a neuroactive steroid used as a general anaesthetic in several species including dogs, cats, rabbits and ferrets. It has a wide margin of safety and a similar anaesthetic profile to propofol. To increase its aqueous solubility, a new formulation with cyclodextrins has been marketed recently. The objective of this study was to evaluate the anaesthetic effect of several doses of alfaxalone alone, considering differences between sexes, and alfaxalone combined with dexmedetomidine and fentanyl in the rat administered by the intraperitoneal route. A total of 40 Sprague Dawley rats, involved in three studies, were used. Firstly, 25, 35 and 45 mg kg -1 of alfaxalone alone were tested. In a second study, alfaxalone (25 mg kg -1 , females; 75 mg kg -1 , males) was combined with dexmedetomidine (0.05 mg kg -1 ). Finally, alfaxalone (20 mg kg -1 , females; 60 mg kg -1 , males) was combined with dexmedetomidine (0.05 mg kg -1 ) and fentanyl (0.1 mg kg -1 ). Times of onset and duration of anaesthesia, and analgesia, deemed as losing of withdrawal pedal reflex, were recorded. Alfaxalone alone produced a 2 - to 3-fold longer time of anaesthesia in females, although surgical anaesthesia was not achieved in either sex. The addition of dexmedetomidine and fentanyl to alfaxalone produced a similar time of analgesia as well as increased time of anaesthesia in both sexes. In conclusion, alfaxalone produces light anaesthesia in rats, and males required a higher dose. The combination with other sedatives or analgesics, such as dexmedetomidine or fentanyl, allows a more prolonged anaesthesia with analgesic effects, potentially suitable for invasive procedures.

Comparison of the effects of oxycodone versus fentanyl on airway reflex to tracheal extubation and postoperative pain during anesthesia recovery after laparoscopic cholecystectomy: A double-blind, randomized clinical consort study.

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Choi, Eun Kyung; Kwon, Nyeongkeon; Park, Sang-Jin

2018-03-01

Fentanyl has been suggested to be effective for controlling airway and hemodynamic responses to tracheal extubation. This study was performed to compare the effects of oxycodone and fentanyl on airway and hemodynamic responses and postoperative pain during the recovery period in patients undergoing laparoscopic cholecystectomy. Ninety patients aged 18 to 65 years were randomly allocated to 1 of 3 groups: fentanyl, oxycodone, and control. Coughing responses (incidence and severity), hemodynamic responses during the recovery period, and acute postoperative pain were assessed. The incidence of cough was decreased in the fentanyl and oxycodone groups compared with that in the control group at the points of awareness and extubation, and no significant difference was observed between the 2 treatment groups. Severe cough response was decreased in the fentanyl and oxycodone groups compared with that in the control group at the point of extubation, and no significant change was observed in cough severity between the 2 treatment groups. Postoperative pain scores were lower in the fentanyl and oxycodone groups than those in the control group at 5 and 30 minutes postoperatively, and no significant difference was observed between the 2 treatment groups. Hemodynamic responses did not differ among the 3 groups during the recovery period. Oxycodone treatment before tracheal extubation reduced cough response and was as effective as fentanyl treatment for improving extubation quality. Furthermore, single boluses of fentanyl and oxycodone showed equal effectiveness in attenuating acute postoperative pain in patients undergoing laparoscopic cholecystectomy.

Comparison of clonidine versus fentanyl as an adjuvant to intrathecal ropivacaine for major lower limb surgeries: A randomized double-blind prospective study

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Anita R Chhabra

2013-01-01

Full Text Available Background: Ropivacaine is a newer local anesthetic, proven to have a better safety margin than bupivacaine and lignocaine. While maintaining this advantage and improving the intraoperative quality of anesthesia, the use of analgesic adjuvants has been proven to be valuable. Aim: To compare the efficacy of clonidine and fentanyl as adjuvants to intrathecal isobaric ropivacaine for major lower limb surgeries. Settings and Designs: Randomized double-blind control trial. Materials and Methods: Seventy patients were randomly divided in two groups. Ropivacaine-Clonidine group (RC received 60 mcg of clonidine with 15 mg of 0.5% isobaric ropivacaine, Ropivacaine Fentanyl group (RF received 25 mcg of fentanyl with 15 mg of 0.5% isobaric ropivacaine intrathecally. The onset and duration of sensory-motor block were recorded. The total analgesia time, sedation score, hemodynamic parameters, and side-effects were noted. Statistical Analysis: SPSS statistical package was used for statistical analysis. Paired and unpaired t-test, analysis of variance and chi-square test were used for statistical calculation. Result: The duration of sensory block in RC (329.42 ± 33.86, RF (226 ± 46.98, and motor block in RC (248.51 ± 55, RF (212.60 ± 43.52 out lasted the duration of surgery (125.61 + 64.46. In clonidine group, there was significant prolongation of sensory block (P < 0.001, motor block (P < 0.01 and the total analgesia time (P < 0.001. Hypotension and bradycardia occurred in 8.6% patients in clonidine group, whereas pruritus was experienced by 8.6% patients in fentanyl group. Conclusion: Ropivacaine when combined with clonidine or fentanyl provided adequate subarachnoid block for major surgeries, wherein clonidine has advantage over fentanyl as it increased the duration of subarachnoid block and prolonged the postoperative analgesia.

Hyperbaric bupivacaine 2.5 mg prolongs analgesia compared with plain bupivacaine when added to intrathecal fentanyl 25 microg in advanced labor.

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Teoh, Wendy H L; Sia, Alex T H

2003-09-01

We investigated the effect of sequential administration of intrathecal (IT) hyperbaric bupivacaine (after the initial administration of IT hypobaric fentanyl) on the duration of spinal analgesia. Thirty-seven nulliparous parturients with a cervical dilation >/= 5 cm were randomized to receive either IT fentanyl 25 micro g and plain bupivacaine 2.5 mg (group P; n = 19) or IT fentanyl 25 micro g and hyperbaric (with 8% glucose) bupivacaine 2.5 mg (group H; n = 18). The two components of the IT injectate were administered sequentially (fentanyl 25 micro g diluted in 2 mL of normal saline, immediately followed by 0.5 mL of 0.5% bupivacaine). Patients were then positioned with their torso elevated at 30 degrees for 30 min. Pain scores using 0-100 visual analog scales were collected before combined spinal/epidural analgesia and at 5, 15, and 30 min after the block. Patients in Group H had a longer median duration of analgesia (122 min; range, 80-210 min) than Group P (95 min; range, 75-125 min) (P hyperbaric bupivacaine conferred an increased duration of IT analgesia compared with plain bupivacaine.

Comparación entre los diagramas TTS obtenidos mediante los ensayos normalizados Huey y Strauss modificado para el acero inoxidable AISI 304

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Otero, E.

1996-04-01

Full Text Available This work presents a comparison of Temperature-Time-Sensitization TTS diagrams obtained by Huey and modified Strauss standard, for detecting susceptibility to intergranular attack. The difference between these tests is the use of a strong or a slightly smooth oxidizing electrolyte. The diagrams obtained are different and if a sample tested by modified Strauss is sensitized, then it will be sensitized in the Huey test, but the contrary is not always true. This difference is because a sensitized sample has to have a continuous band lacking in chromium along the grain boundary in order to be sensitized in the modified Strauss test. This condition is not necessary in the Huey test.

Se comparan los diagramas Temperatura-Tiempo-Sensibilización TTS, obtenidos mediante los ensayos normalizados de corrosión intergranular Huey y Strauss modificado, que, respectivamente, utilizan electrólitos fuerte y suavemente oxidantes, mostrándose que los diagramas obtenidos son diferentes. Si una muestra evaluada mediante el ensayo Strauss modificado se encuentra sensibilizada, entonces lo estará también en el ensayo Huey, pero no necesariamente ocurrirá lo contrario; esta diferencia se asocia a la necesidad de la existencia de una zona continua empobrecida en cromo a lo largo del límite de grano para que el material se sensibilice con respecto al ensayo Strauss modificado, condición innecesaria para el caso del ensayo Huey.

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

Treatment of intractable chronic pelvic pain syndrome by injecting a compound of Bupivacaine and Fentanyl into sacral spinal space

Institute of Scientific and Technical Information of China (English)

ZHOU Zhan-song; SONG Bo; NIE Fa-chuan; CHEN Jin-mei

2006-01-01

Objective:To investigate the effect of injecting a compound of Bupivacaine and Fentanyl into sacral spinal space to treat chronic pelvic pain syndrome (CPPS). Methods: A total of 36 men with recalcitrant CPPS refractory to multiple prior therapies were treated with the injection of a compound of Bupivacaine and Fentanyl (10 ml of 0. 125% upivacaine, .05 mg Fentanyl, 5 mg Dexamethasone, 100 mg Vitamin B1 and 1 mg Vitamin B12) into sacral space once a week for 4 weeks. The National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI), maximum and average flow rate were performed at the start and the end of 4 weeks' therapy. Results :Mean NIH-CPSI total score was decreased from 26.5±.6 to 13.4±2.0 (P＜0. 001). Significant improvement was seen in each subscore domain. A total of 32 patients (89%) had at least 25% improvement on NIH-CPSI and 22 (61%) had at least 50% improvement. Maximal and average flow rate were increased from 19. 5±3.8 to 23. 6±4. 2 and 10. 9±2.6 to 14.3± 2.4 respectively. Conclusion: Injection of this compound of Bupivacaine, Fentanyl and Dexamethasone into sacral spinal space is an effective and safe approach for recalcitrant CPPS. Further study of the mechanisms and prospective placebo controlled trials are warranted.

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

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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

Birth Control Patch

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... Health Food & Fitness Diseases & Conditions Infections Drugs & Alcohol School & Jobs Sports Expert Answers (Q&A) Staying Safe Videos for Educators Search English Español Birth Control Patch KidsHealth / For Teens / Birth Control Patch What's ...

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.

Granisetron Transdermal Patch

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Granisetron transdermal patches are used to prevent nausea and vomiting caused by chemotherapy. Granisetron is in a class of medications called 5HT3 ... Granisetron transdermal comes as a patch to apply to the skin. It is usually applied 24 to ...

Non-standard patch test

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Astri Adelia

2018-06-01

Full Text Available In managing contact dermatitis, identification of the causative agent is essential to prevent recurrent complaints. Patch test is the gold standard to identify the causative agent. Nowadays, there are many patch test standard materials available in the market, but do not include all the materials that potentially cause contact dermatitis. Patch test using patient’s own products or later we refer to as non-standard materials, is very helpful in identifying the causative agents of contact dermatitis. Guidance is needed in producing non-standard patch test materials in order to avoid test results discrepancy.

Stability of Fentanyl Citrate, Hydromorphone Hydrochloride, Ketamine Hydrochloride, Midazolam, Morphine Sulfate, and Pentobarbital Sodium in Polypropylene Syringes.

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Anderson, Collin; MacKay, Mark

2015-12-16

Determine the stability of fentanyl 10 mcg/mL in 0.9% sodium chloride, fentanyl 10 mcg/mL in 5% dextrose, fentanyl 50 mcg/mL, hydromorphone 100 mcg/mL in 0.9% sodium chloride, ketamine 10 mg/mL, midazolam 0.4 mg/mL in 5% dextrose, midazolam 5 mg/mL, morphine 1 mg/mL in 0.9% sodium chloride, morphine 1 mg/mL in 5% dextrose, and pentobarbital 50 mg/mL when stored as single drug entities at room temperature in polypropylene syringes. Four 5 mL samples of each drug and concentration were prepared in 10 mL polypropylene syringes. The samples were stored at ambient room temperature in a locked cabinet. Triplicate determinations of drug concentration for each sample were performed initially, on day 50 or 51, and on day 100 using high-performance liquid chromatography with diode-array detection. With the exception of the hydromorphone 100 mcg/mL dilution, all compounds were found to contain greater than 95% of their initial concentration remaining at 100 days. Each sample remained clear and colorless when visually inspected.

Fentanyl Patch Can Be Deadly to Children

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... pets can easily remove discarded medicines from household trash. FDA and other federal agencies recommend following instructions ... They should not be placed in the household trash where children or pets can find them. FDA ...

Today's fentanyl crisis: Prohibition's Iron Law, revisited.

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Beletsky, Leo; Davis, Corey S

2017-08-01

More than a decade in the making, America's opioid crisis has morphed from being driven by prescription drugs to one fuelled by heroin and, increasingly, fentanyl. Drawing on historical lessons of the era of National Alcohol Prohibition highlights the unintended, but predictable impact of supply-side interventions on the dynamics of illicit drug markets. Under the Iron Law of Prohibition, efforts to interrupt and suppress the illicit drug supply produce economic and logistical pressures favouring ever-more compact substitutes. This iatrogenic progression towards increasingly potent illicit drugs can be curtailed only through evidence-based harm reduction and demand reduction policies that acknowledge the structural determinants of health. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of intrathecal plain articaine and levobupivacaine with fentanyl for Caesarean section.

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Demircioglu, Rüveyda I; Gozdemir, Muhammet; Usta, Burhanettin; Sert, Hüseyin; Karabayirli, Safinaz; Muslu, Bünyamin; Keskin, Esra A

2016-12-01

Articaine is used as a local anesthetic for outpatient surgery because it offers rapid onset of anesthesia and short duration motor block. Levobupivacaine is often preferred for Caesarean section. We evaluated the anesthetic characteristics of fentanyl-supplemented plain articaine and levobupivacaine for Caesarean section under combine spinal epidural anesthesia. Patients undergoing Caesarean section received in random order plain articaine 40 mg (Group A, n=50) or plain levobupivacaine 10 mg (Group L, n=50) mixed with fentanyl 20 µg intrathecally. The onset and duration of sensory and motor block, first analgesic request, and hemodynamic parameters were recorded. Onset times of maximum motor block were longer in Group L than Group A (P=0,001). Time to two-segment regression of sensory block were 70 min for Group A and 90 min group L (P=0.001). Times to complete regression of motor blockade were significantly longer in group L than group A (P =0,001). To have a faster onset and shorter duration of spinal anesthesia, we recommend the use of plain articaine for Caesarean section.

Patch Test Negative Generalized Dermatitis.

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Spiker, Alison; Mowad, Christen

2016-01-01

Allergic contact dermatitis is a common condition in dermatology. Patch testing is the criterion standard for diagnosis. However, dermatitis is not always caused by an allergen, and patch testing does not identify a culprit in every patient. Generalized dermatitis, defined as eczematous dermatitis affecting greater than 3 body sites, is often encountered in dermatology practice, especially patch test referral centers. Management for patients with generalized dermatitis who are patch test negative is challenging. The purpose of this article is to outline an approach to this challenging scenario and summarize the paucity of existing literature on patch test negative generalized dermatitis.

An evaluation of total disintegration time for three different doses of sublingual fentanyl tablets in patients with breakthrough pain.

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Nalamachu, Srinivas

2013-12-01

Breakthrough pain is common among patients with cancer and presents challenges to effective pain management. Breakthrough pain is characterized by rapid onset, severe intensity, and duration typically lasting disintegration time of three different doses of sublingual fentanyl tablets in opioid-tolerant patients. This was a single-center, non-randomized, open-label study. Opioid-tolerant adult patients (N = 30) with chronic pain were assigned to one of three dose groups and self-administered a single 100, 200, or 300 μg sublingual fentanyl tablet (Abstral(®), Galena Biopharma, Portland, OR, USA). Time to complete disintegration was measured by each patient with a stopwatch and independently verified by study personnel. Disintegration time (mean ± SD) for sublingual fentanyl tablets (all doses) was 88.2 ± 55.1 s. Mean disintegration times tended to be slightly longer for the 200 μg (96.7 ± 57.9 s) and 300 μg doses (98.6 ± 64.8 s) compared to the 100 μg dose (69.5 ± 40.5 s). Differences were not statistically significant. Disintegration time was not significantly different between men and women and was not affected by age. Sublingual fentanyl tablets dissolved rapidly (average time <2 min) in all patients, with the higher doses taking slightly more time to dissolve.

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

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......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...

Multiple Fentanyl Overdoses - New Haven, Connecticut, June 23, 2016.

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Tomassoni, Anthony J; Hawk, Kathryn F; Jubanyik, Karen; Nogee, Daniel P; Durant, Thomas; Lynch, Kara L; Patel, Rushaben; Dinh, David; Ulrich, Andrew; D'Onofrio, Gail

2017-02-03

On the evening of June 23, 2016, a white powder advertised as cocaine was purchased off the streets from multiple sources and used by an unknown number of persons in New Haven, Connecticut. During a period of less than 8 hours, 12 patients were brought to the emergency department (ED) at Yale New Haven Hospital, experiencing signs and symptoms consistent with opioid overdose. The route of intoxication was not known, but presumed to be insufflation ("snorting") in most cases. Some patients required doses of the opioid antidote naloxone exceeding 4 mg (usual initial dose = 0.1-0.2 mg intravenously), and several patients who were alert after receiving naloxone subsequently developed respiratory failure. Nine patients were admitted to the hospital, including four to the intensive care unit (ICU); three required endotracheal intubation, and one required continuous naloxone infusion. Three patients died. The white powder was determined to be fentanyl, a drug 50 times more potent than heroin, and it included trace amounts of cocaine. The episode triggered rapid notification of public health and law enforcement agencies, interviews of patients and their family members to trace and limit further use or distribution of the fentanyl, immediate naloxone resupply and augmentation for emergency medical services (EMS) crews, public health alerts, and plans to accelerate naloxone distribution to opioid users and their friends and families. Effective communication and timely, coordinated, collaborative actions of community partners reduced the harm caused by this event and prevented potential subsequent episodes.

Dose sparing of induction dose of propofol by fentanyl and butorphanol: A comparison based on entropy analysis

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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.

Influence of fentanyl and morphine on intestinal circulation

International Nuclear Information System (INIS)

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

1985-01-01

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 86 Rb and 9-micron spheres labeled with 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 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

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.

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

Patch-augmented rotator cuff repair: influence of the patch fixation technique on primary biomechanical stability.

Science.gov (United States)

Jung, Christian; Spreiter, Gregor; Audigé, Laurent; Ferguson, Stephen J; Flury, Matthias

2016-05-01

There is an ongoing debate about the potential of patch augmentation to improve biomechanical stability and healing associated with rotator cuff repair. The biomechanical properties of three different patch-augmented rotator cuff repair techniques were assessed in vitro and compared with a standard repair. Dermal collagen patch augmentation may increase the primary stability and strength of the repaired tendon in vitro, depending on the technique used for patch application. Forty cadaveric sheep shoulders with dissected infraspinatus tendons were randomized into four groups (n = 10/group) for tendon repair using a knotless double-row suture anchor technique. A xenologous dermal extracellular matrix patch was used for augmentation in the three test groups using an "integrated", "cover", or "hybrid" technique. Tendons were preconditioned, cyclically loaded from 10 to 30 N at 1 Hz, and then loaded monotonically to failure. Biomechanical properties and the mode of failure were evaluated. Patch augmentation significantly increased the maximum load at failure by 61 % in the "cover" technique test group (225.8 N) and 51 % in the "hybrid" technique test group (211.4 N) compared with the non-augmented control group (140.2 N) (P ≤ 0.015). For the test group with "integrated" patch augmentation, the load at failure was 28 % lower (101.6 N) compared with the control group (P = 0.043). There was no significant difference in initial and linear stiffness among the four experimental groups. The most common mode of failure was tendon pullout. No anchor dislocation, patch disruption or knot breakage was observed. Additional patch augmentation with a collagen patch influences the biomechanical properties of a rotator cuff repair in a cadaveric sheep model. Primary repair stability can be significantly improved depending on the augmentation technique.

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.

The Influence of Low Salivary Flow Rates on the Absorption of a Sublingual Fentanyl Citrate Formulation for Breakthrough Cancer Pain.

Science.gov (United States)

Davies, Andrew; Mundin, Gill; Vriens, Joanna; Webber, Kath; Buchanan, Alison; Waghorn, Melanie

2016-03-01

Salivary gland hypofunction may affect the absorption of drugs through the oral mucosa, which in turn may affect their clinical efficacy (e.g., onset of action). The aim of this study was to assess the pharmacokinetics of a sublingual fentanyl orally disintegrating tablet (Abstral, Prostrakan Inc.) in a group of cancer patients with salivary gland hypofunction. Nine cancer patients with salivary gland hypofunction underwent a series of three pharmacokinetic studies with the sublingual fentanyl orally disintegrating tablet. In the first phase, the patients received no pretreatment; in the second phase, the patients were allowed to moisten the oral cavity before dosing; in the third phase, the patients were given pilocarpine hydrochloride (saliva stimulant) before dosing. Fentanyl concentrations were measured using a method of high-performance liquid chromatography with validated tandem mass spectrometric detection. The Tmax was longer, the Cmax was lower, the AUC0-30 lower, and the AUClast lower in the phase involving no pretreatment; the Tmax/Cmax/AUC0-30/AUClast were similar in the phase involving moistening of the oral cavity and the phase involving giving pilocarpine hydrochloride. The pharmacokinetics of the sublingual fentanyl orally disintegrating tablet appear to be negatively affected by the presence of salivary gland hypofunction, although the moistening of the oral cavity before dosing results in a pharmacokinetic profile similar to that seen with the giving of pilocarpine hydrochloride. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Strategies and actions for the mitigation of the phenomenon DENTING in the tube sheet (TTS Denting) steam generators of the NPP Asco Denting at the top of the SG tube sheet (TTS tube denting) has recently been experienced in new and replacement SGs at several plants; Estrategias y acciones para la mitigacion del fenomeno DENTING en la placa tubular de generadores de vapor (TTS DENTING) de la Central Nuclear de Asco

Energy Technology Data Exchange (ETDEWEB)

Espanol Villar, J.

2013-07-01

It is highly likely that the accumulation of sludge (deposits) on the tube sheet is clearly associated with the denting occurrence. More specifically, it is commonly believed that an aggressive crevice environment formed within the deposits or in the shallow tight tube sheet to tube crevice below the deposits is at the origin of the denting (tube deformation), and, when present, the consequent stress corrosion cracking (SCC). There are described a set of strategies that have been followed since the emergence of the TTS denting phenomenon on Steam Generator of the Nuclear Power Plants Asco I and II, influenced by the presence of hard sludge in the tube plate of Steam Generators, their results and the evolution of the phenomenon in relation to the various measures taken.

A Comparison of Fentanyl and Flurbiprofen Axetil on Serum VEGF-C, TNF-α, and IL-1ß Concentrations in Women Undergoing Surgery for Breast Cancer.

Science.gov (United States)

Wen, Yiyun; Wang, Mingde; Yang, Jinfeng; Wang, Yichun; Sun, Huiping; Zhao, Jianghong; Liu, Weizhen; Zhou, Zhengyu; Deng, Hongwu; Castillo-Pedraza, Catalina; Zhang, Yi; Candiotti, Keith A

2015-07-01

Vascular endothelial growth factor-C (VEGF-C), tumor necrosis factor-α (TNF-α), and interleukin-1ß(IL-1ß) have been shown to be associated with the recurrence and metastasis of breast cancer after surgery. This study tested the hypothesis that patients undergoing surgery for breast cancer, who received postoperative analgesia with flurbiprofen axetil combined with small doses of fentanyl (FA), exhibited reduced levels of VEGF-C, TNF-α, and IL-1ß compared with those patients receiving fentanyl alone (F). Forty-women with primary breast cancer undergoing a modified radical mastectomy were randomized to receive postoperative analgesia with flurbiprofen axetil combined with fentanyl or fentanyl alone. Venous blood was sampled before anesthesia, at the end of surgery, and at 48 hours after surgery, and the serum was analyzed. The primary endpoint was changes in the VEGF-C concentrations in serum. Group FA patients reported similar analgesic effects as group F patients at 2, 24, and 48 hours. At 48 hours, mean postoperative concentrations of VEGF-C in group F patients were higher than in group FA patients, 730.9 versus. 354.1 pg/mL (P = 0.003), respectively. The mean postoperative concentrations of TNF-α in group F patients were also higher compared with group FA patients 27.1 vs. 15.8 pg/mL (P = 0.005). Finally, the mean postoperative concentrations of IL-1ß in group F were also significantly higher than in group FA 497.5 vs. 197.7 pg/mL (P = 0.001). In patients undergoing a mastectomy, postoperative analgesia with flurbiprofen axetil, combined with fentanyl, were associated with decreases in serum concentrations of VEGF-C, TNF-α, and IL-1ß compared with patients receiving doses of only fentanyl. © 2014 World Institute of Pain.

Comparison of topical oxybuprocaine and intravenous fentanyl in pediatric strabismus surgery.

Science.gov (United States)

Yousafzai, Ibrahim; Zahoor, Abdul; Andrey, Butrov; Ahmad, Nauman

2017-01-01

To compare the outcomes such as postoperative nausea/vomiting, analgesic requirements, and hospital stay following the use of topical oxybuprocaine hydrochloride 0.4% or intravenous (IV) fentanyl in children undergoing strabismus surgery. This was a prospective cohort study. Children operated under general anesthesia for strabismus were given topical oxybuprocaine hydrochloride 0.4% (Group T) and IV fentanyl (Group F) before surgery. The episodes of nausea/vomiting, pain score, requirement of additional analgesia during postoperative period, and duration of hospital stay were compared in two groups. There were 47 children in Group T and 59 children in Group F. The median pain score in two groups were 2.38 (25% quartile; 2.0) and 3.00 (25% quartile; 3.00), respectively. The difference was significant (K W P < 0.03). The episodes of nausea/vomiting in two groups were in 2 and 6 children in Group T and Group F, respectively. The median hospital stay of children of Group T and Group F were 242 and 285 min, respectively. The difference was not statistically significant ( P = 0.22). Using intraoperative topical oxybuprocaine drops, one can achieve better analgesic outcomes and reduce risk of nausea and vomiting compared to intravenous opioid analgesics and therefore, the hospital stay could also be marginally reduced.

A comparative study of the effect of clonidine, fentanyl, and the combination of both as adjuvant to intrathecal bupivacaine for postoperative analgesia in total abdominal hysterectomy

Science.gov (United States)

Ahmed, Fareed; Khandelwal, Mamta; Sharma, Anil

2017-01-01

Background and Aims: The aim of this study was to evaluate the level of sensory block, onset and duration of motor block, postoperative analgesia, and adverse effects of combination of clonidine and fentanyl given intrathecally with hyperbaric bupivacaine (HB). Material and Methods: Three hundred and twenty eight patients were randomized into four groups. Group bupivacaine (group B) received 15 mg of HB; group bupivacaine clonidine (group BC) received 15 mg of HB plus 25 μg clonidine; group bupivacaine fentanyl (group BF) received 15 mg of HB plus 25 μg fentanyl and group bupivacaine clonidine fentanyl (group BCF) received 15 mg of HB plus 25 μg clonidine and 25 μg fentanyl intrathecally. All groups were evaluated for level of sensory block, onset and duration of motor block, postoperative analgesia, VAS score, sedation score and adverse effects of study drugs. All the data were analyzed using unpaired t-test. P < 0.05 was considered significant. Results: The level of sensory block, onset, and duration of motor block were comparable in all groups. Total duration of analgesia was 407.3 ± 20 min in group BCF compared to 242.1 ± 2 min and 209.2 ± 16 in groups BC and BF, respectively. Lesser doses of rescue analgesic were required in group BCF. The time interval from intrathecal injection to two-segment regression was statistically significant in study groups. Only 2.4% patients showed mild sedation in BCF group. Conclusion: We found that combination of intrathecal clonidine and fentanyl along with bupivacaine increases the total duration of analgesia without significant side effects. PMID:28413281

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

minor, and were not treated with naloxone.   Conclusions: Our results suggest that non-medical personnel safely can administer IV fentanyl to selected groups of patients with a satisfactory result in terms of a considerable reduction in pain score and an acceptable rate of negative coincident events....

Transdermal patches: history, development and pharmacology

Science.gov (United States)

Pastore, Michael N; Kalia, Yogeshvar N; Horstmann, Michael; Roberts, Michael S

2015-01-01

Transdermal patches are now widely used as cosmetic, topical and transdermal delivery systems. These patches represent a key outcome from the growth in skin science, technology and expertise developed through trial and error, clinical observation and evidence-based studies that date back to the first existing human records. This review begins with the earliest topical therapies and traces topical delivery to the present-day transdermal patches, describing along the way the initial trials, devices and drug delivery systems that underpin current transdermal patches and their actives. This is followed by consideration of the evolution in the various patch designs and their limitations as well as requirements for actives to be used for transdermal delivery. The properties of and issues associated with the use of currently marketed products, such as variability, safety and regulatory aspects, are then described. The review concludes by examining future prospects for transdermal patches and drug delivery systems, such as the combination of active delivery systems with patches, minimally invasive microneedle patches and cutaneous solutions, including metered-dose systems. PMID:25560046

Method optimization of ocular patches

Directory of Open Access Journals (Sweden)

Kamalesh Upreti

2012-01-01

Full Text Available The intraocular patches were prepared using gelatin as the polymer. Ocular patch were prepared by solvent casting method. The patches were prepared for six formulations GP1, GP2, GP3, GP4, GP5 and GP6. Petri dishes were used for formulation of ocular patch. Gelatin was used as a polymer of choice. Glutaraldehyde used as cross linking agent and (DMSO dimethylsulfoxide used as solubility enhancer. The elasticity depends upon the concentration of gelatin. 400 mg amount of polymer i.e gelatin gave the required elasticity for the formulation.

Cardiovascular effects, induction and recovery characteristics and alfaxalone dose assessment in alfaxalone versus alfaxalone-fentanyl total intravenous anaesthesia in dogs.

Science.gov (United States)

Dehuisser, Virginie; Bosmans, Tim; Kitshoff, Adriaan; Duchateau, Luc; de Rooster, Hilde; Polis, Ingeborgh

2017-11-01

To compare cardiovascular effects and anaesthetic quality of alfaxalone alone or in combination with a fentanyl constant rate infusion (CRI) when used for total intravenous anaesthesia (TIVA) in dogs. Prospective, blinded, randomized, experimental study. A group of 12 intact female dogs. Following intramuscular dexmedetomidine (10 μg kg -1 ) and methadone (0.1 mg kg -1 ) administration, anaesthesia was induced intravenously with alfaxalone (2 mg kg -1 ) (group AP) or alfaxalone (2 mg kg -1 ) preceded by fentanyl (2 μg kg -1 ) (group AF). Anaesthetic maintenance was obtained with an alfaxalone variable rate infusion (VRI) started at 0.15 mg kg -1 minute -1 (group AP) or an alfaxalone VRI (same starting rate) combined with a CRI of fentanyl (10 μg kg -1 hour -1 ) (group AF). The alfaxalone VRI was adjusted every 5 minutes, based on clinical assessment. Cardiovascular parameters (recorded every 5 minutes) and recovery characteristics (using a numerical rating scale) were compared between groups. A mixed model statistical approach was used to compare the mean VRI alfaxalone dose and cardiovascular parameters between groups; recovery scores were analysed using the Wilcoxon rank-sum test (α = 0.05). The mean CRI alfaxalone dose for anaesthetic maintenance differed significantly between treatments [0.16 ± 0.01 mg kg -1 minute -1 (group AP) versus 0.13 ± 0.01 mg kg -1 minute -1 (group AF)]. Overall heart rate, systolic, mean and diastolic arterial pressures were lower in group AF than in group AP (p < 0.0001, p = 0.0058, p < 0.0001 and p < 0.0001, respectively. Recovery quality scores did not differ significantly and were poor in both groups. In combination with a fentanyl CRI, an alfaxalone TIVA provides a cardiovascular stable anaesthesia in dogs. The addition of fentanyl results in a significant dose reduction. The quality of anaesthetic recovery remains poor. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia

Patch photopatch test at Manipal

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Panja Arindrajit

1994-01-01

Full Text Available Patch and photopatch testing was performed on 55 patients with history of photosensitivity using Scandanavian photo patch test antigens obtained from Chemotechnique Diagnostics AB Sweden. The commonest reactions were seen to perfume mix 4 (21.0%, PABA 3 (15.78%, promethazine hydrochloride 3 (15.78%, chlorpromazine hydrochloride 3 (15.78%, balsam of peru 2 (10.52%, usnic acid, hexachlorophane, musk ambrette and 6 methyl coumarin showed 1 positive reaction each (5.26% suggesting either phototoxicity or photo sensitization. Patch and photo patch test positive reaction suggesting allergic sensitisation was seen to balsam of peru 3 (23.0% perfume mix 3 (23.0% promethazine hydrochloride 2 (15.3% and PABA, 6 methyl coumarin, tribromosalicylanilide, atranorin and wood mix showed positive reaction in one case each (7.69%. We conclude that photoxic or photo allergic reaction is a problem in India and patch photo patch test should be performed in all cases of idiopathic light eruptions to rule out photo sensitisation and in cases where photo sensitivity of exogenous origin is suspected.

Epidural 0.5% levobupivacaine with dexmedetomidine versus fentanyl for vaginal hysterectomy: A prospective study

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Kumkum Gupta

2014-01-01

Full Text Available Background: Epidural adjuvants enhance the quality and duration of surgical anesthesia. The present study was aimed to compare the hemodynamic, sedative, and analgesia potentiating effects of dexmedetomidine versus fentanyl with epidural 0.5% levobupivacaine for vaginal hysterectomy. Patients and Methods: Sixty consented females of ASA physical status I and II aged 35-65 years weighing 55-75 kg, were double blindly randomized into two treatment groups. Patients received epidural 0.5% levobupivacaine 15 ml either with of 25 μg dexmedetomidine (Group LD or 50 μg fentanyl (Group LF and the total volume of study solution was kept 16 ml. Onset of analgesia at T10, sensory and motor block levels and duration of analgesia were observed. Intra-operatively, they were assessed for sedation, hemodynamic changes, respiratory efficiency, and side effects. The data obtained, was compiled systematically and analyzed statistically using Chi-square test and ANOVA. Value of P < 0.05 is considered significant. Result: The demographic profile was comparable between groups. The onset of sensory analgesia at T10 (7.25 ± 2.3 versus 9.27 ± 2.79 min and time to achieve complete motor blockade (19.27 ± 4.7 versus 22.78 ± 5.57 min was significantly earlier in patients of LD Group. The intraoperative hemodynamic changes were comparable between groups. Ramsey Sedation score was better in LD group with statistically significance. Postoperative analgesia was significantly prolonged in LD Group. Incidence of nausea, vomiting, and pruritus was high in LF group. Conclusion: Dexmedetomidine was better than fentanyl as an epidural adjuvant for providing early onset of sensory analgesia, adequate sedation with no respiratory depression and prolonged postoperative analgesia.

Transdermal fentanyl for pain caused by radiotherapy in head and neck cancer patients treated in an outpatient setting. A multicenter trial in Taiwan

International Nuclear Information System (INIS)

Chang, J.T.C.; Lin Chienyu; Wang Hungming; Lin Jinching; Lee Moonsing; Chen Yujen

2010-01-01

This study evaluated the efficacy and safety of transdermal fentanyl in the outpatient treatment of head and neck cancer patients with pain caused by radiotherapy. Patients with a visual analogue scale score ≥4 were invited to participate in the study. The following variables were collected: visual analogue scale, the Brief Pain Inventory, concomitant pain medications and adverse effects. A total of 163 head and neck cancer patients were enrolled (148 males and 15 females; median age, 53 years; age range, 21-72 years). Seventy-two (44%) patients had a visual analogue scale score >6 at enrollment, despite the use of non-steroidal anti-inflammatory drugs or weak opioids. Ninety-four (57.7%) patients received concurrent chemotherapy. A total of 88 patients completed the study, whereas 55 underwent a drop-out by side effects. The most frequently reported adverse events were vomiting (23.9%) and nausea (16.6%). Treatment with transdermal fentanyl resulted in a significant decrease in visual analogue scale and Brief Pain Inventory scores that persisted during treatment. In the overall efficacy evaluation, the pain-alleviating effect, the easiness of application and the overall impression of transdermal fentanyl were rated as good by 54.5%, 65.9% and 59.1% of the completers, respectively. Effects of transdermal fentanyl were rated as good by 64.8% of the investigators. Our data provide evidence that transdermal fentanyl is effective and relatively easy to use for outpatient treatment of pain control in head and neck cancer patients following radiotherapy in selected patients. Reduction of side effects and effective pain management need to be paramount in the management of head and neck cancer patients undergoing radiotherapy. (author)

Patch size has no effect on insect visitation rate per unit area in garden-scale flower patches

Science.gov (United States)

Garbuzov, Mihail; Madsen, Andy; Ratnieks, Francis L. W.

2015-01-01

Previous studies investigating the effect of flower patch size on insect flower visitation rate have compared relatively large patches (10-1000s m2) and have generally found a negative relationship per unit area or per flower. Here, we investigate the effects of patch size on insect visitation in patches of smaller area (range c. 0.1-3.1 m2), which are of particular relevance to ornamental flower beds in parks and gardens. We studied two common garden plant species in full bloom with 6 patch sizes each: borage (Borago officinalis) and lavender (Lavandula × intermedia 'Grosso'). We quantified flower visitation by insects by making repeated counts of the insects foraging at each patch. On borage, all insects were honey bees (Apis mellifera, n = 5506 counts). On lavender, insects (n = 737 counts) were bumble bees (Bombus spp., 76.9%), flies (Diptera, 22.4%), and butterflies (Lepidoptera, 0.7%). On both plant species we found positive linear effects of patch size on insect numbers. However, there was no effect of patch size on the number of insects per unit area or per flower and, on lavender, for all insects combined or only bumble bees. The results show that it is possible to make unbiased comparisons of the attractiveness of plant species or varieties to flower-visiting insects using patches of different size within the small scale range studied and make possible projects aimed at comparing ornamental plant varieties using existing garden flower patches of variable area.

A comparative study of low concentration of levobupivacaine versus ropivacaine with fentanyl for patient-controlled epidural labour analgesia

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Priyanka Chuttani

2018-01-01

Full Text Available >Background and Aims: Lumbar epidural analgesia is considered the modality of choice for labour analgesia. Despite its super analgesia and improved safety profile, it has been associated with maternal adverse effects like higher incidence of instrumental assisted vaginal delivery (AVD and motor block leading to decreased ambulation. This study was designed to evaluate the efficacy of low concentrations of local anaesthetics (0.1% ropivacaine and 0.1% levobupivacaine with 2 μg/ml fentanyl as a patient controlled epidural analgesia (PCEA technique on the incidence of instrumental AVD along with evaluation of obstetric, maternal, and foetal outcomes.Materials and Methods: In this prospective study, 60 labouring parturients were randomly allocated into two equal groups to receive either 0.1% ropivacaine with 2 μg/ml fentanyl or 0.1% levobupivacaine with 2 μg/ml fentanyl as epidural solutions via PCEA pump infusions (4 ml/h after 15 ml loading dose of the respective solutions. The incidence of instrumental AVD was noted as the primary outcome along with demographic data, maternal and foetal vital parameters, maternal VAS scores, degree of motor blockade and total epidural drug consumption.Results: The incidence of instrumental AVD was found to be 43.3% in the levobupivacaine group and 30% in the ropivacaine group. This difference was not statistically significant. Both the groups were comparable in terms of demographic data, maternal VAS scores, total epidural drug consumption and foetal APGAR scores.Conclusion: The use of newer local anaesthetics (levobupivacaine and ropivacaine in low concentrations with opioids (fentanyl as a PCEA technique may offer high maternal satisfaction in terms of quality of pain relief with fewer adverse events like instrumental AVD and adverse foetal outcomes.

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

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

Epidural labor analgesia: A comparison of ropivacaine 0.125% versus 0.2% with fentanyl

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Yogesh Kumar Chhetty

2013-01-01

Conclusion: We conclude that both the concentrations of ropivacaine (0.2% and 0.125% with fentanyl are effective in producing epidural labor analgesia. However, 0.2% concentration was found superior in terms of faster onset, prolonged duration, lesser breakthrough pain requiring lesser top-ups, and hence a lesser consumption of opioids.

Large-scale binding ligand prediction by improved patch-based method Patch-Surfer2.0.

Science.gov (United States)

Zhu, Xiaolei; Xiong, Yi; Kihara, Daisuke

2015-03-01

Ligand binding is a key aspect of the function of many proteins. Thus, binding ligand prediction provides important insight in understanding the biological function of proteins. Binding ligand prediction is also useful for drug design and examining potential drug side effects. We present a computational method named Patch-Surfer2.0, which predicts binding ligands for a protein pocket. By representing and comparing pockets at the level of small local surface patches that characterize physicochemical properties of the local regions, the method can identify binding pockets of the same ligand even if they do not share globally similar shapes. Properties of local patches are represented by an efficient mathematical representation, 3D Zernike Descriptor. Patch-Surfer2.0 has significant technical improvements over our previous prototype, which includes a new feature that captures approximate patch position with a geodesic distance histogram. Moreover, we constructed a large comprehensive database of ligand binding pockets that will be searched against by a query. The benchmark shows better performance of Patch-Surfer2.0 over existing methods. http://kiharalab.org/patchsurfer2.0/ CONTACT: dkihara@purdue.edu Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Evaluation of dexmedetomidine and fentanyl as additives to ropivacaine for epidural anesthesia and postoperative analgesia

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S Kiran

2018-01-01

Conclusions: Epidural anesthesia achieved with 10 μg dexmedetomidine as an additive to 0.5% ropivacaine is more effective with respect to duration and intensity of analgesia when compared to 0.5% ropivacaine alone or addition of 20 μg fentanyl to 0.5% ropivacaine.

Comparison of the Effects of Intrathecal Fentanyl and Intrathecal Morphine on Pain in Elective Total Knee Replacement Surgery

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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.

Biocide patch tests

DEFF Research Database (Denmark)

Andersen, Klaus Ejner; Veien, Niels

1985-01-01

Routine patch testing with a series of 6 industrial biocides containing methylene-bis-thiocyanate (Cytox 3522), benzisothiazolin-3-one (BIT), chlorocresol (Preventol CMK), 2-n-octyl-4-isothiazolin-3-one (Kathon 893), polyhydroxymethylene monobenzylether (Preventol D2) or 1,3,5-tris (hydroxy......-ethyl) hexahydrotriazine (Grotan BK) was carried out in 6 Danish out-patient clinics to evaluate guinea pig allergy test results with the same compounds. A total of 1652 consecutive patients with dermatitis were tested. The usefulness of this patch test battery was limited. There were a few positive reactions to Cytox...... of male patients and atopics, but significant differences in the frequencies of occupational cases, hand eczemas, and leg ulcers/stasis dermatitis, indicating possible variations in referral patterns, use of patch tests, and/or environmental factors....

Comparison of the Effects of Fentanyl and Midazolam as a Premedication in Children Undergoing Inguinal Hernial Surgery

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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.

Collection of analytes from microneedle patches.

Science.gov (United States)

Romanyuk, Andrey V; Zvezdin, Vasiliy N; Samant, Pradnya; Grenader, Mark I; Zemlyanova, Marina; Prausnitz, Mark R

2014-11-04

Clinical medicine and public health would benefit from simplified acquisition of biological samples from patients that can be easily obtained at point of care, in the field, and by patients themselves. Microneedle patches are designed to serve this need by collecting dermal interstitial fluid containing biomarkers without the dangers, pain, or expertise needed to collect blood. This study presents novel methods to collect biomarker analytes from microneedle patches for analysis by integration into conventional analytical laboratory microtubes and microplates. Microneedle patches were made out of cross-linked hydrogel composed of poly(methyl vinyl ether-alt-maleic acid) and poly(ethylene glycol) prepared by micromolding. Microneedle patches were shown to swell with water up to 50-fold in volume, depending on degree of polymer cross-linking, and to collect interstitial fluid from the skin of rats. To collect analytes from microneedle patches, the patches were mounted within the cap of microcentrifuge tubes or formed the top of V-bottom multiwell microplates, and fluid was collected in the bottom of the tubes under gentle centrifugation. In another method, microneedle patches were attached to form the bottom of multiwell microplates, thereby enabling in situ analysis. The simplicity of biological sample acquisition using microneedle patches coupled with the simplicity of analyte collection from microneedles patches integrated into conventional analytical equipment could broaden the reach of future screening, diagnosis, and monitoring of biomarkers in healthcare and environmental/workplace settings.

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

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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.

Edge of polar cap patches

Science.gov (United States)

Hosokawa, K.; Taguchi, S.; Ogawa, Y.

2016-04-01

On the night of 4 December 2013, a sequence of polar cap patches was captured by an all-sky airglow imager (ASI) in Longyearbyen, Norway (78.1°N, 15.5°E). The 630.0 nm airglow images from the ASI of 4 second exposure time, oversampled the emission of natural lifetime (with quenching) of at least ˜30 sec, introduce no observational blurring effects. By using such high-quality ASI images, we succeeded in visualizing an asymmetry in the gradients between the leading/trailing edges of the patches in a 2-D fashion. The gradient in the leading edge was found to be 2-3 times steeper than that in the trailing edge. We also identified fingerlike structures, appearing only along the trailing edge of the patches, whose horizontal scale size ranged from 55 to 210 km. These fingers are considered to be manifestations of plasma structuring through the gradient-drift instability (GDI), which is known to occur only along the trailing edge of patches. That is, the current 2-D observations visualized, for the first time, how GDI stirs the patch plasma and such a mixing process makes the trailing edge more gradual. This result strongly implies a close connection between the GDI-driven plasma stirring and the asymmetry in the large-scale shape of patches and then suggests that the fingerlike structures can be used as markers to estimate the fine-scale structure in the plasma flow within patches.

Reinforcement of a plate weakened by multiple holes with several patches for different types of plate-patch attachment

KAUST Repository

Zemlyanova, A.

2014-01-24

The most general situation of the reinforcement of a plate with multiple holes by several patches is considered. There is no restriction on the number and the location of the patches. Two types of patch attachment are considered: only along the boundary of the patch or both along the boundary of the patch and the boundaries of the holes which this patch covers. The unattached boundaries of the holes may be loaded with given in-plane stresses. The mechanical problem is reduced to a system of singular integral equations which can be further reduced to a system of Fredholm equations. A new numerical procedure for the solution of the system of singular integral equations is proposed in this paper. It is demonstrated on numerical examples that this procedure has advantages in the case of multiple patches and holes and allows achievement of better numerical convergence with less computational effort.

DEA deformed stretchable patch antenna

International Nuclear Information System (INIS)

Jiang, X-J; Jalali Mazlouman, S; Menon, C; Mahanfar, A; Vaughan, R G

2012-01-01

A stretchable patch antenna (SPA) whose frequency is tuned by a planar dielectric elastomer actuator (DEA) is presented in this paper. This mechanically reconfigurable antenna system has a configuration resembling a pre-stretched silicone belt. Part of the belt is embedded with a layer of conductive liquid metal to form the patch antenna. Part of the belt is sandwiched between conductive electrodes to form the DEA. Electrical activation of the DEA results in a contraction of the patch antenna, and as a result, in a variation of its resonance frequency. Design and fabrication steps of this system are presented. Measurement results for deformation, resonance frequency variation and efficiency of the patch antenna are also presented. (paper)

Patching. Restitching business portfolios in dynamic markets.

Science.gov (United States)

Eisenhardt, K M; Brown, S L

1999-01-01

In turbulent markets, businesses and opportunities are constantly falling out of alignment. New technologies and emerging markets create fresh opportunities. Converging markets produce more. And of course, some markets fade. In this landscape of continuous flux, it's more important to build corporate-level strategic processes that enable dynamic repositioning than it is to build any particular defensible position. That's why smart corporate strategists use patching, a process of mapping and remapping business units to create a shifting mix of highly focused, tightly aligned businesses that can respond to changing market opportunities. Patching is not just another name for reorganizing; patchers have a distinctive mindset. Traditional managers see structure as stable; patching managers believe structure is inherently temporary. Traditional managers set corporate strategy first, but patching managers keep the organization focused on the right set of business opportunities and let strategy emerge from individual businesses. Although the focus of patching is flexibility, the process itself follows a pattern. Patching changes are usually small in scale and made frequently. Patching should be done quickly; the emphasis is on getting the patch about right and fixing problems later. Patches should have a test drive before they're formalized but then be tightly scripted after they've been announced. And patching won't work without the right infrastructure: modular business units, fine-grained and complete unit-level metrics, and companywide compensation parity. The authors illustrate how patching works and point out some common stumbling blocks.

FuncPatch: a web server for the fast Bayesian inference of conserved functional patches in protein 3D structures.

Science.gov (United States)

Huang, Yi-Fei; Golding, G Brian

2015-02-15

A number of statistical phylogenetic methods have been developed to infer conserved functional sites or regions in proteins. Many methods, e.g. Rate4Site, apply the standard phylogenetic models to infer site-specific substitution rates and totally ignore the spatial correlation of substitution rates in protein tertiary structures, which may reduce their power to identify conserved functional patches in protein tertiary structures when the sequences used in the analysis are highly similar. The 3D sliding window method has been proposed to infer conserved functional patches in protein tertiary structures, but the window size, which reflects the strength of the spatial correlation, must be predefined and is not inferred from data. We recently developed GP4Rate to solve these problems under the Bayesian framework. Unfortunately, GP4Rate is computationally slow. Here, we present an intuitive web server, FuncPatch, to perform a fast approximate Bayesian inference of conserved functional patches in protein tertiary structures. Both simulations and four case studies based on empirical data suggest that FuncPatch is a good approximation to GP4Rate. However, FuncPatch is orders of magnitudes faster than GP4Rate. In addition, simulations suggest that FuncPatch is potentially a useful tool complementary to Rate4Site, but the 3D sliding window method is less powerful than FuncPatch and Rate4Site. The functional patches predicted by FuncPatch in the four case studies are supported by experimental evidence, which corroborates the usefulness of FuncPatch. The software FuncPatch is freely available at the web site, http://info.mcmaster.ca/yifei/FuncPatch golding@mcmaster.ca Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Influence of habitat quality, population size, patch size, and connectivity on patch-occupancy dynamics of the middle spotted woodpecker.

Science.gov (United States)

Robles, Hugo; Ciudad, Carlos

2012-04-01

Despite extensive research on the effects of habitat fragmentation, the ecological mechanisms underlying colonization and extinction processes are poorly known, but knowledge of these mechanisms is essential to understanding the distribution and persistence of populations in fragmented habitats. We examined these mechanisms through multiseason occupancy models that elucidated patch-occupancy dynamics of Middle Spotted Woodpeckers (Dendrocopos medius) in northwestern Spain. The number of occupied patches was relatively stable from 2000 to 2010 (15-24% of 101 patches occupied every year) because extinction was balanced by recolonization. Larger and higher quality patches (i.e., higher density of oaks >37 cm dbh [diameter at breast height]) were more likely to be occupied. Habitat quality (i.e., density of large oaks) explained more variation in patch colonization and extinction than did patch size and connectivity, which were both weakly associated with probabilities of turnover. Patches of higher quality were more likely to be colonized than patches of lower quality. Populations in high-quality patches were less likely to become extinct. In addition, extinction in a patch was strongly associated with local population size but not with patch size, which means the latter may not be a good surrogate of population size in assessments of extinction probability. Our results suggest that habitat quality may be a primary driver of patch-occupancy dynamics and may increase the accuracy of models of population survival. We encourage comparisons of competing models that assess occupancy, colonization, and extinction probabilities in a single analytical framework (e.g., dynamic occupancy models) so as to shed light on the association of habitat quality and patch geometry with colonization and extinction processes in different settings and species. ©2012 Society for Conservation Biology.

Comparison of different doses of magnesium sulphate and fentanyl as adjuvants to bupivacaine for infraumbilical surgeries under subarachnoid block

Directory of Open Access Journals (Sweden)

Sarika Katiyar

2015-01-01

Full Text Available Background and Aims: Spinal anaesthesia is used for many years for surgeries below the level of umbilicus. It has certain disadvantages such as limited duration of blockade and post-operative analgesia. This study was undertaken to evaluate the effects of additives fentanyl and magnesium sulphate along with bupivacaine during spinal anaesthesia for prolongation of analgesia and motor blockade. Methods: This randomised study was conducted in 120 patients of either sex of American Society of Anesthesiologists physical status I and II, posted for infraumbilical surgeries. Patients were randomly allocated to four groups and were given the following drugs intrathecally as per group distribution; group A - bupivacaine 15 mg (0.5% heavy with fentanyl 25 μg, group B - bupivacaine 15 mg (0.5% heavy with magnesium 100 mg, group C - bupivacaine 15 mg (0.5% heavy with magnesium 50 mg and group D - bupivacaine 15 mg (0.5% heavy with 0.5 ml normal saline. Parameters monitored were duration of analgesia along with haemodynamic parameters and side effects. Data were analysed using the Student′s t-test for the continuous variables and two-tailed Fisher exact test or Chi-square test for categorical variables. Results: There was significant increase in duration of analgesia in group A (374.37 min and B (328.13 min as compared to group C (274.87 min and D (246.03 min. In group A, all haemodynamic parameters decreased by more than 20%, compared to baseline parameters, which was clinically and statistically significant as compared to other groups. There was also increase in duration of motor blockade in groups A and B. Conclusion: Addition of magnesium sulphate at 100 mg dose or fentanyl 25 μg as adjuvants to intrathecal bupivacaine significantly prolongs the duration of analgesia, though in the given doses, magnesium provides better haemodynamic stability than fentanyl, with fewer side effects.

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.

Pre-emptive oral dexmethorphan reduces fentanyl-induced cough as well as immediate postoperative adrenocortico-tropic hormone and growth hormone level

Directory of Open Access Journals (Sweden)

Avik Mukherjee

2011-01-01

Full Text Available Background : Fentanyl-induced cough is not always benign and brief and can be remarkably troublesome, spasmodic, and explosive. Dextromethorphan, an opioid derivative with an antitussive action, may be effective in reducing the fentanyl-induced cough. Dextromethorphan, a N-methyl D aspartate receptor antagonist, may have some effect on diminishing the stress response to surgery. This study was undertaken to determine whether preoperative dextromethorphan could effectively attenuate its incidence, severity, and effect on postoperative stress hormone levels. Materials and Methods : Three hundred and twenty patients of American society of anesthesiologists I-II, aged 18-60 years, undergoing elective laparoscopic cholecystectomy or appendicectomy were randomly allocated into two groups (Group C, control; Group D, dextromethorphan consisting of 160 patients each. Patients in Group D received dextromethorphan 40 mg orally and in Group C received placebo tablets 60 minutes before induction of anesthesia. The incidence of cough was recorded for 1 minute after fentanyl injection and graded as none (0, mild (1-2, moderate (3-5, and severe (>5 cough. Blood samples were collected for estimation of stress hormone levels before surgery and again at 1 hour and 24 hours postoperatively and compared. The appearance of adverse reactions was recorded. Results : The incidence of reflex fentanyl cough was lower in dextromethorphan group (3.9% in comparison to placebo (59.8%. Five patients developed mild and one moderate cough in the dextromethorphan group. In the control group, 31 patients developed mild, 29 moderate, and 32 severe cough. The stress hormones were significantly higher at 1 hour and 24 hours postoperatively in both groups in comparison to its preoperative values. However, at 1 hour postoperatively, adrenocorticotropic hormone, epinephrine, and growth hormone values were significantly low in the dextromethorphan group (61.5 ± 21.1 pg/ ml, 142.1 ± 11

Entropy-guided use of a unique cocktail in awake craniotomy

Directory of Open Access Journals (Sweden)

Itee Chowdhury

2016-01-01

Full Text Available The major benefit of awake craniotomy is to enable a tailored resection that can theoretically maximize the extent of the tumor resection and can minimize the neurological damages. There is still no consensus as to the best anesthetic technique. We describe here a case report where a combination of propofol infusion and dexmedetomidine along with intermittent doses of fentanyl, and fentanyl patch was used with entropy monitoring to assess the depth of sedation in a patient for awake craniotomy.

Meta-Analysis of the Ease of Care From the Nurses' Perspective Comparing Fentanyl Iontophoretic Transdermal System (ITS) Vs Morphine Intravenous Patient-Controlled Analgesia (IV PCA) in Postoperative Pain Management.

Science.gov (United States)

Pestano, Cecile R; Lindley, Pam; Ding, Li; Danesi, Hassan; Jones, James B

2017-08-01

The aim of this meta-analysis was to compare the ease of care (EOC) of fentanyl iontophoretic transdermal system (ITS) vs the morphine intravenous patient-controlled analgesia (IV PCA) as assessed by the nurse. Meta-analysis of three phase 3B randomized active-comparator trials. This meta-analysis according to Cochrane's approach assessed EOC using a validated nurse questionnaire (22 items grouped into three subscales, which include time efficiency, convenience, and satisfaction) in adult patients treated with fentanyl ITS or morphine IV PCA for postoperative pain management. The weighted mean difference (WMD) between treatments was calculated. EOC analyses were based on responses to questionnaires from 848 (fentanyl ITS) and 761 (morphine IV PCA) nurses. Fentanyl ITS was reported to provide significant advantages compared with morphine IV PCA in terms of nurses' overall EOC (WMD = -0.57, P PCA. Copyright © 2016 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

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.

Streamlining of plant patches in streams

DEFF Research Database (Denmark)

Jensen, Kaj Sand; Pedersen, Morten Lauge

2008-01-01

. Sediment elevation within patches (avg. 4.1 cm) increased significantly with patch length, but did not differ between unstable sand or more stable coarse sediment for the same patch length. Shape of canopy and root area did not change significantly with sediment type. 4. Pressure drag on the canopy...

Comparative evaluation of dexmedetomidine and fentanyl for epidural analgesia in lower limb orthopedic surgeries

Directory of Open Access Journals (Sweden)

Sukhminder Jit Singh Bajwa

2011-01-01

Full Text Available Background and Aims: Opioids as epidural adjunct to local anesthetics (LA have been in use since long and α-2 agonists are being increasingly used for similar purpose. The present study aims at comparing the hemodynamic, sedative, and analgesia potentiating effects of epidurally administered fentanyl and dexmedetomidine when combined with ropivacaine. Methods: A total of one hundred patients of both gender aged 21-56 years, American Society of Anaesthesiologist (ASA physical status I and II who underwent lower limb orthopedic surgery were enrolled into the present study. Patients were randomly divided into two groups: Ropivacaine + Dexmedetomidine (RD and Ropivacaine + Fentanyl (RF, comprising 50 patie nts each. Inj. Ropivacaine, 15 ml of 0.75%, was administered epidurally in both the groups with addition of 1 μg/kg of dexmedetomidine in RD group and 1 μg/kg of fentanyl in RF group. Besides cardio-respiratory parameters and sedation scores, various block characteristics were also observed which included time to onset of analgesia at T10, maximum sensory analgesic level, time to complete motor blockade, time to two segmental dermatomal regressions, and time to first rescue analgesic. At the end of study, data was compiled systematically and analyzed using ANOVA with post-hoc significance, Chi-square test and Fisher′s exact test. Value of P<0.05 is considered significant and P<0.001 as highly significant. Results: The demographic profile of patients was comparable in both the groups. Onset of sensory analgesia at T10 (7.12±2.44 vs 9.14±2.94 and establishment of complete motor blockade (18.16±4.52 vs 22.98±4.78 was significantly earlier in the RD group. Postoperative analgesia was prolonged significantly in the RD group (366.62±24.42 and consequently low dose consumption of local anaesthetic LA (76.82±14.28 vs 104.35±18.96 during epidural top-ups postoperatively. Sedation scores were much better in the RD group and highly significant on

Sub-Patch Roughness in Earthquake Rupture Investigations

KAUST Repository

Zielke, Olaf; Mai, Paul Martin

2016-01-01

Fault geometric complexities exhibit fractal characteristics over a wide range of spatial scales (<µm to >km) and strongly affect the rupture process at corresponding scales. Numerical rupture simulations provide a framework to quantitatively investigate the relationship between a fault's roughness and its seismic characteristics. Fault discretization however introduces an artificial lower limit to roughness. Individual fault patches are planar and sub-patch roughness –roughness at spatial scales below fault-patch size– is not incorporated. Does negligence of sub-patch roughness measurably affect the outcome of earthquake rupture simulations? We approach this question with a numerical parameter space investigation and demonstrate that sub-patch roughness significantly modifies the slip-strain relationship –a fundamental aspect of dislocation theory. Faults with sub-patch roughness induce less strain than their planar-fault equivalents at distances beyond the length of a slipping fault. We further provide regression functions that characterize the stochastic effect sub-patch roughness.

Sub-Patch Roughness in Earthquake Rupture Investigations

KAUST Repository

Zielke, Olaf

2016-02-13

Fault geometric complexities exhibit fractal characteristics over a wide range of spatial scales (<µm to >km) and strongly affect the rupture process at corresponding scales. Numerical rupture simulations provide a framework to quantitatively investigate the relationship between a fault\\'s roughness and its seismic characteristics. Fault discretization however introduces an artificial lower limit to roughness. Individual fault patches are planar and sub-patch roughness –roughness at spatial scales below fault-patch size– is not incorporated. Does negligence of sub-patch roughness measurably affect the outcome of earthquake rupture simulations? We approach this question with a numerical parameter space investigation and demonstrate that sub-patch roughness significantly modifies the slip-strain relationship –a fundamental aspect of dislocation theory. Faults with sub-patch roughness induce less strain than their planar-fault equivalents at distances beyond the length of a slipping fault. We further provide regression functions that characterize the stochastic effect sub-patch roughness.

Rapid establishment of a regular distribution of adult tropical Drosophila parasitoids in a multi-patch environment by patch defence behaviour.

Science.gov (United States)

de Jong, Peter W; Hemerik, Lia; Gort, Gerrit; van Alphen, Jacques J M

2011-01-01

Females of the larval parasitoid of Drosophila, Asobara citri, from sub-Saharan Africa, defend patches with hosts by fighting and chasing conspecific females upon encounter. Females of the closely related, palearctic species Asobara tabida do not defend patches and often search simultaneously in the same patch. The effect of patch defence by A. citri females on their distribution in a multi-patch environment was investigated, and their distributions were compared with those of A. tabida. For both species 20 females were released from two release-points in replicate experiments. Females of A. citri quickly reached a regular distribution across 16 patches, with a small variance/mean ratio per patch. Conversely, A. tabida females initially showed a clumped distribution, and after gradual dispersion, a more Poisson-like distribution across patches resulted (variance/mean ratio was closer to 1 and higher than for A. citri). The dispersion of A. tabida was most probably an effect of exploitation: these parasitoids increasingly made shorter visits to already exploited patches. We briefly discuss hypotheses on the adaptive significance of patch defence behaviour or its absence in the light of differences in the natural history of both parasitoid species, notably the spatial distribution of their hosts.

*New* CRITICAL Windows Security patch

CERN Multimedia

2003-01-01

On 10 September 2003, Microsoft issued a new CRITICAL security patch, MS03-039. It must be URGENTLY applied on ALL WINDOWS systems, which are not centrally managed for security patches. This includes Experiment computers, Home computers and Windows Portable and Desktop systems not running NICE. Details of the security hole and patch for MS03-039 (which also includes MS03-026) are at: http://cern.ch/it-div/news/hotfix-MS03-039.asp http://www.microsoft.com/technet/security/bulletin/MS03-039.asp

*New*: CRITICAL Windows Security patch

CERN Multimedia

2003-01-01

On 10 September 2003, Microsoft issued a new CRITICAL security patch, MS03-039. It must be URGENTLY applied on ALL WINDOWS systems, which are not centrally managed for security patches. This includes Experiment computers, Home computers and Windows Portable and Desktop systems not running NICE. Details of the security hole and patch for MS03-039 (which also includes MS03-026) are at: http://cern.ch/it-div/news/hotfix-MS03-039.asp http://www.microsoft.com/technet/security/bulletin/MS03-039.asp

Miniaturization of Multiple-Layer Folded Patch Antennas

DEFF Research Database (Denmark)

Zhang, Jiaying; Breinbjerg, Olav

2009-01-01

A new folded patch antenna with multiple layers was developed in this paper, by folding the patch in a proper way, and a highly miniaturized antenna can be realized. The multiple layer patch with 4-layer and 6-layer are designed and evaluated at 2.4 GHz, 915 MHz, and 415 MHz respectively. Then a 4...... layer patch is fabricated and measured to validate the design method. The theoretical analysis, design and simulations, fabrications, as well as the measurements are presented in this paper. All the results show that the folded patch antenna is a good candidate in making a highly miniaturized compact...

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

Reinforcement of a plate weakened by multiple holes with several patches for different types of plate-patch attachment

KAUST Repository

Zemlyanova, A.

2014-01-01

the boundary of the patch or both along the boundary of the patch and the boundaries of the holes which this patch covers. The unattached boundaries of the holes may be loaded with given in-plane stresses. The mechanical problem is reduced to a system

Fentanyl Iontophoretic Transdermal System (IONSYS(®)) can be Safely used in the Hospital Environment with X-Rays, Computerized Tomography and Radiofrequency Identification Devices.

Science.gov (United States)

Lemke, John; Sardariani, Edmond; Phipps, Joseph Bradley; Patel, Niki; Itri, Loretta M; Caravelli, James; Viscusi, Eugene R

2016-09-01

Fentanyl iontophoretic transdermal system (fentanyl ITS, IONSYS(®)) is a patient-controlled analgesia system used for the management of acute postoperative pain, designed to be utilized in a hospital setting. The objective of the two studies was to determine if fentanyl ITS could be safely used with X-rays, computerized tomography (CT) scans and radiofrequency identification (RFID) devices. The ITS system has two components: controller and drug unit; the studies utilized ITS systems without fentanyl, referred to as the ITS Placebo system. The first study evaluated the effect of X-radiation on the operation of an ITS Placebo system. Five ITS Placebo systems were exposed to X-rays (20 and 200 mSv total radiation dose-the 200 mSv radiation dose represents a tenfold higher exposure than in clinical practice) while operating in the Ready Mode and five were exposed while operating in the Dose Mode. The second study evaluated the effect of RFID (worst-case scenario of direct contact with an RFID transmitter) on the operation of an ITS Placebo system. During these tests, observations of the user interface and measurements of output voltage confirmed proper function throughout all operational modes (Ready Mode, Dose Mode, End-of-Use Mode, and End-of-Life Mode). The ITS Placebo system met all specifications and no functional anomalies were observed during and following X-ray exposure at two radiation dose levels or exposure at six different combinations of RFID frequencies and field strengths. The performance of the ITS system was unaffected by X-ray exposure levels well beyond those associated with diagnostic X-rays and CT scans, and by exposure to radiofrequency field strengths typically generated by RFID devices. These results provide added confidence to clinicians that the fentanyl ITS system does not need to be removed during diagnostic X-rays and CT scans and can also be utilized in close proximity to RFID devices. The studies and writing of this manuscript were

Cell-Detection Technique for Automated Patch Clamping

Science.gov (United States)

McDowell, Mark; Gray, Elizabeth

2008-01-01

A unique and customizable machinevision and image-data-processing technique has been developed for use in automated identification of cells that are optimal for patch clamping. [Patch clamping (in which patch electrodes are pressed against cell membranes) is an electrophysiological technique widely applied for the study of ion channels, and of membrane proteins that regulate the flow of ions across the membranes. Patch clamping is used in many biological research fields such as neurobiology, pharmacology, and molecular biology.] While there exist several hardware techniques for automated patch clamping of cells, very few of those techniques incorporate machine vision for locating cells that are ideal subjects for patch clamping. In contrast, the present technique is embodied in a machine-vision algorithm that, in practical application, enables the user to identify good and bad cells for patch clamping in an image captured by a charge-coupled-device (CCD) camera attached to a microscope, within a processing time of one second. Hence, the present technique can save time, thereby increasing efficiency and reducing cost. The present technique involves the utilization of cell-feature metrics to accurately make decisions on the degree to which individual cells are "good" or "bad" candidates for patch clamping. These metrics include position coordinates (x,y) in the image plane, major-axis length, minor-axis length, area, elongation, roundness, smoothness, angle of orientation, and degree of inclusion in the field of view. The present technique does not require any special hardware beyond commercially available, off-the-shelf patch-clamping hardware: A standard patchclamping microscope system with an attached CCD camera, a personal computer with an imagedata- processing board, and some experience in utilizing imagedata- processing software are all that are needed. A cell image is first captured by the microscope CCD camera and image-data-processing board, then the image

Cardiopulmonary and analgesics effects of epidural morphine, fentanyl or tramadol in female dog undergoing a ovariohysterectomy

Directory of Open Access Journals (Sweden)

Odete Duarte de Oliveira Neta

2014-09-01

Full Text Available ABSTRACT. Oliveira Neta O.D., Caires L.P., Clark R.M.O, Ferreira M.L., Said R.A., Munhoz A.D. & Tarazi R. [Cardiopulmonary and analgesics effects of epidural morphine, fentanyl or tramadol in female dog undergoing a ovariohysterectomy.] Efeitos cardiorrespiratórios e analgésicos da morfina, fentanil ou tramadol pela via epidural em cadelas submetidas à ovariosalpingohisterectomia. Revista Brasileira de Medicina Veterinária, 36(3:281-288, 2014. Departamento de Ciências Agrárias e Ambientais, Universidade Estadual de Santa Cruz, Rodovia Jorge Amado, Km 16, Salobrinho, Ilhéus, BA 45662-900, Brasil. E-mail: rosanaclark@gmail.com The objective was to evaluate the cardiorespiratory and analgesic effects provided by epidural morphine, tramadol and fentanyl in female dog submitted to ovariohysterectomy. Eighteen healthy female dogs, aged 3.4±2.2 years old, weithing 31.0±8.0Kg, were premedicated with chlorpromazine (0,5mg/kg, with subsequent propofol (5mg/Kg anesthetic induction by intravenous route and maintenance with isoflurane anesthesia. The animals were distributed in three groups and received: 1,25mg/kg of lignocaine 2% diluted in 0,26ml/kg of saline solution with0,1 mg/kg of morphine (GM group, 5μg/kg of fentanyl (GF group or 2mg/kg of tramadol (GT group epidurally.. Heart rate, arterial blood pressure, respiratory rate, end-tidal carbon dioxide (ETCO2 , oxyhemoglobin saturation (SpO2 and body temperature were evaluated before premedication (M0, 15 minutes after premedication (M1, 10 minutes after epidural opioids administration during maintenance and during postoperative period. Postoperative analgesia was evaluated using the by University of Melbourne pain scale (UMPS and a simple descriptive scale every hour during six hours (M3 – M8. In M2 time, the arterial blood pressure was significantly lower for all treatments and ETCO2 was higher in GM e GT when compared to GF. Pain scores were lower in GM with a UMPS. In the last three

A comparison between post-operative analgesia after intrathecal nalbuphine with bupivacaine and intrathecal fentanyl with bupivacaine after cesarean section

Directory of Open Access Journals (Sweden)

Hala Mostafa Gomaa

2014-10-01

Conclusion: Either intrathecal nalbuphine 0.8 mg or intrathecal fentanyl 25 μg combined with 10 mg bupivacaine provides good intra-operative and early post-operative analgesia in cesarean section.

Windows Security patch required

CERN Multimedia

3004-01-01

This concerns Windows PCs (XP, 2000, NT) which are NOT centrally managed at CERN for security patches, e.g. home PCs, experiment PCs, portables,... A security hole which can give full privileges on Windows systems needs to be URGENTLY patched. Details of the security hole and hotfix are at: http://cern.ch/it-div/news/hotfix-MS03-026.asp http://www.microsoft.com/technet/security/bulletin/MS03-026.asp

Comparison of efficacy of meperidine and fentanyl in terms of pain management and quality of life in patients with cervical cancer receiving intracavitary brachytherapy: a double-blind, randomized controlled trial.

Science.gov (United States)

Thanthong, Saengrawee; Rojthamarat, Sirikorn; Worasawate, Wipra; Vichitvejpaisal, Phongthara; Nantajit, Danupon; Ieumwananontachai, Nantakarn

2017-08-01

The aim of this study was to compare the effectiveness of two sedative regimens, a benzodiazepine with either meperidine or fentanyl, in relieving pain in patients with cervical cancer undergoing intracavitary brachytherapy in terms of pain score and quality of life. Forty unselected outpatients undergoing brachytherapy (160 fractions) were enrolled with informed consent and randomized to receive a benzodiazepine with either meperidine or fentanyl. The perceived pain score according to a standard 10-item numeric rating scale was collected every 15 min during the procedure, and the perceived quality of life was determined at the end of each procedure using the EuroQol five-dimension questionnaire. The patients and medical staff members directly involved with the procedure were blinded to the medication used. The patients' pain levels were mild in both analgesic groups. Meperidine appeared to be slightly more effective than fentanyl, although the differences in the average pain score and quality of life were not statistically significant. Both meperidine and fentanyl in combination with benzodiazepine were effective in relieving pain and discomfort in patients undergoing brachytherapy. NCT02684942, ClinicalTrials.gov.

Generic patch inference

DEFF Research Database (Denmark)

Andersen, Jesper; Lawall, Julia

2010-01-01

A key issue in maintaining Linux device drivers is the need to keep them up to date with respect to evolutions in Linux internal libraries. Currently, there is little tool support for performing and documenting such changes. In this paper we present a tool, spdiff, that identifies common changes...... developers can use it to extract an abstract representation of the set of changes that others have made. Our experiments on recent changes in Linux show that the inferred generic patches are more concise than the corresponding patches found in commits to the Linux source tree while being safe with respect...

Epidural Neostigmine versus Fentanyl to Decrease Bupivacaine Use in Patient-controlled Epidural Analgesia during Labor: A Randomized, Double-blind, Controlled Study.

Science.gov (United States)

Booth, Jessica L; Ross, Vernon H; Nelson, Kenneth E; Harris, Lynnette; Eisenach, James C; Pan, Peter H

2017-07-01

The addition of opioids to epidural local anesthetic reduces local anesthetic consumption by 20% but at the expense of side effects and time spent for regulatory compliance paperwork. Epidural neostigmine also reduces local anesthetic use. The authors hypothesized that epidural bupivacaine with neostigmine would decrease total hourly bupivacaine use compared with epidural bupivacaine with fentanyl for patient-controlled epidural analgesia. A total of 215 American Society of Anesthesiologists physical status II, laboring parturients requesting labor epidural analgesia consented to the study and were randomized to receive 0.125% bupivacaine with the addition of either fentanyl (2 μg/ml) or neostigmine (2, 4, or 8 μg/ml). The primary outcome was total hourly local anesthetic consumption, defined as total patient-controlled epidural analgesia use and top-ups (expressed as milliliters of 0.125% bupivacaine) divided by the infusion duration. A priori analysis determined a group size of 35 was needed to have 80% power at α = 0.05 to detect a 20% difference in the primary outcome. Of 215 subjects consented, 151 patients were evaluable. Demographics, maternal and fetal outcomes, and labor characteristics were similar among groups. Total hourly local anesthetic consumption did not differ among groups (P = 0.55). The total median hourly bupivacaine consumption in the fentanyl group was 16.0 ml/h compared with 15.3, 14.6, and 16.2 ml/h in the 2, 4, and 8 μg/ml neostigmine groups, respectively (P = 0.55). The data do not support any difference in bupivacaine requirements for labor patient-controlled epidural analgesia whether patients receive epidural bupivacaine with 2 to 8 μg/ml neostigmine or epidural bupivacaine with 2 μg/ml fentanyl.

Smart thermal patch for adaptive thermotherapy

KAUST Repository

Hussain, Muhammad Mustafa

2015-11-12

A smart thermal patch for adaptive thermotherapy is provided. In an embodiment, the patch can be a stretchable, non-polymeric, conductive thin film flexible and non-invasive body integrated mobile thermal heater with wireless control capabilities that can be used to provide adaptive thermotherapy. The patch can be geometrically and spatially tunable on various pain locations. Adaptability allows the amount of heating to be tuned based on the temperature of the treated portion.

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

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

A STUDY COMPARING DIFFERENT CONCENTRATIONS OF ROPIVACAINE 0.125% VS. 0.2%, WHEN GIVEN WITH FENTANYL 2 MCG/ML FOR EPIDURAL LABOUR ANALGESIA

Directory of Open Access Journals (Sweden)

Vindhya K

2017-07-01

Full Text Available BACKGROUND Epidural administration of local anaesthetics, with or without opioids, is commonly used for the relief of pain in labor. Lower concentration of local anesthetics is used for providing labor epidural analgesia. MATERIALS AND METHODS After approval of the Institutional Ethical Committee, this study was conducted at a teaching hospital in GGH, Kakinada on 50 term parturients. 50 parturients of ASA I & II, primi or multi gravida with singleton pregnancy having vertex presentation were taken up for the study. They were randomly divided into 2 groups–Group R1 and Group R2 each comprising of 25 parturients. Study patients (n=50 were randomly assigned to one of two groups of 25 each. They received aliquots of epidural injection using either, 10 ml of ropivacaine 0.125 % with 2 μg/ml fentanyl (group R1 or 10 ml of ropivacaine 0.2% with 2 μg/ml fentanyl (group R2. RESULTS Demographic data, obstetric data, and injection delivery interval were comparable in both groups. Effective labor analgesia with no motor blockade was observed in both groups. Duration of analgesia after initial bolus dose was also significantly longer in group R2 (126.45 ± 12.34 min than in group R1 (73.05±27.4min. Ropivacaine at both concentrations (0.2% vs. 0.125% along with fentanyl 2μg / ml decreased visual analog scale (VAS scores to <3 in all parturients uniformly. Mean VAS scores were significantly less in group R2 than in group R1 at 5,60, and 90 min. Requirement of top-up doses was significantly less in group R2 as compared to group R1. Consumption of ropivacaine was comparable in both the groups (58.23 ± 5.48 mg in group R1 and 65.88 ± 6.29 mg in group R2, but consumption of fentanyl was significantly more in group R1 (94.31 ± 4.93 mg as compared to group R2 (31.58 ± 2.38 mg. There were no significant changes in haemodynamics, nor adverse effects related to neonatal or maternal outcomes in both groups. CONCLUSION We conclude that both the concentrations

*NEW* CRITICAL Windows Security patches

CERN Multimedia

2003-01-01

On 3 October and 10 September 2003, Microsoft issued new CRITICAL security patches MS03-040 and MS03-039. They must be URGENTLY applied on ALL WINDOWS systems, which are not centrally managed for security patches. This includes Experiment computers, Home computers and Windows Portable and Desktop systems not running NICE. Details of the security holes and patches are at: MS03-039: http://cern.ch/it-div/news/hotfix-MS03-039.asp http://www.microsoft.com/technet/security/bulletin/MS03-039.asp MS03-040: http://cern.ch/it-div/news/hotfix-MS03-040.asp http://www.microsoft.com/technet/security/bulletin/MS03-040.asp

Patch layout generation by detecting feature networks

KAUST Repository

Cao, Yuanhao

2015-02-01

The patch layout of 3D surfaces reveals the high-level geometric and topological structures. In this paper, we study the patch layout computation by detecting and enclosing feature loops on surfaces. We present a hybrid framework which combines several key ingredients, including feature detection, feature filtering, feature curve extension, patch subdivision and boundary smoothing. Our framework is able to compute patch layouts through concave features as previous approaches, but also able to generate nice layouts through smoothing regions. We demonstrate the effectiveness of our framework by comparing with the state-of-the-art methods.

Injection anaesthesia with fentanyl-midazolam-medetomidine in adult female mice: importance of antagonization and perioperative care.

Science.gov (United States)

Fleischmann, Thea; Jirkof, Paulin; Henke, Julia; Arras, Margarete; Cesarovic, Nikola

2016-08-01

Injection anaesthesia is commonly used in laboratory mice; however, a disadvantage is that post-anaesthesia recovery phases are long. Here, we investigated the potential for shortening the recovery phase after injection anaesthesia with fentanyl-midazolam-medetomidine by antagonization with naloxone-flumazenil-atipamezole. In order to monitor side-effects, the depth of anaesthesia, heart rate (HR), core body temperature (BT) and concentration of blood gases, as well as reflex responses, were assessed during a 50 min anaesthesia. Mice were allowed to recover from the anaesthesia in their home cages either with or without antagonization, while HR, core BT and spontaneous home cage behaviours were recorded for 24 h. Mice lost righting reflex at 330 ± 47 s after intraperitoneal injection of fentanyl-midazolam-medetomidine. During anaesthesia, HR averaged 225 ± 23 beats/min, respiratory rate and core BT reached steady state at 131 ± 15 breaths/min and 34.3 ± 0.25℃, respectively. Positive pedal withdrawal reflex, movement triggered by tail pinch and by toe pinch, still occurred in 25%, 31.2% and 100% of animals, respectively. Arterial blood gas analysis revealed acidosis, hypoxia, hypercapnia and a marked increase in glucose concentration. After anaesthesia reversal by injection with naloxone-flumazenil-atipamezole, animals regained consciousness after 110 ± 18 s and swiftly returned to physiological baseline values, yet they displayed diminished levels of locomotion and disrupted circadian rhythm. Without antagonization, mice showed marked hypothermia (22 ± 1.9℃) and bradycardia (119 ± 69 beats/min) for several hours. Fentanyl-midazolam-medetomidine provided reliable anaesthesia in mice with reasonable intra-anaesthetic side-effects. Post-anaesthetic period and related adverse effects were both reduced substantially by antagonization with naloxone-flumazenil-atipamezole. © The Author(s) 2016.

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. 

Nebulized fentanyl vs intravenous morphine for ED patients with acute abdominal pain: a randomized double-blinded, placebo-controlled clinical trial.

Science.gov (United States)

Deaton, Travis; Auten, Jonathan D; Darracq, Michael A

2015-06-01

Patients with acute abdominal pain commonly present to emergency departments. The safe and effective relief of discomfort is a concern to patients and physicians. Intravenous opioids are the traditional method used to provide pain relief in this setting, but intravenous access is time consuming and not always achievable. Alternative methods of pain control may therefore be necessary for the acute management of painful conditions without adding to the overall physical or psychological discomfort. The purpose of this study was to evaluate the feasibility of nebulized fentanyl (NF) in the alleviation of acute and undifferentiated abdominal pain. We also sought to compare NF with intravenous morphine (IVM) and to assess patient and provider satisfaction with NF. Nebulized fentanyl (2 μg/kg) was compared to IVM (0.1 mg/kg) at 10, 20, 30, and 40 minutes; and patient and physician satisfaction was recorded. The NF group experienced more rapid pain relief and more sustained and clinically significant pain relief over the 40-minute study interval. There were no adverse effects noted in the NF group. Both patient and physician satisfaction scores were higher in the NF group. Fentanyl citrate at a dose of 2 μg/kg through a breath-actuated nebulizer appears to be a feasible and safe alternative to IVM (0.1 mg/kg) in the treatment of acute abdominal pain. Copyright © 2015 Elsevier Inc. All rights reserved.

Characteristic evolutions in numerical relativity using six angular patches

International Nuclear Information System (INIS)

Reisswig, Christian; Bishop, Nigel T; Lai, Chi Wai; Thornburg, Jonathan; Szilagyi, Bela

2007-01-01

The characteristic approach to numerical relativity is a useful tool in evolving gravitational systems. In the past this has been implemented using two patches of stereographic angular coordinates. In other applications, a six-patch angular coordinate system has proved effective. Here we investigate the use of a six-patch system in characteristic numerical relativity, by comparing an existing two-patch implementation (using second-order finite differencing throughout) with a new six-patch implementation (using either second- or fourth-order finite differencing for the angular derivatives). We compare these different codes by monitoring the Einstein constraint equations, numerically evaluated independently from the evolution. We find that, compared to the (second-order) two-patch code at equivalent resolutions, the errors of the second-order six-patch code are smaller by a factor of about 2, and the errors of the fourth-order six-patch code are smaller by a factor of nearly 50

Characteristic evolutions in numerical relativity using six angular patches

Energy Technology Data Exchange (ETDEWEB)

Reisswig, Christian [Max-Planck-Institut fuer Gravitationsphysik, Albert-Einstein-Institut, Am Muehlenberg 1, D-14476 Golm (Germany); Bishop, Nigel T [Department of Mathematical Sciences, University of South Africa, PO Box 392, Unisa 0003, South Africa (South Africa); Lai, Chi Wai [Department of Mathematical Sciences, University of South Africa, PO Box 392, Unisa 0003, South Africa (South Africa); Thornburg, Jonathan [Max-Planck-Institut fuer Gravitationsphysik, Albert-Einstein-Institut, Am Muehlenberg 1, D-14476 Golm (Germany); Szilagyi, Bela [Max-Planck-Institut fuer Gravitationsphysik, Albert-Einstein-Institut, Am Muehlenberg 1, D-14476 Golm (Germany)

2007-06-21

The characteristic approach to numerical relativity is a useful tool in evolving gravitational systems. In the past this has been implemented using two patches of stereographic angular coordinates. In other applications, a six-patch angular coordinate system has proved effective. Here we investigate the use of a six-patch system in characteristic numerical relativity, by comparing an existing two-patch implementation (using second-order finite differencing throughout) with a new six-patch implementation (using either second- or fourth-order finite differencing for the angular derivatives). We compare these different codes by monitoring the Einstein constraint equations, numerically evaluated independently from the evolution. We find that, compared to the (second-order) two-patch code at equivalent resolutions, the errors of the second-order six-patch code are smaller by a factor of about 2, and the errors of the fourth-order six-patch code are smaller by a factor of nearly 50.

Biomaterials for drug delivery patches.

Science.gov (United States)

Santos, Lúcia F; Correia, Ilídio J; Silva, A Sofia; Mano, João F

2018-06-15

The limited efficiency of conventional drugs has been instigated the development of new and more effective drug delivery systems (DDS). Transdermal DDS, are associated with numerous advantages such its painless application and less frequent replacement and greater flexibility of dosing, features that triggered the research and development of such devices. Such systems have been produced using either biopolymer; or synthetic polymers. Although the first ones are safer, biocompatible and present a controlled degradation by human enzymes or water, the second ones are the most currently available in the market due to their greater mechanical resistance and flexibility, and non-degradation over time. This review highlights the most recent advances (mainly in the last five years) of patches aimed for transdermal drug delivery, focusing on the different materials (natural, synthetic and blends) and latest designs for the development of such devices, emphasizing also their combination with drug carriers that enable enhanced drug solubility and a more controlled release of the drug over the time. The benefits and limitations of different patches formulations are considered with reference to their appliance to transdermal drug delivery. Furthermore, a record of the currently available patches on the market is given, featuring their most relevant characteristics. Finally, a list of most recent/ongoing clinical trials regarding the use of patches for skin disorders is detailed and critical insights on the current state of patches for transdermal drug delivery are also provided. Copyright © 2018. Published by Elsevier B.V.

Pharmacokinetic Evaluation of Two Nicotine Patches in Smokers.

Science.gov (United States)

Rasmussen, Scott; Horkan, Kathleen Halabuk; Kotler, Mitchell

2018-02-02

Smoking continues to be a major preventable cause of early mortality worldwide, and nicotine replacement therapy has been demonstrated to increase rates of abstinence among smokers attempting to quit. Nicotine transdermal systems (also known as nicotine patches) attach to the skin via an adhesive layer composed of a mixture of different-molecular-weight polyisobutylenes (PIBs) in a specific ratio. This randomized, single-dose, 2-treatment, crossover pharmacokinetic (PK) trial assessed the bioequivalence of nicotine patches including a replacement PIB adhesive (test) compared with the PIB adhesive historically used on marketed patches (reference). The test and reference patches were bioequivalent, as determined by the PK parameters of C max and AUC 0-t . In addition, the parameters T max and t 1/2 did not significantly differ between the 2 patches, supporting the bioequivalence finding from the primary analysis. The tolerability profiles of the patches containing the replacement and previously used PIB adhesives were similar; application-site adverse events did not significantly differ between test and reference patches. Overall, these data establish the bioequivalence of the nicotine patch with the replacement PIB adhesive formulation and the previously utilized PIB adhesive formulation. © 2018 The Authors. Clinical Pharmacology in Drug Development published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

Nickel patch test reactivity and the menstrual cycle

DEFF Research Database (Denmark)

Rohold, A E; Halkier-Sørensen, L; Thestrup-Pedersen, K

1994-01-01

Premenstrual exacerbation of allergic contact dermatitis and varying allergic patch test responses have been reported at different points of the period. Using a dilution series of nickel sulphate, we studied the variation in patch test reactivity in nickel allergic women in relation to the menstr......Premenstrual exacerbation of allergic contact dermatitis and varying allergic patch test responses have been reported at different points of the period. Using a dilution series of nickel sulphate, we studied the variation in patch test reactivity in nickel allergic women in relation...... were tested first on day 7-10 and the other half first on day 20-24. There was no difference in the degree of patch test reactivity, when the results from day 7-10 and day 20-24 were compared (p > 0.4). However, when we compared the patch test results from the first and second test procedure, we found...... of positive patch tests led to an increased skin reactivity towards the same allergen, when the patients were retested weeks later....

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.

Evaluation of concrete pavement patching techniques.

Science.gov (United States)

1989-01-01

This final report presents the results of a study undertaken to improve in concrete pavement patching techniques. Activities included an evaluation of the suitability of the impact hammer and maturity calculations for determining when a patch is read...

Composite GPS Patch Antenna for the AR Bandwidth Enhancement

Directory of Open Access Journals (Sweden)

Minkil Park

2016-01-01

Full Text Available A composite Global Positioning System (GPS patch antenna with a quadrature 3 dB hybrid coupler was designed and implemented for working RHCP and had a broadband axial ratio (AR bandwidth. We designed two patches as a FR-4 patch and 1.5 mm thickness thin ceramic patch with a quadrature 3 dB hybrid coupler. A CP radiation pattern was achieved, and the AR bandwidth improved by incorporating a quadrature 3 dB hybrid coupler feed structure in a micro-strip patch antenna. SMD by chip elements was applied to the quadrature 3 dB hybrid coupler. For the composite FR-4 and ceramic patch antennas, the VSWR measurement showed a 2 : 1 ratio over the entire design band, and the 3 dB AR bandwidth was 295 and 580 MHz for the FR-4 patch and ceramic patch antennas, respectively. The antenna gains for the composite FR-4 and ceramic patch antennas were measured as 1.36–2.75 and 1.47–2.71 dBi with 15.11–25.3% and 19.25–28.45% efficiency, respectively.

Microneedle Patches as Drug and Vaccine Delivery Platform.

Science.gov (United States)

Li, Junwei; Zeng, Mingtao; Shan, Hu; Tong, Chunyi

2017-01-01

Transcutaneous delivery is the ideal method for delivering therapeutic reagents or vaccines into skin. With their promise of self-administration, cost-effective and high efficiency, microneedle patches have been studied intensively as therapeutic and vaccination delivery platform that replaces injection by syringe. This review aims to summarize the recent advancements of microneedle patches in application for drugs and vaccine delivery. We reviewed the most of recently published papers on microneedle patches, summarized their evolution, classification, state-of the-art capabilities and discussed promising application in drugs and vaccine delivery. With the rapid development of nanotechnology, microneedle patches have been improved by switching from undissolving to dissolving microneedles, and their safety has also improved dramatically. As a drug delivery tool, microneedle patches can deliver bioactive molecular of different physical size. Additionally, microneedle patches can be coated or encapsulate with DNA vaccine, subunit antigen, inactivated or live virus vaccine. Combining clinical results with the results of patient interview, microneedle patches are found to be feasible and are predicated to soon be acceptable for the medical service. In this review, we summarized the evolution, current and future application of microneedle patches as delivery vehicle for drugs and vaccines. Compared with traditional delivery tools, microneedle patches have many advantages, such as providing pain-free, non-invasive, convenient route for reagent administration and delivery, with no cold chain required for storage and transportation as well as decreasing sharp medical waste, needle-caused injury and transmission of blood-borne infectious disease in rural area. However, even though there are dramatic progress in preclinical investigation of microneedle patches, further testing will be required for clinical application. Further research should be implemented in multiple fields

Improving Saliency Models by Predicting Human Fixation Patches

KAUST Repository

Dubey, Rachit

2015-04-16

There is growing interest in studying the Human Visual System (HVS) to supplement and improve the performance of computer vision tasks. A major challenge for current visual saliency models is predicting saliency in cluttered scenes (i.e. high false positive rate). In this paper, we propose a fixation patch detector that predicts image patches that contain human fixations with high probability. Our proposed model detects sparse fixation patches with an accuracy of 84 % and eliminates non-fixation patches with an accuracy of 84 % demonstrating that low-level image features can indeed be used to short-list and identify human fixation patches. We then show how these detected fixation patches can be used as saliency priors for popular saliency models, thus, reducing false positives while maintaining true positives. Extensive experimental results show that our proposed approach allows state-of-the-art saliency methods to achieve better prediction performance on benchmark datasets.

Improving Saliency Models by Predicting Human Fixation Patches

KAUST Repository

Dubey, Rachit; Dave, Akshat; Ghanem, Bernard

2015-01-01

There is growing interest in studying the Human Visual System (HVS) to supplement and improve the performance of computer vision tasks. A major challenge for current visual saliency models is predicting saliency in cluttered scenes (i.e. high false positive rate). In this paper, we propose a fixation patch detector that predicts image patches that contain human fixations with high probability. Our proposed model detects sparse fixation patches with an accuracy of 84 % and eliminates non-fixation patches with an accuracy of 84 % demonstrating that low-level image features can indeed be used to short-list and identify human fixation patches. We then show how these detected fixation patches can be used as saliency priors for popular saliency models, thus, reducing false positives while maintaining true positives. Extensive experimental results show that our proposed approach allows state-of-the-art saliency methods to achieve better prediction performance on benchmark datasets.

Light transmission and preference of eye patches for occlusion treatment.

Directory of Open Access Journals (Sweden)

Hwan Heo

Full Text Available To investigate light transmission and preference for six eye patches for occlusion therapy.Six patches were examined, including; Ortopad Fun Pack, Ortopad Flesh, Kawamoto A-1, Kawamoto A-2, 3M Opticlude, and Everade Eye Guard. The size and the presence of a light blocking pad of patches were investigated. The amount of light transmitted through the patches was evaluated, using a digital light meter and a model eye, in three different environments; indoors with fluorescent light, outdoors on a sunny day, and strong light from illuminator. After patching the normal eye, the flash visual evoked potential (VEP was measured. Thirty patients with amblyopia or horizontal strabismus, who received occlusion therapy as initial treatment, were included. After using all six patches, patients completed a 7-item questionnaire regarding the patch preference for size, color and shape, adhesive power, pain with removal, skin irritation after removing patch, parent's preference and overall opinion.All patches had a light-blocking pad, except the 3M Nexcare. Ortopad had the strongest light blocking power in the three environments, and the 3M Nexcare had the weakest power. In flash VEP, Ortopad and Kawamoto patches showed flat, but 3M Nexcare and Everade Eye Guard showed normal response. There were significant preferential differences among the patches in all the items of the questionnaire (P<0.05. In comparison between the patches respectively, 3M Nexcare received the lowest satisfaction in pain when removing a patch and skin irritation after removing a patch. Kawamoto A-2 received the lowest score in the overall satisfaction.We found differences in the light-blocking power and in the preference of the various patches for the occlusion treatment. This is a pilot study regarding only characteristics and preferences of patches. Further clinical studies regarding the relationship between characteristics or preferences of patches and outcomes of occlusion treatment

The hedgehog receptor patched is involved in cholesterol transport.

Directory of Open Access Journals (Sweden)

Michel Bidet

Full Text Available Sonic hedgehog (Shh signaling plays a crucial role in growth and patterning during embryonic development, and also in stem cell maintenance and tissue regeneration in adults. Aberrant Shh pathway activation is involved in the development of many tumors, and one of the most affected Shh signaling steps found in these tumors is the regulation of the signaling receptor Smoothened by the Shh receptor Patched. In the present work, we investigated Patched activity and the mechanism by which Patched inhibits Smoothened.Using the well-known Shh-responding cell line of mouse fibroblasts NIH 3T3, we first observed that enhancement of the intracellular cholesterol concentration induces Smoothened enrichment in the plasma membrane, which is a crucial step for the signaling activation. We found that binding of Shh protein to its receptor Patched, which involves Patched internalization, increases the intracellular concentration of cholesterol and decreases the efflux of a fluorescent cholesterol derivative (BODIPY-cholesterol from these cells. Treatment of fibroblasts with cyclopamine, an antagonist of Shh signaling, inhibits Patched expression and reduces BODIPY-cholesterol efflux, while treatment with the Shh pathway agonist SAG enhances Patched protein expression and BODIPY-cholesterol efflux. We also show that over-expression of human Patched in the yeast S. cerevisiae results in a significant boost of BODIPY-cholesterol efflux. Furthermore, we demonstrate that purified Patched binds to cholesterol, and that the interaction of Shh with Patched inhibits the binding of Patched to cholesterol.Our results suggest that Patched may contribute to cholesterol efflux from cells, and to modulation of the intracellular cholesterol concentration. This activity is likely responsible for the inhibition of the enrichment of Smoothened in the plasma membrane, which is an important step in Shh pathway activation.

Continuous paravertebral infusion of ropivacaine with or without fentanyl for pain relief in unilateral multiple fractured ribs

Directory of Open Access Journals (Sweden)

Medha Mohta

2013-01-01

Full Text Available Background: Continuous thoracic paravertebral block (TPVB provides effective analgesia for unilateral multiple fractured ribs (MFR. However, prolonged infusion of local anaesthetic (LA in high doses can predispose to risk of LA toxicity, which may be reduced by using safer drugs or drug combinations. This study was conducted to assess efficacy and safety of paravertebral infusion of ropivacaine and adrenaline with or without fentanyl to provide analgesia to patients with unilateral MFR. Methods: Thirty adults, having ≥3 unilateral MFR, with no significant trauma outside chest wall, were studied. All received bolus of 0.5% ropivacaine 0.3 ml/kg through paravertebral catheter, followed by either 0.1-0.2 ml/kg/hr infusion of ropivacaine 0.375% with adrenaline 5 μg/ml in group RA or ropivacaine 0.2% with adrenaline 5 μg/ml and fentanyl 2 μg/ml in group RAF. Rescue analgesia was provided by IV morphine. Results: Statistical analysis was performed using unpaired Student t-test, Chi-square test and repeated measures ANOVA. After TPVB, VAS scores, respiratory rate and PEFR improved in both groups with no significant inter-group differences. Duration of ropivacaine infusion, morphine requirements, length of ICU and hospital stay, incidence of pulmonary complications and opioid-related side-effects were similar in both groups. Ropivacaine requirement was higher in group RA than group RAF. No patient showed signs of LA toxicity. Conclusion: Continuous paravertebral infusion of ropivacaine 0.375% with adrenaline 5 μg/ml at 0.1-0.2 ml/kg/hr provided effective and safe analgesia to patients with unilateral MFR. Addition of fentanyl 2 μg/ml allowed reduction of ropivacaine concentration to 0.2% without decreasing efficacy or increasing opioid-related side-effects.

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.

Factors predisposing to coma and delirium: fentanyl and midazolam exposure; CYP3A5, ABCB1, and ABCG2 genetic polymorphisms; and inflammatory factors.

Science.gov (United States)

Skrobik, Yoanna; Leger, Caroline; Cossette, Mariève; Michaud, Veronique; Turgeon, Jacques

2013-04-01

Delirium and sedative-induced coma are described as incremental manifestations of cerebral dysfunction. Both may be associated with sedative or opiate doses and pharmacokinetic or pharmacogenetic variables, such as drug plasma levels (exposure), drug metabolism, and/or their transport across the blood-brain barrier. To compare biological and drug treatment characteristics in patients with coma and/or delirium while in the ICU. In 99 patients receiving IV fentanyl, midazolam, or both, we evaluated drug doses, covariates likely to influence drug effects (age, body mass index, and renal and hepatic dysfunction); delirium risk factors; concomitant administration of CYP3A and P-glycoprotein substrates/inhibitors; ABCB1, ABCG2, and CYP3A5 genetic polymorphisms; and fentanyl and midazolam plasma levels. Delirium and coma were evaluated daily. In patients with only coma (n=15), only delirium (n=7), and neither ever (n=14), we measured plasma levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-1RA, IL-6, IL-8, IL-10, IL-17,macrophage inflammatory protein-1β, and monocyte chemotactic protein-1. Time to first coma was associated with fentanyl and midazolam doses (p=0.03 and p=0.01, respectively). The number of days in coma was associated with the number of days of coadministration of CYP3A inhibitors (r=0.30; p=0.006). Plasma levels of fentanyl were higher in patients with clinical coma (3.7±4.7 vs. 2.0±1.8 ng/mL, p=0.0001) as were midazolam plasma levels (1050±2232 vs. 168±249 ng/mL, p=0.0001). Delirium occurrence was unrelated to midazolam administration, cumulative doses, or serum levels. Days with delirium were associated with days of coadministration of P-glycoprotein inhibitor (r=0.35; p=0.0004). Delirious patients had higher levels of the inflammatory mediator IL-6 than comatose patients (129.3 vs. 35.0 pg/mL, p=0.05). Coma is associated with fentanyl and midazolam exposure; delirium is unrelated to midazolam and may be linked to inflammatory status

Formaldehyde concentration in diagnostic patch testing

DEFF Research Database (Denmark)

Trattner, A; Johansen, J D; Menné, T

1998-01-01

Exposure to formaldehyde is common from both consumer products and industry. The reliability of the patch test is essential for the diagnosis of formaldehyde allergy as it is difficult to suspect from the patient's history. The recommended formaldehyde patch test concentration has been reduced over...

Immunoisolation Patch System for Cellular Transplantation

Science.gov (United States)

Wang, Taylor G. (Inventor)

2014-01-01

An immunoisolation patch system, and particularly a patch system comprising multiple immunoisolation microcapsules, each encapsulating biological material such as cells for transplantation, which can be used in the prophylactic and therapeutic treatment of disease in large animals and humans without the need for immunosuppression.

Solubility behavior of narcotic analgesics in aqueous media: solubilities and dissociation constants of morphine, fentanyl, and sufentanil.

Science.gov (United States)

Roy, S D; Flynn, G L

1989-02-01

The pH dependence of the aqueous solubility of morphine, fentanyl, and sufentanil was investigated at 35 degrees C. Dissociation constants and corresponding pKa' values of the drugs were obtained from measured free-base solubilities (determined at high pH's) and the concentrations of saturated solutions at intermediate pH's. Morphine, fentanyl, and sufentanil exhibited pKa' values of 8.08, 8.99, and 8.51, respectively. Over the pH range of 5 to 12.5 the apparent solubilities are determined by the intrinsic solubility of the free base plus the concentration of ionized drug necessary to satisfy the dissociation equilibrium at a given pH. Consequently, the drug concentrations of saturated aqueous solutions fall off precipitously as the pH is raised and ionization is suppressed. Further, at low pH's the aqueous solubility of morphine increased in a linear fashion with increases in the molar strength of citric acid which was added to acidify the medium, suggesting the formation of a soluble morphine-citrate complex.

An observational feasibility study to assess the safety and effectiveness of intranasal fentanyl for radiofrequency ablations of the lumbar facet joints

Directory of Open Access Journals (Sweden)

Bartoszek MW

2017-02-01

Full Text Available Michael W Bartoszek,1 Amy McCoart,2 Kyung-soo Jason Hong,3 Chelsey Haley,2 Krista Beth Highland,4 Anthony R Plunkett1 1Department of Anesthesiology, Womack Army Medical Center, Fort Bragg, NC, 2Clinical Investigations, Defense and Veterans Center for Integrative Pain Management, Henry M. Jackson Foundation, Womack Army Medical Center, Fort Bragg, NC, 3Research Department, The Center for Clinical Research, Sceptor Pain Foundation, Winston Salem, NC, 4Defense and Veterans Center for Integrative Pain Management, Henry M. Jackson Foundation, Uniformed Services University, Bethesda, MD, USA Purpose: The purpose of the present observational, feasibility study is to assess the preliminary safety and effectiveness of intranasal fentanyl for lumbar facet radiofrequency ablation procedures.Patients and methods: This cohort observational study included 23 adult patients. Systolic and diastolic blood pressures, heart rate, oxygen saturation percent, Pasero Opioid-Induced Sedation Scale score, and the Defense and Veterans Pain Rating Scale pain score were assessed prior to the procedure and intranasal fentanyl (100 μg administration and every 15 minutes after administration, up to 60 minutes post administration. Follow-up of patient satisfaction with pain control and treatment was assessed 24 hours after discharge. The primary outcome was safety as evidenced by adverse events. Secondary outcomes included the above-mentioned vital signs and pain ratings.Results: No adverse events occurred in the present study and all participants maintained an acceptable level of awareness throughout the assessment period. One-way repeated measures analyses of covariance tests with Bonferroni-adjusted means indicated that oxygen saturation, blood pressure, and heart rate changed from baseline, whereas pain scores were lower at post-administration levels compared with baseline. Finally, the majority of participants reported being satisfied with pain control and treatment

COMBINE MIDAZOLAM-FENTANYL-KETAMIN FOR EVISERATION SURGERY IN PATIENT WITH MULTIDRUG ALERGY IN ACUTE ON CHRONIC EXCACERBATION OF HIPERSENSITIVITY REACTION

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Putu Agus Surya Panji

2018-06-01

Full Text Available ABSTRACT Multidrug Alergy is a relatively rare imunology abnormality. Generally, it caused by congenital genotype and influence with environment. After treated the acute on chronic exacerbation of hypersensivity tipe 1, and the inflamation can alleviate, the patient schedule of eviseration oculi dextra with general anesthesia. And the opthamologist curious about the proceddure because eviseration need antibiotic to wash the oculi, but there are no antibiotic saved for the patient. For general anesthesia, the patient has no history so we can’t predicted about the anesthetic drug’s allergy. We choose combine ketamine-midazolamadn fentanyl to facilitate the anesthesia. Ketamine significantly reduces the production of inflammatory cytokines without affecting the production of anti-inflammatory cytokines. Fentanyl is the opioid which is the most rarely caused allergy and have strong potential. Midazolam can help the sedation

A New Low-Complexity Patch-based Super-Resolution

DEFF Research Database (Denmark)

Rasti, Pejman; Nasrollahi, Kamal; Orlova, Olga

2017-01-01

through an illumination enhancement process resulting in consistency of illumination between neigh- bour patches. This process is applied to all patches of the LR image. Finally, in order to remove the blocking effect caused by merging the patches, an average of the obtained HR image and the interpolated...

Social familiarity governs prey patch-exploitation, -leaving and inter-patch distribution of the group-living predatory mite Phytoseiulus persimilis.

Science.gov (United States)

Zach, Gernot J; Peneder, Stefan; Strodl, Markus A; Schausberger, Peter

2012-01-01

In group-living animals, social interactions and their effects on other life activities such as foraging are commonly determined by discrimination among group members. Accordingly, many group-living species evolved sophisticated social recognition abilities such as the ability to recognize familiar individuals, i.e. individuals encountered before. Social familiarity may affect within-group interactions and between-group movements. In environments with patchily distributed prey, group-living predators must repeatedly decide whether to stay with the group in a given prey patch or to leave and search for new prey patches and groups. Based on the assumption that in group-living animals social familiarity allows to optimize the performance in other tasks, as for example predicted by limited attention theory, we assessed the influence of social familiarity on prey patch exploitation, patch-leaving, and inter-patch distribution of the group-living, plant-inhabiting predatory mite Phytoseiulus persimilis. P. persimilis is highly specialized on herbivorous spider mite prey such as the two-spotted spider mite Tetranychus urticae, which is patchily distributed on its host plants. We conducted two experiments with (1) groups of juvenile P. persimilis under limited food on interconnected detached leaflets, and (2) groups of adult P. persimilis females under limited food on whole plants. Familiar individuals of both juvenile and adult predator groups were more exploratory and dispersed earlier from a given spider mite patch, occupied more leaves and depleted prey more quickly than individuals of unfamiliar groups. Moreover, familiar juvenile predators had higher survival chances than unfamiliar juveniles. We argue that patch-exploitation and -leaving, and inter-patch dispersion were more favorably coordinated in groups of familiar than unfamiliar predators, alleviating intraspecific competition and improving prey utilization and suppression.

Social familiarity governs prey patch-exploitation, -leaving and inter-patch distribution of the group-living predatory mite Phytoseiulus persimilis.

Directory of Open Access Journals (Sweden)

Gernot J Zach

Full Text Available In group-living animals, social interactions and their effects on other life activities such as foraging are commonly determined by discrimination among group members. Accordingly, many group-living species evolved sophisticated social recognition abilities such as the ability to recognize familiar individuals, i.e. individuals encountered before. Social familiarity may affect within-group interactions and between-group movements. In environments with patchily distributed prey, group-living predators must repeatedly decide whether to stay with the group in a given prey patch or to leave and search for new prey patches and groups.Based on the assumption that in group-living animals social familiarity allows to optimize the performance in other tasks, as for example predicted by limited attention theory, we assessed the influence of social familiarity on prey patch exploitation, patch-leaving, and inter-patch distribution of the group-living, plant-inhabiting predatory mite Phytoseiulus persimilis. P. persimilis is highly specialized on herbivorous spider mite prey such as the two-spotted spider mite Tetranychus urticae, which is patchily distributed on its host plants. We conducted two experiments with (1 groups of juvenile P. persimilis under limited food on interconnected detached leaflets, and (2 groups of adult P. persimilis females under limited food on whole plants. Familiar individuals of both juvenile and adult predator groups were more exploratory and dispersed earlier from a given spider mite patch, occupied more leaves and depleted prey more quickly than individuals of unfamiliar groups. Moreover, familiar juvenile predators had higher survival chances than unfamiliar juveniles.We argue that patch-exploitation and -leaving, and inter-patch dispersion were more favorably coordinated in groups of familiar than unfamiliar predators, alleviating intraspecific competition and improving prey utilization and suppression.

Perturbation analysis for patch occupancy dynamics

Science.gov (United States)

Martin, Julien; Nichols, James D.; McIntyre, Carol L.; Ferraz, Goncalo; Hines, James E.

2009-01-01

Perturbation analysis is a powerful tool to study population and community dynamics. This article describes expressions for sensitivity metrics reflecting changes in equilibrium occupancy resulting from small changes in the vital rates of patch occupancy dynamics (i.e., probabilities of local patch colonization and extinction). We illustrate our approach with a case study of occupancy dynamics of Golden Eagle (Aquila chrysaetos) nesting territories. Examination of the hypothesis of system equilibrium suggests that the system satisfies equilibrium conditions. Estimates of vital rates obtained using patch occupancy models are used to estimate equilibrium patch occupancy of eagles. We then compute estimates of sensitivity metrics and discuss their implications for eagle population ecology and management. Finally, we discuss the intuition underlying our sensitivity metrics and then provide examples of ecological questions that can be addressed using perturbation analyses. For instance, the sensitivity metrics lead to predictions about the relative importance of local colonization and local extinction probabilities in influencing equilibrium occupancy for rare and common species.

Erythema-index of clinical patch test reactions

DEFF Research Database (Denmark)

Jemec, G B; Johansen, J D

1995-01-01

that the method could be used for the grading of eczematous reactions in a clinical setting as well. OBJECTIVE: To assess the usefulness of the erythema index for the quantification of eczematous reactions using the Derma-Spectrometer (Cortex technology, Hadsund, Denmark) in a clinical setting. METHOD......: The erythema index of 56 patch test reactions ranging from +? to +++, was compared to regional controls and negative patch tests (189). The effects of intrumental application pressure was studied in 5 volunteers. Statistical analysis was carried out using Mann-Whitney and Jonckheere-Terpstra tests. RESULTS......: The erythema-index was significantly higher in all degrees of patch test reactions than in uninvolved regional skin or negative patch tests. It also showed a significant positive trend for higher values in +, ++ and +++ reactions (P

A missing factor in chip-based patch clamp assay: gigaseal

International Nuclear Information System (INIS)

Ong, W-L; Yobas, L; Ong, W-Y

2006-01-01

The 'gold' standard in the study of ionic currents across biological membranes is the Patch Clamp method. However, this is a slow, labor and skill intensive process. High throughput patch clamp devices are mainly chip-based. A major challenge in these miniaturized devices is the low rate of 'Gigaseal' formation which is critical in the study of Single Channel effect. In a conventional patch clamp, a pipette moves and patches a fixed cell (cell-adhered patch) which is grown on the bottom of a Petri dish. In the chip-based case, the cells are in suspension and move towards the fixed patch clamp sites (cell-suspended patch). In this study, using the proven conventional patch clamp setup, we investigated the effect of the differences in the cell configurations between the convention patch clamp and cell-based patch clamp. It is shown that adhered cells (as used in the conventional setup) have a much higher rate of gigaseal formation as compared to the cells in suspension (as used in chip-based devices). We postulate that the arrangement of the cytoskeleton within the cell plays a major part in the formation of the gigaseal

Boolean Operations with Prism Algebraic Patches

Science.gov (United States)

Bajaj, Chandrajit; Paoluzzi, Alberto; Portuesi, Simone; Lei, Na; Zhao, Wenqi

2009-01-01

In this paper we discuss a symbolic-numeric algorithm for Boolean operations, closed in the algebra of curved polyhedra whose boundary is triangulated with algebraic patches (A-patches). This approach uses a linear polyhedron as a first approximation of both the arguments and the result. On each triangle of a boundary representation of such linear approximation, a piecewise cubic algebraic interpolant is built, using a C1-continuous prism algebraic patch (prism A-patch) that interpolates the three triangle vertices, with given normal vectors. The boundary representation only stores the vertices of the initial triangulation and their external vertex normals. In order to represent also flat and/or sharp local features, the corresponding normal-per-face and/or normal-per-edge may be also given, respectively. The topology is described by storing, for each curved triangle, the two triples of pointers to incident vertices and to adjacent triangles. For each triangle, a scaffolding prism is built, produced by its extreme vertices and normals, which provides a containment volume for the curved interpolating A-patch. When looking for the result of a regularized Boolean operation, the 0-set of a tri-variate polynomial within each such prism is generated, and intersected with the analogous 0-sets of the other curved polyhedron, when two prisms have non-empty intersection. The intersection curves of the boundaries are traced and used to decompose each boundary into the 3 standard classes of subpatches, denoted in, out and on. While tracing the intersection curves, the locally refined triangulation of intersecting patches is produced, and added to the boundary representation. PMID:21516262

Estradiol Transdermal Patch

Science.gov (United States)

... menopause (change of life; the end of monthly menstrual periods). Transdermal estradiol is also used to prevent ... patch. Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.

COMPARISON OF DEXMEDETOMIDINE, BUPRENORPHINE AND FENTANYL AS AN ADJUVANT TO BUPIVACAINE DURING SPINAL ANAESTHESIA FOR HEMIARTHROPLASTY

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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

Selegiline Transdermal Patch

Science.gov (United States)

... patch from direct heat such as heating pads, electric blankets, heat lamps, saunas, hot tubs, and heated ... may make you drowsy. Do not drive a car or operate machinery until you know how this ...

Testosterone Transdermal Patch

Science.gov (United States)

... one else can use it accidentally or on purpose. Keep track of how many patches are left ... to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in ...

Rotigotine Transdermal Patch

Science.gov (United States)

... physical activity. If the edges of the patch lift, use a bandage tape to re-secure it ... burns on your skin if you are having magnetic resonance imaging (MRI; a radiology technique designed to ...

Methylphenidate Transdermal Patch

Science.gov (United States)

... for ADHD, which may include counseling and special education. Make sure to follow all of your doctor's ... that was covered by the patch seizures motion tics or verbal tics believing things that are not ...

Black-hole excision with multiple grid patches

Energy Technology Data Exchange (ETDEWEB)

Thornburg, Jonathan [Max-Planck-Institut fuer Gravitationsphysik, Albert-Einstein-Institut, Am Muehlenberg 1, D-14476 Golm (Germany)

2004-08-07

When using black-hole excision to numerically evolve a black-hole spacetime with no continuous symmetries, most 3 + 1 finite differencing codes use a Cartesian grid. It is difficult to do excision on such a grid because the natural r = constant excision surface must be approximated either by a very different shape such as a contained cube, or by an irregular and non-smooth 'LEGO{sup 1} sphere' which may introduce numerical instabilities into the evolution. In this paper I describe an alternate scheme which uses multiple {l_brace}r x (angular coordinates){r_brace} grid patches, each patch using a different (nonsingular) choice of angular coordinates. This allows excision on a smooth r = constant 2-sphere. I discuss the key design choices in such a multiple-patch scheme, including the choice of ghost-zone versus internal-boundary treatment of the interpatch boundaries (I use a ghost-zone scheme), the number and shape of the patches (I use a 6-patch 'inflated-cube' scheme), the details of how the ghost zones are 'synchronized' by interpolation from neighbouring patches, the tensor basis for the Einstein equations in each patch, and the handling of non-tensor field variables such as the BSSN {gamma}-tilde{sup i} (I use a scheme which requires ghost zones which are twice as wide for the BSSN conformal factor {phi} as for {gamma}-tilde{sup i} and the other BSSN field variables). I present sample numerical results from a prototype implementation of this scheme. This code simulates the time evolution of the (asymptotically flat) spacetime around a single (excised) black hole, using fourth-order finite differencing in space and time. Using Kerr initial data with J/m{sup 2} = 0.6, I present evolutions to t {approx}> 1500m. The lifetime of these evolutions appears to be limited only by outer boundary instabilities, not by any excision instabilities or by any problems inherent to the multiple-patch scheme.

Black-hole excision with multiple grid patches

International Nuclear Information System (INIS)

Thornburg, Jonathan

2004-01-01

When using black-hole excision to numerically evolve a black-hole spacetime with no continuous symmetries, most 3 + 1 finite differencing codes use a Cartesian grid. It is difficult to do excision on such a grid because the natural r = constant excision surface must be approximated either by a very different shape such as a contained cube, or by an irregular and non-smooth 'LEGO 1 sphere' which may introduce numerical instabilities into the evolution. In this paper I describe an alternate scheme which uses multiple {r x (angular coordinates)} grid patches, each patch using a different (nonsingular) choice of angular coordinates. This allows excision on a smooth r = constant 2-sphere. I discuss the key design choices in such a multiple-patch scheme, including the choice of ghost-zone versus internal-boundary treatment of the interpatch boundaries (I use a ghost-zone scheme), the number and shape of the patches (I use a 6-patch 'inflated-cube' scheme), the details of how the ghost zones are 'synchronized' by interpolation from neighbouring patches, the tensor basis for the Einstein equations in each patch, and the handling of non-tensor field variables such as the BSSN Γ-tilde i (I use a scheme which requires ghost zones which are twice as wide for the BSSN conformal factor φ as for Γ-tilde i and the other BSSN field variables). I present sample numerical results from a prototype implementation of this scheme. This code simulates the time evolution of the (asymptotically flat) spacetime around a single (excised) black hole, using fourth-order finite differencing in space and time. Using Kerr initial data with J/m 2 = 0.6, I present evolutions to t ∼> 1500m. The lifetime of these evolutions appears to be limited only by outer boundary instabilities, not by any excision instabilities or by any problems inherent to the multiple-patch scheme

Prior knowledge about spatial pattern affects patch assessment rather than movement between patches in tactile-feeding Mallard

NARCIS (Netherlands)

Klaassen, R.H.G.; Nolet, B.A.; Van Leeuwen, C.H.A.

2007-01-01

1. Heterogeneity in food abundance allows a forager to concentrate foraging effort in patches that are rich in food. This might be problematic when food is cryptic, as the content of patches is unknown prior to foraging. In such case knowledge about the spatial pattern in the distribution of food

Necrotic patches affect Acropora palmata (Scleractinia: Acroporidae) in the Mexican Caribbean.

Science.gov (United States)

Rodríguez-Martínez, R E; Banaszak, A T; Jordán-Dahlgren, E

2001-12-05

An outbreak of necrotic patches was observed affecting Acropora palmata in the Mexican Caribbean in the summer of 1999. This study documents the tissue loss produced by these patches. Following a marked initial increase in the number of patches, there was a decrease in the appearance of new patches but the size of the patches increased throughout the study. In some cases patches expanded but in most cases they enlarged due to fusion of 2 or more patches. Patches recovered but not sufficiently to overcome damage in most colonies surveyed. Percentage tissue loss does not appear to be directly related to temperature but may be related to a combination of factors associated with prolonged summer doldrum-like conditions. The necrotic patch syndrome can have a substantial impact in tissue loss in affected A. palmata colonies.

Physically Connected Stacked Patch Antenna Design with 100% Bandwidth

KAUST Repository

Klionovski, Kirill; Shamim, Atif

2017-01-01

Typically, stacked patch antennas are parasitically coupled and provide larger bandwidth than a single patch antenna. Here, we show a stacked patch antenna design where square patches with semi-circular cutouts are physically connected to each other. This arrangement provides 100% bandwidth from 23.9–72.2 GHz with consistent high gain (5 dBi or more) across the entire bandwidth. In another variation, a single patch loaded with a superstrate provides 83.5% bandwidth from 25.6–62.3 GHz. The mechanism of bandwidth enhancement is explained through electromagnetic simulations. Measured reflection coefficient, radiation patterns and gain results confirm the extremely wideband performance of the design.

Physically Connected Stacked Patch Antenna Design with 100% Bandwidth

KAUST Repository

Klionovski, Kirill

2017-11-01

Typically, stacked patch antennas are parasitically coupled and provide larger bandwidth than a single patch antenna. Here, we show a stacked patch antenna design where square patches with semi-circular cutouts are physically connected to each other. This arrangement provides 100% bandwidth from 23.9–72.2 GHz with consistent high gain (5 dBi or more) across the entire bandwidth. In another variation, a single patch loaded with a superstrate provides 83.5% bandwidth from 25.6–62.3 GHz. The mechanism of bandwidth enhancement is explained through electromagnetic simulations. Measured reflection coefficient, radiation patterns and gain results confirm the extremely wideband performance of the design.

Experimental patch testing with chromium-coated materials

DEFF Research Database (Denmark)

Bregnbak, David; Thyssen, Jacob P; Jellesen, Morten Stendahl

2017-01-01

Chromium coatings on metal alloys can be decorative, and prevent corrosion and metal ion release. We recently showed that handling of a chromium-containing disc resulted in chromium deposition on the skin. To examine patch test reactivity to chromium-coated discs. We included 15 patients: 10...... chromium-allergic patients, and 5 patients without chromium allergy. All were patch tested with potassium dichromate, cobalt chloride, nickel sulfate, and nine different metallic discs. The chromium-allergic patients were also patch tested with serial dilutions of potassium dichromate. Positive...

Effects of patch size on feeding associations in muriquis (Brachyteles arachnoides).

Science.gov (United States)

Strier, K B

1989-01-01

Data were collected on one group of muriquis, or woolly spider monkeys (Brachyteles arachnoides) during a 14-month study at Fazenda Montes Claros, Minas Gerais, Brazil to examine the effects of food patch size on muriqui feeding associations. Muriqui food patches were larger than expected from the availability of patch sizes in the forest; fruit patches were significantly larger than leaf patches. Feeding aggregate size, the maximum number of simultaneous occupants, and patch occupancy time were positively related to the size of fruit patches. However, a greater number of individuals fed at leaf sources than expected from the size of these patches. Adult females tended to feed alone in patches more often than males, whereas males tended to feed in single-sexed groups more often than females. Yet in neither case were these differences statistically significant.

Microneedle patches for vaccination in developing countries.

Science.gov (United States)

Arya, Jaya; Prausnitz, Mark R

2016-10-28

Millions of people die of infectious diseases each year, mostly in developing countries, which could largely be prevented by the use of vaccines. While immunization rates have risen since the introduction of the Expanded Program on Immunization (EPI), there remain major challenges to more effective vaccination in developing countries. As a possible solution, microneedle patches containing an array of micron-sized needles on an adhesive backing have been developed to be used for vaccine delivery to the skin. These microneedle patches can be easily and painlessly applied by pressing against the skin and, in some designs, do not leave behind sharps waste. The patches are single-dose, do not require reconstitution, are easy to administer, have reduced size to simplify storage, transportation and waste disposal, and offer the possibility of improved vaccine immunogenicity, dose sparing and thermostability. This review summarizes vaccination challenges in developing countries and discusses advantages that microneedle patches offer for vaccination to address these challenges. We conclude that microneedle patches offer a powerful new technology that can enable more effective vaccination in developing countries. Copyright © 2015. Published by Elsevier B.V.

Lidocaine patches reduce pain in trauma patients with rib fractures.

Science.gov (United States)

Zink, Karen A; Mayberry, John C; Peck, Ellen G; Schreiber, Martin A

2011-04-01

Rib fracture pain is notoriously difficult to manage. The lidocaine patch is effective in other pain scenarios with an excellent safety profile. This study assesses the efficacy of lidocaine patches for treating rib fracture pain. A prospectively gathered cohort of patients with rib fracture was retrospectively analyzed for use of lidocaine patches. Patients treated with lidocaine patches were matched to control subjects treated without patches. Subjective pain reports and narcotic use before and after patch placement, or equivalent time points for control subjects, were gathered from the chart. All patients underwent long-term follow-up, including a McGill Pain Questionnaire (MPQ). Twenty-nine patients with lidocaine patches (LP) and 29 matched control subjects (C) were analyzed. During the 24 hours before patch placement, pain scores and narcotic use were similar (LP 5.3, C 4.6, P = 0.19 and LP 51, C 32 mg morphine, P = 0.17). In the 24 hours after patch placement, LP patients had a greater decrease in pain scores (LP 1.2, C 0.0, P = 0.01) with no change in narcotic use (LP -8.4, C 0.5-mg change in morphine, P = 0.25). At 60 days, LP patients had a lower MPQ pain score (LP 7.7, C 12.2, P rib fracture pain. Lidocaine patches resulted in a sustained reduction in pain, outlasting the duration of therapy.

Patch layout generation by detecting feature networks

KAUST Repository

Cao, Yuanhao; Yan, Dongming; Wonka, Peter

2015-01-01

The patch layout of 3D surfaces reveals the high-level geometric and topological structures. In this paper, we study the patch layout computation by detecting and enclosing feature loops on surfaces. We present a hybrid framework which combines

Mating success of males with and without wing patch in Drosophila biarmipes.

Science.gov (United States)

Hegde, S N; Chethan, B K; Krishna, M S

2005-10-01

Some males of D. biarmipes--synonym of D. rajasekari and D. raychaudhuri have a black patch on the wing. The patch extends from the apical margin of wing to the third longitudinal vein. Field and laboratory studies have been carried out in D. biarmipes to study role of male's wing patch in mating success. The field study shows that nature favors D. biarmipes males with patch. Although males without patch mated, males with patch have higher mating success suggesting the role of wing patch during courtship. Further, among mating males, males with patch had longer wings than males without patch. During courtship, males with patch oriented and mated faster; performed courtship acts such as tapping, scissoring, vibration, licking and twist dance more times than males without patch in both competitive and non-competitive situations. The results indicate that there is a casual relationship between the presence of wing patch, mating speed and success. Also there is a correlation between presence of wing patch, size of the flies and mating success.

Development and characterization of mucoadhesive buccal patches of salbutamol sulphate.

Science.gov (United States)

Patel, Rajesh Singh; Poddar, S S

2009-01-01

Mucoadhesive patch releasing the drug in the oral cavity at predetermined rate may present distinct advantages over traditional dosage forms such as tablets, gels and solutions. The present study was concerned with the preparation and evaluation of mucoadhesive buccal patches for the controlled systemic delivery of Salbutamol sulphate to avoid first pass hepatic metabolism. The developed patches were evaluated for the physicochemical, mechanical and drug release characteristics. The patches showed desired mechanical and physicochemical properties to withstand environment of oral cavity. The in-vitro release study showed that patches could deliver drug to the oral mucosa for a period of 7 h. the patches exhibited adequate stability when tested under accelerated conditions.

Correlation of open cell-attached and excised patch clamp techniques.

Science.gov (United States)

Filipovic, D; Hayslett, J P

1995-11-01

The excised patch clamp configuration provides a unique technique for some types of single channel analyses, but maintenance of stable, long-lasting preparations may be confounded by rundown and/or rapid loss of seal. Studies were performed on the amiloride-sensitive Na+ channel, located on the apical surface of A6 cells, to determine whether the nystatin-induced open cell-attached patch could serve as an alternative configuration. Compared to excised inside-out patches, stable preparations were achieved more readily with the open cell-attached patch (9% vs. 56% of attempts). In both preparations, the current voltage (I-V) relation was linear, current amplitudes were equal at opposite equivalent clamped voltages, and Erev was zero in symmetrical Na+ solutions, indicating similar Na+ activities on the cytosolic and external surfaces of the patch. Moreover, there was no evidence that nystatin altered channel activity in the patch because slope conductance (3-4pS) and Erev (75 mV), when the bath was perfused with a high K:low Na solution (ENa = 80 mV), were nearly equal in both patch configurations. Our results therefore indicate that the nystatin-induced open cell-attached patch can serve as an alternative approach to the excised inside-out patch when experiments require modulation of univalent ions in the cytosol.

A new low-complexity patch-based image super-resolution

DEFF Research Database (Denmark)

Rasti, Pejman; Nasrollahi, Kamal; Orlova, Olga

2017-01-01

through an illumination enhancement process resulting in consistency of illumination between neigh- bour patches. This process is applied to all patches of the LR image. Finally, in order to remove the blocking effect caused by merging the patches, an average of the obtained HR image and the interpolated...

Force-controlled patch clamp of beating cardiac cells.

Science.gov (United States)

Ossola, Dario; Amarouch, Mohamed-Yassine; Behr, Pascal; Vörös, János; Abriel, Hugues; Zambelli, Tomaso

2015-03-11

From its invention in the 1970s, the patch clamp technique is the gold standard in electrophysiology research and drug screening because it is the only tool enabling accurate investigation of voltage-gated ion channels, which are responsible for action potentials. Because of its key role in drug screening, innovation efforts are being made to reduce its complexity toward more automated systems. While some of these new approaches are being adopted in pharmaceutical companies, conventional patch-clamp remains unmatched in fundamental research due to its versatility. Here, we merged the patch clamp and atomic force microscope (AFM) techniques, thus equipping the patch-clamp with the sensitive AFM force control. This was possible using the FluidFM, a force-controlled nanopipette based on microchanneled AFM cantilevers. First, the compatibility of the system with patch-clamp electronics and its ability to record the activity of voltage-gated ion channels in whole-cell configuration was demonstrated with sodium (NaV1.5) channels. Second, we showed the feasibility of simultaneous recording of membrane current and force development during contraction of isolated cardiomyocytes. Force feedback allowed for a gentle and stable contact between AFM tip and cell membrane enabling serial patch clamping and injection without apparent cell damage.

Living cardiac patch: the elixir for cardiac regeneration.

Science.gov (United States)

Lakshmanan, Rajesh; Krishnan, Uma Maheswari; Sethuraman, Swaminathan

2012-12-01

A thorough understanding of the cellular and muscle fiber orientation in left ventricular cardiac tissue is of paramount importance for the generation of artificial cardiac patches to treat the ischemic myocardium. The major challenge faced during cardiac patch engineering is to choose a perfect combination of three entities; cells, scaffolds and signaling molecules comprising the tissue engineering triad for repair and regeneration. This review provides an overview of various scaffold materials, their mechanical properties and fabrication methods utilized in cardiac patch engineering. Stem cell therapies in clinical trials and the commercially available cardiac patch materials were summarized in an attempt to provide a recent perspective in the treatment of heart failure. Various tissue engineering strategies employed thus far to construct viable thick cardiac patches is schematically illustrated. Though many strategies have been proposed for fabrication of various cardiac scaffold materials, the stage and severity of the disease condition demands the incorporation of additional cues in a suitable scaffold material. The scaffold may be nanofibrous patch, hydrogel or custom designed films. Integration of stem cells and biomolecular cues along with the scaffold may provide the right microenvironment for the repair of unhealthy left ventricular tissue as well as promote its regeneration.

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

Dermoscopy of shagreen patch: A first report

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Shivanand Gundalli

2015-07-01

Full Text Available The name is derived from French phrase peau chagrinee which is usually found on lower back, buttock and thigh. The major manifestations of Tuberous sclerosis include skin lesions in more than 95%, mental retardation in approximately 50%, autism, seizures in approximately 85%. The incidence at birth is estimated to be 1 in 5800. We report case of shagreen patch in a 27 year female which is present since birth. However there is no history of seizures or consanginous marriage in our case. Associated features are naevus comedonicus and naevus collagenosis, facial angiofibroma. Shagreen patch are present in mandibular area of face. Although, diagnosis is easy, it can be mistaken for inflammatory verrucous epidermal nevus, plaques of other inflammatory skin conditions. Diagnosis is usually on clinical background. Sometimes biopsy is necessary to confirm the diagnosis. Dermoscopy, a non-invasive, in vivo technique for the microscopic examination of pigmented skin lesions, has the potential to improve the diagnostic accuracy. Dermoscopy of Shagreen patch showed reddish-brown strands with white dots giving a cobblestone appearance It can be utilized as a diagnostic aide in the diagnosis of Shagreen patch. Authors evaluated the dermoscopic patterns of Shagreen patch and hence, it is useful in diagnosis.

Patch dynamics of a foraging assemblage of bees.

Science.gov (United States)

Wright, David Hamilton

1985-03-01

The composition and dynamics of foraging assemblages of bees were examined from the standpoint of species-level arrival and departure processes in patches of flowers. Experiments with bees visiting 4 different species of flowers in subalpine meadows in Colorado gave the following results: 1) In enriched patches the rates of departure of bees were reduced, resulting in increases in both the number of bees per species and the average number of species present. 2) The reduction in bee departure rates from enriched patches was due to mechanical factors-increased flower handling time, and to behavioral factors-an increase in the number of flowers visited per inflorescence and in the number of inflorescences visited per patch. Bees foraging in enriched patches could collect nectar 30-45% faster than those foraging in control patches. 3) The quantitative changes in foraging assemblages due to enrichment, in terms of means and variances of species population sizes, fraction of time a species was present in a patch, and in mean and variance of the number of species present, were in reasonable agreement with predictions drawn from queuing theory and studies in island biogeography. 4) Experiments performed with 2 species of flowers with different corolla tube lengths demonstrated that manipulation of resources of differing availability had unequal effects on particular subsets of the larger foraging community. The arrival-departure process of bees on flowers and the immigration-extinction process of species on islands are contrasted, and the value of the stochastic, species-level approach to community composition is briefly discussed.

Patch Type Granuloma Annulare Imitating Cutaneous T-Cell Lymphoma

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Şeval Doğruk Kaçar

2015-03-01

Full Text Available Granuloma annulare (GA is a benign inflammatory skin disease with distinct clinical and histopathological findings. Patch type GA is described with erythematous patches beyond the classical clinical appearance and an interstitial pattern is observed without histopathologically granulomas with disseminated histiocytes among collagen bundles and vessels. Here we report 46 year old woman diagnosed as patch type GA after a punch biopsy performed from the annular bordered patches in belly area, which is a classical area for mycosis fungoides (MF evolution, and lesions increasingly spreading out within a 2 year period.

Quantitative Analysis of Range Image Patches by NEB Method

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Wang Wen

2017-01-01

Full Text Available In this paper we analyze sampled high dimensional data with the NEB method from a range image database. Select a large random sample of log-valued, high contrast, normalized, 8×8 range image patches from the Brown database. We make a density estimator and we establish 1-dimensional cell complexes from the range image patch data. We find topological properties of 8×8 range image patches, prove that there exist two types of subsets of 8×8 range image patches modelled as a circle.

Laparoscopic repair of perforated peptic ulcer: patch versus simple closure.

Science.gov (United States)

Abd Ellatif, M E; Salama, A F; Elezaby, A F; El-Kaffas, H F; Hassan, A; Magdy, A; Abdallah, E; El-Morsy, G

2013-01-01

Laparoscopic correction of perforated peptic ulcer (PPU) has become an accepted way of management. Patch omentoplasty stayed for decades the main method of repair. The goal of the present study was to evaluate whether laparoscopic simple repair of PPU is as safe as patch omentoplasty. Since June 2005, 179 consecutive patients of PPU were treated by laparoscopic repair at our centers. We conducted a retrospective chart review in December 2012. Group I (patch group) included patients who were treated with standard patch omentoplasty. Group II (non-patch group) included patients who received simple repair without patch. From June 2007 to Dec. 2012, 179 consecutive patients of PPU who were treated by laparoscopic repair at our centers were enrolled in this multi-center retrospective study. 108 patients belong to patch group. While 71 patients were treated with laparoscopic simple repair. Operative time was significantly shorter in group II (non patch) (p = 0.01). No patient was converted to laparotomy. There was no difference in age, gender, ASA score, surgical risk (Boey's) score, and incidence of co-morbidities. Both groups were comparable in terms of hospital stay, time to resume oral intake, postoperative complications and surgical outcomes. Laparoscopic simple repair of PPU is a safe procedure compared with the traditional patch omentoplasty in presence of certain selection criteria. Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Effect of weed patch size on seed removal by harvester ants

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Westermann, Paula R.

2014-02-01

Full Text Available In dryland cereals in North-eastern Spain, the harvester ant, Messor barbarus L., is responsible for removal of a large proportion of the newly produced weed seeds (40-100%. The probability that seeds will be found by the ants may be influenced by weed patch size. To investigate this source of variability, 30 seed patches were created in each of three, 50 × 50 m, blocks in a cereal field after harvest, by sequentially seeding (10, 16 and 17 August 2010 with 2000 seeds m-2 of Avena sativa L.. Patch size varied from 0.25 to 9 m2. Twenty four hours after seeding, the remaining seeds were collected and seed removal rates estimated. Average seed removal rate was lowest in the smallest (78-94% and highest in the largest patches (99-100%. Differences were mainly caused by the fact that some of the smaller patches (9.7% were not found. However, when patches were found, they were exploited at equal rates (98-100%. As predicted, the probability of finding a patch increased slightly, but significantly, with increasing patch size. When a patch was found, it was almost always fully exploited, resulting in very high seed removal rates, irrespective of patch size. These results indicate that the size of the seed patch is only a minor source of variation influencing this form of biological control of weeds.

Intravenous patient-controlled fentanyl with and without transversus abdominis plane block in cirrhotic patients post liver resection

Directory of Open Access Journals (Sweden)

Serag Eldin M

2014-05-01

Full Text Available Manar Serag Eldin,1 Fatma Mahmoud,1 Rabab El Hassan,2 Mohamed Abdel Raouf,1 Mohamed H Afifi,2 Khaled Yassen,1 Wesam Morad31Department of Anaesthesia, Liver Institute, 2Department of Anaesthesia, Faculty of Medicine, 3Department of Community Medicine and Public Health, Liver Institute, Menoufiya University, Shebin El-Kom, EgyptBackground: Coagulation changes can complicate liver resection, particularly in patients with cirrhosis. The aim of this prospective hospital-based comparative study was to compare the postoperative analgesic efficacy of intravenous fentanyl patient-controlled analgesia (IVPCA with and without transversus abdominis plane (TAP block.Methods: Fifty patients with Child’s A cirrhosis undergoing liver resection were randomly divided into two groups for postoperative analgesia, ie, an IVPCA group receiving a 10 µg/mL fentanyl bolus of 15 µg with a 10-minute lockout and a maximum hourly dose of 90 µg, and an IVPCA + TAP group that additionally received TAP block (15 mL of 0.375% bupivacaine on both sides via a posterior approach with ultrasound guidance before skin incision. Postoperatively, bolus injections of bupivacaine 0.375% were given every 8 hours through a TAP catheter inserted by the surgeon in the open space during closure of the inverted L-shaped right subcostal with midline extension (subcostal approach guided by the visual analog scale score (<3, 5 mL; 3 to <6, 10 mL; 6–10, 15–20 mL according to weight (maximum 2 mg/kg. The top-up dosage of local anesthetic could be omitted if the patient was not in pain. Coagulation was monitored using standard coagulation tests.Results: Age, weight, and sex were comparable between the groups (P<0.05. The visual analog scale score was significantly lower at 12, 18, 24, 48, and 72 hours (P<0.01 in IVPCA + TAP group. The Ramsay sedation score was lower only after 72 hours in the IVPCA + TAP group when compared with the IVPCA group (1.57±0.74 versus 2.2±0.41, respectively, P

Patch time allocation and oviposition behavior in response to patch quality and the presence of a generalist predator in Meteorus pulchricornis (Hymenoptera: Braconidae).

Science.gov (United States)

Sheng, Sheng; Ling, Meng; Fu-An, Wu; Baoping, Li

2015-01-01

Foraging parasitoids often must estimate local risk of predation just as they must estimate local patch value. Here, we investigate the effects a generalist predator Chlaenius bioculatus (Coleoptera: Carabidae), has on the oviposition behavior and the patch residence decisions of a solitary parasitoid Meteorus pulchricornis (Hymenoptera: Braconidae) in response to the varying host quality of Spodoptera litura (Lepidoptera: Noctuidae) larvae (L2 and L4). M. pulchricornis attacked more L4 than on L2 hosts, with the difference in attack rate varying depending on predation treatments, greater in the presence (either actively feeding or not) of the predator than in the absence of it. The parasitoid attacked fewer L2 and L4 hosts when the predator was actively feeding than when it was not feeding or not present in the patch. M. pulchricornis decreased the patch leaving tendency with increasing rejections of hosts, but increased the tendency in response to the presence of the predator as compared with the absence of it, and furthermore, increased the patch leaving tendency when the predator was actively feeding as compared with when it was not. Our study suggests that M. pulchricornis can exploit high quality patches while minimizing predation risk, by attacking more hosts in high quality patches while reducing total patch time in response to risk of predation. © The Author 2015. Published by Oxford University Press on behalf of the Entomological Society of America.

Multi-patch matching for person re-identification

Science.gov (United States)

Labidi, Hocine; Luo, Sen-Lin; Boubekeur, Mohamed B.; Benlefki, Tarek

2015-08-01

Recognizing a target object across non-overlapping distributed cameras is known in the computer vision community as the problem of person re-identification. In this paper, a multi-patch matching method for person reidentification is presented. Starting from the assumption that: the appearance (clothes) of a person does not change during the time of passing in different cameras field of view , which means the regions with the same color in target image will be identical while crossing cameras. First, we extract distinctive features in the training procedure, where each image target is devised into small patches, the SIFT features and LAB color histograms are computed for each patch. Then we use the KNN approach to detect group of patches with high similarity in the target image and then we use a bi-directional weighted group matching mechanism for the re-identification. Experiments on a challenging VIPeR dataset show that the performances of the proposed method outperform several baselines and state of the art approaches.

EFFECTS OF PREANESTHETIC SINGLE DOSE INTRAVENOUS DEXMEDETOMIDINE VERSUS FENTANYL ON HEMODYNAMIC RESPONSE TO ENDOTRACHEAL INTUBATION-A CLINICAL COMPARATIVE STUDY

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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.

Scale-adaptive Local Patches for Robust Visual Object Tracking

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Kang Sun

2014-04-01

Full Text Available This paper discusses the problem of robustly tracking objects which undergo rapid and dramatic scale changes. To remove the weakness of global appearance models, we present a novel scheme that combines object’s global and local appearance features. The local feature is a set of local patches that geometrically constrain the changes in the target’s appearance. In order to adapt to the object’s geometric deformation, the local patches could be removed and added online. The addition of these patches is constrained by the global features such as color, texture and motion. The global visual features are updated via the stable local patches during tracking. To deal with scale changes, we adapt the scale of patches in addition to adapting the object bound box. We evaluate our method by comparing it to several state-of-the-art trackers on publicly available datasets. The experimental results on challenging sequences confirm that, by using this scale-adaptive local patches and global properties, our tracker outperforms the related trackers in many cases by having smaller failure rate as well as better accuracy.

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

Rabies vaccination in dogs using a dissolving microneedle patch.

Science.gov (United States)

Arya, Jaya M; Dewitt, Kristopher; Scott-Garrard, Maya; Chiang, Yu-Wei; Prausnitz, Mark R

2016-10-10

Because humans get rabies primarily through dog bites, stray dog population control and mass or mandatory vaccination of domestic dogs and other animals has virtually eliminated human rabies in industrialized countries. However, thousands of people in developing countries die of rabies each year due to the inability to control dog populations and implement mass vaccination because of financial, logistical and other challenges. The availability of an easier-to-administer and more cost-effective vaccine may help to address some of these issues. Here, we propose the use of dissolving microneedle patches for simple and potentially cost-effective rabies vaccination, and assess the safety and immunogenicity of microneedle patch vaccination using a rabies DNA vaccine in dogs. The vaccine was stable upon formulation and storage for at least 3weeks at 4°C in a microneedle patch. For vaccination, the patches were applied to the inner ear by hand without an applicator. Microneedle patches were well tolerated in the skin, with mild erythema, minimal wheal formation and complete resolution of skin reactions within 7days, and generated no systemic adverse events. Microneedle patches were at least as immunogenic as intramuscular injection at the same dose, as demonstrated by similar serum neutralizing antibody titers. A ten-fold lower vaccine dose administered by microneedle patch generated a weaker immune response compared to full-dose intramuscular vaccination. We conclude that dissolving microneedle patches may provide an innovative approach to mass vaccination of dogs. Copyright © 2016 Elsevier B.V. All rights reserved.

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

OpenAIRE

P K Dilesh; S Eapen; S Kiran; Vivek Chopra

2014-01-01

Context: Combined spinal epidural (CSE) analgesia technique is effective for labor analgesia and various concentrations of bupivacaine and lipophilic opioids like fentanyl have been studied. Dexmedetomidine is a highly selective alpha 2 adrenoreceptor agonist with analgesic properties and has been used intrathecally with bupivacaine for prolonged postoperative analgesia. Recent reviews have shown that it is highly lipophilic and does not cross placenta significantly. Aim: The aim of this s...

Fine-Tuning on the Effective Patch Radius Expression of the Circular Microstrip Patch Antennas

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A. E. Yilmaz

2010-09-01

Full Text Available In this study, the effective patch radius expression for the circular microstrip antennas is improved by means of several manipulations. Departing from previously proposed equations in the literature, one of the most accurate equations is picked up, and this equation is fine-tuned by means of Particle Swarm Optimization technique. Throughout the study, impacts of other parameters (such as the definition of the fitness/objective function, the degree-of-freedom in the proposed effective patch radius expression, the number of measured resonant frequency values are observed in a controlled manner. Finally, about 3% additional improvement is achieved over a very accurate formula, which was proposed earlier.

Tolerability, usability and acceptability of dissolving microneedle patch administration in human subjects.

Science.gov (United States)

Arya, Jaya; Henry, Sebastien; Kalluri, Haripriya; McAllister, Devin V; Pewin, Winston P; Prausnitz, Mark R

2017-06-01

To support translation of microneedle patches from pre-clinical development into clinical trials, this study examined the effect of microneedle patch application on local skin reactions, reliability of use and acceptability to patients. Placebo patches containing dissolving microneedles were administered to fifteen human participants. Microneedle patches were well tolerated in the skin with no pain or swelling and only mild erythema localized to the site of patch administration that resolved fully within seven days. Microneedle patches could be administered by hand without the need of an applicator and delivery efficiencies were similar for investigator-administration and self-administration. Microneedle patch administration was not considered painful and the large majority of subjects were somewhat or fully confident that they self-administered patches correctly. Microneedle patches were overwhelmingly preferred over conventional needle and syringe injection. Altogether, these results demonstrate that dissolving microneedle patches were well tolerated, easily usable and strongly accepted by human subjects, which will facilitate further clinical translation of this technology. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mechanism of inhibition of the tumor suppressor Patched by Sonic Hedgehog.

Science.gov (United States)

Tukachinsky, Hanna; Petrov, Kostadin; Watanabe, Miyako; Salic, Adrian

2016-10-04

The Hedgehog cell-cell signaling pathway is crucial for animal development, and its misregulation is implicated in numerous birth defects and cancers. In unstimulated cells, pathway activity is inhibited by the tumor suppressor membrane protein, Patched. Hedgehog signaling is triggered by the secreted Hedgehog ligand, which binds and inhibits Patched, thus setting in motion the downstream events in signal transduction. Despite its critical importance, the mechanism by which Hedgehog antagonizes Patched has remained unknown. Here, we show that vertebrate Patched1 inhibition is caused by direct, palmitate-dependent interaction with the Sonic Hedgehog ligand. We find that a short palmitoylated N-terminal fragment of Sonic Hedgehog binds Patched1 and, strikingly, is sufficient to inhibit it and to activate signaling. The rest of Sonic Hedgehog confers high-affinity Patched1 binding and internalization through a distinct binding site, but, surprisingly, it is not absolutely required for signaling. The palmitate-dependent interaction with Patched1 is specifically impaired in a Sonic Hedgehog mutant causing human holoprosencephaly, the most frequent congenital brain malformation, explaining its drastically reduced potency. The palmitate-dependent interaction is also abolished in constitutively inhibited Patched1 point mutants causing the Gorlin cancer syndrome, suggesting that they might adopt a conformation distinct from the wild type. Our data demonstrate that Sonic Hedgehog signals via the palmitate-dependent arm of a two-pronged contact with Patched1. Furthermore, our results suggest that, during Hedgehog signaling, ligand binding inhibits Patched by trapping it in an inactive conformation, a mechanism that explains the dramatically reduced activity of oncogenic Patched1 mutants.

Dye-enhanced protein solders and patches in laser-assisted tissue welding.

Science.gov (United States)

Small, W; Heredia, N J; Maitland, D J; Da Silva, L B; Matthews, D L

1997-01-01

This study examines the use of dye-enhanced protein bonding agents in 805 nm diode laser-assisted tissue welding. A comparison of an albumin liquid solder and collagen solid-matrix patches used to repair arteriotomies in an in vitro porcine model is presented. Extrinsic bonding media in the form of solders and patches have been used to enhance the practice of laser tissue welding. Preferential absorption of the laser wavelength has been achieved by the incorporation of chromophores. Both the solder and the patch included indocyanine green dye (ICG) to absorb the 805 nm continuous-wave diode laser light used to perform the welds. Solder-mediated welds were divided into two groups (high power/short exposure and low power/long exposure), and the patches were divided into three thickness groups ranging from 0.1 to 1.3 mm. The power used to activate the patches was constant, but the exposure time was increased with patch thickness. Burst pressure results indicated that solder-mediated and patched welds yielded similar average burst strengths in most cases, but the patches provided a higher success rate (i.e., more often exceeded 150 mmHg) and were more consistent (i.e., smaller standard deviation) than the solder. The strongest welds were obtained using 1.0-1.3 mm thick patches, while the high power/short exposure solder group was the weakest. Though the solder and patches yielded similar acute weld strengths, the solid-matrix patches facilitated the welding process and provided consistently strong welds. The material properties of the extrinsic agents influenced their performance.

Generic Patch Inference

DEFF Research Database (Denmark)

Andersen, Jesper; Lawall, Julia Laetitia

2008-01-01

A key issue in maintaining Linux device drivers is the need to update drivers in response to evolutions in Linux internal libraries. Currently, there is little tool support for performing and documenting such changes. In this paper we present a tool, spfind, that identifies common changes made...... developers can use it to extract an abstract representation of the set of changes that others have made. Our experiments on recent changes in Linux show that the inferred generic patches are more concise than the corresponding patches found in commits to the Linux source tree while being safe with respect...

REMIFENTANIL VS FENTANYL DURING DAY CASE DENTAL SURGERY IN PEOPLE WITH SPECIAL NEEDS: A COMPARATIVE, PILOT STUDY OF THEIR EFFECT ON STRESS RESPONSE AND POSTOPERATIVE PAIN.

Science.gov (United States)

Sklika, Eirini; Kalimeris, Konstantinos; Perrea, Despina; Stavropoulos, Nikolaos; Kostopanagiotou, Georgia; Matsota, Paraskevi

2016-06-01

People with special needs undergoing dental surgery frequently require general anesthesia. We investigated the effect of remifentanil vs fentanyl on stress response and postoperative pain in people with special needs undergoing day-case dental surgery. Forty-six adult patients with cognitive impairment undergoing day-case dental surgery under general anesthesia were allocated to receive intraoperatively either fentanyl 50 μg iv bolus (group F, n = 23) or continuous infusion of remifentanil 0.5-1 μg/kg/min (group R, n = 23). Iintraoperative hemodynamic parameters were recorded and serum inflammatory mediators [tumor necrosis factor-α, substance-P], stress hormons (melatonin, cortisol) and β-endorphin were measured. Postoperative pain was assessed during the first postoperative 12 hours with the Wong-Baker faces pain-rating scale. Demographics were similar in two groups. The two groups did not differ regarding their effects on inflammatory mediators, stress hormons and postoperative pain scores. However, the use of remifentanil prevented intraoperative increases of arterial blood pressure and heart rate. Remifentanil and fentanyl did not affect differently stress and inflammatory hormones during day-case dental surgery, although remifentanil may render intraoperative management of hemodynamic responses easier. Both opioids are equally efficient for postoperative pain management following dental surgery in people with special needs.

Results of patch testing in 10 patients with peristomal dermatitis.

Science.gov (United States)

Landis, Megan N; Keeling, James H; Yiannias, James A; Richardson, Donna M; Nordberg Linehan, Diane L; Davis, Mark D P

2012-09-01

Peristomal dermatitis is a common problem in patients with ostomies that is a source of considerable morbidity. Irritant contact dermatitis is most common, but allergic contact dermatitis can also occur. Because of the lack of published reports on patch testing for this indication, we undertook a retrospective study of patch testing results in patients with suspected peristomal allergic contact dermatitis. We sought to describe our patch testing experience with patients referred with peristomal dermatitis. This was a retrospective review of medical records of patients with ostomies and peristomal dermatitis who underwent patch testing in the Mayo Clinic Departments of Dermatology in Jacksonville, FL; Rochester, MN; and Scottsdale, AZ, during a 10-year period (2000-2010). Ten patients with peristomal dermatitis were referred for patch testing (6 in Minnesota, 2 in Florida, and 2 in Arizona). Patients were patch tested to the materials used in their stoma devices, to the standard series, and in some cases to supplemental series. All 10 had at least one allergic patch test reaction, most commonly to stoma paste (3 of 10 patients). Retrospective nature of study via chart review is a limitation. Patch testing is a useful tool for identification of allergens in patients with peristomal dermatitis. Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Femoral nerve block versus intravenous fentanyl in adult patients with hip fractures - a systematic review

Directory of Open Access Journals (Sweden)

Flávia Vieira Guimarães Hartmann

Full Text Available Abstract Background: Hip fractures configure an important public health issue and are associated with high mortality taxes and lose of functionality. Hip fractures refer to a fracture occurring between the edge of the femoral head and 5 cm below the lesser trochanter. They are common in orthopedic emergencies. The number of proximal femoral fractures is likely to increase as the population ages. The average cost of care during the initial hospitalization for hip fracture can be estimated about US$ 7,000 per patient. Femoral fractures are painful and need immediate adequate analgesia. Treating pain femoral fractures is difficult because there are limited numbers of analgesics available, many of which have side effects that can limit their use. Opiates are the most used drugs, but they can bring some complications. In this context, femoral nerve blocks can be a safe alternative. It is a specific regional anesthetic technique used by doctors in emergency medicine to provide anesthesia and analgesia of the affected leg. Objective: To compare the analgesic efficacy of intravenous fentanyl versus femoral nerve block before positioning to perform spinal anesthesia in patients with femoral fractures assessed by Pain Scales. Methods: A systematic review of scientific literature was conducted. Studies described as randomized controlled trials comparing femoral nerve block and traditional fentanyl are included. Two reviewers (MR and FH independently assessed potentially eligible trials for inclusion. The methodology assessment was based on the tool developed by the Cochrane Collaboration for assessment of bias for randomized controlled trials. The Cochrane Library, Pubmed, Medline and Lilacs were searched for all articles published, without restriction of language or time. Results: Two studies were included in this review. Nerve blockade seemed to be more effective than intravenous fentanyl for preventing pain in patients suffering from a femoral fracture

Effect of novel mucoadhesive buccal patches of carvedilol on isoprenaline-induced tachycardia

Directory of Open Access Journals (Sweden)

Navneet Verma

2014-01-01

Full Text Available The main aim of the study was designed to develop bioadhesive buccal patches of carvedilol (CR and evaluate for isoprenaline-induced tachycardia. Buccal patches of carvedilol were prepared by using chitosan (CH, sodium salt of carboxy methyl cellulose (NaCMC, and polyvinyl alcohol (PVA as mucoadhesive polymers. The solvent evaporation method was used for the preparation of buccal patches. The patches were evaluated for their physical characteristics like patch thickness, weight variation, content uniformity, folding endurance, surface pH, residence time, in vitro drug release, and in vivo pharmacodynamic study. The swelling index of the patches was found to be proportional to the polymer concentration, whereas surface pH of all the formulated bioadhesive patches was found to lie between neutral ranges. In-vitro release study shows that 94.75% drug was release in 8 hours from the patch, which containing 2% w/v chitosan. The folding endurance result shows good elasticity in all the patches.Application of buccal patches on buccal mucosa of rabbit shows a significant result in % inhibition of isoprenaline-induced tachycardia. Prepared buccal patches of chitosan, NaCMC, and PVA containing Carvedilol meet the ideal requirement for the delivery of cardiovascular drugs and inhibit the isoprenaline tachycardia.

Grassland Fire and Cattle Grazing Regulate Reptile and Amphibian Assembly Among Patches

Science.gov (United States)

Larson, Danelle M.

2014-12-01

Fire and grazing are common management schemes of grasslands globally and are potential drivers of reptilian and amphibian (herpetofauna) metacommunity dynamics. Few studies have assessed the impacts of fire and cattle grazing on herpetofauna assemblages in grasslands. A patch-burn grazing study at Osage Prairie, MO, USA in 2011-2012 created landscape patches with treatments of grazing, fire, and such legacies. Response variables were measured before and after the application of treatments, and I used robust-design occupancy modeling to estimate patch occupancy and detection rate within patches, and recolonization and extinction (i.e., dispersal) across patches. I conducted redundancy analysis and a permuted multivariate analysis of variance to determine if patch type and the associated environmental factors explained herpetofauna assemblage. Estimates for reptiles indicate that occupancy was seasonally constant in Control patches ( ψ ~ 0.5), but declined to ψ ~ 0.15 in patches following the applications of fire and grazing. Local extinctions for reptiles were higher in patches with fire or light grazing ( ɛ ~ 0.7) compared to the controls. For the riparian herpetofaunal community, patch type and grass height were important predictors of abundance; further, the turtles, lizards, snakes, and adult amphibians used different patch types. The aquatic amphibian community was predicted by watershed and in-stream characteristics, irrespective of fire or grazing. The varying responses from taxonomic groups demonstrate habitat partitioning across multiple patch types undergoing fire, cattle grazing, and legacy effects. Prairies will need an array of patch types to accommodate multiple herpetofauna species.

Patch dynamics and metapopulation theory: the case of successional species.

Science.gov (United States)

Amarasekare, P; Possingham, H

2001-04-07

We present a mathematical framework that combines extinction-colonization dynamics with the dynamics of patch succession. We draw an analogy between the epidemiological categorization of individuals (infected, susceptible, latent and resistant) and the patch structure of a spatially heterogeneous landscape (occupied-suitable, empty-suitable, occupied-unsuitable and empty-unsuitable). This approach allows one to consider life-history attributes that influence persistence in patchy environments (e.g., longevity, colonization ability) in concert with extrinsic processes (e.g., disturbances, succession) that lead to spatial heterogeneity in patch suitability. It also allows the incorporation of seed banks and other dormant life forms, thus broadening patch occupancy dynamics to include sink habitats. We use the model to investigate how equilibrium patch occupancy is influenced by four critical parameters: colonization rate, extinction rate, disturbance frequency and the rate of habitat succession. This analysis leads to general predictions about how the temporal scaling of patch succession and extinction-colonization dynamics influences long-term persistence. We apply the model to herbaceous, early-successional species that inhabit open patches created by periodic disturbances. We predict the minimum disturbance frequency required for viable management of such species in the Florida scrub ecosystem. Copyright 2001 Academic Press.

Skin patch and vaginal ring versus combined oral contraceptives for contraception.

Science.gov (United States)

Lopez, Laureen M; Grimes, David A; Gallo, Maria F; Stockton, Laurie L; Schulz, Kenneth F

2013-04-30

The delivery of combination contraceptive steroids from a transdermal contraceptive patch or a contraceptive vaginal ring offers potential advantages over the traditional oral route. The transdermal patch and vaginal ring could require a lower dose due to increased bioavailability and improved user compliance. To compare the contraceptive effectiveness, cycle control, compliance (adherence), and safety of the contraceptive patch or the vaginal ring versus combination oral contraceptives (COCs). Through February 2013, we searched MEDLINE, POPLINE, CENTRAL, LILACS, ClinicalTrials.gov, and ICTRP for trials of the contraceptive patch or the vaginal ring. Earlier searches also included EMBASE. For the initial review, we contacted known researchers and manufacturers to identify other trials. We considered randomized controlled trials comparing a transdermal contraceptive patch or a contraceptive vaginal ring with a COC. Data were abstracted by two authors and entered into RevMan. For dichotomous variables, the Peto odds ratio (OR) with 95% confidence intervals (CI) was calculated. For continuous variables, the mean difference was computed. We also assessed the quality of evidence for this review. We found 18 trials that met our inclusion criteria. Of six patch studies, five examined the marketed patch containing norelgestromin plus ethinyl estradiol (EE); one studied a patch in development that contains levonorgestrel (LNG) plus EE. Of 12 vaginal ring trials, 11 examined the same marketing ring containing etonogestrel plus EE; one studied a ring being developed that contains nesterone plus EE.Contraceptive effectiveness was not significantly different for the patch or ring versus the comparison COC. Compliance data were limited. Patch users showed better compliance than COC users in three trials. For the norelgestromin plus EE patch, ORs were 2.05 (95% CI 1.83 to 2.29) and 2.76 (95% CI 2.35 to 3.24). In the levonorgestrel plus EE patch report, patch users were less

The art and science of mission patches and their origins in society

Science.gov (United States)

Brumfitt, A.; Thompson, L. A.; Raitt, D.

2008-06-01

Space exploration utilizes some of the latest and highest technology available to human kind; synonymous with space exploration is the mission patch. This specialized art form popularizes the exploration of space with millions of mission patches sold around the world. Space tourism and education centres like the Kennedy Space Centre rely heavily on each space shuttle launch to support their merchandising of mission patches, from the traditional sew on badge to T shirts. Do mission patches tell a story? Are they Art? What is the origin and role of this art form in society? The art form of space mission patches combines the 21st century relevance with heraldic origins predating the ninth century. The space mission patch is designed by the astronauts themselves if it is a manned mission. As an education tool teachers and educators use the space mission patch to engage their students in the excitement of space exploration, the mission patch design is utilized as an education tool in literature, science and art. The space mission patch is a particularly powerful message medium. This paper looks at the origins of the space mission patch, its relevance to art and its impact on society.

Experimental patch testing with chromium-coated materials.

Science.gov (United States)

Bregnbak, David; Thyssen, Jacob P; Jellesen, Morten S; Zachariae, Claus; Johansen, Jeanne D

2017-06-01

Chromium coatings on metal alloys can be decorative, and prevent corrosion and metal ion release. We recently showed that handling of a chromium-containing disc resulted in chromium deposition on the skin. To examine patch test reactivity to chromium-coated discs. We included 15 patients: 10 chromium-allergic patients, and 5 patients without chromium allergy. All were patch tested with potassium dichromate, cobalt chloride, nickel sulfate, and nine different metallic discs. The chromium-allergic patients were also patch tested with serial dilutions of potassium dichromate. Positive/weaker reactions were observed to disc B (1 of 10), disc C (1 of 10), and disc D, disc E, and disc I (4 of 10 each). As no controls reacted to any of the discs, the weak reactions indicate allergic reactions. Positive patch test reactions to 1770 ppm chromium(VI) in the serial dilutions of potassium dichromate were observed in 7 of 10 patients. When the case group was narrowed down to include only the patients with a current positive patch test reaction to potassium dichromate, elicitation of dermatitis by both chromium(III) and chromium(VI) discs was observed in 4 of 7 of patients. Many of the patients reacted to both chromium(III) and chromium(VI) surfaces. Our results indicate that both chromium(VI) and chromium(III) pose a risk to chromium-allergic patients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Diurnal and seasonal occurrence of polar patches

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A. S. Rodger

1996-05-01

Full Text Available Analysis of the diurnal and seasonal variation of polar patches, as identified in two years of HF-radar data from Halley, Antarctica during a period near sunspot maximum, shows that there is a broad maximum in occurrence centred about magnetic noon, not local noon. There are minima in occurrence near midsummer and midwinter, with maxima in occurrence between equinox and winter. There are no significant correlations between the occurrence of polar patches and the corresponding hourly averages of the solar wind and IMF parameters, except that patches usually occur when the interplanetary magnetic field has a southward component. The results can be understood in terms of UT and seasonal differences in the plasma concentration being convected from the dayside ionosphere into the polar cap. In summer and winter the electron concentrations in the polar cap are high and low, respectively, but relatively unstructured. About equinox, a tongue of enhanced ionisation is convected into the polar cap; this tongue is then structured by the effects of the interplanetary magnetic field, but these Halley data cannot be used to separate the various competing mechanisms for patch formation. The observed diurnal and seasonal variation in the occurrence of polar patches are largely consistent with predictions of Sojka et al. (1994 when their results are translated into the southern hemisphere. However, the ionospheric effects of flux transfer events are still considered essential in their formation, a feature not yet included in the Sojka et al. model.

Pretreatment with remifentanil, fentanyl, or lidocaine to prevent withdrawal after rocuronium using venous occlusion technique in children and adolescents: a prospective randomized placebo-controlled double-blind study.

Science.gov (United States)

Abu-Halaweh, S A; Aloweidi, A K; Qudaisat, I Y; Al-Hussami, M O; Al Zaben, K R; Abu-Halaweh, A S

2014-12-01

Pain caused by intravenous injection of the muscle relaxant rocuronium bromide is common in children and adolescents. The cause of this unwanted effect is still unclear, and different pretreatment drugs have been administered in attempts to alleviate this side effect, with varying degrees of success. This study used a 60-s venous occlusion technique to evaluate the effectiveness of pretreatment with lidocaine, fentanyl, or remifentanil in preventing pain-induced withdrawal caused by intravenous injection of rocuronium bromide during the induction of general anesthesia. One hundred and one child and adolescent patients, ASA Ι-II, requiring various surgical procedures under general anesthesia with muscle relaxation and mechanical ventilation, were enrolled. Patients were allocated randomly using computer-generated randomization into one of four pretreatment groups: a remifentanil group (1 µg/kg, n = 25), fentanyl group (1 µg/kg, n = 26), lidocaine 1% group (0.5 mg/kg, n = 25), and normal saline group (n = 25). Drug doses were prepared in normal saline to a total volume of 5 ml. Venous occlusion was applied 10 cm above the venous access site. Pretreatment drugs were injected and retained for 60 s at the site of injection by an anesthetist blinded to group allocation. After release of the tourniquet, rocuronium (0.5 mg/kg) was then injected over 5 s, and withdrawal was recorded by another anesthetist blinded to group allocation. Descriptive statistics, analysis of variance, and a chi-squared test were used to statistically analyze the results as appropriate. Compared to normal saline, all other pretreatment groups scored a significantly lower mean of withdrawal response (P rocuronium injection. Remifentanil was superior to fentanyl in suppressing the withdrawal response caused by rocuronium injection (P rocuronium injection in children and adolescents. Lidocaine was superior to remifentanil which, in turn, was more effective than fentanyl.

An Electronic Patch for wearable health monitoring by reflectance pulse oximetry.

Science.gov (United States)

Haahr, Rasmus G; Duun, Sune B; Toft, Mette H; Belhage, Bo; Larsen, Jan; Birkelund, Karen; Thomsen, Erik V

2012-02-01

We report the development of an Electronic Patch for wearable health monitoring. The Electronic Patch is a new health monitoring system incorporating biomedical sensors, microelectronics, radio frequency (RF) communication, and a battery embedded in a 3-dimensional hydrocolloid polymer. In this paper the Electronic Patch is demonstrated with a new optical biomedical sensor for reflectance pulse oximetry so that the Electronic Patch in this case can measure the pulse and the oxygen saturation. The reflectance pulse oximetry solution is based on a recently developed annular backside silicon photodiode to enable low power consumption by the light emitting components. The Electronic Patch has a disposable part of soft adhesive hydrocolloid polymer and a reusable part of hard polylaurinlactam. The disposable part contains the battery. The reusable part contains the reflectance pulse oximetry sensor and microelectronics. The reusable part is 'clicked' into the disposable part when the patch is prepared for use. The patch has a size of 88 mm by 60 mm and a thickness of 5 mm.

Rotator cuff repair with a tendon-fibrocartilage-bone composite bridging patch.

Science.gov (United States)

Ji, Xiaoxi; Chen, Qingshan; Thoreson, Andrew R; Qu, Jin; An, Kai-Nan; Amadio, Peter C; Steinmann, Scott P; Zhao, Chunfeng

2015-11-01

To compare the mechanical performance of a rotator cuff repaired with a novel tendon-fibrocartilage-bone composite bridging patch vs the traditional Mason-Allen repair in an in vitro canine model. Twenty shoulders and 10 bridging patches from patellar tendon were harvested. The patches were trimmed and sliced into 2 layers. An infraspinatus tendon tear was created in each shoulder. Modified Mason-Allen sutures were used to repair the infraspinatus tendon to the greater tuberosity, with or without the bridging patch (bridging patch group and controls, respectively). Shoulders were loaded to failure under displacement control at a rate of 0.5mm/s. The ultimate tensile load was significantly higher in the bridging patch group than control (mean [SD], 365.46 [36.45] vs 272.79 [48.88] N; Pfibrocartilage-bone composite bridging patch achieved higher ultimate tensile load and stiffness at the patch-greater tuberosity repair site compared with traditional repair in a canine model. This composite tissue transforms the traditional tendon-to-bone healing interface (with dissimilar tissues) into a pair of bone-to-bone and tendon-to-tendon interfaces, which may improve healing quality and reduce retear rate. Copyright © 2015 Elsevier Ltd. All rights reserved.

EISCAT observations of plasma patches at sub-auroral cusp latitudes

Directory of Open Access Journals (Sweden)

J. Moen

2006-09-01

Full Text Available A sequence of 3 patches of high-density (10¹² m⁻³ cold plasma on a horizontal scale-size of 300–700 km was observed near magnetic noon by the EISCAT VHF radar above Svalbard on 17 December 2001. The patches followed a trajectory towards the cusp inflow region. The combination of radar and all-sky observations demonstrates that the patches must have been segmented equatorward of the cusp/cleft auroral display, and hence their properties had not yet been influenced by cusp particle showers and electrodynamics on open flux tubes. The last patch in the sequence was intersected by radio tomography observations, and was found to be located adjacent to a broader region of the same high electron density further south. The patches occurred under moderately active conditions (Kp=3 and the total electron content (TEC of the high-density plasma was 45 TEC units. The train of patches appeared as a segmentation of the tongue of ionization. The sequence of patches occurred in association with a sequence of flow bursts in the dusk cell return flow. It is proposed that reconnection driven pulsed convection is able to create sub-auroral patches in the region where high density mid-latitude plasma is diverted poleward toward the cusp. It is the downward Birkeland current sheet located at the equatorward boundary of the flow disturbance that represents the actual cutting mechanism.

EISCAT observations of plasma patches at sub-auroral cusp latitudes

Directory of Open Access Journals (Sweden)

J. Moen

2006-09-01

Full Text Available A sequence of 3 patches of high-density (1012 m−3 cold plasma on a horizontal scale-size of 300–700 km was observed near magnetic noon by the EISCAT VHF radar above Svalbard on 17 December 2001. The patches followed a trajectory towards the cusp inflow region. The combination of radar and all-sky observations demonstrates that the patches must have been segmented equatorward of the cusp/cleft auroral display, and hence their properties had not yet been influenced by cusp particle showers and electrodynamics on open flux tubes. The last patch in the sequence was intersected by radio tomography observations, and was found to be located adjacent to a broader region of the same high electron density further south. The patches occurred under moderately active conditions (Kp=3 and the total electron content (TEC of the high-density plasma was 45 TEC units. The train of patches appeared as a segmentation of the tongue of ionization. The sequence of patches occurred in association with a sequence of flow bursts in the dusk cell return flow. It is proposed that reconnection driven pulsed convection is able to create sub-auroral patches in the region where high density mid-latitude plasma is diverted poleward toward the cusp. It is the downward Birkeland current sheet located at the equatorward boundary of the flow disturbance that represents the actual cutting mechanism.

Microneedle patches: usability and acceptability for self-vaccination against influenza.

Science.gov (United States)

Norman, James J; Arya, Jaya M; McClain, Maxine A; Frew, Paula M; Meltzer, Martin I; Prausnitz, Mark R

2014-04-01

While therapeutic drugs are routinely self-administered by patients, there is little precedent for self-vaccination. Convenient self-vaccination may expand vaccination coverage and reduce administration costs. Microneedle patches are in development for many vaccines, but no reports exist on usability or acceptability. We hypothesized that naïve patients could apply patches and that self-administered patches would improve stated intent to receive an influenza vaccine. We conducted a randomized, repeated measures study with 91 venue-recruited adults. To simulate vaccination, subjects received placebo microneedle patches given three times by self-administration and once by the investigator, as well as an intramuscular injection of saline. Seventy participants inserted patches with thumb pressure alone and the remainder used snap-based devices that closed shut at a certain force. Usability was assessed by skin staining and acceptability was measured with an adaptive-choice analysis. The best usability was seen with the snap device, with users inserting a median value of 93-96% of microneedles over three repetitions. When a self-administered microneedle patch was offered, intent to vaccinate increased from 44% to 65% (CI: 55-74%). The majority of those intending vaccination would prefer to self-vaccinate: 64% (CI: 51-75%). There were no serious adverse events associated with use of microneedle patches. The findings from this initial study indicate that microneedle patches for self-vaccination against influenza are usable and may lead to improved vaccination coverage. Copyright © 2014 Elsevier Ltd. All rights reserved.

Relevance of positive patch-test reactions to fragrance mix.

Science.gov (United States)

Devos, Steven A; Constandt, Lieve; Tupker, Ron A; Noz, Kathy C; Lucker, Georges P H; Bruynzeel, Derk P; Schuttelaar, Marie-Louise A; Kruyswijk, Mente R J; van Zuuren, Esther J; Vink, Jaqueline; Coenraads, Pieter-Jan; Kiemeney, Lambertus A L M; van der Valk, Pieter G M

2008-01-01

Fragrances are an important cause of allergic contact dermatitis. We presume that the traditional fragrance mix (FM) detects 70 to 80% of fragrance-allergic patients. FM has an irritant potential. Weak positive reactions may have a greater chance of being irrelevant than strong reactions. To improve the appraisal of FM patch-test reactions, we studied the relevance of reactions of different strength. We also studied the predictive value of the following on the relevance of the initial FM patch-test results: patch-test results of a repeated FM test; results of patch tests with balsam of Peru, colophony, and ingredients of the mix; and (history of) atopic dermatitis. One hundred thirty-eight patients who had doubtful positive (?+) or positive (+ to +++) reactions were included in the study. We determined relevance by history taking, location and course of the dermatitis, and additional patch testing. Patients were retested with FM and with each ingredient separately. The relevance of reactions to FM increases with the strength of the reactions. Predictors of relevance are the results of retesting with FM, the results of tests with the ingredients, and a history and/or present symptoms of atopic dermatitis. Retesting with FM and its ingredients may add to the benefit of patch testing.

Improved image registration by sparse patch-based deformation estimation.

Science.gov (United States)

Kim, Minjeong; Wu, Guorong; Wang, Qian; Lee, Seong-Whan; Shen, Dinggang

2015-01-15

Despite intensive efforts for decades, deformable image registration is still a challenging problem due to the potential large anatomical differences across individual images, which limits the registration performance. Fortunately, this issue could be alleviated if a good initial deformation can be provided for the two images under registration, which are often termed as the moving subject and the fixed template, respectively. In this work, we present a novel patch-based initial deformation prediction framework for improving the performance of existing registration algorithms. Our main idea is to estimate the initial deformation between subject and template in a patch-wise fashion by using the sparse representation technique. We argue that two image patches should follow the same deformation toward the template image if their patch-wise appearance patterns are similar. To this end, our framework consists of two stages, i.e., the training stage and the application stage. In the training stage, we register all training images to the pre-selected template, such that the deformation of each training image with respect to the template is known. In the application stage, we apply the following four steps to efficiently calculate the initial deformation field for the new test subject: (1) We pick a small number of key points in the distinctive regions of the test subject; (2) for each key point, we extract a local patch and form a coupled appearance-deformation dictionary from training images where each dictionary atom consists of the image intensity patch as well as their respective local deformations; (3) a small set of training image patches in the coupled dictionary are selected to represent the image patch of each subject key point by sparse representation. Then, we can predict the initial deformation for each subject key point by propagating the pre-estimated deformations on the selected training patches with the same sparse representation coefficients; and (4) we

THE PHARMACODYNAMICS AND PHARMACOKINETICS OF ORG-9426, A NEW NONDEPOLARIZING NEUROMUSCULAR BLOCKING-AGENT, IN PATIENTS ANESTHETIZED WITH NITROUS-OXIDE, HALOTHANE AND FENTANYL

NARCIS (Netherlands)

WIERDA, JMKH; KLEEF, UW; LAMBALK, LM; KLOPPENBURG, WD; AGOSTON, S

The pharmacodynamics and pharmacokinetics of a new non-depolarizing neuromuscular blocking agent, Org 9426, were investigated. Ten patients undergoing elective head and neck surgery and anaesthetized with nitrous oxide, halothane and fentanyl, received a bolus dose of Org 9426 (1 mg.kg-1, 3 x ED90).

Preparation of Mucoadhesive Patches for Buccal Administration of ...

African Journals Online (AJOL)

Purpose: To develop mucoadhesive patches for buccal administration of metoprolol succinate and to evaluate their in vitro and in vivo bioadhesion. Methods: The mucoadhesive buccal patches were prepared by solvent casting technique using two different mucoadhesive polymers. The formulations were tested for in vitro ...

Robust Tracking with Discriminative Ranking Middle-Level Patches

Directory of Open Access Journals (Sweden)

Hong Liu

2014-04-01

Full Text Available The appearance model has been shown to be essential for robust visual tracking since it is the basic criterion to locating targets in video sequences. Though existing tracking-by-detection algorithms have shown to be greatly promising, they still suffer from the drift problem, which is caused by updating appearance models. In this paper, we propose a new appearance model composed of ranking middle-level patches to capture more object distinctiveness than traditional tracking-by-detection models. Targets and backgrounds are represented by both low-level bottom-up features and high-level top-down patches, which can compensate each other. Bottom-up features are defined at the pixel level, and each feature gets its discrimination score through selective feature attention mechanism. In top-down feature extraction, rectangular patches are ranked according to their bottom-up discrimination scores, by which all of them are clustered into irregular patches, named ranking middle-level patches. In addition, at the stage of classifier training, the online random forests algorithm is specially refined to reduce drifting problems. Experiments on challenging public datasets and our test videos demonstrate that our approach can effectively prevent the tracker drifting problem and obtain competitive performance in visual tracking.

On the Road to Development of an in Vitro Permeation Test (IVPT) Model to Compare Heat Effects on Transdermal Delivery Systems: Exploratory Studies with Nicotine and Fentanyl.

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Shin, Soo Hyeon; Ghosh, Priyanka; Newman, Bryan; Hammell, Dana C; Raney, Sam G; Hassan, Hazem E; Stinchcomb, Audra L

2017-09-01

At elevated temperatures, the rate of drug release and skin permeation from transdermal delivery systems (TDS) may be higher than at a normal skin temperature. The aim of this study was to compare the effect of heat on the transdermal delivery of two model drugs, nicotine and fentanyl, from matrix-type TDSs with different formulations, using in vitro permeation tests (IVPT). IVPT experiments using pig skin were performed on two nicotine and three fentanyl TDSs. Both continuous and transient heat exposures were investigated by applying heat either for the maximum recommended TDS wear duration or for short duration. Continuous heat exposure for the two nicotine TDSs resulted in different effects, showing a prolonged heat effect for one product but not the other. The J max enhancement ratio due to the continuous heat effect was comparable between the two nicotine TDS, but significantly different (p drug from the skin depot after TDS removal differently for two drugs, with fentanyl exhibiting a longer heat effect. This exploratory work suggests that an IVPT study may be able to discriminate differences in transdermal drug delivery when different TDS are exposed to elevated temperatures. However, the clinical significance of IVPT heat effects studies should be further explored by conducting in vivo clinical studies with similar study designs.

Nicotine patches in pregnant smokers: randomised, placebo controlled, multicentre trial of efficacy

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Grangé, Gilles; Jacob, Nelly; Tanguy, Marie-Laure

2014-01-01

Objective To determine the efficacy of 16 hour nicotine patches among pregnant smokers, with the dose individually adjusted according to saliva cotinine levels (potential range 10-30 mg/day). Design Randomised, double blind, placebo controlled, parallel group, multicentre trial (Study of Nicotine Patch in Pregnancy, SNIPP) between October 2007 and January 2013. Setting 23 maternity wards in France. Participants 476 pregnant smokers aged more than 18 years and between 12 and 20 weeks’ gestation, who smoked at least five cigarettes a day. After exclusions, 402 women were randomised: 203 to nicotine patches and 199 to placebo patches. Data were available on 192 live births in each group. Interventions Nicotine and identical placebo patches were administered from quit day up to the time of delivery. Doses were adjusted to saliva cotinine levels when smoking to yield a substitution rate of 100%. Participants were assessed monthly and received behavioural smoking cessation support. Main outcome measures The primary outcomes were complete abstinence (self report confirmed by carbon monoxide level in expired air ≤8 ppm) from quit date to delivery, and birth weight. The secondary outcomes were point prevalence of abstinence, time to lapse (a few puffs) or relapse, and delivery and birth characteristics. All data were analysed on an intention to treat basis. Results Complete abstinence was achieved by 5.5% (n=11) of women in the nicotine patch group and 5.1% (n=10) in the placebo patch group (odds ratio 1.08, 95% confidence interval 0.45 to 2.60). The median time to the first cigarette smoked after target quit day was 15 days in both groups (interquartile range 13-18 in the nicotine patch group, 13-20 in the placebo patch group). The point prevalence abstinence ranged from 8% to 12.5% in the nicotine patch group and 8% to 9.5% in the placebo patch group without statistically significant differences. The nicotine substitution rate did not differ from 100%, and the self

Using an index of habitat patch proximity for landscape design

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Eric J. Gustafson; George R. Parker

1994-01-01

A proximity index (PX) inspired by island biogeography theory is described which quantifies the spatial context of a habitat patch in relation to its neighbors. The index distinguishes sparse distributions of small habitat patches from clusters of large patches. An evaluation of the relationship between PX and variation in the spatial characteristics of clusters of...

Robust Face Recognition via Multi-Scale Patch-Based Matrix Regression.

Directory of Open Access Journals (Sweden)

Guangwei Gao

Full Text Available In many real-world applications such as smart card solutions, law enforcement, surveillance and access control, the limited training sample size is the most fundamental problem. By making use of the low-rank structural information of the reconstructed error image, the so-called nuclear norm-based matrix regression has been demonstrated to be effective for robust face recognition with continuous occlusions. However, the recognition performance of nuclear norm-based matrix regression degrades greatly in the face of the small sample size problem. An alternative solution to tackle this problem is performing matrix regression on each patch and then integrating the outputs from all patches. However, it is difficult to set an optimal patch size across different databases. To fully utilize the complementary information from different patch scales for the final decision, we propose a multi-scale patch-based matrix regression scheme based on which the ensemble of multi-scale outputs can be achieved optimally. Extensive experiments on benchmark face databases validate the effectiveness and robustness of our method, which outperforms several state-of-the-art patch-based face recognition algorithms.

Investigation of the homogeneity of methacrylate allergens in commercially available patch test preparations

DEFF Research Database (Denmark)

Mose, Kristian Fredløv; Andersen, Klaus Ejner; Christensen, Lars Porskjaer

2013-01-01

The homogeneity of methacrylates in commercial patch test preparations has not yet been investigated. Inhomogeneous patch test preparations may give rise to false-negative or false-positive patch test results in patients suspected of having methacrylate allergy.......The homogeneity of methacrylates in commercial patch test preparations has not yet been investigated. Inhomogeneous patch test preparations may give rise to false-negative or false-positive patch test results in patients suspected of having methacrylate allergy....

Volatility of fragrance chemicals: patch testing implications.

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Gilpin, Sarah J; Hui, Xiaoying; Maibach, Howard I

2009-01-01

Diagnostic and predictive patch testing to determine contact allergy due to fragrance materials requires applying a fixed dose of material to the skin. This dose can be affected by the volatile nature of fragrances; little data exist on how the loss of fragrance dose due to volatility affects patch testing. (1) To evaluate pH dependence and evaporation rates of two fragrance chemicals, geraniol, citronellol, and a common fragrance solvent, diethyl phthalate (DEP) and (2) Assess implications for predictive patch-testing methods for fragrances. pH analysis of each material at 1% for three values (4.0, 5.0, 7.0) was done over 40 hours. Volatility experiments for each material, nonradiolabeled and radiolabeled, were conducted over a 24-hour period, taking readings at six time points (5 minutes, 15 minutes, 40 minutes, 1 hour, 3 hours, and 24 hours). Evaporation rates were not sensitive to pH shifts from 4.0 to 7.0. Evaporation rates for nonradiolabeled materials were low: after 24 hours, geraniol lost 8.9%, citronellol 27.0% and DEP 14.5%. The volatility data for radiolabeled materials demonstrated that geraniol loses up to 39% of its dose, citronellol loses up to 26%, and DEP up to 14% within 40 minutes. The tendency of fragrance materials to evaporate can impact the dose being applied to the patch and therefore the result of the patch and ultimately the decision-making process regarding that fragrance material's safety. These data, developed with DEP, utilized in a predictive sensitization assay cannot be generalized.

A clinical study of transdermal contraceptive patch in Thai adolescence women.

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Piyasirisilp, Rachatapon; Taneepanichskul, Surasak

2008-02-01

To study cycle control, compliance and safety of a transdermal contraceptive patch in adolescent Thai women. Fifty-eight healthy women were assigned to receive 3 cycles of contraceptive patch (ethinyl estradiol 20 microg and norelgestromin 150 microg/day). All participants aged 16-20 years were invited to participate from the family planning clinic at King Chulalongkorn Memorial Hospital. Data were collected on adverse effects, perceived advantages and disadvantages, body weight, blood pressure, patch detachments and compliance. Data were analyzed using mean, percentage and student's t-test. The participants' average age was 19.4 years, height 158.8 cm, weight 51.8 kg, BMI 20.8 Kg/m2. The most location of patch application was the abdomen and the most adverse event was breast tenderness (31.0%) followed by application site reaction, nausea vomiting and headache respectively. The breast symptom was mild in severity. The participants reported decrease in dysmenorrhea and shorter duration of bleeding. There were no significant changes in body weight and blood pressure. The improvement of their facial acne was reported. There were no pregnancies during use and the adhesion of the contraceptive patch is excellent. Partial patch detachment was reported in only 6.9%. No completed patch detachment was found. The present study found an overall positive impression of a new transdermal contraceptive patch. The good compliance and few side effects were demonstrated. The adhesive patch contraceptive was excellent.

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....... The NIRS-determined arm muscle oxygenation (Smo2), heart rate (HR), and cardiac output (CO) were monitored, endtidal carbon dioxide tension was controlled at 3.5 to 4.5 kPa, and central blood volume was maintained. Before anesthesia, the median (range) MAP, HR, and CO were 93 mm Hg (61-126 mm Hg), 76 beats......, the median (range) NIRS-determined Smo2 also decreased (73% [54%-94%] to 71% [52%-87%]), whereas Sco2 increased from 67% (46%-93%) to 74% (48%-95%) (P anesthesia induction, variables recovered and remained at preanesthetic levels during surgery. The findings...

Planar patch clamp: advances in electrophysiology.

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Brüggemann, Andrea; Farre, Cecilia; Haarmann, Claudia; Haythornthwaite, Ali; Kreir, Mohamed; Stoelzle, Sonja; George, Michael; Fertig, Niels

2008-01-01

Ion channels have gained increased interest as therapeutic targets over recent years, since a growing number of human and animal diseases have been attributed to defects in ion channel function. Potassium channels are the largest and most diverse family of ion channels. Pharmaceutical agents such as Glibenclamide, an inhibitor of K(ATP) channel activity which promotes insulin release, have been successfully sold on the market for many years. So far, only a small group of the known ion channels have been addressed as potential drug targets. The functional testing of drugs on these ion channels has always been the bottleneck in the development of these types of pharmaceutical compounds.New generations of automated patch clamp screening platforms allow a higher throughput for drug testing and widen this bottleneck. Due to their planar chip design not only is a higher throughput achieved, but new applications have also become possible. One of the advantages of planar patch clamp is the possibility of perfusing the intracellular side of the membrane during a patch clamp experiment in the whole-cell configuration. Furthermore, the extracellular membrane remains accessible for compound application during the experiment.Internal perfusion can be used not only for patch clamp experiments with cell membranes, but also for those with artificial lipid bilayers. In this chapter we describe how internal perfusion can be applied to potassium channels expressed in Jurkat cells, and to Gramicidin channels reconstituted in a lipid bilayer.

Successful application of large microneedle patches by human volunteers.

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Ripolin, Anastasia; Quinn, James; Larrañeta, Eneko; Vicente-Perez, Eva Maria; Barry, Johanne; Donnelly, Ryan F

2017-04-15

We describe, for the first time, the design, production and evaluation of large microneedle patches. Such systems, based on 16 individual microneedle arrays (needle height 600μm), were prepared from aqueous blends of 15% w/w Gantrez ® S97 and 7.5% w/w poly(ethyleneglycol) 10,000Da. Ester-based crosslinking was confirmed by FTIR and mechanical strength was good. Insertion depths in a validated skin model were approximately 500μm. Ten human volunteers successfully self-inserted the microneedles of these larger patches in their skin, following appropriate instruction, as confirmed by transepidermal water loss measurements. The mean insertion depth ranged between 300 and 450μm over the area of the large patches. That this was not significantly different to a single unit MN patch self-applied by the same volunteers is encouraging. Microneedle patch sizes much larger than the 1-2cm 2 will be required if this technology is to be successfully translated to clinic for delivery of drug substances. The work described here suggests that use of such larger patches by patients can be successful, potentially opening up the possibility for a significant expansion of the size of the market for transdermal drug delivery. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Corridor Length and Patch Colonization by a Butterfly Junonia coenia

Energy Technology Data Exchange (ETDEWEB)

Nick Haddad

2000-06-01

Habitat corridors have been proposed to reduce patch isolation and increase population persistence in fragmented landscapes. This study tested whether patch colonization was increased by the presence and various length corridors. The specific butterfly species tested has been shown to use corridors, however, the results indicate that neither the distance between patches or the presence of a corridor influenced colonization.

A randomized controlled trial to compare fentanyl-propofol and ketamine-propofol combination for procedural sedation and analgesia in laparoscopic tubal ligation

Directory of Open Access Journals (Sweden)

Ranju Singh

2013-01-01

Full Text Available Background: Procedural sedation and analgesia is widely being used for female laparoscopic sterilization using combinations of different drugs at varying doses. This study compared the combination of fentanyl and propofol, and ketamine and propofol in patients undergoing outpatient laparoscopic tubal ligation, with respect to their hemodynamic effects, postoperative recovery characteristics, duration of hospital stay, adverse effects, and patient comfort and acceptability. Settings and Design: Randomized, double blind. Methods: Patients were assigned to receive premixed injection of either fentanyl 1.5 μg/kg + propofol 2 mg/kg (Group PF, n0=50 or ketamine 0.5 mg/kg + propofol 2 mg/kg (Group PK, n=50. Hemodynamic data, peripheral oxygen saturation, and respiratory rate were recorded perioperatively. Recovery time, time to discharge, and comfort score were noted. Statistical Analysis: Chi-square (χ2 test was used for categorical data. Student′s t-test was used for quantitative variables for comparison between the two groups. For intragroup comparison, paired t-test was used. SPSS 14.0 was used for analysis. Results: Although the heart rate was comparable, blood pressures were consistently higher in group PK. Postoperative nausea and vomiting and delay in voiding were more frequent in group PK ( P<0.05. The time to reach Aldrete score ≥8 was significantly longer in group PK (11.14±3.29 min in group PF vs. 17.3±6.32 min in group PK, P<0.01. The time to discharge was significantly longer in group PK (105.8±13.07 min in group PF vs.138.18±13.20 min in group PK, P<0.01. Patient comfort and acceptability was better in group PF, P<0.01. Conclusion: As compared to ketamine-propofol, fentanyl-propofol combination is associated with faster recovery, earlier discharge, and better patient acceptability.

Increase in specific density of levobupivacaine and fentanyl solution ensures lower incidence of inadequate block.