Reversal of rocuronium-induced (1.2 mg/kg) profound neuromuscular block by sugammadex: a multicenter, dose-finding and safety study.

NARCIS (Netherlands)

Boer, H.D. de; Driessen, J.J.; Marcus, M.A.; Kerkkamp, H.E.M.; Heeringa, M.; Klimek, M.

2007-01-01

BACKGROUND: Reversal of rocuronium-induced neuromuscular blockade can be accomplished by chemical encapsulation of rocuronium by sugammadex, a modified gamma-cyclodextrin derivative. This study investigated the efficacy and safety of sugammadex in reversing rocuronium-induced profound neuromuscular

Effect of nitrous oxide on pain due to rocuronium injection: A randomised, double-blind, controlled clinical trial

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Sonal Sharma

2010-01-01

Full Text Available A prospective, randomised, double-blind, placebo-controlled study was carried out to determine the effect of nitrous oxide (N 2 O on the frequency and severity of pain and withdrawal reactions after injection of rocuronium. Eighty ASA physical status I and II patients undergoing general anaesthesia for elective surgery were enrolled. The patients were randomised to receive 100% oxygen (O 2 , or 50% N 2 O in O 2 for 3 minutes followed by a subparalysing dose of rocuronium 0.06 mg/kg. After induction of anaesthesia with thiopentone 5 mg/kg, an intubating dose of rocuronium 0.6 mg/kg was given. The patients were observed after injection of rocuronium 0.06 mg/kg, and asked to rate pain in the arm on a 4-point (0-3 verbal rating scale (none, mild, moderate or severe. After the intubating dose of rocuronium, withdrawal reactions were recorded. Thirty-six patients (90% in the group N 2 O and 15 patients (37.5% in the group O 2 reported no pain (P < 0.001. The pain was mild in 1 (2.5% and 9 (22.5% patients in N 2 O and O 2 groups, respectively (P = 0.006. Moderate pain occurred in 2 (5% patients in group N 2 O and 15 (37.5% patients in group O 2 (P = 0.001. Severe pain was reported by one patient in each group (P = 0.47. Withdrawal response after an intubating dose of rocuronium was observed in 6 (15% and 18 (45% patients in the N 2 O and O 2 groups, respectively (P < 0.05. Inhalation of 50% N 2 O in O 2 reduces the incidence and severity of pain and the withdrawal reactions associated with rocuronium injection.

A suspected case of rocuronium-sugammadex complex-induced anaphylactic shock after cesarean section.

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Yamaoka, Masakazu; Deguchi, Miki; Ninomiya, Kiichiro; Kurasako, Toshiaki; Matsumoto, Mutsuko

2017-02-01

An anaphylactic reaction during a cesarean section occurs rarely, and rocuronium is thought to be one of the common agents causing perioperative anaphylaxis. Here we report an anaphylactic shock after cesarean section that is suggested to be induced by the rocuronium-sugammadex complex. A 36-year-old primigravida underwent an elective cesarean section under general anesthesia due to placenta previa. While the operation was completed uneventfully, she developed anaphylactic shock following sugammadex administration. She was successfully managed with rapid treatments. Serum tryptase level was significantly elevated. Although sugammadex was first suspected to be the causative agent, the result of intradermal skin tests with sugammadex were negative. Surprisingly, a subsequent intradermal test with undiluted rocuronium caused the patient to fall into a state of shock. Furthermore, a later skin-prick test with pre-mixed rocuronium-sugammadex complex also revealed a strong positive reaction, and a test with only rocuronium showed negative. We finally concluded that the rocuronium-sugammadex complex is the causative agent in this case. To the best of our knowledge, this is the first report suggesting anaphylaxis caused by the rocuronium-sugammadex complex. This case highlights the importance of appropriate examinations to determinate the pathogenesis of anaphylaxis in order to establish risk reduction strategies.

Comparison of rocuronium-induced neuromuscular blockade in second trimester pregnant women and non-pregnant women.

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Jun, I J; Jun, J; Kim, E M; Lee, K Y; Kim, N; Chung, M H; Choi, Y R; Choi, E M

2018-05-01

This study set out to compare the onset and duration of rocuronium-induced neuromuscular blockade in second trimester pregnant women and non-pregnant women receiving general anesthesia. Forty-seven pregnant (Group P) and forty-seven non-pregnant (Group C) women were enrolled. Anesthesia was induced with propofol 2.0 mg/kg and rocuronium 0.6 mg/kg, and neuromuscular blockade was assessed with an accelerometric sensor using train-of-four stimulation (TOF-Watch® SX). Tracheal intubation was performed at maximum depression of the first twitch (T1) and anesthesia was maintained with sevoflurane 1.5-2.5% and 50% oxygen in air. We recorded the times to maximum T1 depression and 5% and 25% T1 recovery, as well as the mean arterial pressure and heart rate at baseline, injection of rocuronium, intubation, and 5% and 25% T1 recovery. The onset of rocuronium-induced neuromuscular blockade (time to maximum T1 depression) did not differ significantly between the groups. The duration (time to 25% T1 recovery) was significantly longer in Group P than in Group C (45.7 ± 12.9 min vs 40.6 ± 10.4 min, P rocuronium-induced neuromuscular blockade did not significantly differ in onset but lasted significantly longer in second trimester pregnant women compared with non-pregnant women. Copyright © 2018 Elsevier Ltd. All rights reserved.

Population pharmacokinetic–pharmacodynamic analysis for sugammadex-mediated reversal of rocuronium-induced neuromuscular blockade

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Kleijn, Huub J; Zollinger, Daniel P; van den Heuvel, Michiel W; Kerbusch, Thomas

2011-01-01

AIMS An integrated population pharmacokinetic–pharmacodynamic model was developed with the following aims: to simultaneously describe pharmacokinetic behaviour of sugammadex and rocuronium; to establish the pharmacokinetic–pharmacodynamic model for rocuronium-induced neuromuscular blockade and reversal by sugammadex; to evaluate covariate effects; and to explore, by simulation, typical covariate effects on reversal time. METHODS Data (n = 446) from eight sugammadex clinical studies covering men, women, non-Asians, Asians, paediatrics, adults and the elderly, with various degrees of renal impairment, were used. Modelling and simulation techniques based on physiological principles were applied to capture rocuronium and sugammadex pharmacokinetics and pharmacodynamics and to identify and quantify covariate effects. RESULTS Sugammadex pharmacokinetics were affected by renal function, bodyweight and race, and rocuronium pharmacokinetics were affected by age, renal function and race. Sevoflurane potentiated rocuronium-induced neuromuscular blockade. Posterior predictive checks and bootstrapping illustrated the accuracy and robustness of the model. External validation showed concordance between observed and predicted reversal times, but interindividual variability in reversal time was pronounced. Simulated reversal times in typical adults were 0.8, 1.5 and 1.4 min upon reversal with sugammadex 16 mg kg−1 3 min after rocuronium, sugammadex 4 mg kg−1 during deep neuromuscular blockade and sugammadex 2 mg kg−1 during moderate blockade, respectively. Simulations indicated that reversal times were faster in paediatric patients and slightly slower in elderly patients compared with adults. Renal function did not affect reversal time. CONCLUSIONS Simulations of the therapeutic dosing regimens demonstrated limited impact of age, renal function and sevoflurane use, as predicted reversal time in typical subjects was always <2 min. PMID:21535448

Sugammadex 4.0 mg kg-1 reversal of deep rocuronium-induced neuromuscular blockade

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Yu, Buwei; Wang, Xiangrui; Hansen, Søren Helbo

2014-01-01

Objective: Maintenance of deep Neuro Muscular Blockade (NMB) until the end of surgery may be beneficial in some surgical procedures. The selective relaxant binding agent sugammadex rapidly reverses deep levels of rocuronium-induced NMB. The purpose of this study was to evaluate the efficacy...... and safety of sugammadex 4.0 mg kg-1 for reversal of deep rocuronium-induced NMB in Chinese and Caucasian patients. Methods: This was an open-label, multicenter, prospective Phase III efficacy study in adult American Society of Anesthesiologists Class 1-3 patients scheduled for surgery under general...... anesthesia and requiring deep NMB. All patients received intravenous propofol and opioids for induction and maintenance of anesthesia, and a single intubation dose of rocuronium 0.6 mg/kg, with maintenance doses of 0.1-0.2 mg/kg as required. Sugammadex 4.0 mg/kg was administered after the last dose...

Reversal with sugammadex for rocuronium-induced deep neuromuscular block after pretreatment of magnesium sulfate in rabbits.

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Kang, Woon Seok; Kim, Kyo Sang; Song, Shin Mi

2017-04-01

Magnesium sulfate (MgSO 4 ) has been used in the treatment of pre-eclampsia, hypertension and arrhythmia. Magnesium enhances the neuromuscular block of rocuronium. This study has been conducted to evaluate the reversal efficacy of sugammadex from deep rocuronium-induced neuromuscular block (NMB) during consistent pretreatment of MgSO 4 in rabbits. Twenty-eight rabbits were randomly assigned to four groups, a control group or study groups (50% MgSO 4 150-200 mg/kg and 25 mg/kg/h IV), and received rocuronium 0.6 mg/kg. When post-tetanic count 1-2 appeared, sugammadex 2, 4, and 8 mg/kg was administered in the 2-mg group, control and 4-mg group, and 8-mg group, respectively. The recovery course after reversal of sugammadex administration was evaluated in each group. The mean serum concentration of magnesium was maintained at more than 2 mmol/L in the study groups, and the total dose of MgSO 4 was more than 590 mg. The reversal effect of sugammadex on rocuronium-induced NMB in pretreated MgSO 4 was not different from that in the group without MgSO 4 . The recovery time to train-of-four ratio 0.9 after sugammadex administration in the 2-mg group was longer than in the other groups (P rocuronium-induced NMB during large pretreatment of MgSO 4 was not affected. However, we should consider that the reversal effect of sugammadex varied depending on the dose.

Sugammadex given for rocuronium-induced neuromuscular blockade in infants: a retrospectıve study.

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Ozmete, Ozlem; Bali, Cagla; Cok, Oya Yalcin; Turk, Hatice Evren Eker; Ozyilkan, Nesrın Bozdogan; Civi, Soner; Aribogan, Anıs

2016-12-01

To evaluate the efficacy and safety of sugammadex in reversing profound neuromuscular block induced by rocuronium in infant patients. Retrospective observational study. University teaching hospital. Twenty-six infants (2-12 months of age; 3-11 kg) with an American Society of Anesthesiologists classification I, II, or III who were scheduled to undergo neurosurgical procedures were included in the study. Anesthesia was induced with 5 mg/kg thiopental, 1 μg/kg fentanyl and 0.6 mg/kg rocuronium. Sevoflurane was administered to all patients after intubation. The neuromuscular block was monitored with acceleromyography using train-of-four (TOF) stimuli. Patients received additional doses of rocuronium to maintain a deep block during surgery. If profound neuromuscular block (TOF, 0) persisted at the end of the surgery, 3mg/kg sugammadex was administered. The demographic data, surgeries, and anesthetic agents were recorded. The time from sugammadex administration to recovery of neuromuscular function (TOF ratio, >0.9) and complications during and after extubation were also recorded. Twenty-six infants who had a deep neuromuscular block (TOF, 0) at the end of surgery received 3 mg/kg sugammadex. The mean recovery time of the T4/T1 ratio of 0.9 was 112 seconds. No clinical evidence of recurarization or residual curarization was observed. The efficacy and safety of sugammadex were confirmed in infant surgical patients for reversal of deep neuromuscular block induced by rocuronium. Copyright © 2016 Elsevier Inc. All rights reserved.

Dexamethasone Does Not Inhibit Sugammadex Reversal After Rocuronium-Induced Neuromuscular Block.

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Buonanno, Pasquale; Laiola, Anna; Palumbo, Chiara; Spinelli, Gianmario; Servillo, Giuseppe; Di Minno, Raffaele Maria; Cafiero, Tullio; Di Iorio, Carlo

2016-06-01

Sugammadex is a relatively new molecule that reverses neuromuscular block induced by rocuronium. The particular structure of sugammadex traps the cyclopentanoperhydrophenanthrene ring of rocuronium in its hydrophobic cavity. Dexamethasone shares the same steroidal structure with rocuronium. Studies in vitro have demonstrated that dexamethasone interacts with sugammadex, reducing its efficacy. In this study, we investigated the clinical relevance of this interaction and its influence on neuromuscular reversal. In this retrospective case-control study, we analyzed data from 45 patients divided into 3 groups: dexamethasone after induction group (15 patients) treated with 8 mg dexamethasone as an antiemetic drug shortly after induction of anesthesia; dexamethasone before reversal group (15 patients) treated with dexamethasone just before sugammadex injection; and control group (15 patients) treated with 8 mg ondansetron. All groups received 0.6 mg/kg rocuronium at induction, 0.15 mg/kg rocuronium at train-of-four ratio (TOF) 2 for neuromuscular relaxation, and 2 mg/kg sugammadex for reversal at the end of the procedure at TOF2. Neuromuscular relaxation was monitored with a TOF-Watch® system. The control group had a recovery time of 154 ± 54 seconds (mean ± SD), the dexamethasone after induction group 134 ± 55 seconds, and the dexamethasone before reversal group 131 ± 68 seconds. The differences among groups were not statistically significant (P = 0.5141). Our results show that the use of dexamethasone as an antiemetic drug for the prevention of postoperative nausea and vomiting does not interfere with reversal of neuromuscular blockade with sugammadex in patients undergoing elective surgery with general anesthesia in contrast to in vitro studies that support this hypothesis.

Early reversal of profound rocuronium-induced neuromuscular blockade by sugammadex in a randomized multicenter study - Efficacy, safety, and pharmacokinetics

NARCIS (Netherlands)

Sparr, Harald J.; Vermeyen, Karel M.; Beaufort, Anton M.; Rietbergen, Henk; Proost, Johannes H.; Saldien, Vera; Velik-Salchner, Corinna; Wierda, J. Mark K. H.

Background: Sugammadex reverses the neuromuscular blocking effects of rocuronium by chemical encapsulation. The efficacy, safety, and pharmacokinetics of sugammadex for reversal of profound rocuronium-induced neuromuscular blockade were evaluated. Methods: Ninety-eight male adult patients were

Pharmacological and non-pharmacological interventions for reducing rocuronium bromide induced pain on injection in children and adults.

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Prabhakar, Hemanshu; Singh, Gyaninder Pal; Ali, Zulfiqar; Kalaivani, Mani; Smith, Martha A

2016-02-12

Rocuronium bromide is a routinely used muscle relaxant in anaesthetic practice. Its use, however, is associated with intense pain on injection. While it is well established that rocuronium bromide injection causes pain in awake patients, anaesthetized patients also tend to show withdrawal movements of the limbs when this muscle relaxant is administered. Various strategies, both pharmacological and non-pharmacological, have been studied to reduce the incidence and severity of pain on rocuronium bromide injection. We wanted to find out which of the existing modalities was best to reduce pain on rocuronium injection. The objectives of this review were to assess the ability of both pharmacological and non-pharmacological interventions to reduce or eliminate the pain that accompanies rocuronium bromide administration. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 7), MEDLINE via Ovid SP (1966 to July 2013) and EMBASE via Ovid SP (1980 to July 2013). We also searched specific websites. We reran the searches in February 2015 and will deal with the 11 studies of interest found through this search when we update the review. We included all randomized controlled trials (RCTs) that compared the use of any drug or a non-pharmacological method with control patients, or those receiving no treatment to reduce the severity of pain with rocuronium injection. Our primary outcome was pain on rocuronium bromide injection measured by a pain score assessment. Our secondary outcomes were rise in heart rate and blood pressure following administration of rocuronium and adverse events related to the interventions. We used the standardized methods for conducting a systematic review as described in the Cochrane Handbook for Systematic Reviews of Interventions. Two authors independently extracted details of trial methodology and outcome data from reports of all trials considered eligible for inclusion. We made all analyses on an intention-to-treat basis

Sugammadex efficacy for reversal of rocuronium- and vecuronium-induced neuromuscular blockade: A pooled analysis of 26 studies.

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Herring, William Joseph; Woo, Tiffany; Assaid, Christopher A; Lupinacci, Robert J; Lemmens, Hendrikus J; Blobner, Manfred; Khuenl-Brady, Karin S

2017-09-01

To summarize and compare efficacy of sugammadex with neostigmine or placebo for reversal of rocuronium- or vecuronium-induced neuromuscular blockade (NMB), and to demonstrate consistency of sugammadex results across various patient populations. Pooled analysis on data from 26 multicenter, randomized, Phase II and III studies. Operating room. 1855 adults undergoing surgery under general anesthesia and receiving rocuronium or vecuronium for NMB. Sugammadex (2.0mg/kg at second twitch reappearance [T 2 ; moderate NMB], 4.0mg/kg at 1-2 post-tetanic counts [PTC; deep NMB] or 16.0mg/kg at 3min after rocuronium 1.2mg/kg), neostigmine or placebo. Time to recovery of the train-of-four (TOF) ratio to 0.9. Geometric mean (95% CI) times to recovery to TOF ratio of 0.9 were 1.9 (1.8-2.0) min following sugammadex 2.0mg/kg and 10.6 (9.8-11.6) min following neostigmine administration at T 2 after rocuronium, and 2.9 (2.5-3.4) min and 17.4 (13.4-22.6) min, respectively, after vecuronium. Recovery times were 2.2 (2.1-2.3) min following sugammadex 4.0mg/kg and 19.0 (14.8-24.6) min following neostigmine administered at a target of 1-2 PTC after rocuronium, and 3.8 (3.0-5.0) min and 67.6 (56.3-81.2) min after vecuronium. Sugammadex administered 3min after rocuronium 1.2mg/kg resulted in rapid recovery (1.7 [1.5-2.0] min). Modest increases in mean recovery time were associated with vecuronium use (+1.6min [78%; (61%-98%)] versus rocuronium), mild-to-moderate renal impairment (+0.4min [20%; (9%-32%)] versus normal renal function) and geographic location (+1.0min [38%; (25%-52%)] in subjects in USA/Canada versus Europe/Japan). Sugammadex administered at recommended doses provides rapid and predictable reversal of rocuronium and vecuronium-induced moderate and deep NMB, and effective reversal 3min after rocuronium 1.2mg/kg. Robust recovery was seen across various patient factors, providing further confirmation of labeled dose recommendations. Copyright © 2017 Elsevier Inc. All rights

Reversal of rocuronium-induced neuromuscular block by the selective relaxant binding agent sugammadex: a dose-finding and safety study

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Sorgenfrei, Iben F; Norrild, Kathrine; Larsen, Per Bo

2006-01-01

Sugammadex (Org 25969) forms a complex with steroidal neuromuscular blocking agents, thereby reversing neuromuscular block. This study investigated the dose-response relation, safety, and pharmacokinetics of sugammadex to reverse rocuronium-induced block.......Sugammadex (Org 25969) forms a complex with steroidal neuromuscular blocking agents, thereby reversing neuromuscular block. This study investigated the dose-response relation, safety, and pharmacokinetics of sugammadex to reverse rocuronium-induced block....

Dexmedetomidine reduces pain associated with rocuronium injection without causing a decrease in BIS values: a dose-response study.

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Joo, Jin; Baek, Jungwon; Lee, Jaemin

2014-09-01

To examine whether dexmedetomidine reduces the injection pain of propofol and rocuronium and to investigate whether the decrease in injection pain is associated with the known sedative action of dexmedetomidine. Randomized, double-blind, placebo-controlled clinical comparison study. Patients undergoing general anesthesia with intubation received 40 mg of 1% lidocaine (lidocaine group; n = 28), 0.25 μg/kg of dexmedetomidine (low-dose group; n = 27), 0.5 μg/kg of dexmedetomidine (subclinical dose group; n = 28), 1.0 μg/kg of dexmedetomidine (clinical dose group, n = 27), or normal saline (saline group; n = 28) before anesthetic induction. Pain associated with propofol and rocuronium injection was assessed using a 10-point verbal analog scale (VAS) and a 4-point withdrawal movement scale, respectively. The BIS value was measured 60 seconds after administration of the study drug, and at the time of rocuronium injection and intubation. The overall incidence of withdrawal movements due to rocuronium decreased significantly as the dose of dexmedetomidine increased (92.8%, 85.2%, 78.6%, and 51.9% in the saline, low-dose, subclinical dose, and clinical dose groups, respectively; P = 0.001). There was no significant difference in BIS values among the groups 60 seconds after study drug administration or at the time of rocuronium injection. Dexmedetomidine reduced pain associated with rocuronium injection in a dose-dependent manner. This effect was not associated with the decrease in BIS value. Copyright © 2014 Elsevier Inc. All rights reserved.

Sugammadex reversal of rocuronium-induced neuromuscular block in a patient with ataxia-telangiectasia

International Nuclear Information System (INIS)

Kang, E.; Jung, J.W.

2015-01-01

A 17-year-old adolescent with ataxia-telangiectasia was scheduled to have laparoscopic colectomy for a resection of colon cancer. He had symptoms and signs of dyspnea, generalized dystonia, dysmetria, ataxia, and telangiectasia on the orbit. General anesthesia was performed, and rocuronium 30 mg was administered for muscle relaxation. Deep neuromuscular block (post-tetanic count: 0-8) was maintained for 95 minutes without additional rocuronium. On completion of surgery, sugammadex 80 mg was injected and train-of-four ratio was 0.93 at 210 seconds after administration. The tracheal tube was removed 5 min after the end of surgery. He recovered full spontaneous respiration and voluntary movements within 1 minute after extubation. After the surgery, he transferred to the intensive care unit and discharged 14 days after the surgery without any concrete problem. The reversal of rocuronium induced neuromuscular block by sugammadex was fast, complete, and recovered to the initial preoperative level of neuromuscular function in this patient. (author)

Reversal of rocuronium-induced (1.2 mg kg-1) profound neuromuscular block by accidental high dose of sugammadex (40 mg kg-1).

NARCIS (Netherlands)

Molina, A.L.; Boer, H.D. de; Klimek, M.; Heeringa, M.; Klein, J.

2007-01-01

Sugammadex is the first selective relaxant binding agent and reverses rocuronium-induced neuromuscular block. A case is reported in which a patient accidentally received a high dose of sugammadex (40 mg kg-1) to reverse a rocuronium-induced (1.2 mg kg-1) profound neuromuscular block. A fast and

Evaluation of intubating conditions after rocuronium bromide in adults induced with propofol or thiopentone sodium

Directory of Open Access Journals (Sweden)

Moazzam Md Shahnawaz

2011-01-01

Full Text Available Aim: The aims of present study were to compare the propofol and rocuronium with thiopentone and rocuronium in terms of clinically satisfactory intubating conditions and to co-relate intubating conditions with degree of paralysis in adductor pollicis muscle using train of four ratio (TOFR. The intubating conditions were evaluated after rocuronium bromide 0.6 mg kg−1 at 60 s. Materials and Methods : 60 patients of ASA grades I-II of either sex, age 18-50 years, undergoing various elective surgical procedures were randomly divided into two groups, propofol rocuronium (PR group and thiopentone rocuronium (TR group of 30 patients in each. In the PR group, patients received propofol 2.5 mg kg−1 and rocuronium 0.6 mg kg−1 ; in TR group, patients received thiopentone 5 mg kg−1 and rocuronium 0.6 mg kg−1 . In all patients the intubating conditions were evaluated by the observer at 60 s. TOFR was measured at the time of intubation by an assistant. Results : In the PR group the number of the patients placed in intubating conditions grades I, II, III and IV were 40%, 36.67%, 13.33% and 10% and their mean TOFR were 31.8±17.9%, 61.8±;14.6%, 61.7±27.9%, and 78.3±5.7% respectively. While in theTR group the number of patients placed in intubating condition grade I, II, and III were 60%, 26.67%, and 13.33% and their mean TOFR , 41.2±28.3%, 68.0±10.9% and 78.7±6.8%, respectively. There was no patient in grade lV in theTR group. Conclusion : The clinical intubating conditions and degree of paralysis of adductor pollicis muscle after rocuronium 0.6 mg kg−1 at 60 s in adults induced with propofol or thiopentone sodium are comparable.

Effects of methylprednisolone on the duration of rocuronium-induced neuromuscular block

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Geng, Weilian; Nie, Yuyan; Huang, Shaoqiang

2017-01-01

Abstract Background: We aim to investigate whether intraoperative use of methylprednisolone could affect the duration of rocuronium-induced neuromuscular blockade. Methods: A double blind, randomized, placebo-controlled trial was conducted. A total of 136 patients underwent gynecologic laparoscopic surgery were randomly divided into 3 groups: pregroup, receiving intravenous injection of methylprednisolone (40 mg) 30 minutes before induction of anesthesia; postgroup, receiving intravenous injection of methylprednisolone (40 mg) immediately after induction of anesthesia and intubation; and control group, receiving intravenous injection of normal saline. Patients were intravenously administrated with rocuronium 0.6 mg/kg, and changes in adductor policies evoked twitch responses were measured by ulnar nerve stimulator. Results: We found that all patients achieved maximum blockade effects, and there was no difference in onset time among the 2 groups. For time required to achieve train-of-four ratio (TOFR) 90%, pregroup (64.50 ± 10.52 minutes) and postgroup (65.29 ± 11.64 minutes) were significantly shorter than that of the control group (71.04 ± 10.55 minutes, P = .027), whereas clinical duration and total duration were significantly shorter in the 2 groups received methylprednisolone than the control group. However, there was no significant difference between the 2 treatment groups either in clinical duration and total duration of muscle relaxants, or time required to achieve TOFR 90%. No significant difference was found in recovery index among the 3 groups. Conclusion: Our findings suggest that a single intravenous injection of methylprednisolone, no matter preoperatively or intraoperatively, could shorten the duration of rocuronium-induced neuromuscular blockade. PMID:28953616

[Comparison of neostigmine induced reversal of rocuronium in different age children].

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Liu, Jinzhu; Cheng, Zhaoyu

2016-03-15

To compare the effectiveness of neostigmine induced reversal of rocuronium in neonates, infants, young children and children. One hundred and sixty ASA I or II pediatric patients undergoings elective surgical procedures under total intravenous anesthesia were enrolled during July 2014 to April 2015 in Tianjin Children's Hospital. The patients were divided into four groups according to ages: neonate group, infant group, young children group and children group.Then control subgroup and neostigmine reversal subgroup including twenty patients were randomly selected from every different age groups by the method of random number table. After induction of anesthesia, 0.6 mg/kg rocuronium was administered, and 0.2 mg/kg maintenance doses given as required during period of operation. Neuromuscular block was monitored using acceleromyographic train of four (TOF). When T1/control returned to 15%, 0.03 mg/kg neostigmine and 0.01 mg/kg atropine were given to patients of reversal subgroups, and saline 0.1 ml/kg was given to patients of control subgroups. The recovery time of T25, T75, TR0.7, recovery index, blood pressure, heart rate and adverse reactions were observed and recorded. In control subgroups, the recovery time of T75 for neonates, infants, young children and children were (27.10±8.72), (16.70±6.35), (13.05±1.96), (14.40±3.08) min, respectively (F=25.052, P0.05). But the recovery time of T75, TR0.7 and recovery index in neonate group were longer than other age groups (all Procuronium are comparable in infant, young children and children. There are obviously reversal effects in all of age groups when neostigmine is given to antagonize rocuronium. Either spontaneous recovery time or reversal recovery time of neostigmine to rocuronium is longer for neonates than other age's children.

A case series of re-establishment of neuromuscular block with rocuronium after sugammadex reversal.

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Iwasaki, Hajime; Sasakawa, Tomoki; Takahoko, Kenichi; Takagi, Shunichi; Nakatsuka, Hideki; Suzuki, Takahiro; Iwasaki, Hiroshi

2016-06-01

We report the use of rocuronium to re-establish neuromuscular block after reversal with sugammadex. The aim of this study was to investigate the relationship between the dose of rocuronium needed to re-establish neuromuscular block and the time interval between sugammadex administration and re-administration of rocuronium. Patients who required re-establishment of neuromuscular block within 12 h after the reversal of rocuronium-induced neuromuscular block with sugammadex were included. After inducing general anesthesia and placing the neuromuscular monitor, the protocol to re-establish neuromuscular block was as follows. An initial rocuronium dose of 0.6 mg/kg was followed by additional 0.3 mg/kg doses every 2 min until train-of-four responses were abolished. A total of 11 patients were enrolled in this study. Intervals between sugammadex and second rocuronium were 12-465 min. Total dose of rocuronium needed to re-establish neuromuscular block was 0.6-1.2 mg/kg. 0.6 mg/kg rocuronium re-established neuromuscular block in all patients who received initial sugammadex more than 3 h previously. However, when the interval between sugammadex and second rocuronium was less than 2 h, more than 0.6 mg/kg rocuronium was necessary to re-establish neuromuscular block.

Effect of lung-protective ventilation-induced respiratory acidosis on the duration of neuromuscular blockade by rocuronium.

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Taguchi, Shinya; Ono, Kazumi; Hidaka, Hidekuni; Koyama, Yusuke

2016-12-01

The purpose of this study was to elucidate whether lung-protective ventilation-induced respiratory acidosis increased the duration of neuromuscular blockade by rocuronium. A total of 72 patients were enrolled. After the induction of general anesthesia, rocuronium 0.6 mg/kg real body weight was administered. Tidal volume and positive end-expiratory pressure were randomly assigned as either 10 ml/kg predicted body weight and 0 cmH 2 O (group S) or 6 ml/kg and 5 cmH 2 O (group L), respectively. Respiratory rate was started at 10/min. Neuromuscular blockade was monitored by acceleromyography at the adductor pollicis with train-of-four stimulation. The time from the initial bolus injection of rocuronium to first recovery of the first twitch was defined as DUR1. Immediately, rocuronium 0.15 mg/kg was administered. The time from first recovery of the first twitch to second recovery of the first twitch was defined as DUR2. We also measured arterial pH (pH1 and pH2, respectively). Data from 66 patients (33 each in groups L and S) were eventually available. pH1 and pH2 were significantly lower in group L compared with group S [pH1: 7.308 (7.288-7.334) vs. 7.439 (7.423-7.466); p respiratory acidosis increased the duration of neuromuscular blockade by rocuronium.

Sugammadex is effective in reversing rocuronium in the presence of antibiotics.

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Hudson, Mark E; Rietbergen, Henk; Chelly, Jacques E

2014-01-01

The effectiveness of sugammadex in reversing rocuronium-induced neuromuscular blockade (NMB) in the presence of drugs that may potentiate NMB remains to be fully established. The aim of this post-hoc analysis of data from a Phase III clinical trial (VISTA; NCT00298831) was to investigate the impact of antibiotics on recovery from rocuronium-induced NMB after administration of sugammadex for reversal, and compared the neuromuscular recovery in patients who received antibiotics preoperatively with those who did not. A Phase III, multicenter, open-label study designed to reflect potential use of sugammadex in clinical practice was conducted at 19 sites. Data obtained from patients who received antibiotics were compared with the cohort of patients who underwent the same protocol without antibiotics. Each subject received rocuronium 0.6 mg/kg for muscle relaxation, after which tracheal intubation was performed; patients were also permitted to receive maintenance doses of rocuronium 0.15 mg/kg to maintain the desired level of NMB throughout the operation, as required.. At least 15 min after the last rocuronium dose, patients received sugammadex 4.0 mg/kg for reversal. Neuromuscular monitoring was continued until a train-of-four (TOF) ratio of ≥0.9 was achieved or the anesthetic was discontinued. The presence of antibiotics prior to the administration of sugammadex did not affect the recovery time from rocuronium-induced NMB when sugammadex 4.0 mg/kg was administered at least 15 min after the last dose of rocuronium. In the presence of antibiotics, the geometric mean (95% CI) time from administration of sugammadex 4.0 mg/kg to recovery of the TOF ratio to ≥0.9 was 1.6 (1.4-1.9) min (range: 0.7-10.5 min), compared with 2.0 (1.8-2.3) min (range: 0.7-22.3 min) for patients who did not receive antibiotics. These findings suggest that prophylactic antibiotic use is unlikely to have a major impact on the recovery time from rocuronium-induced NMB with sugammadex

Time course of action of sugammadex (Org 25969) on rocuronium-induced block in the Rhesus monkey, using a simple model of equilibration of complex formation.

NARCIS (Netherlands)

Boer, H.D. de; Egmond, J. van; Pol, F. van de; Bom, A.; Driessen, J.J.; Booij, L.H.D.J.

2006-01-01

BACKGROUND: Reversal of neuromuscular block can be accomplished by chemical encapsulation of rocuronium by sugammadex (Org 25969), a synthetic gamma-cyclodextrin derivative. The present study determined the time course of the reversal action of sugammadex on rocuronium-induced block in the

Reversal of profound rocuronium neuromuscular blockade by sugammadex in anesthetized rhesus monkeys.

NARCIS (Netherlands)

Boer, H.D. de; Egmond, J. van; Pol, F. van de; Bom, A.; Booij, L.H.D.J.

2006-01-01

BACKGROUND: Reversal of neuromuscular blockade can be accomplished by chemical encapsulation of rocuronium by sugammadex, a synthetic gamma-cyclodextrin derivative. The current study determined the feasibility of reversal of rocuronium-induced profound neuromuscular blockade with sugammadex in the

Sugammadex, a new reversal agent for neuromuscular block induced by rocuronium in the anaesthetized Rhesus monkey.

NARCIS (Netherlands)

Boer, H.D. de; Egmond, J. van; Pol, F. van de; Bom, A.; Booij, L.H.D.J.

2006-01-01

BACKGROUND: Binding of the steroidal molecule of rocuronium by a cyclodextrin is a new concept for reversal of neuromuscular block. The present study evaluated the ability of Sugammadex Org 25969, a synthetic gamma-cyclodextrin derivative, to reverse constant neuromuscular block of about 90% induced

Negative Pressure Pulmonary Edema after Reversing Rocuronium-Induced Neuromuscular Blockade by Sugammadex

Directory of Open Access Journals (Sweden)

Manzo Suzuki

2014-01-01

Full Text Available Negative pressure pulmonary edema (NPPE is a rare complication that accompanies general anesthesia, especially after extubation. We experienced a case of negative pressure pulmonary edema after tracheal extubation following reversal of rocuronium-induced neuromuscular blockade by sugammadex. In this case, the contribution of residual muscular block on the upper airway muscle as well as large inspiratory forces created by the respiratory muscle which has a low response to muscle relaxants, is suspected as the cause.

Reversal of profound, high-dose rocuronium-induced neuromuscular blockade by sugammadex at two different time points - An international, multicenter, randomized, dose-finding, safety assessor-blinded, phase II trial

DEFF Research Database (Denmark)

Puhringer, F.K.; Rex, C.; Sielenkamper, A.W.

2008-01-01

Background: Sugammadex (Org 25969), a novel, selective relaxant binding agent, was specifically designed to rapidly reverse rocuronium-induced neuromuscular blockade. The efficacy and safety of sugammadex for the reversal of profound, high-dose rocuronium-induced neuromuscular blockade...... was evaluated. Methods: A total of 176 adult patients were randomly assigned to receive sugammadex (2, 4, 8, 12, or 16 mg/kg) or placebo at 3 or 15 min after high-dose rocuronium (1.0 or 1.2 mg/kg) during propofol anesthesia. The primary endpoint was time to recovery of the train-of-four ratio to 0.......9. Neuromuscular monitoring was performed using acceleromyography. Results: Sugammadex administered 3 or 15 min after injection of 1 mg/kg rocuronium decreased the median recovery time of the train-of-four ratio to 0.9 in a dose-dependent manner from 111.1 min and 91.0 min (placebo) to 1.6 min and 0.9 min (16 mg...

Optimal precurarizing dose of rocuronium to decrease fasciculation and myalgia following succinylcholine administration.

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Kim, Kyu Nam; Kim, Kyo Sang; Choi, Hoon Il; Jeong, Ji Seon; Lee, Hee-Jong

2014-06-01

Succinylcholine commonly produces frequent adverse effects, including muscle fasciculation and myalgia. The current study identified the optimal dose of rocuronium to prevent succinylcholine-induced fasciculation and myalgia and evaluated the influence of rocuronium on the speed of onset produced by succinylcholine. This randomized, double-blinded study was conducted in 100 patients randomly allocated into five groups of 20 patients each. Patients were randomized to receive 0.02, 0.03, 0.04, 0.05 and 0.06 mg/kg rocuronium as a precurarizing dose. Neuromuscular monitoring after each precurarizing dose was recorded from the adductor pollicis muscle using acceleromyography with train-of-four stimulation of the ulnar nerve. All patients received succinylcholine 1.5 mg/kg at 2 minutes after the precurarization, and were assessed the incidence and severity of fasciculations, while myalgia was assessed at 24 hours after surgery. The incidence and severity of visible muscle fasciculation was significantly less with increasing the amount of precurarizing dose of rocuronium (P rocuronium, but there was no significance (P = 0.072). The onset time of succinylcholine was significantly longer with increasing the amount of precurarizing dose of rocuronium (P rocuronium was the optimal dose considering the reduction in the incidence and severity of fasciculation and myalgia with acceptable onset time, and the safe and effective precurarization.

Recovery from prolonged deep rocuronium-induced neuromuscular blockade: A randomized comparison of sugammadex reversal with spontaneous recovery.

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Rahe-Meyer, N; Berger, C; Wittmann, M; Solomon, C; Abels, E A M; Rietbergen, H; Reuter, D A

2015-07-01

Deep neuromuscular blockade (NMB) may not always be maintained to the end of surgery and the depth of block may be allowed to gradually diminish over time, particularly if reversal of NMB is not routinely performed. The current study aimed to assess recovery from deep rocuronium-induced NMB with sugammadex compared with placebo, provide data regarding the extent of residual blockade after deep rocuronium-induced NMB (placebo group), and to determine whether complete and reliable recovery could be provided by sugammadex (sugammadex group). This was a randomized, placebo-controlled, safety-assessor-blinded study in adult patients of American Society of Anesthesiologists Class I to III. Patients with clinically relevant kidney or liver insufficiency were excluded. Anesthesia was administered as routinely practiced at each study site. Rocuronium 0.6 mg/kg was administered for intubation, with maintenance doses of 0.1-0.2 mg/kg as needed. After the last rocuronium dose, at deep NMB (target depth 1-2 post-tetanic counts), patients received a single dose of sugammadex 4.0 mg/kg or placebo as randomized. The primary endpoint was time from sugammadex or placebo administration to recovery of the train-of-four (TOF) ratio to 0.9. Safety was assessed through monitoring of adverse events, vital signs and physical examination. Patients were also assessed for evidence of residual or recurrence of NMB. With this design, the study will provide data regarding the extent of residual blockade under these conditions (placebo group), and determine whether complete and reliable recovery could be provided by sugammadex (sugammadex group). Recovery to a TOF ratio of ≥ 0.9 with sugammadex was significantly faster (~ 40 times) than spontaneous recovery: geometric mean (95 % confidence interval) times were 2.2 (1.9-2.5) and 89.8 (80.1-100.7) min, respectively (p sugammadex, with median time to recovery > 1.5 h in the placebo group and one patient taking 4.8 h to achieve a

Non-IgE-Dependent Hypersensitivity to Rocuronium Reversed by Sugammadex: Report of Three Cases and Hypothesis on the Underlying Mechanism.

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Spoerl, David; D'Incau, Stéphanie; Roux-Lombard, Pascale; Harr, Thomas; Czarnetzki, Christoph

2016-01-01

We present 3 cases of pseudoallergic (anaphylactoid) reactions to perioperatively administered rocuronium, which rapidly resolved after sugammadex injection. Allergological workup showed no evidence for immediate-type hypersensitivity to the drugs used for anesthesia, including rocuronium. However, rocuronium induced an irritative reaction in skin tests in all 3 patients and in 3 healthy individuals. This reaction was specifically suppressed by adding sugammadex at a 1:1 molecular proportion to rocuronium before the skin tests. This observation suggests that the patients suffered from a pseudoallergic reaction, and indicates that sugammadex might act via the inhibition of non-IgE mediated MRGPRX2 (Mas-related G-protein-coupled receptor member X2)-triggered mast cell degranulation induced by rocuronium. © 2016 S. Karger AG, Basel.

EARLY AND LATE REVERSIBILITY OF ROCURONIUM BROMIDE

NARCIS (Netherlands)

VANDENBROEK, L; PROOST, JH; WIERDA, JMKH

A computer simulation has been developed based on pharmacodynamic-pharmacokinetic modelling of the effect of neostigmine on rocuronium-induced neuromuscular blockade. The results of a previous study involving 60 patients were used as a test of the model. The model predicts that administration of

Reversal of rocuronium-induced neuromuscular block by sugammadex is independent of renal perfusion in anesthetized cats

NARCIS (Netherlands)

Staals, L.M.; Boer, H.D. de; Egmond, J. van; Hope, F.; Pol, F.M. van de; Bom, A.H.; Driessen, J.J.; Booij, L.H.D.J.

2011-01-01

PURPOSE: Sugammadex is a selective relaxant binding agent designed to encapsulate the aminosteroidal neuromuscular blocking agent rocuronium, thereby reversing its effect. Both sugammadex and the sugammadex-rocuronium complex are eliminated by the kidneys. This study investigated the effect of

Competitive inhibition of the nondepolarizing muscle relaxant rocuronium on nicotinic acetylcholine receptor channels in the rat superior cervical ganglia.

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Zhang, Chengmi; Wang, Zhenmeng; Zhang, Jinmin; Qiu, Haibo; Sun, Yuming; Yang, Liqun; Wu, Feixiang; Zheng, Jijian; Yu, Weifeng

2014-05-01

A number of case reports now indicate that rocuronium can induce a number of serious side effects. We hypothesized that these side effects might be mediated by the inhibition of nicotinic acetylcholine receptors (nAChRs) at superior cervical ganglion (SCG) neurons. Conventional patch clamp recordings were used to study the effects of rocuronium on nAChR currents from enzymatically dissociated rat SCG neurons. We found that ACh induced a peak transient inward current in rat SCG neurons. Additionally, rocuronium suppressed the peak ACh-evoked currents in rat SCG neurons in a concentration-dependent and competitive manner, and it increased the extent of desensitization of nAChRs. The inhibitory rate of rocuronium on nAChR currents did not change significantly at membrane potentials between -70 and -20 mV, suggesting that this inhibition was voltage independent. Lastly, rocuronium preapplication enhanced its inhibitory effect, indicating that this drug might prefer to act on the closed state of nAChR channels. In conclusion, rocuronium, at clinically relevant concentrations, directly inhibits nAChRs at the SCG by interacting with both opened and closed states. This inhibition is competitive, dose dependent, and voltage independent. Blockade of synaptic transmission in the sympathetic ganglia by rocuronium might have potentially inhibitory effects on the cardiovascular system.

Interaction of rocuronium with human liver cytochromes P450.

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Anzenbacherova, Eva; Spicakova, Alena; Jourova, Lenka; Ulrichova, Jitka; Adamus, Milan; Bachleda, Petr; Anzenbacher, Pavel

2015-02-01

Rocuronium is a neuromuscular blocking agent acting as a competitive antagonist of acetylcholine. Results of an inhibition of eight individual liver microsomal cytochromes P450 (CYP) are presented. As the patients are routinely premedicated with diazepam, possible interaction of diazepam with rocuronium has been also studied. Results indicated that rocuronium interacts with human liver microsomal CYPs by binding to the substrate site. Next, concentration dependent inhibition of liver microsomal CYP3A4 down to 42% (at rocuronium concentration 189 μM) was found. This effect has been confirmed with two CYP3A4 substrates, testosterone (formation of 6β-hydroxytestosterone) and diazepam (temazepam formation). CYP2C9 and CYP2C19 activities were inhibited down to 75-80% (at the same rocuronium concentration). Activities of other microsomal CYPs have not been inhibited by rocuronium. To prove the possibility of rocuronium interaction with other drugs (diazepam), the effect of rocuronium on formation of main diazepam metabolites, temazepam (by CYP3A4) and desmethyldiazepam, (also known as nordiazepam; formed by CYP2C19) in primary culture of human hepatocytes has been examined. Rocuronium has caused inhibition of both reactions by 20 and 15%, respectively. The results open a possibility that interactions of rocuronium with drugs metabolized by CYP3A4 (and possibly also CYP2C19) may be observed. Copyright © 2014 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.

Effects of nicardipine on the onset time and intubation conditions of rocuronium-induced neuromuscular blockade.

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Lee, Sun-Yeul; Kim, Yoon-Hee; Ko, Young-Kwon; Park, Sang-Il; Lee, Jung-Un; Chung, Woo-Suk; Lim, Chae-Seong

2016-08-01

The objective of this study was to identify the effects of nicardipine on neuromuscular blockade of rocuronium, such as the onset time and intubation conditions, using a nicardipine dose that attenuates cardiovascular responses during endotracheal intubation. Randomized, double-blinded, placebo-controlled clinical comparison was used as the design of this study The study was conducted at the operating room of a university hospital. Participants of this study comprise 78 American Society of Anesthesiologists physical status 1 and 2 patients, aged 18 to 60 years who were undergoing elective surgery under general anesthesia. The nicardipine group was given an intravenous bolus of 20 μg/kg nicardipine before tracheal intubation: the control group was given an intravenous bolus of a comparable volume of normal saline before tracheal intubation. Using a TOF-Watch SX monitor, the time from the end of the injection of rocuronium to maximum depression of T1 (onset time) was measured. Intubation was performed 1 minute after rocuronium administration, and the status of the intubation conditions was assessed. The mean blood pressure and heart rate were each measured after endotracheal intubation. Rate pressure product values were also calculated. Intubation conditions were clinically acceptable in 37 (94.9%) of 39 patients in group N compared with 29 (74.4%) of 39 in group C (P rocuronium was significantly faster in group N than in group C (P .05). Pretreatment with 20 μg/kg nicardipine improves intubation conditions, shortens the onset time of rocuronium, and attenuates cardiovascular responses to tracheal intubation. Copyright © 2016 Elsevier Inc. All rights reserved.

Intubation conditions in young infants after propofol and remifentanil induction with and without low-dose rocuronium.

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Gelberg, J; Kongstad, L; Werner, O

2014-08-01

Bolus injections of intravenous propofol and remifentanil can be used in the tracheal intubation of infants and children, but relatively large doses are needed. We hypothesised that addition of a small bolus of rocuronium would ensure good intubation conditions when modest propofol and remifentanil doses were used. Seventy infants between 3 weeks and 4 months of age were randomised to receive either placebo or rocuronium. Anaesthesia was induced with IV propofol, 3 (3-5) mg/kg [median (range)]. Rocuronium (0.2 mg/kg) or placebo was then injected, followed 15 s later by 2 μg/kg remifentanil. One anaesthetist attempted tracheal intubation 1 min after the rocuronium/placebo injection and used the 'Copenhagen scoring system' to assess intubation conditions. The neuromuscular effect of 0.2 mg/kg rocuronium was recorded in another eight, already intubated, infants using thumb accelerometry during train-of-four stimulation of the ulnar nerve. Intubation conditions were classified as 'poor' in 14 of 34 (41%) patients given placebo and in 10 of 36 (28%) patients given rocuronium (P = 0.32). There were four failed first attempts at intubation in the placebo group and none in the rocuronium group (P = 0.051). Maximum neuromuscular depression occurred 4 (3-8) after injection of 0.2 mg/kg rocuronium. Intubation conditions were poor in almost one third of the patients receiving propofol-remifentanil. Adding a low-dose rocuronium did not significantly improve intubation conditions. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

A randomized, dose-response study of sugammadex given for the reversal of deep rocuronium- or vecuronium-induced neuromuscular blockade under sevoflurane anesthesia

DEFF Research Database (Denmark)

Duvaldestin, Philippe; Kuizenga, Karel; Saldien, Vera

2010-01-01

Sugammadex is the first of a new class of selective muscle relaxant binding drugs developed for the rapid and complete reversal of neuromuscular blockade induced by rocuronium and vecuronium. Many studies have demonstrated a dose-response relationship with sugammadex for reversal of neuromuscular...

A Randomized, Dose-Response Study of Sugammadex Given for the Reversal of Deep Rocuronium- or Vecuronium-Induced Neuromuscular Blockade Under Sevoflurane Anesthesia

NARCIS (Netherlands)

Duvaldestin, Philippe; Kuizenga, Karel; Saldien, Vera; Claudius, Casper; Servin, Frederique; Klein, Jan; Debaene, Bertrand; Heeringa, Marten

BACKGROUND: Sugammadex is the first of a new class of selective muscle relaxant binding drugs developed for the rapid and complete reversal of neuromuscular blockade induced by rocuronium and vecuronium. Many studies have demonstrated a close-response relationship with sugammadex for reversal of

Sugammadex ED90 dose to reverse the rocuronium neuromuscular blockade in obese patients

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MAURO PRADO DA SILVA

Full Text Available ABSTRACT Objective: to determine the ED90 (minimum effective dose in 90% of patients of sugammadex for the reversal of rocuronium-induced moderate neuromuscular blockade (NMB in patients with grade III obesity undergoing bariatric surgery. Methods: we conducted a prospective study with the biased coin up-and-down sequential design. We chosen the following doses: 2.0mg/Kg, 2.2mg/Kg, 2.4mg/Kg, 2.6mg/Kg, 2.8mg/Kg. The complete reversal of rocuronium-induced NMB considered a T4/T1 ratio ≥0.9 as measured by TOF. After induction of general anesthesia and calibration of the peripheral nerve stimulator and accelerometer, we injected rocuronium 0.6mg/kg. We administered propofol and remifentanil by continuous infusion, and intermittent boluses of rocuronium throughout the procedure. Results: we evaluated 31 patients, of whom 26 had displayed successful reversal of the NMB with sugammadex, and failure in five. The mean time to complete moderate NMB reversal was 213 seconds (172-300, median 25-75%. The ED90 of sugammadex calculated by regression was 2.39mg/kg, with a 95% confidence interval of 2.27-2.46 mg/kg. Conclusion: the ED90 of sugammadex in patients with grade III obesity or higher was 2.39mg/kg.

Rocuronium is more hepatotoxic than succinylcholine in vitro.

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Sauer, Martin; Piel, Ines; Haubner, Cristof; Richter, Georg; Mann, Miriam; Nöldge-Schomburg, Gabriele; Mencke, Thomas

2017-09-01

The development of liver failure is a major problem in critically ill patients. The hepatotoxicity of many drugs, as one important reason for liver failure, is poorly screened for in human models. Rocuronium and succinylcholine are neuromuscular blocking agents used for tracheal intubation and for rapid-sequence induction. We used an in-vitro test with a permanent cell line and compared rocuronium and succinylcholine for hepatotoxicity. In-vitro study. A basic science laboratory, University Hospital Rostock, Germany. The basic test compound is the permanent human liver cell line HepG2/C3A. In a standardised microtitre plate assay the toxicity of different concentrations of rocuronium, succinylcholine and plasma control was tested. After two incubation periods of 3 days, the viability of cells (XTT test, lactate dehydrogenase release and trypan blue staining), micro-albumin synthesis and the cytochrome 1A2 activity (metabolism of ethoxyresorufin) were measured. Differences between rocuronium and succinylcholine were assessed using the Kruskal-Wallis one-way test and two-tailed Mann-Whitney U test. Rocuronium, but not succinylcholine, led to a significant dose-dependent decrease of viability, albumin synthesis and cytochrome 1A2 activity of test cells. An in-vitro test with a cell line showed hepatotoxicity of rocuronium that was dose-dependent. Further studies are needed to investigate the underlying mechanisms of the effects of rocuronium on hepatic cellular integrity. Not suitable.

Pharmacokinetics and pharmacodynamics of rocuronium in young adult and elderly patients undergoing elective surgery.

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Varrique, Renan M; Lauretti, Gabriela R; Matsumoto, Julia A; Lanchote, Vera L; de Moraes, Natalia V

2016-11-01

To evaluate the impact of advanced age on rocuronium kinetic disposition in ASA I-III patients undergoing elective surgeries. Young adult (20-50 years, n = 15) and elderly patients (65-85 years, n = 14) submitted to surgery under general anaesthesia were investigated. All patients were induced with individual intravenous doses of midazolam, rocuronium, fentanyl and propofol. Rocuronium-induced neuromuscular block was monitored by train of four stimulations of the adductor muscle of the thumb on the ulnar nerve. The pharmacokinetic parameters were calculated by non-compartmental analysis. The relationship between rocuronium plasma concentration and the neuromuscular blockade was described by a sigmoidal Emax model. Elderly patients presented decreased Cl (2.1 ml/kg per min vs 2.8 ml/kg per min; P = 0.0123); increased AUC/dose (507.8 μg min/ml (mg/kg) vs 392.2 μg min/ml/(mg/kg); P = 0.0168) and reduced volume of distribution (285.4 ml/kg vs 435.6 ml/kg, P = 0.0434) compared to young adults. The concentrations required to achieve 50% of maximum neuromuscular block (EC50) were similar for young adult (338.8 ng/ml) and elderly (462.7 ng/ml) patients (P > 0.05). Elderly patients showed increased AUC/D and reduced total Cl compared to young adult patients due to the age-related reduced renal function. Differences in the PK-PD properties of rocuronium in elderly population are due to changes in drug disposition rather than to alterations in the sensitivity to the drug. © 2016 Royal Pharmaceutical Society.

Influence of obstructive jaundice on pharmacodynamics of rocuronium.

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Wang, Zhen-Meng; Zhang, Peng; Lin, Mi-Jia; Tan, Bo; Qiu, Hai-Bo; Yu, Wei-Feng

2013-01-01

Anesthetics are variable in patients with obstructive jaundice. The minimum alveolar concentration awake of desflurane is reduced in patients with obstructive jaundice, while it has no effect on pharmacodynamics and pharmacokinetics of propofol. In this study, we investigated the influence of obstructive jaundice on the pharmacodynamics and blood concentration of rocuronium. Included in this study were 26 control patients and 27 patients with obstructive jaundice. Neuromuscular block of rocuronium was monitored by acceleromyography. Onset time, spontaneous recovery of the height of twitch first (T1) to 25% of the final T1 value (Duration 25%, Dur 25%), recovery index (RI), and spontaneous recovery of train-of-four (TOF) ratios to 70% were measured. The plasma rocuronium concentrations were determined by high performance liquid chromatography using berberine as an internal standard. There was no significant difference in onset time between the two groups. The Dur 25%, the recovery index and the time of recovery of the TOF ratios to 70% were all prolonged in the obstructive jaundice group compared with the control group. The plasma concentration of rocuronium at 60, 90 and 120 min after bolus administration was significantly higher in the obstructive jaundice group. The neuromuscular blockade by rocuronium is prolonged in obstructive jaundice patients, and therefore precautions should be taken in case of postoperative residual neuromuscular block. The possible reason is impedance of rocuronium excretion due to biliary obstruction and increased plasma unbound rocuronium because of free bilirubin competing with it for albumin binding.

Biochemical changes following succinylcholine administration after pretreatment with rocuronium at different intervals

International Nuclear Information System (INIS)

Farhat, K.; Jaffery, N.; Pasha, A.K.

2014-01-01

Objective: To evaluate the biochemical changes associated with succinylcholine administration after pretreatment with rocuronium at different time intervals. Method: The prospective, randomised, single-blinded study was conducted at the Combined Military Hospital, Rawalpindi, from January to May 2010. Ninety male, aged 18-60 years, American Society of Anaesthesiology I or II patients undergoing elective inguinal herniotomy or external haemorrhoidectomy were included. The patients were randomly divided into three equal groups. Group A received a normal saline 5ml as placebo 1 minute before succinylcholine; Group B received rocuronium 0.06 mg/kg 1 intravenously minute before succinylcholine, while Group C received intravenous injection of rocuronium 0.06 mg/kg 5 minute before succinylcholine. Venous blood samples for creatinine phosphokinase, lactate dehydrogenase and myoglobin plasma concentrations were obtained at 0, 30 minutes, 6 hours and 24 hours after succinylcholine administration. Results: Mean serum creatinine phosphokinase and myoglobin concentrations were significantly decreased in Groups B and C compared to Group A at 30 minutes and 24 hours (p<0.05). However, no significant difference in the enzyme levels at any time interval was observed among the rocuronium groups. There was a significant rise in lactate dehydrogenase concentrations at 6 hours and 24 hours in Group A compared to Groups B and C (p<0.05). Conclusion: Pretreatment with rocuronium effectively reduces the biochemical changes associated with succinylcholine-induced muscle fasciculations. However, whether it is given 1 minute or 5 minutes before succinylcholine does not make much difference. (author)

Sugammadex for reversal of rocuronium-induced neuromuscular blockade in pediatric patients

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Won, Young Ju; Lim, Byung Gun; Lee, Dong Kyu; Kim, Heezoo; Kong, Myoung Hoon; Lee, Il Ok

2016-01-01

Abstract Background: Previous studies have shown that sugammadex, a modified γ-cyclodextrin, is a well-tolerated agent for the reversal of neuromuscular blockade (NMB) induced by a steroidal neuromuscular blocking drug in adult patients. However, its use has not been reviewed in pediatric patients. The aim of this meta-analysis was to evaluate the efficacy and safety of sugammadex in the reversal of rocuronium-induced NMB during surgery under general anesthesia in pediatric patients. Methods: A literature search was performed using the Pubmed, EMBASE: Drugs and pharmacology, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. Analysis was conducted using RevMan 5.3. Data collected from different trials were pooled; the weighted mean difference or the pooled risk ratio and the corresponding 95% confidence interval (CI) were used for analysis, and heterogeneity (I2) assessment was performed. Results: Six randomized controlled trials comparing 253 pediatric patients (age range, 2–18 years) were included in the final analysis. The mean time taken to reach a train-of-four ratio of ≥0.9 was significantly shorter in the sugammadex groups (2 and 4 mg/kg) than in the control group (neostigmine or placebo), although the heterogeneity was high. The weighted mean differences of the 2 and 4 mg/kg sugammadex groups were −7.15 (95% CI: −10.77 to −3.54; I2 = 96%; P = 0.0001) and −17.32 (95% CI: −29.31 to −5.32; I2 = 98%; P = 0.005), respectively. The extubation time in the sugammadex group was shorter than that in the control group; the weighted mean difference of the sugammadex group was −6.00 (95% CI: −11.46 to −0.53; I2 = 99%; P = 0.03). There was no significant difference between the groups in terms of the incidence of postanesthetic adverse events; the pooled risk ratio was 0.67 (95% CI: 0.27–1.71; I2 = 59%; P = 0.41). Conclusion: We suggest that sugammadex is fast and

Tracheal intubation with rocuronium using a "modified timing principle".

Science.gov (United States)

Kwon, Min A; Song, Jaegyok; Kim, Ju-Ri

2013-03-01

Rapid sequence induction (RSI) is indicated in various situations. Succinylcholine has been the muscle relaxant of choice for RSI, and rocuronium has become an alternative medicine for patients who cannot be administered succinylcholine for various reasons. Although rocuronium has the most rapid onset time among non-depolarizing muscle relaxants, the standard dose of rocuronium (0.6 mg/kg) takes 60 seconds to achieve appropriate muscle relaxation. We evaluated intubating conditions using the "modified timing principle" with rocuronium and succinylcholine. In this prospective controlled blinded study, all patients received 1.5 µg/kg fentanyl intravenously with preoxygenation for 2 minutes and were randomized to receive 0.6 mg/kg rocuronium followed by 1.5 mg/kg propofol or 1.5 mg/kg propofol and 1.5 mg/kg succinylcholine. The rocuronium group was intubated just after confirming loss of consciousness, and the succinylcholine group was intubated 1 minute after injecting succinylcholine. Intubation condition, timing of events, and complications were recorded. All patients were successfully intubated in both groups. Apnea time of the rocuronium group (38.5 seconds) was significantly shorter than that in the succinylcholine group (100.7 seconds). No significant differences were observed in loss of consciousness time or intubation time. The succinylcholine group tended to show better intubation conditions, but no significant difference was observed. None of the patients complained awareness of the intubation procedure or had respiratory difficulty during a postoperative interview. The modified RSI with rocuronium showed shorter intubation sequence, acceptable intubation conditions, and a similar level of complications compared to those of conventional RSI with succinylcholine.

Suxamethonium administration prolongs the duration of action of subsequent rocuronium.

NARCIS (Netherlands)

Robertson, E.N.; Driessen, J.J.; Booij, L.H.D.J.

2004-01-01

BACKGROUND AND AIM: Rocuronium may be given to patients for intubation and also after they have received suxamethonium for intubation. The neuromuscular profile of rocuronium given after recovery from suxamethonium may not be identical to that when rocuronium has been given alone. The neuromuscular

Effect of Paracetamol Pretreatment on Rocuronium-Induced Injection Pain: A Randomized, Double-Blind, Placebo-Controlled Comparison with Lidocaine

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Gulnaz Ates

2013-10-01

Full Text Available Aim: To compare the effect of intravenous paracetamol on rocuronium-induced injection pain with that of lidocaine. Material and Method: One hundred and eighty patients scheduled for elective surgery under general anesthesia were recruited to this prospective, randomized, double-blinded, placebo-controlled study. A 20-gauge cannula was inserted into a vein on the dorsum of the patient%u2019s left hand and lactated Ringer%u2019s solution was infused at 100 ml/h. After 5 minutes, infusion was stopped and the left arm of the patient%u2019s was elevated for 15 seconds for gravity of venous blood. While venous occlusion was applied to the left upper arm using a pneumatic tourniquet, one of the pretreatment solutions (normal saline 5 mL, lidocaine 40 mg, paracetamol 50 mg was injected over a period of 10 seconds. The intensity of the pain patients experienced was assessed using a 4-point verbal rating scale in Group C (normal saline 5 mL, n=60, Group L (lidocaine 40 mg, n=60 and Group P (paracetamol 50 mg, n=60. After 2 minutes, the venous occlusion was released and the patients received 0.06 mg/kg rocuronim bromide over 10 seconds and the rocuronim-induced pain was assessed. Results: The overall incidence of rocuronium-induced injection pain was significantly more in Group C than the other groups (p

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.

Saline Flush After Rocuronium Bolus Reduces Onset Time and Prolongs Duration of Effect: A Randomized Clinical Trial.

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Ishigaki, Sayaka; Masui, Kenichi; Kazama, Tomiei

2016-03-01

Circulatory factors modify the onset time of neuromuscular-blocking drugs. Therefore, we hypothesized that infusion of a saline flush immediately after rocuronium administration would shorten the onset time without influencing the duration of the rocuronium effect. Forty-eight patients were randomly allocated to the control or saline flush group. Anesthesia was induced and maintained with propofol and remifentanil, and all patients received 0.6 mg/kg rocuronium in 10 mL of normal saline. In the saline flush group, 20 mL normal saline was immediately infused after rocuronium administration. Neuromuscular blockade was assessed using acceleromyography at the adductor pollicis muscle with train-of-four (TOF) stimulation. The neuromuscular indices for rocuronium were calculated as follows: the latent onset time, defined as the time from the start of rocuronium infusion until first occurrence of depression of the first twitch of the TOF (T1) ≥5%; onset time, defined as the time from the start of rocuronium infusion until first occurrence of depression of the T1 ≥95%; clinical duration, defined as the time from the start of rocuronium administration until T1 recovered to 25% of the final T1 value; recovery index, defined as the time for recovery of T1 from 25% to 75% of the final T1 value; and the total recovery time, defined as the time from the start of rocuronium administration until reaching a TOF ratio of 0.9. Significance was designated at P rocuronium bolus by 17%, 24%, and 14%, respectively. In addition, the recovery phase was significantly prolonged in the saline flush group. The mean clinical duration (5th-95th percentile range) in the saline flush group and control group was 35 minutes (27-63 minutes) and 31 minutes (19-48 minutes; P = 0.032), respectively; the recovery index was 13 minutes (8-25 minutes) and 10 minutes (7-19 minutes; P = 0.019), respectively; and the total recovery time was 61 minutes (44-108 minutes) and 50 minutes (35-93 minutes; P = 0

Interaction of rocuronium with human liver cytochromes P450

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Anzenbacherova, Eva; Spicakova, Alena; Jourova, Lenka; Ulrichova, Jitka; Adamus, Milan; Bachleda, Petr; Anzenbacher, Pavel

2015-01-01

Rocuronium is a neuromuscular blocking agent acting as a competitive antagonist of acetylcholine. Results of an inhibition of eight individual liver microsomal cytochromes P450 (CYP) are presented. As the patients are routinely premedicated with diazepam, possible interaction of diazepam with rocuronium has been also studied. Results indicated that rocuronium interacts with human liver microsomal CYPs by binding to the substrate site. Next, concentration dependent inhibition of liver micro...

Effects of Combined Rocuronium and Cisatracurium in Laparoscopic Cholecystectomy.

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Park, Woo Young; Lee, Kwang Ho; Lee, Young Bok; Kim, Myeong Hoon; Lim, Hyun Kyo; Choi, Jong Bum

2017-01-01

Laparoscopic upper abdominal surgery can cause spontaneous respiration due to diaphragmatic stimulation and intra-abdominal CO 2 inflation. Therefore, sufficient muscle relaxation is necessary for a safe surgical environment. We investigated if the combination of rocuronium and cisatracurium can counteract the delayed onset of cisatracurium's action and delayed recovery of muscle relaxation and whether the dosage of rocuronium, which is metabolized hepatically, can be reduced. A total of 75 patients scheduled for laparoscopic cholecystectomy with an American Society of Anesthesiology physical status I-II, in the age range of 20-60 years, and with a 20-30 kg/m 2 body mass index were included in the study. The patients were divided into the following groups: combination group (Group RC, rocuronium 0.3 mg/kg and cisatracurium 0.05 mg/kg), rocuronium group (Group R, rocuronium 0.6 mg/kg), and cisatracurium group (Group C, cisatracurium 0.1 mg/kg), and the onset, 25% duration, recovery index, and addition/time ratio were measured. Patients in Group RC exhibited a significantly different addition/time ratio compared with patients in the other two groups (p = 0.003). During laparoscopic cholecystectomy, the 95% effective dose of rocuronium in combination with cisatracurium is expected to provide a sufficient muscle relaxant effect.

Rocuronium-sugammadex use for electroconvulsive therapy in a hemodialysis patient: a case report.

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Kurita, Shigeaki; Moriwaki, Katsuyuki; Shiroyama, Kazuhisa; Sanuki, Mikako; Toyota, Yukari; Takebayashi, Minoru

2016-01-01

Recently, rocuronium with subsequent use of sugammadex was proposed for electroconvulsive therapy (ECT) as an alternative to succinylcholine. Because sugammadex is cleared via the kidney with no metabolism, it is unknown that rocuronium-sugammadex use is safe in hemodialysis patients who received ECT. In this case report, we used rocuronium with subsequent administration of sugammadex in a 69-year-old female, hemodialysis patient, scheduled for ten ECT sessions for severe major depression. In the initial eight sessions, we tested the feasibility of rocuronium-sugammadex use for ECT. During the series of four ECT sessions, we measured plasma concentrations for the sum of sugammadex and sugammadex-rocuronium complex and observed whether possible residual sugammadex affected muscle relaxation during subsequent sessions of ECT. The results showed the feasibility of rocuronium-sugammadex use as muscle relaxants for ECT in patients undergoing hemodialysis. However, an accumulation of sugammadex did occur even after two sessions of hemodialysis, and residual sugammadex decreased the effect of the rocuronium given in the subsequent ECT sessions. Rocuronium-sugammadex was successfully utilized as muscle relaxants for ECT in this patient. Our experience in this case may indicate that if succinylcholine is contraindicated, rocuronium-sugammadex can be an alternative method for muscle relaxation during ECT in patients undergoing hemodialysis. When this rocuronium-sugammadex procedure is used, the effect of residual sugammadex after hemodialysis on the subsequently administered rocuronium should be considered.

Pharmacological interventions for acceleration of the onset time of rocuronium: a meta-analysis.

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Dong, Jing; Gao, Lingqi; Lu, Wenqing; Xu, Zifeng; Zheng, Jijian

2014-01-01

Rocuronium is an acceptable alternative when succinylcholine is contraindicated for facilitating the endotracheal intubation. However, the onset time of rocuronium for good intubation condition is still slower than that condition of succinylcholine. This study systematically investigated the most efficacious pharmacological interventions for accelerating the onset time of rocuronium. Medline, Embase, Cochrane Library databases, www.clinicaltrials.gov, and hand searching from the reference lists of identified papers were searched for randomized controlled trials comparing drug interventions with placebo or another drug to shorten the onset time of rocuronium. Statistical analyses were performed using RevMan5.2 and ADDIS 1.16.5 softwares. Mean differences (MDs) with their 95% confidence intervals (95% CIs) were used to analyze the effects of drug interventions on the onset time of rocuronium. 43 randomized controlled trials with 2,465 patients were analyzed. The average onset time of rocuronium was 102.4±24.9 s. Priming with rocuronium [Mean difference (MD) -21.0 s, 95% confidence interval (95% CI) (-27.6 to -14.3 s)], pretreatment with ephedrine [-22.3 s (-29.1 to -15.5 s)], pretreatment with magnesium sulphate [-28.2 s (-50.9 to -5.6 s)] were all effective in reducing the onset time of rocuronium. Statistical testing of indirect comparisons showed that rocuronium priming, pretreatment with ephedrine, and pretreatment with magnesium sulphate had the similar efficacy. Rocuronium priming, pretreatment with ephedrine, and pretreatment with magnesium sulphate were all effective in accelerating the onset time of rocuronium, and furthermore their efficacies were similar. Considering the convenience and efficacy, priming with rocuronium is recommended for accelerating the onset time of rocuronium. However, more strict clinical trials are still needed to reach a more solid conclusion due to the large heterogeneities exist among different studies.

Gut microbiota modulates alcohol withdrawal-induced anxiety in mice.

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Xiao, Hui-Wen; Ge, Chang; Feng, Guo-Xing; Li, Yuan; Luo, Dan; Dong, Jia-Li; Li, Hang; Wang, Haichao; Cui, Ming; Fan, Sai-Jun

2018-05-01

Excessive alcohol consumption remains a major public health problem that affects millions of people worldwide. Accumulative experimental evidence has suggested an important involvement of gut microbiota in the modulation of host's immunological and neurological functions. However, it is previously unknown whether enteric microbiota is implicated in the formation of alcohol withdrawal-induced anxiety. Using a murine model of chronic alcoholism and withdrawal, we examined the impact of alcohol consumption on the possible alterations of gut microbiota as well as alcohol withdrawal-induced anxiety and behavior changes. The 16S rRNA sequencing revealed that alcohol consumption did not alter the abundance of bacteria, but markedly changed the composition of gut microbiota. Moreover, the transplantation of enteric microbes from alcohol-fed mice to normal healthy controls remarkably shaped the composition of gut bacteria, and elicited behavioral signs of alcohol withdrawal-induced anxiety. Using quantitative real-time polymerase chain reaction, we further confirmed that the expression of genes implicated in alcohol addiction, BDNF, CRHR1 and OPRM1, was also altered by transplantation of gut microbes from alcohol-exposed donors. Collectively, our findings suggested a possibility that the alterations of gut microbiota composition might contribute to the development of alcohol withdrawal-induced anxiety, and reveal potentially new etiologies for treating alcohol addiction. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

Sugammadex antagonism of rocuronium-induced neuromuscular blockade in patients with liver cirrhosis undergoing liver resection: a randomized controlled study.

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Abdulatif, Mohamed; Lotfy, Maha; Mousa, Mahmoud; Afifi, Mohamed H; Yassen, Khaled

2018-02-05

This randomized controlled study compared the recovery times of sugammadex and neostigmine as antagonists of moderate rocuroniuminduced neuromuscular block in patients with liver cirrhosis and controls undergoing liver resection. The study enrolled 27 adult patients with Child class "A" liver cirrhosis and 28 patients with normal liver functions. Normal patients and patients with liver cirrhosis were randomized according to the type of antagonist (sugammadex 2mg/kg or neostigmine 50μg/kg). The primary outcome was the time from antagonist administration to a trainoffour (TOF) ratio of 0.9 using mechanosensor neuromuscular transmission module. The durations of the intubating and topup doses of rocuronium, the length of stay in the postanesthesia care unit (PACU), and the incidence of postoperative re curarization were recorded. The durations of the intubating and topup doses of rocuronium were prolonged in patients with liver cirrhosis than controls. The times to a TOF ratio of 0.9 were 3.1 (1.0) and 2.6 (1.0) min after sugammadex administration in patients with liver cirrhosis and controls, respectively, p=1.00. The corresponding times after neostigmine administration were longer than sugammadex 14.5 (3.6) and 15.7 (3.6) min, respectively, psugammadex compared to neostigmine. We did not encounter postoperative recurarization after sugammadex or neostigmine. Sugammadex rapidly antagonize moderate residual rocuronium induced neuromuscular block in patients with Child class "A" liver cirrhosis undergoing liver resection. Sugammadex antagonism is associated with 80% reduction in the time to adequate neuromuscular recovery compared to neostigmine.

The effects of intra-cerebroventricular administered rocuronium on the central nervous system of rats and determination of its epileptic seizure-inducing dose.

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Baykal, Mehmet; Gökmen, Necati; Doğan, Alper; Erbayraktar, Serhat; Yılmaz, Osman; Ocmen, Elvan; Erdost, Hale Aksu; Arkan, Atalay

The aim of this study was to investigate the effects of intracerebroventricularly administered rocuronium bromide on the central nervous system, determine the seizure threshold dose of rocuronium bromide in rats, and investigate the effects of rocuronium on the central nervous system at 1/5, 1/10, and 1/100 dilutions of the determined seizure threshold dose. A permanent cannula was placed in the lateral cerebral ventricle of the animals. The study was designed in two phases. In the first phase, the seizure threshold dose of rocuronium bromide was determined. In the second phase, Group R 1/5 (n=6), Group 1/10 (n=6), and Group 1/100 (n=6) were formed using doses of 1/5, 1/10, and 1/100, respectively, of the obtained rocuronium bromide seizure threshold dose. The rocuronium bromide seizure threshold value was found to be 0.056±0.009μmoL. The seizure threshold, as a function of the body weight of rats, was calculated as 0.286μmoL/kg -1 . A dose of 1/5 of the seizure threshold dose primarily caused splayed limbs, posturing, and tremors of the entire body, whereas the dose of 1/10 of the seizure threshold dose caused agitation and shivering. A dose of 1/100 of the seizure threshold dose was associated with decreased locomotor activity. This study showed that rocuronium bromide has dose-related deleterious effects on the central nervous system and can produce dose-dependent excitatory effects and seizures. Published by Elsevier Editora Ltda.

[The effects of intra-cerebroventricular administered rocuronium on the central nervous system of rats and determination of its epileptic seizure-inducing dose].

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Baykal, Mehmet; Gökmen, Necati; Doğan, Alper; Erbayraktar, Serhat; Yılmaz, Osman; Ocmen, Elvan; Erdost, Hale Aksu; Arkan, Atalay

The aim of this study was to investigate the effects of intracerebroventricularly administered rocuronium bromide on the central nervous system, determine the seizure threshold dose of rocuronium bromide in rats, and investigate the effects of rocuronium on the central nervous system at 1/5, 1/10, and 1/100 dilutions of the determined seizure threshold dose. A permanent cannula was placed in the lateral cerebral ventricle of the animals. The study was designed in two phases. In the first phase, the seizure threshold dose of rocuronium bromide was determined. In the second phase, Group R 1/5 (n=6), Group 1/10 (n=6), and Group 1/100 (n=6) were formed using doses of 1/5, 1/10, and 1/100, respectively, of the obtained rocuronium bromide seizure threshold dose. The rocuronium bromide seizure threshold value was found to be 0.056±0.009μmoL. The seizure threshold, as a function of the body weight of rats, was calculated as 0.286μmoL/kg -1 . A dose of 1/5 of the seizure threshold dose primarily caused splayed limbs, posturing, and tremors of the entire body, whereas the dose of 1/10 of the seizure threshold dose caused agitation and shivering. A dose of 1/100 of the seizure threshold dose was associated with decreased locomotor activity. This study showed that rocuronium bromide has dose-related deleterious effects on the central nervous system and can produce dose-dependent excitatory effects and seizures. Publicado por Elsevier Editora Ltda.

The Pringle maneuver reduces the infusion rate of rocuronium required to maintain surgical muscle relaxation during hepatectomy.

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Kajiura, Akira; Nagata, Osamu; Sanui, Masamitsu

2018-04-27

We investigated the continuous infusion rates of rocuronium necessary to obtain the surgical muscle relaxation before, during, and after the Pringle maneuver on patients who underwent hepatectomy. Fifteen patients were induced by total intravenous anesthesia with propofol. After obtaining the calibration of acceleromyography, the patient was intubated with rocuronium 0.6 mg/kg. Fifteen minutes after initial rocuronium injection, the continuous infusion was started at 7.5 µg/kg/min. The infusion rate was adjusted every 15 min so that the first twitch height (% T1) might become from 3 to 10% of control. The infusion rates at the time when the state of surgical muscle relaxation was achieved for more than 15 min were recorded before, during and after the Pringle maneuver. The 25% recovery time was measured after discontinuing the continuous infusion. The infusion rate of rocuronium before, during, and after the Pringle maneuver was 7.2 ± 1.8, 4.2 ± 1.4, and 4.7 ± 1.5 µg/kg/min (mean ± SD), respectively. The rocuronium infusion rate during the Pringle maneuver was decreased about 40% compared to that before this maneuver, and that after completion of the Pringle maneuver was not recovered to that before the Pringle maneuver. The 25% recovery time was 20 ± 7 min. In case of continuous administration of rocuronium during surgery performing the Pringle maneuver, it was considered necessary to regulate the administration of rocuronium using muscle relaxant monitoring in order to deal with the decrease in muscle relaxant requirement by the Pringle maneuver.

Changes in duration of action of rocuronium following decrease in hepatic blood flow during pneumoperitoneum for laparoscopic gynaecological surgery.

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Liu, Yang; Cao, Wen; Liu, Yu; Wang, Yun; Lang, Ren; Yue, Yun; Wu, An-Shi

2017-03-20

A moderate insufflation pressure and deep neuromuscular blockade (NMB) have been recommended in laparoscopic surgery in consideration of the possible reduction in splanchnic perfusion due to the CO 2 -pneumoperitoneum. Since the liver is the major organ for rocuronium metabolism, the question of whether NMB of rocuronium would change with the variation of liver perfusion during pneumoperitoneum during laparoscopic surgery merits investigation. In this prospective study, a total of sixty female patients scheduled for either selective laparoscopic gynaecological surgery (group laparoscopy) or laparotomy for gynaecological surgery (group control) were analyzed. Rocuronium was administered with closed-loop feedback infusion system, which was also applied to monitor NMB complied with good clinical research practice (GCRP). The onset time, clinical duration, and recovery index were measured. Hepatic blood flow was assessed by laparoscopic intraoperative ultrasonography before insufflation/after entering the abdominal cavity (T1), 5 min after insufflation in the Trendelenburg position/5 min after skin incision (T2), 15 min after insufflation in the Trendelenburg position/15 min after skin incision (T3), 30 min after insufflation in the Trendelenburg position/30 min after skin incision (T4), and 5 min after deflation/before closing the abdomen (T5) in group laparoscopy/group control respectively. The relationship between the clinical duration of rocuronium and portal venous blood flow was analyzed using linear or quadratic regression. The clinical duration and RI of rocuronium were both prolonged significantly in group laparoscopy (36.8 ± 8.3 min; 12.8 ± 5.5 min) compared to group control (29.0 ± 5.8 min; 9.8 ± 4.0 min) (P rocuronium and portal venous blood flow (Y = 51.800-0.043X + (1.86E-005) X 2 ; r 2  = 0.491; P Rocuronium-induced NMB during laparoscopic gynaecological surgery might be prolonged due to the decrease in portal

Oral Mucosal Injection of a Local Anesthetic Solution Containing Epinephrine Enhances Muscle Relaxant Effects of Rocuronium

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Ninomiya, Asako; Terakawa, Yui; Matsuura, Nobuyuki; Ichinohe, Tatsuya; Kaneko, Yuzuru

2012-01-01

The purpose of this study was to examine how submucosal injection of a clinically relevant dose of a lidocaine hydrochloride solution containing epinephrine affects the muscle relaxant effects of rocuronium bromide. Sixteen patients scheduled for orthognathic surgery participated in this study. All patients were induced with fentanyl citrate, a target-controlled infusion of propofol and rocuronium bromide. Anesthesia was maintained by total intravenous anesthesia. After nasotracheal intubation, an infusion of rocuronium bromide was started at 7 µg/kg/min, and the infusion rate was then adjusted to maintain a train of four (TOF) ratio at 10 to 15%. The TOF ratio just prior to oral mucosal injection of a 1% lidocaine hydrochloride solution containing 10 µg/mL epinephrine (LE) was taken as the baseline. TOF ratio was observed for 20 minutes, with 1-minute intervals following the start of injection. Mean epinephrine dose was 85.6 ± 18.6 µg and mean infusion rate of rocuronium bromide was 6.3 ± 1.6 µg/kg/min. TOF ratio began to decrease 2 minutes after the injection of LE, reached the minimum value at 3.1 ± 3.6% 12 minutes after the injection, and then began to recover. We conclude that oral mucosal injection of LE enhances the muscle relaxant effects of rocuronium bromide. PMID:22428970

Administration of rocuronium based on real body weight versus fat-free mass in patients with lymphedema.

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Jing, Zhang; Muheremu, Aikeremujiang; Liu, Pengfei; Hu, Xiaoyun; Binjiang, Zhao

2017-12-01

Objective To compare the clinical pharmacokinetics of rocuronium when applied according to fat-free mass versus real body weight during anesthetic induction of patients with lymphedema. Methods Sixty patients with lymphedema (age, 18-60 years; American Society of Anesthesiologists physical status, I-II) undergoing elective surgery with general anesthesia were randomly divided into two groups. Rocuronium was administered based on the fat-free mass in 30 patients and real body weight in 30 patients. General anesthesia was induced with propofol and remifentanil by target-controlled infusion. Intubation was attempted when the onset time (T1) (time from end of bolus injection to 100% twitch depression) reached maximal inhibition, and respiratory support with mechanical ventilation was then applied. The T1, clinical duration (time from end of bolus injection to recovery of twitch tension to 25% of control), recovery index (time from 25% to 75% of recovery of T1), and dosage were recorded. Results Complete data were recorded for 59 patients, and there were no significant differences in the general condition, intubation condition, or median duration of action of rocuronium between the two groups. However, the median T1, recovery index, and dosage of rocuronium were significantly different. Conclusion Good intubation conditions and a shortened clinical duration can be obtained for patients with lymphedema when induction with rocuronium is based on the fat-free mass.

Preferences of Mexican anesthesiologists for vecuronium, rocuronium, or other neuromuscular blocking agents: a survey

Directory of Open Access Journals (Sweden)

Garduño-Espinosa J

2002-05-01

Full Text Available Abstract Background Several neuromuscular blocking (NMB agents are available for clinical use in anesthesia. The present study was performed in order to identify preferences and behaviors of anesthesiologists for using vecuronium, rocuronium or other NMB agents in their clinical practice. Material and methods The cross-sectional survey was applied at the Updated Course of the Colegio Mexicano de Anestesiología performed last year. Of 989, 282 (28.5% surveys were returned. Results Most anesthesiologists were working at both public and private hospitals, performed anesthetic procedures for hospitalized and ambulatory patients, and anesthetized children as well as adults. Respondents did not consider mechanomyography as the gold standard method for neuromuscular monitoring. The T25 was not recognized as a pharmacodynamic parameter that represents the clinical duration of the neuromuscular block. Most answered that vecuronium induces less histamine release than rocuronium, had never used any neuromuscular monitor, did not know the cost of vecuronium and rocuronium, and preferred rocuronium in multiple-sampling vials and vecuronium in either a vial for single or multiple sampling. Rocuronium was preferred for emergency surgery in patients with full stomach only. Almost all of anesthesiologists that conserve the unused drug did it without refrigeration and more than 30% conserve the unused drug in one syringe for further use. Conclusion Vecuronium was preferred for most clinical situations, and the decision for this choice was not based on costs. Storage of unused drugs without refrigeration in a single syringe for purpose of future use in several patients represented a dangerous common practice.

Neuromuscular Effects of Rocuronium Bromide in Patients in Statin Therapy for at least Three Months.

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Ren, Hongwei; Lv, Huangwei

2016-12-01

Statins cause skeletal muscle myopathy. However, the neuromuscular effects of non-depolarizing neuromuscular-blocking agent in patients in long-term statin therapy remain unclear. Hence, we investigated the neuromuscular effects of rocuronium and muscle injury in patients in long-term statin therapy. Eighteen statin users using statins for at least 3 months were included in the statin group and 18 non-statin users were included in the non-statin group. General anaesthesia was induced with intravenous midazolam, etomidate, sufentanil and rocuronium 0.9 mg/kg (3ED 95 ) for intubation. Anaesthesia was maintained with 1% propofol and remifentanil. The onset time and duration 10% T 1 and 25% T 1 of rocuronium were recorded. Blood samples were obtained before induction and 5 min., 1 hr, 2 hr, 4 hr, 12 hr and 24 hr after rocuronium administration to measure creatine kinase (CK), myoglobin and potassium. Myalgia was determined at 2 and 24 hr after surgery. There were no significant differences in the basic clinical characteristics between the two groups. The onset time of the statin group was significantly shorter than that of the non-statin group (p = 0.02), while the duration 10% T 1 and duration 25% T 1 of the statin group were significantly longer than those of the non-statin group (p = 0.006; p = 0.045). The myoglobin and CK concentrations increased after rocuronium administration as compared to baseline in both groups. CK concentration in the statin group was significantly higher than in the non-statin group just at 24 hr (p = 0.000003). However, myoglobin showed no significant difference between the two groups. The onset time of rocuronium decreases and its duration time increases in patients in long-term statin therapy. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Withdrawal of repeated morphine enhances histamine-induced scratching responses in mice.

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Abe, Kenji; Kobayashi, Kanayo; Yoshino, Saori; Taguchi, Kyoji; Nojima, Hiroshi

2015-04-01

An itch is experientially well known that the scratching response of conditions such as atopic dermatitis is enhanced under psychological stress. Morphine is typical narcotic drug that induces a scratching response upon local application as an adverse drug reaction. Although long-term treatment with morphine will cause tolerance and dependence, morphine withdrawal can cause psychologically and physiologically stressful changes in humans. In this study, we evaluated the effects of morphine withdrawal on histamine-induced scratching behavior in mice. Administration of morphine with progressively increasing doses (10-50 mg/kg, i.p.) was performed for 5 consecutive days. At 3, 24, 48, and 72 hr after spontaneous withdrawal from the final morphine dose, histamine was intradermally injected into the rostral part of the back and then the number of bouts of scratching in 60 min was recorded and summed. We found that at 24 hr after morphine withdrawal there was a significant increase in histamine-induced scratching behavior. The spinal c-Fos positive cells were also significantly increased. The relative adrenal weight increased and the relative thymus weight decreased, both significantly. Moreover, the plasma corticosterone levels changed in parallel with the number of scratching bouts. These results suggest that morphine withdrawal induces a stressed state and enhances in histamine-induced scratching behavior. Increased reaction against histamine in the cervical vertebrae will participate in this stress-induced itch enhancement.

Rapid reversal of neuromuscular blockade by sugammadex after continuous infusion of rocuronium in patients with liver dysfunction undergoing hepatic surgery.

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Fujita, Ai; Ishibe, Natsuki; Yoshihara, Tatsuya; Ohashi, Jun; Makino, Hideichi; Ikeda, Mizuko; Setoguchi, Hidekazu

2014-06-01

Sugammadex rapidly reverses neuromuscular blockade (NMB) induced by rocuronium. NMB induced by rocuronium is prolonged in patients with liver dysfunction, because the drug is mainly excreted into the bile. However, the efficacy and safety of sugammadex in terms of reversing rocuronium-induced NMB in patients with liver dysfunction undergoing hepatic surgery have not been evaluated. This observational study investigated the efficacy and safety of sugammadex after continuous infusion of rocuronium in patients with liver dysfunction undergoing hepatic surgery. Remifentanil/propofol anesthesia was administered to 31 patients: 15 patients in the control group, and 16 patients from a group with liver dysfunction. Rocuronium (0.6 mg/kg) was administered, followed by continuous infusion. The enrolled patients were then subdivided into two groups according to the dose of sugammadex. In the first group a single dose of sugammadex (2.0 mg/kg) was given at the reappearance of the second twitch (T2). In the second group a single dose of sugammadex (4.0 mg/kg) was given at the first twitch response if T2 did not reappear in 15 minutes after stopping rocuronium. The primary outcome was time from administration of sugammadex to recovery of a train-of-four ratio to 0.9. The dose of rocuronium required in the liver dysfunction group was lower than that in the control group (6.2 vs. 8.2 μg/kg/min, p = 0.002). The mean time from the administration of sugammadex to recovery of the train-of-four ratio to 0.9 was not significantly different between the liver dysfunction group and the control group (2.2 minutes vs. 2.0 minutes in the 2 mg/kg administration group, p = 0.44 and 1.9 minutes vs. 1.7 minutes in the 4 mg/kg administration group, p = 0.70, respectively). No evidence of recurarization was observed in any of the patients. Most of the adverse events were found to be mild and such events were not related to the use of sugammadex. None of the patients was eliminated from the study

Pharmacodynamics and pharmacokinetics of rocuronium in intensive care patients

NARCIS (Netherlands)

Sparr, H.J; Wierda, J.MKH; Proost, Johannes H.; Keller, C; Khuenl-Brady, K.S

We have studied dose requirements, recovery times and pharmacokinetics of rocuronium in 32 intensive care patients. After an initial dose of 50 mg, rocuronium was administered as maintenance doses of 25 mg whenever two responses to train-of-four (TOF) stimulation reappeared (bolus group; n=27) or by

COMPARATIVE STUDY OF ROCURONIUM AND SUXAMETHONIUM IN ENDOTRACHEAL INTUBATION

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Dadichiluka Veeragouri Sankararao

2017-06-01

Full Text Available BACKGROUND Tracheal intubation is one of the best methods of securing a patent airway. Good intubating conditions minimise the risk of trauma associated with tracheal intubation. Intubating conditions (muscle tone, vocal cords position, reaction to laryngoscopy and tube positioning depend on depth of anaesthesia and kind of anaesthetic used. Tracheal intubation is commonly facilitated by muscle relaxation. Rocuronium has rapid onset of action, which is comparable to suxamethonium. It has been shown to produce intubating conditions similar to those produced by suxamethonium. This study compares rocuronium and suxamethonium in tracheal intubation. MATERIALS AND METHODS A total of 100 patients of ASA grade 1 and 2 for elective surgeries under general anaesthesia were recruited for this study after obtaining clearance from institutional ethics committee and informed consent from the patients. These 100 patients were divided into 2 groups, group R received rocuronium and group S received suxamethonium. All patients underwent through preanaesthetic checkup on the day before surgery. Thorough airway assesssment was done to rule out difficult intubation. Patients were advised to be nil orally from 10 p.m. onwards, the night before surgery. RESULTS The intubating conditions in the rocuronium group were found to be excellent in 50%, fair in 34% and satisfactory in 16% of the patients compared to excellent in 68%, fair in 32% in suxamethonium group. Clinically, acceptable intubating conditions were seen in 84% and 100% of patients administered rocuronium and suxamethonium, respectively. CONCLUSION Rocuronium in a dose of 0.6 mg/kg is a suitable alternative to suxamethonium in a dose of 1.5 mg/kg in premedicated and anaesthetised patients scheduled for elective surgeries.

The effect of magnesium sulfate concentration on the effective concentration of rocuronium, and sugammadex-mediated reversal, in isolated left phrenic nerve hemi-diaphragm preparations from the rat.

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Cho, Choon-Kyu; Sung, Tae-Yun; Choi, Seok-Jun; Choi, Hey-Ran; Kim, Yong Beom; Lee, Jung-Un; Yang, Hong-Seuk

2018-05-30

Perioperative magnesium sulfate (MgSO4) is used for analgesic, anti-arrhythmic, and obstetric purposes. The effects of MgSO4 on the neuromuscular blockade (NMB) induced by rocuronium, and the sugammadex reversal thereof, have not been clearly quantified. We investigated the effect increase concentrations of MgSO4 on the NMB by rocuronium, and sugammadex reversal, in isolated left phrenic nerve hemi-diaphragm (PNHD) preparations from the rat. Rat PNHD preparations were randomly allocated to one of four groups varying in terms of MgSO4 concentration (1, 2, 3, and 4 mM, each n = 10, in Krebs solution). The train-of-four (TOF) and twitch height responses were recorded mechanomyographically. The preparations were treated with incrementally increasing doses of rocuronium and each group's effective concentration (EC)50, EC90, and EC95 of rocuronium were calculated via nonlinear regression. Then, sugammadex was administered in doses equimolar to rocuronium. The recovery index, time to T1 height >95% of control, and the time to a TOF ratio (TOFR) >0.9 after sugammadex administration were measured. The EC50, EC90, and EC95 of rocuronium fell significantly as the magnesium level increased. The EC50, EC90, and EC95 of rocuronium did not differ between the 3 and 4 mM groups. The recovery index, time to T1 height >95% of control, and time to a TOFR >0.9 after sugammadex administration did not differ among the four groups. Increases in the magnesium concentration in rat PNHD preparations proportionally enhanced the NMB induced by rocuronium but did not affect reversal by equimolar amounts of sugammadex.

Suicide by intravenous injection of rocuronium-bromide: Case report

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Nikolić Slobodan

2005-01-01

Full Text Available Suicides by intravenous injection of an overdose of medicaments are uncommon. In this paper, we present the case of a suicide by rocuronium-bromide injection in combination with an oral overdose of metoprolol. Unfortunately, in Belgrade, there is no toxicological laboratory capable of detecting rocuronium. The interpretation of autopsy and toxicological data in this case was made difficult due to the extreme putrefaction of the body of the deceased. So, by forensic investigation, the case was solved indirectly, through circumstantial evidence: an empty ampoule of rocuronium found near the body, as well as a plastic syringe and cloth-bandage found in the left hand of the deceased.

Efficacy and safety of sugammadex in the reversal of deep neuromuscular blockade induced by rocuronium in patients with end-stage renal disease: A comparative prospective clinical trial.

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de Souza, Camila M; Tardelli, Maria A; Tedesco, Helio; Garcia, Natalia N; Caparros, Mario P; Alvarez-Gomez, Jose A; de Oliveira Junior, Itamar S

2015-10-01

Renal failure affects the pharmacology of nondepolarizing neuromuscular blockers making recovery of neuromuscular function unpredictable. Sugammadex antagonises rocuronium-induced neuromuscular blockade by encapsulating rocuronium, creating a stable complex molecule that is mainly excreted by the kidneys. Previous studies suggest that sugammadex is effective in reversing moderate neuromuscular block in the presence of renal failure, but no data are available regarding reversal of profound neuromuscular block in patients with renal failure. The objective of this study is to compare the efficacy and safety of sugammadex in reversing profound neuromuscular block induced by rocuronium in patients with end-stage renal disease and those with normal renal function. A prospective clinical trial. Two university hospitals, from 1 October 2011 to 31 January 2012. Forty patients undergoing kidney transplant: 20 with renal failure [creatinine clearance (ClCr) 90 ml min). Neuromuscular monitoring was performed by acceleromyography and train-of-four (TOF) stimulation. Profound neuromuscular block (posttetanic count, one to three responses) was maintained during surgery. Sugammadex 4 mg kg was administered on completion of skin closure. Recovery of the TOF ratio to 0.9 was recorded. Monitoring of neuromuscular function continued in the postanesthesia care unit for a further 2 h. The efficacy of sugammadex was evaluated by the time taken for the TOF ratio to recover to 0.9. The safety of sugammadex was assessed by monitoring for recurrence of neuromuscular block every 15 min for 2 h. Secondary variables were time to recovery of TOF ratio to 0.7 and 0.8. After sugammadex administration, the mean time for recovery of the TOF ratio to 0.9 was prolonged in the renal failure group (5.6 ± 3.6 min) compared with the control group (2.7 ± 1.3 min, P = 0.003). No adverse events or evidence of recurrence of neuromuscular block were observed. In patients with

Effects of magnesium chloride on rocuronium-induced neuromuscular blockade and sugammadex reversal in an isolated rat phrenic nerve-hemidiaphragm preparation: An in-vitro study.

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Sung, Tae-Yun; You, Hwang-Ju; Cho, Choon-Kyu; Choi, Hey Ran; Kim, Yong Beom; Shin, Yong Sup; Yang, Hong Seuk

2018-03-01

Magnesium potentiates the effects of nondepolarising muscle relaxants. However, few studies have used magnesium chloride (MgCl2). Sugammadex reverses neuromuscular block by steroidal nondepolarising muscle relaxants. To assess the effects of MgCl2 on rocuronium-induced neuromuscular blockade and its reversal by sugammadex. In-vitro experimental study. Animal laboratory, Asan Medical Center, Seoul, South Korea, from 20 March 2016 to 3 April 2016. Forty male Sprague Dawley rats. Left phrenic nerve-hemidiaphragms from 40 Sprague Dawley rats were allocated randomly to four groups (1, 2, 3 and 4 mmol l MgCl2 group, n = 10 each). Rocuronium was administered cumulatively until the first twitch of train-of-four (TOF) disappeared completely. Then, equimolar sugammadex was administered. The effective concentration (EC) of rocuronium was obtained in each group. After administering sugammadex, recovery of the first twitch height and the TOF ratio were measured for 30 min. EC50, EC90 and EC95 significantly decreased as the concentration of MgCl2 increased (all P ≤ 0.001), except the comparison between the 3 and 4 mmol l MgCl2 groups. After administration of sugammadex, the maximal TOF ratio (%) was lower in the 4 mmol l MgCl2 group than the 1 mmol l MgCl2 group [median 91.7 interquartile range (83.4 to 95.8) vs. 98.3 interquartile range (92.2 to 103.4), P = 0.049]. The mean time (s) from sugammadex injection to achieving maximal first twitch was significantly prolonged in the 4 mmol l MgCl2 group vs. the 1 mmol l MgCl2 and 2 mmol l MgCl2 groups [1483.9 (± 237.0) vs. 1039.0 (± 351.8) and 926.0 (± 278.1), P = 0.022 and 0.002, respectively]. Increases in MgCl2 concentration reduce the ECs of rocuronium. In addition, administering sugammadex equimolar to the administered rocuronium shows limited efficacy as MgCl2 concentration is increased. The in-vitro study was not registered in a database.

Urinary, biliary and faecal excretion of rocuronium in humans

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Proost, JH; Eriksson, LI; Mirakhur, RK; Wierda, JMKH

2000-01-01

The excretion of rocuronium and its potential metabolites was studied in 38 anaesthetized patients, ASA I-III and 21-69 yr old. Rocuronium bromide was administered as an i.v. bolus dose of 0.3 or 0.9 mg kg(-1). in Part A of the study, the excretion into urine and bile, and the liver content were

Prevention of laryngospasm with rocuronium in cats: a dose-finding study.

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Martin-Flores, Manuel; Sakai, Daniel M; Portela, Diego A; Borlle, Lucia; Campoy, Luis; Gleed, Robin D

2016-09-01

To identify the dose of rocuronium that will prevent a laryngeal response to water spraying of the glottis in anesthetized cats. Randomized crossover study. Eight healthy, adult, short-haired cats, aged 1-4 years, weighing 3.2-6.0 kg. Each cat was anesthetized four times and administered one of four doses of rocuronium (0.1, 0.2, 0.3 and 0.6 mg kg(-1) ) in random order. The larynx was observed with a video-endoscope inserted through a laryngeal mask airway. Video-clips of the laryngeal response to a sterile water spray (0.2 mL) were obtained at baseline (without rocuronium) and at maximal effect of each treatment. Glottal closure score (0-2), duration of glottal closure, and number of adductive arytenoid movements were obtained from video-clips of laryngeal responses (reproduced in slow motion) at baseline and after treatment. Two observers blinded to treatment allocation scored the vigor of the laryngeal response on a visual analog scale (VAS). The duration of apnea (up to 5 minutes) was recorded for each treatment. Compared with baseline, rocuronium 0.3 mg kg(-1) and 0.6 mg kg(-1) significantly decreased all glottal scores obtained from the videos (all p rocuronium 0.1, 0.2, 0.3 and 0.6 mg kg(-1) , respectively. Rocuronium 0.3 mg kg(-1) and 0.6 mg kg(-1) consistently decreased the completeness and duration of the laryngeal response to water spray, and reduced the number of arytenoid adductive movements in response to that stimulus. However, a laryngeal response was never completely prevented. Rocuronium 0.3 mg kg(-1) may be useful for facilitating tracheal intubation. Positive pressure ventilation must be available for cats administered rocuronium. © 2016 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Comparison of reversal with neostigmine of low-dose rocuronium vs. reversal with sugammadex of high-dose rocuronium for a short procedure.

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Choi, E S; Oh, A Y; Koo, B W; Hwang, J W; Han, J W; Seo, K S; Ahn, S H; Jeong, W J

2017-10-01

Some short procedures require deep neuromuscular blockade, which needs to be reversed at the end of the procedure. Forty-four patients undergoing elective laryngeal micro-surgery were randomly allocated into two groups: rocuronium 0.45 mg.kg -1 with neostigmine (50 μg.kg -1 with glycopyrrolate 10 μg.kg -1 ) reversal (moderate block group) vs. rocuronium 0.90 mg.kg -1 with sugammadex (4 mg.kg -1 ) reversal (deep block group). The primary outcome was the intubating conditions during laryngoscopy secondary outcomes included recovery of neuromuscular block; conditions for tracheal intubation; satisfaction score as determined by the surgeon; onset of neuromuscular block; and postoperative sore throat. The onset of neuromuscular block was more rapid, and intubation conditions and ease of intra-operative laryngoscopy were more favourable, and the satisfaction score was lower in the moderate block group compared with the deep block group. No difference was found in the incidence of postoperative sore throat. In laryngeal micro-surgery, the use of rocuronium 0.9 mg.kg -1 with sugammadex for reversal was associated with better surgical conditions and a shorter recovery time than rocuronium 0.45 mg.kg -1 with neostigmine. © 2017 The Association of Anaesthetists of Great Britain and Ireland.

Succinylcholine versus rocuronium for rapid sequence intubation in intensive care: a prospective, randomized controlled trial

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2011-01-01

Introduction Succinylcholine and rocuronium are widely used to facilitate rapid sequence induction (RSI) intubation in intensive care. Concerns relate to the side effects of succinylcholine and to slower onset and inferior intubation conditions associated with rocuronium. So far, succinylcholine and rocuronium have not been compared in an adequately powered randomized trial in intensive care. Accordingly, the aim of the present study was to compare the incidence of hypoxemia after rocuronium or succinylcholine in critically ill patients requiring an emergent RSI. Methods This was a prospective randomized controlled single-blind trial conducted from 2006 to 2010 at the University Hospital of Basel. Participants were 401 critically ill patients requiring emergent RSI. Patients were randomized to receive 1 mg/kg succinylcholine or 0.6 mg/kg rocuronium for neuromuscular blockade. The primary outcome was the incidence of oxygen desaturations defined as a decrease in oxygen saturation ≥ 5%, assessed by continuous pulse oxymetry, at any time between the start of the induction sequence and two minutes after the completion of the intubation. A severe oxygen desaturation was defined as a decrease in oxygen saturation ≥ 5% leading to a saturation value of ≤ 80%. Results There was no difference between succinylcholine and rocuronium regarding oxygen desaturations (succinylcholine 73/196; rocuronium 66/195; P = 0.67); severe oxygen desaturations (succinylcholine 20/196; rocuronium 20/195; P = 1.0); and extent of oxygen desaturations (succinylcholine -14 ± 12%; rocuronium -16 ± 13%; P = 0.77). The duration of the intubation sequence was shorter after succinycholine than after rocuronium (81 ± 38 sec versus 95 ± 48 sec; P = 0.002). Intubation conditions (succinylcholine 8.3 ± 0.8; rocuronium 8.2 ± 0.9; P = 0.7) and failed first intubation attempts (succinylcholine 32/200; rocuronium 36/201; P = 1.0) did not differ between the groups. Conclusions In critically ill

Dosage effect of rocuronium on intraoperative neuromonitoring in patients undergoing thyroid surgery.

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Han, Yang-dong; Liang, Feng; Chen, Peng

2015-01-01

The effect of different concentrations of rocuronium bromide used for anesthesia induction during thyroid surgery on the intraoperative recurrent laryngeal nerve monitoring was evaluated. One hundred patients undergoing thyroid operation were randomized into five groups (20 patients per group). Patients in group I were operated and monitored without the use of rocuronium bromide. Patients in groups II-V were respectively injected with 0.5x, 1x, 1.5x, and 2x ED95 rocuronium bromide intravenously. The time from injecting the rocuronium bromide to the beginning of tube insertion was recorded, the conditions of tracheal intubation were evaluated, and the changes in blood pressure and pulse during the intubation process were monitored. Vagus nerve/recurrent laryngeal nerve evoked muscle potential was monitored using the NIM-Response3.0 nerve electromyography monitor. The amplitude of electromyography signal was recorded every 5 min during 30 min after successful tracheal intubation. The tracheal intubation success rate was 100% in all groups. Compared with group I, intubating condition scores (Cooper scores) in the patients of groups II-V were higher (P rocuronium bromide during the anesthesia induction can improve the tracheal tube conditions without affecting the intraoperative recurrent laryngeal nerve monitoring. The use of 1x ED95 rocuronium bromide induction was associated with the best results.

Rocuronium versus succinylcholine for rapid sequence induction intubation.

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Tran, Diem T T; Newton, Ethan K; Mount, Victoria A H; Lee, Jacques S; Wells, George A; Perry, Jeffrey J

2015-10-29

Patients often require a rapid sequence induction (RSI) endotracheal intubation technique during emergencies or electively to protect against aspiration, increased intracranial pressure, or to facilitate intubation. Traditionally succinylcholine has been the most commonly used muscle relaxant for this purpose because of its fast onset and short duration; unfortunately, it can have serious side effects. Rocuronium has been suggested as an alternative to succinylcholine for intubation. This is an update of our Cochrane review published first in 2003 and then updated in 2008 and now in 2015. To determine whether rocuronium creates intubating conditions comparable to those of succinylcholine during RSI intubation. In our initial review we searched all databases until March 2000, followed by an update to June 2007. This latest update included searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 2), MEDLINE (1966 to February Week 2 2015), and EMBASE (1988 to February 14 2015 ) for randomized controlled trials (RCTs) or controlled clinical trials (CCTs) relating to the use of rocuronium and succinylcholine. We included foreign language journals and handsearched the references of identified studies for additional citations. We included any RCT or CCT that reported intubating conditions in comparing the use of rocuronium and succinylcholine for RSI or modified RSI in any age group or clinical setting. The dose of rocuronium was at least 0.6 mg/kg and succinylcholine was at least 1 mg/kg. Two authors (EN and DT) independently extracted data and assessed methodological quality for the 'Risk of bias' tables. We combined the outcomes in Review Manager 5 using a risk ratio (RR) with a random-effects model. The previous update (2008) had identified 53 potential studies and included 37 combined for meta-analysis. In this latest update we identified a further 13 studies and included 11, summarizing the results of 50 trials including 4151 participants

Memantine reverses social withdrawal induced by ketamine in rats.

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Uribe, Ezequiel; Landaeta, José; Wix, Richard; Eblen, Antonio

2013-03-01

The objective of this study was to determine the effect of memantine on schizophrenia-like symptoms in a ketamine-induced social withdrawal model in rats. We examined therapeutic effects of memantine, an NMDA antagonist, and haloperidol, a classic antipsychotic drug, on this behavioral model. Administration of memantine (10 or 15 mg·kg(-1)) significantly reduced ketamine-induced social withdrawal, and this effect was more effective than that of haloperidol (0.25 mg·kg(-1)) by restoring the social interaction between rats with no modification in general motor activity. These results suggest that memantine could have a therapeutic potential for schizophrenia.

The Effect of Rapacuronium or Succinylcholine on the Duration of Action of Rocuronium

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2001-10-01

THESIS APPROVAL FORM THE EFFECT OF RAPACURONIUM OR SUCCINYLCHOLINE ON THE DURATION OF ACTION OF ROCURONIUM Rachael Fontanilla, Capt...on the Duration of Action of Rocuronium ” beyond brief excerpts is with the permission of the copyright owner, and will save and hold harmless...side effects. Non-depolarizing neuromuscular blocking agents achieve the same efficacy as succinylcholine without the adverse effects. Rocuronium , an

Chemical encapsulation of rocuronium by synthetic cyclodextrin derivatives: reversal of neuromuscular block in anaesthetized Rhesus monkeys.

NARCIS (Netherlands)

Boer, H.D. de; Egmond, J. van; Pol, F. van de; Bom, A.; Booij, L.H.D.J.

2006-01-01

BACKGROUND: At present, reversal of neuromuscular block induced by steroidal neuromuscular blocking agents (NMBAs) is achieved by administration of cholinesterase inhibitors. Chemical encapsulation of steroidal NMBAs, such as rocuronium, by a cyclodextrin is a new concept in neuromuscular block

The adequate rocuronium dose required for complete block of the adductor muscles of the thigh.

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Fujimoto, M; Kawano, K; Yamamoto, T

2018-03-01

Rocuronium can prevent the obturator jerk during transurethral resection of bladder tumors. We investigated the adequate rocuronium dose required for complete block of the thigh adductor muscles, and its correlation with individual responses of the adductor pollicis muscle to rocuronium. Eleven patients scheduled for transurethral resection of bladder tumors under general anesthesia were investigated. After general anesthesia induction, neuromuscular monitoring of the adductor pollicis muscle and ultrasonography-guided stimulation of the obturator nerve was commenced. Rocuronium, 0.15 mg/kg, was repeatedly administered intravenously. The adequate rocuronium dose required for complete block of the thigh muscles, defined as the cumulative dose of rocuronium administered until that time, and its correlation with the first twitch response of the adductor pollicis muscle on train-of-four stimulation after initial rocuronium administration was analyzed. The rocuronium dose found adequate for complete block of the thigh muscles was 0.30 mg/kg in seven patients and 0.45 mg/kg in the remaining four patients, which did not correlate with the first twitch response. At the time of complete block of the thigh muscles, the neuromuscular blockade level of the adductor pollicis muscle varied greatly, although the level was never more profound than a post-tetanic count of 1. Although the response of the adductor pollicis muscle to rocuronium cannot be used to determine the adequate rocuronium dose required for complete block of the thigh muscles, intense blockade, with maintenance of post-tetanic count at ≤ 1 in the adductor pollicis muscle is essential to prevent the obturator jerk. © 2017 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Dose of rocuronium for rapid tracheal intubation following remifentanil 2 μg kg-1 and propofol 2 mg kg-1.

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Oh, Ah-Young; Cho, Suk-Ju; Seo, Kwang-Suk; Ryu, Jung-Hee; Han, Sung-Hee; Hwang, Jung-Won

2013-09-01

Full relaxation is not mandatory for successful tracheal intubation. We tried to find the dose of rocuronium that gave acceptable intubation conditions in a rapid sequence intubation with remifentanil and propofol. A dose-finding study of rocuronium using a modified Dixon's up-and-down method. A single tertiary care teaching hospital. Patients undergoing elective surgery under general anaesthesia. After premedication with midazolam and glycopyrrolate, anaesthesia was induced using remifentanil 2 μg kg and propofol 2 mg kg, and a predetermined dose of rocuronium was administered. The dose of rocuronium was determined by a modified Dixon's up-and-down method starting from 0.8 mg kg with an interval of 0.1 or 0.05 mg kg. Intubation was performed 60 s after the start of the rocuronium injection. Intubation conditions were graded as excellent, good or poor. Excellent or good were regarded as clinically acceptable. A dose of rocuronium needed for acceptable intubation condition in 50% of patients (ED50) during rapid tracheal intubation after induction of anaesthesia with remifentanil and propofol. Twenty-eight patients were enrolled to obtain six crossovers. The ED50 of rocuronium was 0.20 mg kg (95% confidence interval, CI 0.17 to 0.23 mg kg) by a modified Dixon's up-and-down method. After induction of anaesthesia with remifentanil 2 μg kg and propofol 2 mg kg, the ED50 of rocuronium for acceptable intubation condition was 0.20 mg kg (95% CI, 0.17 to 0.23 mg kg) for rapid sequence intubation. Thus, we recommend that the intubation dose should be 0.8 mg kg. Clinical trial registration KCT0000094.

Rocuronium duration of action under sevoflurane, desflurane or propofol anaesthesia.

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Maidatsi, P G; Zaralidou, A Th; Gorgias, N K; Amaniti, E N; Karakoulas, K A; Giala, M M

2004-10-01

We conducted a prospective randomized study to evaluate whether the duration of action of a single bolus dose of rocuronium is influenced by maintenance of anaesthesia with sevoflurane, desflurane or propofol infusion. Fifty-seven ASA I-II patients undergoing elective abdominal surgery were enrolled in this study. Anaesthesia was induced with thiopental 3-5 mg kg(-1) or propofol 2.5 mg kg(-1) and fentanyl 5 microg kg(-1) and tracheal intubation was facilitated with rocuronium 0.9 mg kg(-1). Thereafter patients were randomly allocated to three different groups to receive sevoflurane, desflurane or propofol for maintenance of anaesthesia. Recovery of neuromuscular function was monitored by single twitch stimulation of the ulnar nerve and by recording the adductor pollicis response using accelerometry. Intergroup recovery times to 5% of control value of single twitch were analysed using analysis of variance with Bonferroni correction. The mean (95% confidence interval) recovery time to 5% of control value of single twitch during desflurane anaesthesia was 90.18 (86.11-94.25) min. Significantly shorter recovery times were observed during sevoflurane or propofol anaesthesia, 58.86 (54.73-62.99) min and 51.11 (45.47-56.74) min, respectively (P < 0.001). There were also significant differences in the recovery time between groups receiving desflurane vs. sevoflurane (P < 0.001) and desflurane vs. propofol (P < 0.001). Desflurane anaesthesia significantly prolongs the duration of action of rocuronium at 0.9 mg kg(-1) single bolus dose, compared to sevoflurane or propofol anaesthesia maintenance regimens.

The Efficacy and Safety of Topical Rocuronium Bromide to Induce Bilateral Mydriasis in Hispaniolan Amazon Parrots ( Amazona ventralis ).

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Baine, Katherine; Hendrix, Diane V H; Kuhn, Sonia E; Souza, Marcy J; Jones, Michael P

2016-03-01

The efficacy and safety of topically applied rocuronium in Hispaniolan Amazon parrots ( Amazona ventralis ) was assessed in a group of 10 adult birds. A complete ophthalmic examination (including Schirmer tear test, ocular reflexes, applanation tonometry, fluorescein staining, and slit-lamp biomicroscopy) was performed, and rocuronium bromide (0.15 mg in both eyes) was administered. Pupillary light reflex (PLR) and pupillary diameter were recorded in a darkened room at the following time points: 0, 10, 20, 30, 40, 50, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 300, and 360 minutes, and 24 hours. Fluorescein staining in both eyes was performed at 24 hours. By 10 minutes, PLR was absent in all birds (at 5 minutes, 8 birds; at 10 minutes, remaining 2 birds). Pupil diameter differed significantly from baseline at all time points. Additionally, PLR was decreased in 7/10 birds at 360 minutes and normal in all birds at 24 hours. Superficial corneal ulceration was observed at 24 hours in the left eye of 2/10 of the birds after fluorescein stain application. This study demonstrated that rocuronium bromide was an effective mydriatic agent in Hispaniolan Amazon parrots with rapid onset and prolonged duration of action.

Priming with Rocuronium to Accelerate the Onset Time of Cisatracurium During Intubation

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Shih-Pin Lin

2009-01-01

Conclusion: Priming with rocuronium or cisatracurium for 3 minutes significantly accelerated the onset of cisatracurium. Priming with rocuronium for 3 minutes improved the onset time of cisatracurium even more than priming with cisatracurium itself.

A comparative study of effect of sevoflurane on intubating conditions with rocuronium in neurosurgical patients.

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Mitra, Saikat; Purohit, Shobha; Bhatia, Sonali; Kalra, Poonam; Sharma, Satya Prakash

2015-12-01

Rocuronium may not always be the preferred relaxant for rapid sequence intubation. When 2% sevoflurane is used in conjunction with rocuronium, it may reduce the time required for achieving complete skeletal muscle relaxation with the intubating dose of rocuronium. This study was prospective, randomised, double-blind in nature and compared the effect of sevoflurane on intubation time and intubating conditions when used along with rocuronium. Thirty adult patients belonging to American Society of Anesthesiologists physical status Grades 1 and 2, of either gender aged between 30 and 65 years undergoing neurosurgical operations were randomly allocated into two equal groups: Group R received 0.8 mg/kg rocuronium, and Group RS received 0.8 mg/kg of rocuronium with 2% sevoflurane. Onset time of intubation was assessed using train-of-four stimuli. The intubating conditions were compared using the Cooper scoring system and the haemodynamic responses were compared between the two groups. The onset time of intubation was 101.73 ± 10.28 s in Group R and 60.4 ± 4.1 s in Group RS (P Rocuronium 0.8 mg/kg along with 2% sevoflurane provides excellent intubating conditions within 60-66 s from its administration.

Social transfer of alcohol withdrawal-induced hyperalgesia in female prairie voles.

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Walcott, Andre T; Smith, Monique L; Loftis, Jennifer M; Ryabinin, Andrey E

2018-03-27

The expression of pain serves as a way for animals to communicate potential dangers to nearby conspecifics. Recent research demonstrated that mice undergoing alcohol or morphine withdrawal, or inflammation, could socially communicate their hyperalgesia to nearby mice. However, it is unknown whether such social transfer of hyperalgesia can be observed in other species of rodents. Therefore, the present study investigated if the social transfer of hyperalgesia occurs in the highly social prairie vole (Microtus ochrogaster). We observe that adult female prairie voles undergoing withdrawal from voluntary two-bottle choice alcohol drinking display an increase in nociception. This alcohol withdrawal-induced hypersensitiity is socially transferred to female siblings within the same cage and female strangers housed in separate cages within the same room. These experiments reveal that the social transfer of pain phenomenon is not specific to inbred mouse strains and that prairie voles display alcohol withdrawal and social transfer-induced hyperalgesia.

PHARMACOKINETICS OF ROCURONIUM BROMIDE IN PATIENTS WITH AND WITHOUT RENAL-FAILURE

NARCIS (Netherlands)

COOPER, RA; MIRAKHUR, RK; WIERDA, JMKH; MADDINENI, VR

We studied the onset and duration of action and pharmacokinetics of rocuronium bromide during anaesthesia with nitrous oxide, fentanyl and isoflurane after a single bolus dose of rocuronium (0.6 mg kg(-1)) in nine patients with chronic renal failure requiring regular haemodialysis, and in nine

The neuromuscular effects of rocuronium under sevoflurane-remifentanil or propofol-remifentanil anesthesia: a randomized clinical comparative study in an Asian population.

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Lee, Sangseok; Ro, Young Jin; Koh, Won Uk; Nishiyama, Tomoki; Yang, Hong-Seuk

2016-08-22

We conducted a prospective, randomized, multicenter study to evaluate the differences in the blocking effect of different doses of rocuronium between sevoflurane- or propofol-remifentanil anesthesia in an Asian population. A total of 368 ASA I-II patients was enrolled. Anesthesia was induced with 2.0 mg/kg propofol and 0.1 μg/kg/min remifentanil (TIVA) or 5.0 vol.% sevoflurane with 0.1 μg/kg/min remifentanil (SEVO). Tracheal intubation was facilitated at 180 s after the administration of rocuronium at 0.3, 0.6, or 0.9 mg/kg and then intubation condition was evaluated. The time to maximum block and recovery profile were monitored by TOF stimulation of the ulnar nerve and by recording the adductor pollicis response using acceleromyography. The numbers of patients with clinically acceptable intubation conditions were 41, 82, and 97 % (TIVA) and 34, 85, and 90 % (SEVO) at each dose of rocuronium, respectively. There were no significant differences in the time to maximum block between groups at each rocuronium dose. There were significant differences in the recovery to a train-of-four ratio of 90 % between the groups: 42.7 (19.5), 74.8 (29.9), and 118.4 (35.1) min (TIVA) and 66.5 (39.3), 110.2 (43.5), and 144.4 (57.5) min (SEVO) at 0.3, 0.6, and 0.9 mg/kg, respectively (P rocuronium. The type of anesthetic does not significantly influence the time to maximum block by rocuronium. Rocuronium at a dose of 0.9 mg/kg should be used for better intubation conditions with both anesthesia regimens in an Asian population. UMIN-CTR Clinical Trial ( http://www.umin.ac.jp/ctr/index.htm ; UMIN#000007289 ; date of registration 14(th) February 2012).

Phencyclidine-induced social withdrawal results from deficient stimulation of cannabinoid CB₁ receptors: implications for schizophrenia.

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Seillier, Alexandre; Martinez, Alex A; Giuffrida, Andrea

2013-08-01

The neuronal mechanisms underlying social withdrawal, one of the core negative symptoms of schizophrenia, are not well understood. Recent studies suggest an involvement of the endocannabinoid system in the pathophysiology of schizophrenia and, in particular, of negative symptoms. We used biochemical, pharmacological, and behavioral approaches to investigate the role played by the endocannabinoid system in social withdrawal induced by sub-chronic administration of phencyclidine (PCP). Pharmacological enhancement of endocannabinoid levels via systemic administration of URB597, an inhibitor of endocannabinoid degradation, reversed social withdrawal in PCP-treated rats via stimulation of CB1 receptors, but reduced social interaction in control animals through activation of a cannabinoid/vanilloid-sensitive receptor. In addition, the potent CB agonist CP55,940 reversed PCP-induced social withdrawal in a CB₁-dependent manner, whereas pharmacological blockade of CB₁ receptors by either AM251 or SR141716 reduced the time spent in social interaction in control animals. PCP-induced social withdrawal was accompanied by a decrease of anandamide (AEA) levels in the amygdala and prefrontal cortex, and these deficits were reversed by URB597. As CB₁ receptors are predominantly expressed on GABAergic interneurons containing the anxiogenic peptide cholecystokinin (CCK), we also examined whether the PCP-induced social withdrawal resulted from deficient CB₁-mediated modulation of CCK transmission. The selective CCK2 antagonist LY225910 blocked both PCP- and AM251-induced social withdrawal, but not URB597 effect in control rats. Taken together, these findings indicate that AEA-mediated activation of CB₁ receptors is crucial for social interaction, and that PCP-induced social withdrawal results from deficient endocannabinoid transmission.

Rocuronium-sugammadex use for electroconvulsive therapy in a hemodialysis patient: a case report

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Kurita, Shigeaki; Moriwaki, Katsuyuki; Shiroyama, Kazuhisa; Sanuki, Mikako; Toyota, Yukari; Takebayashi, Minoru

2016-01-01

Background Recently, rocuronium with subsequent use of sugammadex was proposed for electroconvulsive therapy (ECT) as an alternative to succinylcholine. Because sugammadex is cleared via the kidney with no metabolism, it is unknown that rocuronium-sugammadex use is safe in hemodialysis patients who received ECT. Case presentation In this case report, we used rocuronium with subsequent administration of sugammadex in a 69-year-old female, hemodialysis patient, scheduled for ten ECT sessions fo...

Sugammadex rescue following prolonged rocuronium neuromuscular blockade with ‘recurarisation’ in a patient with severe renal failure

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Lobaz, Steven; Sammut, Mario; Damodaran, Anand

2013-01-01

We describe our experience of a 71-year-old patient with severe renal failure, who exhibited an unusually prolonged rocuronium-induced neuromuscular blockade (>4 h) and apparent recurarisation, following emergency rapid sequence induction (RSI). At the end of operation, 45 min post induction, train-of-four (TOF) testing had been 4/4 prior to wake up. No respiratory effort was seen 150 min postinduction, despite further neostigmine/glycopyrrolate and repeat TOF 4/4. The patient was resedated and transferred to the intensive care unit (ICU). At 180 min postinduction, fade was evident on TOF, suggestive of rocuronium reblockade. At 285 min, the patient was extubated safely following sugammadex administration and discharged uneventfully from the ICU. An important lesson to recognise is the potential for extremely prolonged neuromuscular blockade following rocuronium in patients with severe renal failure, particularly when using the higher doses (1.2 mg/kg) required for RSI, and that TOF in such cases may not be reliable in detecting residual blockade. PMID:23396837

Sugammadex for reversal of rocuronium-induced neuromuscular blockade in pediatric patients: A systematic review and meta-analysis.

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Won, Young Ju; Lim, Byung Gun; Lee, Dong Kyu; Kim, Heezoo; Kong, Myoung Hoon; Lee, Il Ok

2016-08-01

Previous studies have shown that sugammadex, a modified γ-cyclodextrin, is a well-tolerated agent for the reversal of neuromuscular blockade (NMB) induced by a steroidal neuromuscular blocking drug in adult patients. However, its use has not been reviewed in pediatric patients. The aim of this meta-analysis was to evaluate the efficacy and safety of sugammadex in the reversal of rocuronium-induced NMB during surgery under general anesthesia in pediatric patients. A literature search was performed using the Pubmed, EMBASE: Drugs and pharmacology, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. Analysis was conducted using RevMan 5.3. Data collected from different trials were pooled; the weighted mean difference or the pooled risk ratio and the corresponding 95% confidence interval (CI) were used for analysis, and heterogeneity (I) assessment was performed. Six randomized controlled trials comparing 253 pediatric patients (age range, 2-18 years) were included in the final analysis. The mean time taken to reach a train-of-four ratio of ≥0.9 was significantly shorter in the sugammadex groups (2 and 4 mg/kg) than in the control group (neostigmine or placebo), although the heterogeneity was high. The weighted mean differences of the 2 and 4 mg/kg sugammadex groups were -7.15 (95% CI: -10.77 to -3.54; I = 96%; P = 0.0001) and -17.32 (95% CI: -29.31 to -5.32; I = 98%; P = 0.005), respectively. The extubation time in the sugammadex group was shorter than that in the control group; the weighted mean difference of the sugammadex group was -6.00 (95% CI: -11.46 to -0.53; I = 99%; P = 0.03). There was no significant difference between the groups in terms of the incidence of postanesthetic adverse events; the pooled risk ratio was 0.67 (95% CI: 0.27-1.71; I = 59%; P = 0.41). We suggest that sugammadex is fast and effective in reversing rocuronium-induced NMB in pediatric patients. Although there

A comparison of granisetron and nitroglycerine for attenuating rocuronium pain: A double-blinded randomized, placebo controlled trial

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Rohit Goyal

2014-01-01

Full Text Available Background: The incidence of pain reported in literature after IV administration of rocuronium is 50-80%. The aim of our study was to determine whether pre-treatment with intravenous granisetron and nitroglycerine would reduce rocuronium-induced pain. Methods: One hundred fifty patients of either sex, aged 18-65 years, American society of Anaesthesiologist grading (ASA I-II, scheduled for various surgeries under general anesthesia were randomly assigned to one of the groups. Group G: received 2 granisetron (1mg/ml diluted with 3 ml of 0.9% normal saline while the Group C: received 5 ml of 0.9% normal saline. Group N: received 200΅g of nitroglycerine diluted to a total of 5 ml(with 0.9% normal saline. It was accompanied by manual venous occlusion for 20 seconds. Then 0.06mg/kg of rocuronium was injected through same cannula over 10-15 sec.Patients were asked by a blinded investigator to score the pain on injection of rocuronium using visual analogue scale (0-10 with 0-no pain,1-3 mild pain, 4-6 moderate and >=7 severe pain. At the same time discomfort in the form of patient′s movement, such as no movement (grade 0, movement only wrist (grade 1, movement to the upper arm and shoulder of injected arm (grade 2 or generalized movements (grade3 was observed. Statistical analysis using independent t test, Mann-Whitney test and reverse ANOVA was done. Results: 1. At 0 seconds, in group G number of patients who experienced withdrawl score of 0-1 were 92%,group N were 82% while only 26% of patients in group C had favourable withdrawl score.74% of patients in group C had score of 2-3 at same time. 2. At 0 sec, in group G number of patients who experienced VAS score of 0-3 were 96%, group N 72%. At same time Group C 48 % of patients had VAS score of 2-3. Conclusion: We conclude that pre-treatment with granisetron or nitroglycerine both are highly effective in attenuation of rocuronium induced pain.

Rocuronium-Sugammadex in Anesthesia for Electroconvulsive Therapy

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Nilay Tas

2016-03-01

Full Text Available Electroconvulsive therapy (ECT is a form of treatment which is very effective in many psychiatric disorders. The administration of anesthesia plays a positive role in the success of ECT and improves the oxygenation of the body during the process. Succinylcholine, is a depolarizing neuromuscular blocker of choice, the most common agent used to provide muscular relaxation during ECT. Alternative neuromusculer blokers have been used during anesthesia because of contraindications and serious side effects of succinylcholine. Rocuronium is a nondepolarizing neuromuscular blocker with inter-mediate time of action which may be used safely during ECT. Although relatively late onset of action and long half life compared to succinylcholine may seem as drawbacks, the new generation reversing agents like suggamadex have made these disadvantages ignorable. Sugammadex, a new generation neuromuscular blocker reversal agent, not having serious side effects as much as the classic reversals, such as cardiovascular side effects, is playing an important role in anesthesiology practice. In recent years, rocuronium-sugammadex combination is being included in the ECT practice extensively. In this paper, the usability of rocuronium-sugammadex combination as an alternative to succinylcholine has been revised. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2016; 8(1: 76-84

Infusion dose requirement of rocuronium in patients on phenytoin therapy - A prospective comparative study.

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Sheshadri, Veena; Radhakrishnan, Arathi; Halemani, Kusuma; Keshavan, Venkatesh H

2017-10-01

Patients with intracranial tumour are usually on anticonvulsants. Patients on phenytoin therapy demonstrate rapid metabolism of nondepolarising muscle relaxants secondary to enzyme induction. Infusion dose requirement of rocuronium in such patients has been sparingly studied. We studied the continuous infusion dose requirement of rocuronium bromide in patients on phenytoin therapy and its correlation with serum levels of phenytoin. Seventy-five patients scheduled for supratentorial tumour surgery were included in the study. Patients not on phenytoin were taken as control. The primary outcome variable studied was the infusion dose requirement of rocuronium in patients on phenytoin. Based on pre-operative serum phenytoin levels, study group patients were divided into two groups: sub-therapeutic level group (phenytoin level 10 μg/mL). Following anaesthesia induction, rocuronium bromide 0.6 mg/kg was administered to achieve tracheal intubation. Rocuronium infusion was titrated to maintain zero response on the train-of-four response. Demographic data were comparable. Patients receiving phenytoin required higher infusion dose compared to the control group (0.429 ± 0.2 mg/kg/h vs. 0.265 ± 0.15 mg/kg/h, P rocuronium (0.429 ± 0.205 mg/kg/h vs. 0.429 ± 0.265 mg/kg/h ( P = 0.815). The recovery was faster in the phenytoin group compared to the control group. Haowever, it was not clinically significant. The infusion dose requirement of rocuronium bromide in patients on phenytoin is higher and the serum levels of phenytoin does not influence the dose required.

Drug-induced GABA transporter currents enhance GABA release to induce opioid withdrawal behaviors.

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Bagley, Elena E; Hacker, Jennifer; Chefer, Vladimir I; Mallet, Christophe; McNally, Gavan P; Chieng, Billy C H; Perroud, Julie; Shippenberg, Toni S; Christie, MacDonald J

2011-10-30

Neurotransmitter transporters can affect neuronal excitability indirectly via modulation of neurotransmitter concentrations or directly via transporter currents. A physiological or pathophysiological role for transporter currents has not been described. We found that GABA transporter 1 (GAT-1) cation currents directly increased GABAergic neuronal excitability and synaptic GABA release in the periaqueductal gray (PAG) during opioid withdrawal in rodents. In contrast, GAT-1 did not indirectly alter GABA receptor responses via modulation of extracellular GABA concentrations. Notably, we found that GAT-1-induced increases in GABAergic activity contributed to many PAG-mediated signs of opioid withdrawal. Together, these data support the hypothesis that GAT-1 activity directly produces opioid withdrawal signs through direct hyperexcitation of GABAergic PAG neurons and nerve terminals, which presumably enhances GABAergic inhibition of PAG output neurons. These data provide, to the best of our knowledge, the first evidence that dysregulation of a neurotransmitter transporter current is important for the maladaptive plasticity that underlies opiate withdrawal.

Rocuronium Versus Suxamethonium: A Survey of First-line Muscle Relaxant Use in UK Prehospital Rapid Sequence Induction.

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Hartley, Emma L; Alcock, Roger

2015-04-01

Prehospital anaesthesia in the United Kingdom (UK) is provided by Helicopter Emergency Medical Service (HEMS) and British Association for Immediate Care (BASICS), a road-based service. Muscle relaxation in rapid sequence induction (RSI) has been traditionally undertaken with the use of suxamethonium; however, rocuronium at higher doses has comparable intubating conditions with fewer side effects. The aim of this survey was to establish how many prehospital services in the UK are now using rocuronium as first line in RSI. An online survey was constructed identifying choice of first-line muscle relaxant for RSI and emailed to lead clinicians for BASICS and HEMS services across the UK. If rocuronium was used, further questions regarding optimal dose, sugammadex, contraindications, and difference in intubating conditions were asked. A total of 29 full responses (93.5%) were obtained from 31 services contacted. Suxamethonium was used first line by 17 prehospital services (58.6%) and rocuronium by 12 (41.4%). In 11 services (91.7%), a dose of 1 mg/kg of rocuronium was used, and in one service, 1.2 mg/kg (8.3%) was used. No services using rocuronium carried sugammadex. In five services, slower relaxation time was found using rocuronium (41.7%), and in seven services, no difference in intubation conditions were noted (58.3%). Contraindications to rocuronium use included high probability of difficult airway and anaphylaxis. Use of rocuronium as first-line muscle relaxant in prehospital RSI is increasing. Continued auditing of practice will ascertain which services have adopted change and identify if complications of failed intubation increase as a result.

Evoked electromyography to rocuronium in orbicularis oris and gastrocnemius in facial nerve injury in rabbits.

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Xing, Yian; Chen, Lianhua; Li, Shitong

2013-11-01

Muscles innervated by the facial nerve show different sensitivities to muscle relaxants than muscles innervated by somatic nerves, especially in the presence of facial nerve injury. We compared the evoked electromyography (EEMG) response of orbicularis oris and gastrocnemius in with and without a non-depolarizing muscle relaxant in a rabbit model of graded facial nerve injury. Differences in EEMG response and inhibition by rocuronium were measured in the orbicularis oris and gastrocnemius muscles 7 to 42 d after different levels of facial nerve crush injuries in adult rabbits. Baseline EEMG of orbicularis oris was significantly smaller than those of the gastrocnemius. Gastrocnemius was more sensitive to rocuronium than the facial muscles (P rocuronium was negatively correlated with the magnitude of facial nerve injury but the sensitivity to rocuronium was not. No significant difference was found in the onset time and the recovery time of rocuronium among gastrocnemius and normal or damaged facial muscles. Muscles innervated by somatic nerves are more sensitive to rocuronium than those innervated by the facial nerve, but while facial nerve injury reduced EEMG responses, the sensitivity to rocuronium is not altered. Partial neuromuscular blockade may be a suitable technique for conducting anesthesia and surgery safely when EEMG monitoring is needed to preserve and protect the facial nerve. Additional caution should be used if there is a risk of preexisting facial nerve injury. Copyright © 2013 Elsevier Inc. All rights reserved.

A comparative study of effect of sevoflurane on intubating conditions with rocuronium in neurosurgical patients

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Saikat Mitra

2015-01-01

Full Text Available Background and Aims: Rocuronium may not always be the preferred relaxant for rapid sequence intubation. When 2% sevoflurane is used in conjunction with rocuronium, it may reduce the time required for achieving complete skeletal muscle relaxation with the intubating dose of rocuronium. Methods: This study was prospective, randomised, double-blind in nature and compared the effect of sevoflurane on intubation time and intubating conditions when used along with rocuronium. Thirty adult patients belonging to American Society of Anesthesiologists physical status Grades 1 and 2, of either gender aged between 30 and 65 years undergoing neurosurgical operations were randomly allocated into two equal groups: Group R received 0.8 mg/kg rocuronium, and Group RS received 0.8 mg/kg of rocuronium with 2% sevoflurane. Onset time of intubation was assessed using train-of-four stimuli. The intubating conditions were compared using the Cooper scoring system and the haemodynamic responses were compared between the two groups. Results: The onset time of intubation was 101.73 ± 10.28 s in Group R and 60.4 ± 4.1 s in Group RS (P < 0.001, with excellent intubating conditions in both groups and without any adverse effects. Significant differences in heart rate and mean arterial pressure were seen immediately after intubation, at 1 and 3 min (P < 0.05 between the two groups. Conclusion: Rocuronium 0.8 mg/kg along with 2% sevoflurane provides excellent intubating conditions within 60-66 s from its administration.

Impact of Rocuronium and Succinylcholine on Sedation Initiation After Rapid Sequence Intubation.

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Johnson, Eric G; Meier, Alex; Shirakbari, Alicia; Weant, Kyle; Baker Justice, Stephanie

2015-07-01

Rapid sequence intubation (RSI) involves a rapidly acting sedative plus a neuromuscular blocking agent (NMBA) to facilitate endotracheal intubation. Rocuronium and succinylcholine are NMBAs commonly used in RSI with drastically different durations of action. Evaluate whether patients receiving RSI with a longer-acting NMBA had a greater delay in sedation or analgesia than patients that received a short-acting NMBA. This was a retrospective review of patients presenting to the emergency department requiring endotracheal intubation. Exclusions included age rocuronium or succinylcholine. Secondary endpoints included hospital length of stay (HLOS), intensive care unit length of stay (ICU LOS), and impact of an emergency medicine pharmacist (EPh). A total 106 patients met inclusion criteria, 76 patients receiving rocuronium and 30 receiving succinylcholine. Mean time to sedation or analgesia was longer in the rocuronium group when compared to the succinylcholine group at 34 ± 36 min vs. 16 ± 21 min (p = 0.002). In the presence of an EPh, the mean time to sedation or analgesia was 20 ± 21 min, vs. 49 ± 45 min (p rocuronium in RSI had a significantly longer time to sedation or analgesia when compared to patients receiving succinylcholine. The presence of an EPh significantly decreased the time to administration of sedation or analgesia after RSI. Copyright © 2015 Elsevier Inc. All rights reserved.

Phencyclidine-Induced Social Withdrawal Results from Deficient Stimulation of Cannabinoid CB1 Receptors: Implications for Schizophrenia

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Seillier, Alexandre; Martinez, Alex A; Giuffrida, Andrea

2013-01-01

The neuronal mechanisms underlying social withdrawal, one of the core negative symptoms of schizophrenia, are not well understood. Recent studies suggest an involvement of the endocannabinoid system in the pathophysiology of schizophrenia and, in particular, of negative symptoms. We used biochemical, pharmacological, and behavioral approaches to investigate the role played by the endocannabinoid system in social withdrawal induced by sub-chronic administration of phencyclidine (PCP). Pharmacological enhancement of endocannabinoid levels via systemic administration of URB597, an inhibitor of endocannabinoid degradation, reversed social withdrawal in PCP-treated rats via stimulation of CB1 receptors, but reduced social interaction in control animals through activation of a cannabinoid/vanilloid-sensitive receptor. In addition, the potent CB agonist CP55,940 reversed PCP-induced social withdrawal in a CB1-dependent manner, whereas pharmacological blockade of CB1 receptors by either AM251 or SR141716 reduced the time spent in social interaction in control animals. PCP-induced social withdrawal was accompanied by a decrease of anandamide (AEA) levels in the amygdala and prefrontal cortex, and these deficits were reversed by URB597. As CB1 receptors are predominantly expressed on GABAergic interneurons containing the anxiogenic peptide cholecystokinin (CCK), we also examined whether the PCP-induced social withdrawal resulted from deficient CB1-mediated modulation of CCK transmission. The selective CCK2 antagonist LY225910 blocked both PCP- and AM251-induced social withdrawal, but not URB597 effect in control rats. Taken together, these findings indicate that AEA-mediated activation of CB1 receptors is crucial for social interaction, and that PCP-induced social withdrawal results from deficient endocannabinoid transmission. PMID:23563893

DETERMINATION OF ROCURONIUM AND ITS PUTATIVE METABOLITES IN BODY-FLUIDS AND TISSUE-HOMOGENATES

NARCIS (Netherlands)

KLEEF, UW; PROOST, JH; ROGGEVELD, J

1993-01-01

A sensitive and selective HPLC method was developed for the quantification of the neuromuscular blocking agent rocuronium and its putative metabolites (the 17-desacetyl derivative and the N-desallyl derivative of rocuronium) in plasma, urine, bile, tissue homogenates and stoma fluid. Samples were

Gradual withdrawal of remifentanil infusion may prevent opioid-induced hyperalgesia.

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Comelon, M; Raeder, J; Stubhaug, A; Nielsen, C S; Draegni, T; Lenz, H

2016-04-01

The aim of this study was to examine if gradual withdrawal of remifentanil infusion prevented opioid-induced hyperalgesia (OIH) as opposed to abrupt withdrawal. OIH duration was also evaluated. Nineteen volunteers were enrolled in this randomized, double-blinded, placebo-controlled, crossover study. All went through three sessions: abrupt or gradual withdrawal of remifentanil infusion and placebo. Remifentanil was administered at 2.5 ng ml(-1) for 30 min before abrupt withdrawal or gradual withdrawal by 0.6 ng ml(-1) every five min. Pain was assessed at baseline, during infusion, 45-50 min and 105-110 min after end of infusions using the heat pain test (HPT) and the cold pressor test (CPT). The HPT 45 min after infusion indicated OIH development in the abrupt withdrawal session with higher pain scores compared with the gradual withdrawal and placebo sessions (both Pwithdrawal compared with placebo (P=0.93). In the CPT 50 min after end of infusion there was OIH in both remifentanil sessions compared with placebo (gradual P=0.01, abrupt Pwithdrawal of remifentanil infusion in the HPT. After abrupt withdrawal OIH was present in the HPT. In the CPT there was OIH after both gradual and abrupt withdrawal of infusion. The duration of OIH was less than 105 min for both pain modalities. NCT 01702389. EudraCT number 2011-002734-39. © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Synergism between rocuronium and cisatracurium: comparison of the Minto and Greco interaction models.

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Jeon, Soeun; Kwon, Jae Young; Kim, Hae-Kyu; Kim, Tae Kyun

2016-08-01

This study was conducted to investigate the pharmacodynamic interaction between rocuronium and cisatracurium using the response surface model, which is not subject to the limitations of traditional isobolographic analysis. One hundred and twenty patients were randomly allocated to receive one of the fifteen predefined combinations of rocuronium and cisatracurium. To study single drugs, cisatracurium 0.2, 0.15, or 0.1 mg/kg or rocuronium 0.8, 0.6 or 0.4 mg/kg doses were administered alone. To study the pharmacodynamic interaction, drugs were applied in three types of combination ratio, i.e., half dose of each drug alone, 75% of each single dose of rocuronium and 25% of each single dose of cisatracurium, and vice versa. Train-of-four (TOF) ratio and T1% (first twitch of the TOF presented as percentage compared to the initial T1) were used as pharmacodynamic endpoints, and the Greco and Minto models were used as surface interaction models. The interaction term α of the Greco model for TOF ratio and T1% measurements showed synergism with values of 0.977 and 1.12, respectively. Application of the Minto model resulted in U50 (θ) values (normalized unit of concentration that produces 50% of the maximal effect in the 0 rocuronium and cisatracurium exhibit synergism. Response surface modeling of the interaction between rocuronium and cisatracurium, based on considerations of their effects on muscle relaxation as measured by TOF ratio and T1%, indicated that the two drugs show considerable synergism.

Reduced clearance of rocuronium and sugammadex in patients with severe to end-stage renal failure: a pharmacokinetic study.

NARCIS (Netherlands)

Staals, L.M.; Snoeck, M.M.J.; Driessen, J.J.; Hamersvelt, H.W. van; Flockton, E.A.; Heuvel, M.W. van den; Hunter, J.M.

2010-01-01

BACKGROUND: Sugammadex is a selective relaxant binding agent designed to encapsulate the neuromuscular blocking agent, rocuronium. The sugammadex-rocuronium complex is eliminated by the kidneys. This trial investigated the pharmacokinetics (PKs) of sugammadex and rocuronium in patients with renal

Repeated restraint stress exposure during early withdrawal accelerates incubation of cue-induced cocaine craving.

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Glynn, Ryan M; Rosenkranz, J Amiel; Wolf, Marina E; Caccamise, Aaron; Shroff, Freya; Smith, Alyssa B; Loweth, Jessica A

2018-01-01

A major challenge for treating cocaine addiction is the propensity for abstinent users to relapse. Two important triggers for relapse are cues associated with prior drug use and stressful life events. To study their interaction in promoting relapse during abstinence, we used the incubation model of craving and relapse in which cue-induced drug seeking progressively intensifies ('incubates') during withdrawal from extended-access cocaine self-administration. We tested rats for cue-induced cocaine seeking on withdrawal day (WD) 1. Rats were then subjected to repeated restraint stress or control conditions (seven sessions held between WD6 and WD14). All rats were tested again for cue-induced cocaine seeking on WD15, 1 day after the last stress or control session. Although controls showed a time-dependent increase in cue-induced cocaine seeking (incubation), rats exposed to repeated stress in early withdrawal exhibited a more robust increase in seeking behavior between WD1 and WD15. In separate stressed and control rats, equivalent cocaine seeking was observed on WD48. These results indicate that repeated stress in early withdrawal accelerates incubation of cocaine craving, although craving plateaus at the same level were observed in controls. However, 1 month after the WD48 test, rats subjected to repeated stress in early withdrawal showed enhanced cue-induced cocaine seeking following acute (24 hours) food deprivation stress. Together, these data indicate that chronic stress exposure enhances the initial rate of incubation of craving during early withdrawal, resulting in increased vulnerability to cue-induced relapse during this period, and may lead to a persistent increase in vulnerability to the relapse-promoting effects of stress. © 2016 Society for the Study of Addiction.

Onset and Duration of Intravenous and Intraosseous Rocuronium in Swine

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Loughren, Michael; Banks, Sarah; Naluan, Carleo; Portenlanger, Paul; Wendorf, Arthur; Johnson, Don

2014-01-01

Introduction The intraosseous (IO) route has become a popular method to gain access to the peripheral circulation in emergency situations. Despite little supporting data, it is generally believed that IO absorption is immediate and equivalent to the intravenous (IV) route. It is important to determine if rocuronium can effectively be administered by the IO route. The aim of the study was to determine and compare the onset and duration of rocuronium when administered via the IO and IV routes in a normovolemic pig model. Methods We recorded electromyographic (EMG) data following tibial IO and peripheral IV administration of rocuronium (1.2 mg/kg) in 10 swine weighing between 56 and 71 Kg. We transformed data were transformed to percent of baseline, determined onset and recovery characteristics. Results The onset EMG-time profiles for IO and IV administration were very similar: tibial IO compared to IV administration did not statistically alter the onset of paralysis. The IO group took statistically longer than the IV group to return to 50 (p=0.042), 75 (p=0.034) and 95 (p=0.036) percent of baseline activity. Conclusion The duration of effect is statistically longer after IO administration but is more of an academic interest than a clinical concern. The results of this study suggest that rocuronium can effectively be administered via the IO route without the need for dose adjustments. PMID:24672619

Microinjection of Orexin-A into the Locus Coeruleus Area Induces Morphine Withdrawal Behaviors in Morphine Independent Rats

Directory of Open Access Journals (Sweden)

Hosin Azizi

2012-02-01

Full Text Available Introduction: Orexin neuropeptide has a role in opioid withdrawal behaviors. Orexin-expressing neurons that are present in the hypothalamic nuclei send dense projections to the Locus Coeruleus (LC. Withdrawal syndrome is temporally associated with hyperactivity of LC neurons. LC neurons do not show withdrawal-induced hyperactivity in brain slices from morphine-dependent rats. Thus, it has been suggested that the increase in LC neuronal activity seen in vivo is mediated by extrinsic factors. Therefore, this study was carried out to find whether LC microinjection of orexin-A can induce withdrawal behaviors. Method: Adult male Wistar rats were used in this study. Intra-LC microinjection of orexin-A or orexin-A vehicle was performed one week after LC cannulation. Thereafter, somatic signs of withdrawal were evaluated during a period of 25 min.Findings: Orexin-A induced several signs of morphine withdrawal. Conclusion: It may be concluded that orexin at LC acts as an extrinsic factor in the expression of morphine withdrawal syndrome.

Synergistic effect of sevoflurane and isoflurane on inhibition of the adult-type muscle nicotinic acetylcholine receptor by rocuronium.

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Liu, Li; Li, Wei; Wei, Ke; Cao, Jun; Luo, Jie; Wang, Bin; Min, Su

2013-06-01

Inhaled anesthetics increase the incidence of postoperative residual neuromuscular blockade, and the mechanism is still unclear. We have investigated the synergistic effect of low-concentration inhaled anesthetics and rocuronium on inhibition of the inward current of the adult-type muscle nicotinic acetylcholine receptor (ε-nAChR). Adult-type mouse muscle ε-nAChR was expressed in HEK293 cells by liposome transfection. The inward current of the ε-nAChR was activated by use of 10 μmol/L acetylcholine alone or in combination with different concentrations of sevoflurane, isoflurane, or rocuronium. The concentration-response curves of five cells were constructed, and the data yielded the 5, 25, and 50 % inhibitory concentrations (IC5, IC25, and IC50, respectively) for single-drug application. Subsequently, the functional channels were perfused by adding 0.5 IC5 of either sevoflurane or isoflurane (aqueous concentrations 140 and 100 μmol/L, respectively) to the solution, followed by addition of IC5, IC25, or IC50 rocuronium. The amount of inhibition was calculated to quantify their synergistic effect. The inhibitory effect of rocuronium was enhanced by sevoflurane or isoflurane in a concentration-dependent manner. Sevoflurane or isoflurane (0.5 IC5) with rocuronium at IC5, IC25, and IC50 synergistically inhibited the current amplitude of adult-type muscle ε-nAChR. When the IC5 of rocuronium was used, isoflurane had a stronger synergistic effect than sevoflurane (p rocuronium was applied at higher concentrations (IC25 and IC50), sevoflurane had an effect similar to that of isoflurane. For both inhaled anesthetics, the synergistic effect was more intense for rocuronium at IC5 than for rocuronium at IC25 or IC50. Residual-concentration sevoflurane or isoflurane has a strong synergistic effect with rocuronium at clinically relevant residual concentrations. A lower rocuronium concentration resulted in a stronger synergistic effect.

Comparison of rocuronium at two different doses and succinylcholine for endotracheal intubation in adult patients for elective surgeries.

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Chavan, S G; Gangadharan, S; Gopakumar, A K

2016-01-01

The effects of rocuronium at two different doses, that is, 0.6 mg/kg (2 × ED95) and 0.9 mg/kg (3 × ED95), were compared with succinylcholine (2 mg/kg) when used for endotracheal intubation in adult patients for elective surgeries under general anesthesia. Ninety patients were divided into three groups of 30 each. Groups A, B received injection rocuronium at 0.6 mg/kg, 0.9 mg/kg respectively and Group C received succinylcholine at 2 mg/kg. Onset of action of relaxant, intubation conditions, time taken to intubate and duration of action were compared. To compare the statistical difference in the age, weight, height of the study subjects, onset of action of relaxant, intubation conditions, time taken to intubate, and duration of action analysis of variance and unpaired t -test were used. The onset time was considerably shorter with rocuronium 0.9 mg/kg than 0.6 mg/kg. The onset time of rocuronium 0.9 mg/kg was found to be significantly longer than succinylcholine 2 mg/kg. Time taken to intubate was shortest with succinylcholine 2 mg/kg. The time taken to intubate with the rocuronium 0.9 mg/kg was found to be comparable to that of rocuronium 0.6 mg/kg. Intubation score of rocuronium 0.9 mg/kg was the best (17.75), which was comparable with succinylcholine. However, the intubation score obtained with rocuronium 0.6 mg/kg was inferior. Duration of action was shortest with succinylcholine. The duration of action is prolonged when the dose of rocuronium is increased from 0.6 to 0.9 mg/kg. Rapid sequence induction of anesthesia with propofol and fentanyl, succinylcholine allowed a more rapid endotracheal intubation sequence and created superior intubation conditions than rocuronium. However, the technique of using a large dose of rocuronium to achieve perfect conditions for tracheal intubation may have application whenever succinylcholine is relatively contraindicated.

Onset and duration of action of rocuronium - from tracheal intubation, through intense block to complete recovery

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Schultz, P.; Ibsen, M.; Østergaard, Doris

2001-01-01

pharmacodynamic, neuromuscular relaxant, rocuronium, neuromuscular transmission, nerve stimulator, post tetanic count......pharmacodynamic, neuromuscular relaxant, rocuronium, neuromuscular transmission, nerve stimulator, post tetanic count...

Emergency Department Intubation Success With Succinylcholine Versus Rocuronium: A National Emergency Airway Registry Study.

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April, Michael D; Arana, Allyson; Pallin, Daniel J; Schauer, Steven G; Fantegrossi, Andrea; Fernandez, Jessie; Maddry, Joseph K; Summers, Shane M; Antonacci, Mark A; Brown, Calvin A

2018-05-07

Although both succinylcholine and rocuronium are used to facilitate emergency department (ED) rapid sequence intubation, the difference in intubation success rate between them is unknown. We compare first-pass intubation success between ED rapid sequence intubation facilitated by succinylcholine versus rocuronium. We analyzed prospectively collected data from the National Emergency Airway Registry, a multicenter registry collecting data on all intubations performed in 22 EDs. We included intubations of patients older than 14 years who received succinylcholine or rocuronium during 2016. We compared the first-pass intubation success between patients receiving succinylcholine and those receiving rocuronium. We also compared the incidence of adverse events (cardiac arrest, dental trauma, direct airway injury, dysrhythmias, epistaxis, esophageal intubation, hypotension, hypoxia, iatrogenic bleeding, laryngoscope failure, laryngospasm, lip laceration, main-stem bronchus intubation, malignant hyperthermia, medication error, pharyngeal laceration, pneumothorax, endotracheal tube cuff failure, and vomiting). We conducted subgroup analyses stratified by paralytic weight-based dose. There were 2,275 rapid sequence intubations facilitated by succinylcholine and 1,800 by rocuronium. Patients receiving succinylcholine were younger and more likely to undergo intubation with video laryngoscopy and by more experienced providers. First-pass intubation success rate was 87.0% with succinylcholine versus 87.5% with rocuronium (adjusted odds ratio 0.9; 95% confidence interval 0.6 to 1.3). The incidence of any adverse event was also comparable between these agents: 14.7% for succinylcholine versus 14.8% for rocuronium (adjusted odds ratio 1.1; 95% confidence interval 0.9 to 1.3). We observed similar results when they were stratified by paralytic weight-based dose. In this large observational series, we did not detect an association between paralytic choice and first-pass rapid sequence

The effect of cisatracurium and rocuronium on lung function in anesthetized children.

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Yang, Charles I; Fine, Gavin F; Jooste, Edmund H; Mutich, Rebecca; Walczak, Stephen A; Motoyama, Etsuro K

2013-12-01

Neuromuscular blocking drugs have been implicated in intraoperative bronchoconstrictive episodes. We examined the effects of clinically relevant doses of cisatracurium and rocuronium on the lung mechanics of pediatric subjects. We hypothesized that cisatracurium and rocuronium would have bronchoconstrictive effects. We studied ASA physical status I and II pediatric subjects having elective dental or urological procedures, requiring general anesthesia with endotracheal intubations with either cisatracurium or rocuronium. Pulmonary function tests were performed before and after neuromuscular blocking drug dosing and again after albuterol administration. Using forced deflation and passive deflation techniques, forced vital capacity (FVC) and maximum expiratory flow rate at 10% (MEF10) of FVC were obtained. Fractional changes from the baseline were used to compare subjects. Changes in MEF10 of >30% were considered clinically significant. A Shapiro-Wilk test, paired t test, and Wilcoxon rank sum test were used to analyze the data. Twenty-five subjects (median age = 5.25 years; range = 9 months-9.9 years) were studied; 12 subjects received cisatracurium and 13 subjects received rocuronium. Data are shown as mean proportional change ± SD or, in the case of not normally distributed, median proportional change (first, third quartile) with P values. In the cisatracurium group, there were no differences between baseline and postneuromuscular blocker administration in the fractional change from the baselines of FVC (1.00 ± 0.04, P = 0.5), but there was a significant decrease in MEF10 (0.80 ± 0.18, P = 0.002). In the rocuronium group, there were small yet significant decreases of FVC (0.99 [first quartile 0.97, third quartile 1], P = 0.02) and significant decreases in MEF10 (0.78 ± 0.26, P = 0.008). After administration of albuterol in the cisatracurium group, FVC increased slightly but significantly from baseline values (1.02 ± 0.02, P = 0.005). MEF10 increased

The presumed central nervous system effects of rocuronium in a neonate and its reversal with sugammadex.

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Langley, Ross J; McFadzean, Jillian; McCormack, Jon

2016-01-01

We describe a 2-day-old male infant who received rocuronium as part of general anesthesia for a tracheal esophageal fistula repair. Postoperatively, he had prolonged central and peripheral neuromuscular blockade despite cessation of the rocuronium infusion several hours previously. This case discusses the presumed central nervous system effects of rocuronium in a neonate and its effective reversal with sugammadex. © 2015 John Wiley & Sons Ltd.

Timing of nicotine lozenge administration to minimize trigger induced craving and withdrawal symptoms.

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Kotlyar, Michael; Lindgren, Bruce R; Vuchetich, John P; Le, Chap; Mills, Anne M; Amiot, Elizabeth; Hatsukami, Dorothy K

2017-08-01

Smokers are often advised to use nicotine lozenge when craving or withdrawal symptoms occur. This may be too late to prevent lapses. This study assessed if nicotine lozenge use prior to a common smoking trigger can minimize trigger induced increases in craving and withdrawal symptoms. Eighty-four smokers completed two laboratory sessions in random order. At one session, nicotine lozenge was given immediately after a stressor (to approximate current recommended use - i.e., after craving and withdrawal symptoms occur); at the other session subjects were randomized to receive nicotine lozenge at time points ranging from immediately to 30min prior to the stressor. Withdrawal symptoms and urge to smoke were measured using the Minnesota Nicotine Withdrawal Scale and the Questionnaire of Smoking Urges (QSU). Relative to receiving lozenge after the stressor, a smaller increase in pre-stressor to post-stressor withdrawal symptom scores occurred when lozenge was used immediately (p=0.03) and 10min prior (p=0.044) to the stressor. Results were similar for factors 1 and 2 of the QSU when lozenge was used immediately prior to the stressor (pnicotine lozenge prior to a smoking trigger can decrease trigger induced craving and withdrawal symptoms. Future studies are needed to determine if such use would increase cessation rates. Clinicaltrials.gov # NCT01522963. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ease of intubation: A randomized, double-blind study to compare two doses of rocuronium bromide for endotracheal intubation.

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Shukla, Aparna; Misra, Shilpi

2016-01-01

Clinical need for a nondepolarizing agent with a rapid onset time and a brief duration of action has led to the development of rocuronium bromide. The aim of this study was to evaluate optimal dose of rocuronium bromide for intubation and to compare the onset time, duration of action, intubating conditions, and hemodynamic effects of two doses of rocuronium bromide. A prospective, randomized, double-blind study. All the patients were divided in a randomized, double-blind fashion into two groups of twenty patients each. Group I patients received rocuronium bromide 0.6 mg/kg intravenously and intubated at 60 s, Group II patients received rocuronium bromide 0.9 mg/kg and intubated at 60 s. The neuromuscular block was assessed using single twitch stimulation of 0.1 Hz at adductor pollicis muscle of hand at every 10 s. The results were compiled and analyzed statistically using Chi-square test for qualitative data and Student's t -test for quantitative data. Time of onset was significantly shorter ( P Rocuronium bromide 0.9 mg/kg is a safer alternative to rocuronium bromide 0.6 mg/kg for endotracheal intubation with shorter time of onset and better intubating conditions.

Comparison of rocuronium and succinylcholine on postintubation sedative and analgesic dosing in the emergency department.

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Korinek, Justin D; Thomas, Rachel M; Goddard, Luke A; St John, Alexander E; Sakles, John C; Patanwala, Asad E

2014-06-01

Rocuronium and succinylcholine are both commonly used neuromuscular blockers for rapid sequence intubation in the emergency department (ED). The objective of this study was to determine if patients who receive rocuronium are more likely to receive lower doses of postintubation sedatives and analgesics compared with patients who receive succinylcholine. This was a retrospective cohort study carried out in a tertiary, academic ED. Consecutive adult patients, who were intubated using etomidate for induction of sedation, were included. Patients were categorized on the basis of whether they received (a) rocuronium or (b) succinylcholine for paralysis. The dosing of postintubation sedative and analgesic infusions were compared 30 min after initiation between the two groups. A total of 254 patients were included in the final analysis (rocuronium=127 and succinylcholine=127). In the overall cohort, 90.2% (n=229) of patients were administered a sedative postintubation in the ED. Most of these patients were initiated on propofol infusions. The mean propofol infusion rate at 30 min was 30±23 mcg/kg/min in the rocuronium group and 42±24 mcg/kg/min in the succinylcholine group (P=0.002). A total of 42.5% of patients (n=108) received an analgesic infusion (all patients received fentanyl). The mean fentanyl infusion rate at 30 min was 0.65±0.55 and 0.86±0.49 mcg/kg/h in the rocuronium and succinylcholine groups, respectively (P=0.041). Patients who receive rocuronium are more likely to receive lower doses of sedative and analgesic infusions after intubation. This may place them at risk of being awake under paralysis.

[Rocuronium and sugammadex in emergency medicine: requirements of a muscle relaxant for rapid sequence induction].

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Luxen, J; Trentzsch, H; Urban, B

2014-04-01

The required characteristics of neuromuscular blockers for rapid sequence induction (RSI) are clearly defined: nearly immediate effectiveness and short duration of effect. These demands are not only necessary for ideal conditions of quick endotracheal intubation without mask-bag intermediate ventilation but are also essential to enable a quick return to sufficient spontaneous breathing in case of a cannot intubate cannot ventilate situation. Until recently only succinylcholine had these characteristics; however, a considerable number of dangerous side effects and contraindications had to be accepted. In 1996, rocuronium was introduced, which was capable of immediately establishing good intubation conditions similar to succinylcholine. However, the median duration of effect is 45-60 min and it therefore contains a risk if the patient cannot be ventilated and oxygenated. Therefore, rocuronium is considered a good alternative but not a complete substitute for succinylcholine. The introduction of sugammadex in 2008 for quick reversal of rocuronium changed matters. Comparative studies from the past 4 years dealing with rocuronium/sugammadex versus uccinylcholine in RSI showed that rocuronium and sugammadex combined enabled a significantly faster return to sufficient spontaneous ventilation in emergency situations and also proved that the use of rocuronium significantly reduced the degree of desaturation during the interval between injection and ventilation postintubation. rocuronium used in hospital is a very good substitute for succinylcholine as a neuromuscular blocker during RSI as long as sugammadex is at hand for reversal. It remains to be considered that in a situation with severe problems of the airway and breathing, which are the main preclinical indications for intubation, a forward strategy for ventilation of the patient is the only acceptable way in most cases and the return to spontaneous breathing is not an alternative. Therefore, the value of sugammadex

[Effects of sevoflurane and desflurane on pharmacodynamics of rocuronium in children].

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Kang, D X; Rao, Y Q; Ji, B; Li, J

2017-02-14

Objective: To observe the intraoperative influences on pharmacodynamics of rocuronium in children inhaling sevoflurane and desflurane for 40 min balance. Methods: Ninety children (ASAⅠ-Ⅱ) undergoing elective surgery with general anesthesia in Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University from July 2015 to May 2016 were randomly assigned into six groups ( n =15): Sevoflurane group (group S1 and S2), Desflurane group (group D1 and D2) and Propofol group (group P1 and P2). Children in group D1, S1 and P1 were allocated to research the dose-effect relationship of rocuronium, children in group D2, S2 and P2 were allocated to research the time-effect relationship of rocuronium. TOF-Watch SX monitor was used to exert a train-of-four stimulation (TOF) at ulnar nerve in wrist, then the adductor pollicis muscle appeared muscle twitch 4 times in turn which was recorded T(1, )T(2, )T(3) and T(4) respectively. After the success of the muscle relaxant calibration, 1.3 MAC sevoflurane and desflurane were inhaled and maintained for 40 min respectively in children in Sevoflurane group (group S1 and S2) and Desflurane group (group D1 and D2), Plasma target controlled infusion of 3.5-4.0 μg/ml propofol was always administered in Propofol group (group P1 and P2). 75 μg/kg rocuronium was injected each time in group S1, D1 and P1 respectively. Maximum inhibited effect of T(1) was recorded after every injection until inhibition of T(1) more than 95% eventually. The method of cumulative dose four times was used to calculate the efficiency curve of rocuronium[median effective dose (ED(50)), 90% effective dose (ED(90)) and 95% effective dose (ED(95))]. 0.6 mg/kg rocuronium was injected respectively through vein in group S2, D2 and P2. The recovery times of muscle relaxant were recorded which including time of T(1) disappeared (onset time), T(1) from 0% to 5% (peak effect time), T(1) from 0% to 25% (clinical effect time), T(1) from 25% to 75

Low-Dose or High-Dose Rocuronium Reversed with Neostigmine or Sugammadex for Cesarean Delivery Anesthesia: A Randomized Controlled Noninferiority Trial of Time to Tracheal Intubation and Extubation.

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Stourac, Petr; Adamus, Milan; Seidlova, Dagmar; Pavlik, Tomas; Janku, Petr; Krikava, Ivo; Mrozek, Zdenek; Prochazka, Martin; Klucka, Jozef; Stoudek, Roman; Bartikova, Ivana; Kosinova, Martina; Harazim, Hana; Robotkova, Hana; Hejduk, Karel; Hodicka, Zuzana; Kirchnerova, Martina; Francakova, Jana; Obare Pyszkova, Lenka; Hlozkova, Jarmila; Sevcik, Pavel

2016-05-01

Rocuronium for cesarean delivery under general anesthesia is an alternative to succinylcholine for rapid-sequence induction of anesthesia because of the availability of sugammadex for reversal of neuromuscular blockade. However, there are no large well-controlled studies in women undergoing general anesthesia for cesarean delivery. The aim of this noninferiority trial was to determine whether rocuronium and sugammadex confer benefit in time to tracheal intubation (primary outcome) and other neuromuscular blockade outcomes compared with succinylcholine, rocuronium, and neostigmine in women undergoing general anesthesia for cesarean delivery. We aimed to enroll all women undergoing general anesthesia for cesarean delivery in the 2 participating university hospitals (Brno, Olomouc, Czech Republic) in this single-blinded, randomized, controlled study. Women were randomly assigned to the ROC group (muscle relaxation induced with rocuronium 1 mg/kg and reversed with sugammadex 2-4 mg/kg) or the SUX group (succinylcholine 1 mg/kg for induction, rocuronium 0.3 mg/kg for maintenance, and neostigmine 0.03 mg/kg for reversal of the neuromuscular blockade). The interval from the end of propofol administration to tracheal intubation was the primary end point with a noninferiority margin of 20 seconds. We recorded intubating conditions (modified Viby-Mogensen score), neonatal outcome (Apgar score rocuronium for rapid-sequence induction is noninferior for time to tracheal intubation and is accompanied by more frequent absence of laryngoscopy resistance and lower incidence of myalgia in comparison with succinylcholine for cesarean delivery under general anesthesia.

Onset and Duration of Intravenous and Intraosseous Rocuronium in Swine

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Michael Loughren

2014-03-01

Full Text Available Introduction: The intraosseous (IO route has become a popular method to gain access to the peripheral circulation in emergency situations. Despite little supporting data, it is generally believed that IO absorption is immediate and equivalent to the intravenous (IV route. It is important to determine if rocuronium can effectively be administered by the IO route. The aim of the study was to determine and compare the onset and duration of rocuronium when administered via the IO and IV routes in a normovolemic pig model. Methods: We recorded electromyographic (EMG data following tibial IO and peripheral IV administration of rocuronium (1.2 mg/kg in 10 swine weighing between 56 and 71 Kg. We transformed data were transformed to percent of baseline, determined onset and recovery characteristics. Results: The onset EMG-time profiles for IO and IV administration were very similar: tibial IO compared to IV administration did not statistically alter the onset of paralysis. The IO group took statistically longer than the IV group to return to 50 (p=0.042, 75 (p=0.034 and 95 (p=0.036 percent of baseline activity. Conclusion: The duration of effect is statistically longer after IO administration but is more of an academic interest than a clinical concern. The results of this study suggest that rocuronium can effectively be administered via the IO route without the need for dose adjustments. [West J Emerg Med. 2014;15(2:241-245.

Effect of rocuronium on the bispectral index under anesthesia and tracheal intubation.

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Yue, Hui; Han, Jinyu; Liu, Ling; Wang, Kaiyuan; Li, Jincheng

2016-12-01

The aim of the present study was to investigate the effect of various doses of rocuronium on bispectral index (BIS) responses to propofol induction and tracheal intubation, as well as the role of the non-depolarization muscle relaxant rocuronium on the depth of sedation. A total of 72 patients (American Society of Anesthesiologists physical status I-II) were anaesthetized with propofol using a target-controlled infusion, and randomly divided into two sedation level groups (n=36). The patients were divided into 2 groups according to the BIS value: A normal sedation group (group 1), with a stable BIS value at 40-60, and a deep sedation group (group 2), with a BIS value rocuronium (0.3, 0.6, 0.9 and 1.2 mg/kg). Tracheal intubation was performed after 2 min of rocuronium administration. BIS, electromyography (EMG), heart rate (HR) and mean arterial pressure (MAP) were recorded continuously and averaged over 1 min during baseline (T1), steady state (T2), 2 min after rocuronium infusion (T3), and 0, 2 and 5 min after tracheal intubation. The results demonstrated that HR and MAP decreased significantly at T2 and T3 compared with T1. Following tracheal intubation (L0), HR and MAP significantly increased compared with T2 and T3, and returned to levels similar to those prior to intubation after 5 min. In group 1C and 1D, BIS was significantly decreased at T3 compared with T2; BIS was significantly increased at L0 compared with T3 in group 1A and 1B. EMG at earlier stages of anesthesia was significantly higher compared with other points, and was significantly increased at L0 compared with T3 in group 1A and 1B. These results demonstrated that BIS response may be associated with the dosage of rocuronium in the normal sedation group, although no association was observed with the deep sedation group. Tracheal intubation resulted in marked hemodynamic changes under both normal and deep sedation.

Resistance to rocuronium of rat diaphragm as compared with limb muscles.

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Huang, Lina; Yang, Meirong; Chen, Lianhua; Li, Shitong

2014-12-01

Skeletal muscles are composed of different muscle fiber types. We investigated the different potency to rocuronium among diaphragm (DIA), extensor digitorum longus (EDL), and soleus (SOL) in vitro as well as to investigate the differences of acetylcholine receptors (AChRs) among these three typical kinds of muscles. The isolated left hemidiaphragm nerve-muscle preparations, the EDL sciatic nerve-muscle preparations, and the SOL sciatic nerve-muscle preparations were established to evaluate the potency to rocuronium. Concentration-response curves were constructed and the values of IC50 were obtained. The density of AChRs at the end plate and the number of AChRs per unit fiber cross fiber area (CSA), AChR affinity for muscle relaxants were evaluated. The concentration-twitch tension curves of rocuronium were significantly different. The curves demonstrated a shift to the right of the DIA compared with the EDL and SOL (P  0.05). IC50 was significantly largest in DIA, second largest in SOL, and smallest in EDL (P rocuronium of DIA compared with EDL and SOL was verified. The DIA was characterized by the largest number of AChRs per unit fiber CSA and the lowest affinity of the AChRs. Although compared with SOL, EDL was proved to have larger number of AChRs per unit fiber CSA and the lower affinity of the AChRs. These findings may be the mechanisms of different potency to rocuronium in DIA, EDL, and SOL. The results of the study could help to explain the relationship between different composition of muscle fibers and the potency to muscle relaxants. Extra caution should be taken in clinical practice when monitoring muscle relaxation in anesthetic management using different muscles. Copyright © 2014 Elsevier Inc. All rights reserved.

Response to rocuronium and its determinants in patients with myasthenia gravis: A case-control study.

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Fujimoto, Masafumi; Terasaki, Shuhei; Nishi, Masaaki; Yamamoto, Tatsuo

2015-10-01

Several previous studies using univariate analysis have suggested that the pre-anaesthetic train-of-four (TOF) ratio, concentration of anti-acetylcholine receptor (AChR) antibodies and the presence of preoperative generalised muscular involvement are determinants of an increased response to neuromuscular blocking agents (NMBAs) in patients with myasthenia gravis. However, the determinants of the response of patients with myasthenia gravis to rocuronium, which is expected to be used more frequently since the advent of sugammadex, have not been studied. To clarify whether previously suggested determinants of the response to other intermediate-acting NMBAs would also affect the response to rocuronium and to reveal the determinants of the increased response to rocuronium in individual patients with myasthenia gravis using multivariate analysis. Case control study. Kumamoto University Hospital, November 2010 to September 2013. Thirty-eight patients with myasthenia gravis having surgery using a total intravenous anaesthetic technique were investigated. After induction of general anaesthesia, the 95% effective dose (ED95) of rocuronium was calculated using cumulative dose-finding methods. Neuromuscular function was monitored by acceleromyographic assessment of TOF responses of the adductor pollicis muscle to ulnar nerve stimulation. Patients were then divided into the increased response (ED95 rocuronium injection (baseline TOF ratio), concentration of anti-AChR antibodies, Osserman classification and treatment for myasthenia gravis in the two groups were compared. Stepwise logistic regression identified baseline TOF ratio and age of onset of myasthenia gravis as determinants of the increased response to rocuronium in patients with myasthenia gravis [odds ratios (95% confidence interval) of 0.87 (0.77 to 0.98; P = 0.02) and 0.92 (0.86 to 0.99; P = 0.03), respectively]. Multivariate analysis identified baseline TOF ratio and age of disease onset as determinants of

Effect of the addition of rocuronium to 2% lignocaine in peribulbar block for cataract surgery.

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Patil, Vishalakshi; Farooqy, Allauddin; Chaluvadi, Balaraju Thayappa; Rajashekhar, Vinayak; Malshetty, Ashwini

2017-01-01

Peribulbar anesthesia is associated with delayed orbital akinesia compared with retrobulbar anesthesia. To test the hypothesis that rocuronium added to a mixture of local anesthetics (LAs) could improve speed of onset of akinesia in peribulbar block (PB), we designed this study. This study examined the effects of adding rocuronium 5 mg to 2% lignocaine with adrenaline to note orbital and eyelid akinesia in patients undergoing cataract surgery. In a prospective, randomized, double-blind study, 100 patients were equally randomized to receive a mixture of 0.5 ml normal saline, 6 ml lidocaine 2% with adrenaline and hyaluronidase 50 IU/ml (Group I), a mixture of rocuronium 0.5 ml (5 mg), 6 ml lidocaine 2% with adrenaline and hyaluronidase 50 IU/ml (Group II). Orbital akinesia was assessed on a 0-8 score (0 = no movement, 8 = normal) at 2 min intervals for 10 min. Time to adequate anesthesia was also recorded. Results are presented as mean ± standard deviation. Rocuronium group demonstrated significantly better akinesia scores than control group at 2 min intervals post-PB (significant P value obtained). No significant complications were recorded. Rocuronium added to a mixture of LA improved the quality of akinesia in PB and reduced the need for supplementary injections. The addition of rocuronium 5 mg to a mixture of lidocaine 2% with adrenaline and hyaluronidase 50 IU/ml shortened the onset time of peribulbar anesthesia in patients undergoing cataract surgery without causing adverse effects.

Increased Renal Clearance of Rocuronium Compensates for Chronic Loss of Bile Excretion, via upregulation of Oatp2.

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Wang, Long; Zhou, Mai-Tao; Chen, Cai-Yang; Yin, Wen; Wen, Da-Xiang; Cheung, Chi-Wai; Yang, Li-Qun; Yu, Wei-Feng

2017-01-13

Requirement for rocuronium upon surgery changes only minimally in patients with end-stage liver diseases. Our study consisted of both human and rat studies to explore the reason. The reduction rate of rocuronium infusion required to maintain neuromuscular blockade during the anhepatic phase (relative to paleohepatic phase) was examined in 16 children with congenital biliary atresia receiving orthotopic liver transplantation. Pharmacodynamics and pharmacokinetics of rocuronium were studied based on BDL rats. The role of increased Oatp2 and decrease Oatp1 expressions in renal compensation were explored. The reduction of rocuronium requirements significantly decreased in obstructively jaundiced children (24 ± 9 vs. 39 ± 11%). TOF50 in BDL rats was increased by functional removal of the kidneys but not the liver, and the percentage of rocuronium excretion through urine increased (20.3 ± 6.9 vs. 8.6 ± 1.8%), while that decreased through bile in 28d-BDL compared with control group. However, this enhanced renal secretion for rocuronium was eliminated by Oatp2 knock-down, rather than Oatp1 overexpression (28-d BDL vs. Oatp1-ShRNA or Oatp2-ShRNA, 20.3 ± 6.9 vs. 17.0 ± 6.6 or 9.3 ± 3.2%). Upon chronic/sub-chronic loss of bile excretion, rocuronium clearance via the kidneys is enhanced, by Oatp2 up-regulation.

Effects of presynaptic muscarinic cholinoreceptor blockade on neuromuscular transmission as assessed by the train-of-four and the tetanic fade response to rocuronium.

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Kim, Yong Beom; Lee, Sangseok; Lee, Kyeong Chun; Kim, Ha Jung; Ro, Young Jin; Yang, Hong-Seuk

2017-07-01

This study investigated the effect of muscarinic M 1 and M 2 receptor antagonists on the rocuronium-induced train of four (TOF) fade and tetanic fade, respectively. Ex-vivo phrenic nerves and diaphragms were obtained from adult Sprague-Dawley rats and stabilized in Krebs buffer; the nerve-stimulated muscle TOF fade was observed at 20 s intervals. For the TOF study, phrenic nerves and diaphragms were incubated with pirenzepine (an M 1 blocker) at concentrations of 0 nmol L -1 (control), 10 nmol L -1 (PZP10), or 100 nmol L -1 (PZP100). Rocuronium was then administered incrementally until the first twitch tension had depressed by >95% during TOF stimulation. The mean TOF ratios were compared when the first twitch tensions were depressed by 40%-50%. For the tetanic fade study, 50 Hz/5 s tetani was applied initially, 30 min after the administration of a loading dose of rocuronium and methoctramine (an M 2 receptor blocker, loaded at 0 μmol L -1 [control], 1 μmol L -1 [MET1], or 10 μmol L -1 [MET10]). The EC 95 of rocuronium was significantly lower in the PZP10 group than in the control group. In the PZP10 group, the TOF ratios at 50% and first twitch tension depression were significantly lower than those in the control group (P=.02). During tetanic stimulation, the tetanic fade was significantly enhanced in the MET10 group compared to the other groups. This study shows that antagonists of muscarinic M 1 and M 2 receptors affect the rocuronium-induced neuromuscular block as demonstrated by the reduced EC 95 and TOF ratios (M 1 antagonist, pirenzepine) or the enhanced 50-Hz tetanic fade (M 2 antagonist, methoctramine). © 2017 The Authors. Clinical and Experimental Pharmacology and Physiology Published by John Wiley & Sons Australia, Ltd.

Intravenous rocuronium 0.3 mg/kg improves the conditions for tracheal intubation in cats: a randomized, placebo-controlled trial.

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Sakai, Daniel M; Zornow, Kailee Anne; Campoy, Luis; Cable, Christina; Appel, Leslie D; Putnam, Holly J; Martin-Flores, Manuel

2018-01-01

Objectives We evaluated the use of rocuronium 0.3 mg/kg intravenously (IV) to facilitate tracheal intubation in cats anesthetized for elective ovariohysterectomy. Methods Thirty female cats were randomly allocated to receive rocuronium 0.3 mg/kg IV or an equal volume of normal saline, following induction of anesthesia with ketamine and midazolam. Thirty seconds after induction, a single investigator, unaware of treatment allocation, attempted tracheal intubation. The number of attempts and the time to complete intubation were measured. Intubating conditions were assessed as acceptable or unacceptable based on a composite score consisting of five different components. Duration of apnea after induction was measured and cases of hemoglobin desaturation (SpO 2 rocuronium 12 s [range 8-75 s]; saline 60 s [range 9-120 s]) and with fewer attempts (rocuronium 1 [range 1-2]; saline 2 [range 1-3], both P = 0.006) in cats receiving rocuronium. Unacceptable intubating conditions on the first attempt occurred in 3/15 cats with rocuronium and in 10/15 with saline ( P = 0.01). Apnea lasted 4 ± 1.6 mins with rocuronium and 2.3 ± 0.5 mins with saline ( P = 0.0007). No cases of desaturation were observed. Conclusions and relevance Rocuronium 0.3 mg/kg IV improves intubating conditions compared with saline and reduces the time and number of attempts to intubate with only a short period of apnea in cats.

Disrupting the memory of places induced by drugs of abuse weakens motivational withdrawal in a context-dependent manner.

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Taubenfeld, Stephen M; Muravieva, Elizaveta V; Garcia-Osta, Ana; Alberini, Cristina M

2010-07-06

Addicts repeatedly relapse to drug seeking even after years of abstinence, and this behavior is frequently induced by the recall of memories of the rewarding effects of the drug. Established memories, including those induced by drugs of abuse, can become transiently fragile if reactivated, and during this labile phase, known as reconsolidation, can be persistently disrupted. Here we show that, in rats, a morphine-induced place preference (mCPP) memory is linked to context-dependent withdrawal as disrupting the reconsolidation of the memory leads to a significant reduction of withdrawal evoked in the same context. Moreover, the hippocampus plays a critical role in linking the place preference memory with the context-conditioned withdrawal, as disrupting hippocampal protein synthesis and cAMP-dependent-protein kinase A after the reactivation of mCPP significantly weakens the withdrawal. Hence, targeting memories induced by drugs may represent an important strategy for attenuating context-conditioned withdrawal and therefore subsequent relapse in opiate addicts.

The increases in potassium concentrations are greater with succinylcholine than with rocuronium-sugammadex in outpatient surgery: a randomized, multicentre trial.

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Sabo, Daniel; Jahr, Jonathan; Pavlin, Janet; Philip, Beverly; Shimode, Noriko; Rowe, Everton; Woo, Tiffany; Soto, Roy

2014-05-01

Succinylcholine provides rapid onset of neuromuscular blockade and short duration of action, but its administration may be associated with hyperkalemia. Rocuronium is not known to increase potassium concentration, has fast onset of activity, and can be rapidly reversed by sugammadex. This study evaluated changes in plasma potassium concentrations in patients randomized either to rocuronium followed by sugammadex reversal or to succinylcholine in ambulatory surgery. In this multicentre randomized active-controlled study, adult patients undergoing short surgical procedures in an outpatient setting received either rocuronium 0.6 mg·kg(-1) for intubation with sugammadex 4.0 mg·kg(-1) for reversal (n = 70) or succinylcholine 1.0 mg·kg(-1) with spontaneous recovery (n = 80). Blood potassium concentrations were assessed at baseline (before study drug administration) and at intervals up to 15 min after rocuronium, sugammadex, and succinylcholine. At the primary endpoint, five minutes post-administration, the changes in potassium concentrations from baseline were significantly smaller in patients treated with rocuronium than in those given succinylcholine [mean (SD): -0.06 (0.32) vs 0.30 (0.34) mmol·L(-1), respectively; P rocuronium (P rocuronium baseline. No adverse effects related to hyperkalemia were observed. Succinylcholine was associated with a modest increase in potassium concentration; these changes were not seen after rocuronium or sugammadex ( NCT00751179).

Rocuronium: automatic infusion versus manual administration with TOF monitorisation.

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Ozturk Arikan, Fatma Gulcin; Turan, Guldem; Ozgultekin, Asu; Sivrikaya, Zubeyir; Cosar, Bekir Cem; Onder, Dondu Nisa

2016-10-01

TOF (train-of-four) monitoring provides objective data in application of neuromuscular blocking agent. Thus, applicator-based differences are eliminated and optimum muscle relaxation is maintained during operation. In the present study, we aimed to compare the effects of target-controlled infusion system and standard TOF monitoring, on use of rocuronium. ASA I-II patients, who were aged between 18 and 75 years and scheduled for elective abdominal surgery at Haydarpaşa Numune Training and Research Hospital, were enrolled in the study. In order to evaluate neuromuscular blockade, the patients in Group 1 were connected to the acceleromyography device of the target-controlled infusion pump (Veryark-CLMRIS-I-China) while the ones in Group 2 were connected to the routinely used acceleromyography device (TOF Watch SX). There was no significant difference between groups regarding patient characteristics, the durations of anaesthesia and surgery, quality of intubation, time to extubation and time to recovery (TOF ratio of 0.9). Intubation time was significantly longer in Group 1 (Automated group) as compared to Group 2 (Control group) (p rocuronium amount used in Group 1 was found to be significantly higher than the amount used in Group 2 (p rocuronium was administered via automatical infusion pump during anaesthesia.

The effect of intravenous paracetamol for the prevention of rocuronium injection pain.

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Uzun, Sennur; Erden, Ismail A; Canbay, Ozgur; Aypar, Ulku

2014-11-01

Rocuronium is a nondepolarizing neuromuscular blocking agent used in anesthesia induction and is associated with considerable discomfort and burning pain during injection, which is reported to occur in 50-80% of patients. This study was carried out to investigate the effectiveness of intravenous paracetamol pretreatment compared with lidocaine and normal saline to prevent rocuronium injection pain. The study included 150 ASA I-II patients undergoing elective orthopedic, gastrointestinal, and gynecological procedures under general anesthesia. They were allocated into three groups according to pretreatment drugs: lidocaine (40 mg) (n = 50), paracetamol (n = 50), and normal saline group (n = 50). Before anesthesia induction with propofol, all patients were pretreated with rocuronium. The pain caused by the injection was evaluated. Local signs were assessed on the arm at the end of the injection, as well as 24 hours after recovery from anesthesia. There were no patients with blurred speech or vision and there was no respiratory depression in any group after pretreatment with the study drug. The level of pain on injection was statistically lower in those who had received paracetamol compared to normal saline (p = 0.009). There were more patients in the saline group with severe pain (p rocuronium injection pain better than normal saline but lidocaine was the best of the three drugs (p < 0.001). Copyright © 2014. Published by Elsevier Taiwan.

Effects of single-shot and steady-state propofol anaesthesia on rocuronium dose-response relationship: a randomised trial.

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Stäuble, C G; Stäuble, R B; Schaller, S J; Unterbuchner, C; Fink, H; Blobner, M

2015-08-01

Similar to volatile anaesthetics, propofol may influence neuromuscular transmission. We hypothesised that the administration of propofol influenced the potency of rocuronium depending on the duration of the administration. After consent, patients scheduled for elective surgery randomly received rocuronium either after induction of anaesthesia with propofol (2 min of propofol, n = 36) or after 30 min of propofol infusion (30 min of propofol, n = 36). Remifentanil was given in both groups. Neuromuscular monitoring was performed by calibrated electromyography. The dose-response relationship of rocuronium was determined with a single-bolus technique (0.07, 0.1, 0.15, 0.2, 0.3 and 0.45 mg/kg rocuronium). The primary endpoints were the ED50 and ED95 of rocuronium after 2 and 30 min propofol. Data are presented as means with (95% confidence interval). The trial is registered with the Eudra-CT: 2009-012815-16. A total of 72 patients were included. Time to maximal neuromuscular blockade was significantly shorter in patients after 30 min of propofol [3.3 min (2.9-3.7)] compared with patients anaesthetised with 2 min of propofol [4.6 min (4.0-5.2)]. After 30 min of propofol, the slope of the dose-response curve was significantly steeper (30 min of propofol: 4.34 [3.62-5.05]; 2 min of propofol: [3.34 (2.72-3.96)], resulting in lower ED95 values of rocuronium (30 min of propofol: 0.287 mg/kg [0.221-0.368]; 2 min of propofol [0.391 mg/kg (0.296-0.520)]. The ED50 were not different between groups. The potency of rocuronium was significantly enhanced after propofol infusion for 30 min. Estimates of potency those are usually determined during steady-state anaesthesia might underestimate rocuronium requirements for endotracheal intubation at the time of induction. © 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

COMPARISON OF ROCURONIUM BROMIDE AND SUCCINYLCHOLINE CHLORIDE FOR USE DURING RAPID SEQUENCE INTUBATION IN ADULTS

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Ch. Penchalaiah

2015-08-01

Full Text Available BACKGROUND AND OBJECTIVE : The goal of rapid sequence intubation is to secure the patients airway smoothly and quickly, minimizing the chances of regurgitation and aspiration of gastric contents. Traditionally succinylcholine chloride has been the neuromuscular blocking drug of choi ce for use in rapid sequence intubation because of its rapid onset of action and profound relaxation. Succinylcholine chloride remains unsurpassed in providing ideal intubating conditions. However the use of succinylcholine chloride is associated with many side effects like muscle pain, bradycardia, hyperkalaemia and rise in intragastric and intraocular pressure. Rocuronium bromide is the only drug currently available which has the rapidity of onset of action like succinylcholine chloride. Hence the present study was undertaken to compare rocuronium bromide with succinylcholine chloride for use during rapid sequence intubation in adult patients. METHODOLOGY : The study population consisted of 90 patients aged between 18 - 60 years posted for various elective su rgeries requiring general anaesthesia . S tudy population was randomly divided into 3 groups with 30 patients in each sub group. 1. Group I : Intubated with 1 mg kg - 1 of succinylcholine chloride (n=30 . 2. Grou p II : Intubated with rocuronium bromide 0.6 mg kg - 1 (n=30 . 3. Group III : Intubated with rocuronium bromide 0.9 mg kg - 1 (n=30 . Intubating conditions were assessed at 60 seconds based on the scale adopted by Toni Magorian et al. 1993. The haemodynamic para meters in the present study were compared using p - value obtained from student t - test . RESULTS : It was noted that succinylcholine chloride 1 mg kg - 1 body weight produced excellent intubating conditions in all patients. Rocuronium bromide 0.6 mg kg - 1 body we ight produced excellent intubating conditions in 53.33% of patients but produced good to excellent intubating conditions in 96.67% of patients. Rocuronium bromide 0.9 mg kg - 1

Effects of the mGluR5 antagonist MPEP on ethanol withdrawal induced anxiety-like syndrome in rats.

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Kumar, Jaya; Hapidin, Hermizi; Bee, Yvonne-Tee Get; Ismail, Zalina

2013-11-26

Abstinence from chronic ethanol consumption leads to the manifestation of a variety of symptoms attributed to central nervous system hyperexcitability, such as increased irritability, anxiety, and restlessness. Recent studies have demonstrated the importance of metabotropic glutamate receptor 5 (mGluR5) in addictive behaviours. This study investigates the effects of the mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) on ethanol withdrawal induced anxiety using two behavioural paradigms. Male Wistar rats were fed a Modified Liquid Diet (MLD) containing low fat cow milk, sucrose, and maltodextrin with a gradual introduction of 2.4%, 4.8% and 7.2% ethanol for 20 days. Six hours into ethanol withdrawal, the rats were intraperitoneally injected with normal saline and MPEP (2.5, 5.0, 10, 20, 30 mg/kg) and were assessed for ethanol withdrawal induced anxiety-like syndrome using an automated elevated plus maze and an open field. MPEP at 10 mg/kg significantly attenuated ethanol withdrawal induced anxiety without any compromising effects on locomotor activities. Despite reversing several indices of ethanol withdrawal induced anxiety in both the elevated plus maze and the open field, low doses of MPEP (2.5, 5 mg/kg) significantly compromised the locomotor activities of ethanol withdrawn rats. High doses of MPEP (20 and 30 mg/kg) significantly attenuated withdrawal anxiety when tested in the elevated plus maze but not in the open field. Administration of MPEP (2.5, 5, 10, 20, 30 mg/kg) has no significant compromising effect on the locomotor activities of ethanol naïve rats. Despite significantly reducing withdrawal anxiety in both behavioural paradigms at 10 mg/kg, the compromising effects of low and high doses of MPEP must be further explored along with the therapeutic efficiency of this drug for relieving withdrawal induced anxiety.

The effect of low dose rocuronium on globe position, muscle relaxation and ventilation in dogs: a clinical study.

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Auer, Ulrike; Mosing, Martina; Moens, Yves P S

2007-01-01

The purpose of this study was to evaluate globe position, muscle relaxation and changes in ventilatory parameters after intravenous administration of 0.1 mg/kg rocuronium. Prospective clinical study. Sixteen dogs of different breeds, with a body weight of 22.1 +/- 13 kg and age of 5.6 +/- 2.8 years (mean +/- SD), were anesthetized for a short ophthalmic examination requiring central position of the globe. All dogs were premedicated with 0.005 mg/kg medetomidine and 0.1 mg/kg methadone IV. Anesthesia was induced with propofol to effect and maintained with 10 mg/kg/h propofol by continuous rate infusion. Following endotracheal intubation all dogs breathed 100% oxygen via an anesthetic circle system. Neuromuscular function was assessed with an acceleromyograph (TOF-Guard, Organon Teknika NV, Turnhout, Belgium) and by stimulation of the nervus peroneus superficialis. The ventilation parameters were measured using spirometry and capnography. After baseline measurements 0.1 mg/kg rocuronium was administered IV. Minute volume (MV), tidal volume (Vt), respiratory rate (RR), end expiratory carbon dioxide concentration (PE'CO(2)) and maximal depression of the response of the first twitch (T1) of train-of-four (TOF) stimulation and train-of-four ratio (TOFR) was measured. The change in the position of the globe was recorded. T1 decreased to 61 +/- 18% and the TOF ratio to 45 +/- 21% of baseline values. Both parameters returned to baseline after 9 min. There was no significant reduction in MV, TV and RR and no increase in PE'CO(2). The globe rotated to a central position of 45 +/- 7.7 s after administration of rocuronium and remained there for 23 +/- 10.8 min in all dogs. Rocuronium administered intravenously at a dose of 0.1 mg/kg to dogs causes a central position of the globe but minimal impairment of ventilation parameters.

The effect of intravenous paracetamol for the prevention of rocuronium injection pain

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Sennur Uzun

2014-11-01

Full Text Available Rocuronium is a nondepolarizing neuromuscular blocking agent used in anesthesia induction and is associated with considerable discomfort and burning pain during injection, which is reported to occur in 50–80% of patients. This study was carried out to investigate the effectiveness of intravenous paracetamol pretreatment compared with lidocaine and normal saline to prevent rocuronium injection pain. The study included 150 ASA I–II patients undergoing elective orthopedic, gastrointestinal, and gynecological procedures under general anesthesia. They were allocated into three groups according to pretreatment drugs: lidocaine (40 mg (n = 50, paracetamol (n = 50, and normal saline group (n = 50. Before anesthesia induction with propofol, all patients were pretreated with rocuronium. The pain caused by the injection was evaluated. Local signs were assessed on the arm at the end of the injection, as well as 24 hours after recovery from anesthesia. There were no patients with blurred speech or vision and there was no respiratory depression in any group after pretreatment with the study drug. The level of pain on injection was statistically lower in those who had received paracetamol compared to normal saline (p = 0.009. There were more patients in the saline group with severe pain (p < 0.001. Paracetamol relieved the rocuronium injection pain better than normal saline but lidocaine was the best of the three drugs (p < 0.001.

Effects of conventional vs high-dose rocuronium on the QTc interval during anesthesia induction and intubation in patients undergoing coronary artery surgery: a randomized, double-blind, parallel trial

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Öztürk, T.; Ağdanlı, D.; Bayturan, Ö.; Çıkrıkcı, C.; Keleş, G.T.

2015-01-01

Myocardial ischemia, as well as the induction agents used in anesthesia, may cause corrected QT interval (QTc) prolongation. The objective of this randomized, double-blind trial was to determine the effects of high- vs conventional-dose bolus rocuronium on QTc duration and the incidence of dysrhythmias following anesthesia induction and intubation. Fifty patients about to undergo coronary artery surgery were randomly allocated to receive conventional-dose (0.6 mg/kg, group C, n=25) or high-dose (1.2 mg/kg, group H, n=25) rocuronium after induction with etomidate and fentanyl. QTc, heart rate, and mean arterial pressure were recorded before induction (T0), after induction (T1), after rocuronium (just before laryngoscopy; T2), 2 min after intubation (T3), and 5 min after intubation (T4). The occurrence of dysrhythmias was recorded. In both groups, QTc was significantly longer at T3 than at baseline [475 vs 429 ms in group C (P=0.001), and 459 vs 434 ms in group H (P=0.005)]. The incidence of dysrhythmias in group C (28%) and in group H (24%) was similar. The QTc after high-dose rocuronium was not significantly longer than after conventional-dose rocuronium in patients about to undergo coronary artery surgery who were induced with etomidate and fentanyl. In both groups, compared with baseline, QTc was most prolonged at 2 min after intubation, suggesting that QTc prolongation may be due to the nociceptive stimulus of intubation. PMID:25714880

Effects of conventional vs high-dose rocuronium on the QTc interval during anesthesia induction and intubation in patients undergoing coronary artery surgery: a randomized, double-blind, parallel trial

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T. Öztürk

2015-04-01

Full Text Available Myocardial ischemia, as well as the induction agents used in anesthesia, may cause corrected QT interval (QTc prolongation. The objective of this randomized, double-blind trial was to determine the effects of high- vs conventional-dose bolus rocuronium on QTc duration and the incidence of dysrhythmias following anesthesia induction and intubation. Fifty patients about to undergo coronary artery surgery were randomly allocated to receive conventional-dose (0.6 mg/kg, group C, n=25 or high-dose (1.2 mg/kg, group H, n=25 rocuronium after induction with etomidate and fentanyl. QTc, heart rate, and mean arterial pressure were recorded before induction (T0, after induction (T1, after rocuronium (just before laryngoscopy; T2, 2 min after intubation (T3, and 5 min after intubation (T4. The occurrence of dysrhythmias was recorded. In both groups, QTc was significantly longer at T3 than at baseline [475 vs 429 ms in group C (P=0.001, and 459 vs 434 ms in group H (P=0.005]. The incidence of dysrhythmias in group C (28% and in group H (24% was similar. The QTc after high-dose rocuronium was not significantly longer than after conventional-dose rocuronium in patients about to undergo coronary artery surgery who were induced with etomidate and fentanyl. In both groups, compared with baseline, QTc was most prolonged at 2 min after intubation, suggesting that QTc prolongation may be due to the nociceptive stimulus of intubation.

Influence of preoperative oral rehydration on arterial plasma rocuronium concentrations and neuromuscular blocking effects: A randomised controlled trial.

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Ishigaki, Sayaka; Ogura, Takahiro; Kanaya, Ayana; Miyake, Yu; Masui, Kenichi; Kazama, Tomiei

2017-01-01

The influence of preoperative rehydration on the action of rocuronium has not yet been investigated. The objective is to evaluate the hypothesis that preoperative rehydration lowers arterial rocuronium plasma concentrations and changes its associated neuromuscular blocking effects during induction of anaesthesia. Randomised, single-blinded study. A secondary hospital from October 2013 to July 2014. In total, 46 men undergoing elective surgery were eligible to participate and were randomly allocated into two groups. Exclusion criteria were severe hepatic, renal or cardiovascular disorder; neuromuscular disease; history of allergy to rocuronium; BMI more than 30 kg m; receiving medication known to influence neuromuscular function. Participants received 1500 ml of oral rehydration solution (rehydration group) or none (control group) until 2 hours before anaesthesia. Arterial blood samples were obtained 60, 90 and 120 s and 30 min after rocuronium (0.6 mg kg) administration during total intravenous anaesthesia. Responses to 0.1-Hz twitch stimuli were measured at the adductor pollicis muscle using acceleromyography. Arterial plasma rocuronium concentrations. Arterial plasma rocuronium concentrations at 60, 90 and 120 s in the rehydration and control groups were 9.9 and 13.7, 6.8 and 9.5 and 6.2 and 8.1 μg ml, respectively (P = 0.02, 0.003 and 0.02, respectively); the onset times in the rehydration and control groups were 92.0 and 69.5 s (P = 0.01), and the times to twitch re-appearance were 25.3 and 30.4 min (P = 0.004), respectively. Preoperative rehydration significantly reduces arterial plasma rocuronium concentrations in the first 2 minutes after administration, prolonging the onset time and shortening the duration of effect. A higher dose or earlier administration should be considered for patients who receive preoperative rehydration. Umin identifier: UMIN000011981.

Reversal of rocuronium-induced neuromuscular blockade by sugammadex allows for optimization of neural monitoring of the recurrent laryngeal nerve.

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Lu, I-Cheng; Wu, Che-Wei; Chang, Pi-Ying; Chen, Hsiu-Ya; Tseng, Kuang-Yi; Randolph, Gregory W; Cheng, Kuang-I; Chiang, Feng-Yu

2016-04-01

The use of neuromuscular blocking agent may effect intraoperative neuromonitoring (IONM) during thyroid surgery. An enhanced neuromuscular-blockade (NMB) recovery protocol was investigated in a porcine model and subsequently clinically applied during human thyroid neural monitoring surgery. Prospective animal and retrospective clinical study. In the animal experiment, 12 piglets were injected with rocuronium 0.6 mg/kg and randomly allocated to receive normal saline, sugammadex 2 mg/kg, or sugammadex 4 mg/kg to compare the recovery of laryngeal electromyography (EMG). In a subsequent clinical application study, 50 patients who underwent thyroidectomy with IONM followed an enhanced NMB recovery protocol-rocuronium 0.6 mg/kg at anesthesia induction and sugammadex 2 mg/kg at the operation start. The train-of-four (TOF) ratio was used for continuous quantitative monitoring of neuromuscular transmission. In our porcine model, it took 49 ± 15, 13.2 ± 5.6, and 4.2 ± 1.5 minutes for the 80% recovery of laryngeal EMG after injection of saline, sugammadex 2 mg/kg, and sugammadex 4 mg/kg, respectively. In subsequent clinical human application, the TOF ratio recovered from 0 to >0.9 within 5 minutes after administration of sugammadex 2 mg/kg at the operation start. All patients had positive and high EMG amplitude at the early stage of the operation, and intubation was without difficulty in 96% of patients. Both porcine modeling and clinical human application demonstrated that sugammadex 2 mg/kg allows effective and rapid restoration of neuromuscular function suppressed by rocuronium. Implementation of this enhanced NMB recovery protocol assures optimal conditions for tracheal intubation as well as IONM in thyroid surgery. NA. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

[Sugammadex. New pharmacological concept for antagonizing rocuronium and vecuronium

NARCIS (Netherlands)

Sparr, H.J.; Booij, L.H.D.J.; Fuchs-Buder, T.

2009-01-01

Up to now only acetylcholine esterase inhibitors, such as neostigmine, were available as antagonists of residual neuromuscular blocks. Sugammadex is a modified gamma-cyclodextrin that binds rocuronium and chemically similar aminosteroidal muscle relaxants, such as vecuronium. The underlying

Neuronal Effects of Sugammadex in combination with Rocuronium or Vecuronium

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Aldasoro, Martin; Jorda, Adrian; Aldasoro, Constanza; Marchio, Patricia; Guerra-Ojeda, Sol; Gimeno-Raga, Marc; Mauricio, Mª Dolores; Iradi, Antonio; Obrador, Elena; Vila, Jose Mª; Valles, Soraya L.

2017-01-01

Rocuronium (ROC) and Vecuronium (VEC) are the most currently used steroidal non-depolarizing neuromuscular blocking (MNB) agents. Sugammadex (SUG) rapidly reverses steroidal NMB agents after anaesthesia. The present study was conducted in order to evaluate neuronal effects of SUG alone and in combination with both ROC and VEC. Using MTT, CASP-3 activity and Western-blot we determined the toxicity of SUG, ROC or VEC in neurons in primary culture. SUG induces apoptosis/necrosis in neurons in primary culture and increases cytochrome C (CytC), apoptosis-inducing factor (AIF), Smac/Diablo and Caspase 3 (CASP-3) protein expression. Our results also demonstrated that both ROC and VEC prevent these SUG effects. The protective role of both ROC and VEC could be explained by the fact that SUG encapsulates NMB drugs. In BBB impaired conditions it would be desirable to control SUG doses to prevent the excess of free SUG in plasma that may induce neuronal damage. A balance between SUG, ROC or VEC would be necessary to prevent the risk of cell damage. PMID:28367082

A temporary decrease in twitch response during reversal of rocuronium-induced muscle relaxation with a small dose of sugammadex

NARCIS (Netherlands)

Eleveld, Douglas J.; Kuizenga, Karel; Proost, Johannes H.; Wierda, J. Mark K. H.

BACKGROUND: We present a case in which a temporary decrease in train-of-four (TOF) response was observed after reversal of muscle relaxation with a small dose (0.5 mg/kg) of sugammadex administered 42 min after 0.9 mg/kg of rocuronium. At the end of the operation, the TOF ratio was > 0.9, and the

Duration of the action of rocuronium in patients with BMI of less than 25: An observational study.

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Takahata, Osamu; Takahoko, Ken-Ichi; Sasakawa, Tomoki; Inagaki, Yasuyoshi; Takahoko, Hiroyuki; Kunisawa, Takayuki

2018-05-02

The duration of rocuronium in patients with BMI more than 30 kg m is prolonged. Whether the reverse is true when BMI is less than 18.5 kg m is unclear. The objective of this study was to investigate whether a BMI less than 25 kg m affects the duration of rocuronium in doses adjusted for actual body weight. A prospective, observational, single-centre study. The operating room of a teaching hospital from 1 June 2008 to 30 June 2015. Thirty patients with American Society of Anesthesiologists physical status I or II who were scheduled to undergo elective surgery (BMI rocuronium (D1) was defined as the time from injection of rocuronium 0.6 mg kg to return of first twitch height to 25% of the control. Duration of additional doses (D2) was the time from a supplement of 0.15 mg kg rocuronium to return of first twitch height to 25% of the control. The relationship between D1 or D2 and BMI was examined using linear regression analysis. Linear regression analysis revealed a significant correlation between duration of initial dose and BMI (R = 0.246; P = 0.00531). A significant correlation between the duration of the additional dose and BMI was also found (R = 0.316; P = 0.00122). The lower the BMI, the shorter the duration of rocuronium at initial and additional doses determined by the actual body weight in adult patients with a BMI less than 25 kg m. www.umin.ac.jp/ctr/index/htm with registry number UMIN 00009337 and UMIN 000015407.

Sugammadex ED90 dose to reverse the rocuronium neuromuscular blockade in obese patients.

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Silva, Mauro Prado DA; Matsui, Christiano; Kim, Daniel Dongiou; Vieira, Joaquim Edson; Malheiros, Carlos Alberto; Mathias, Ligia Andrade Silva Telles

2017-01-01

to determine the ED90 (minimum effective dose in 90% of patients) of sugammadex for the reversal of rocuronium-induced moderate neuromuscular blockade (NMB) in patients with grade III obesity undergoing bariatric surgery. we conducted a prospective study with the biased coin up-and-down sequential design. We chosen the following doses: 2.0mg/Kg, 2.2mg/Kg, 2.4mg/Kg, 2.6mg/Kg, 2.8mg/Kg. The complete reversal of rocuronium-induced NMB considered a T4/T1 ratio ≥0.9 as measured by TOF. After induction of general anesthesia and calibration of the peripheral nerve stimulator and accelerometer, we injected rocuronium 0.6mg/kg. We administered propofol and remifentanil by continuous infusion, and intermittent boluses of rocuronium throughout the procedure. we evaluated 31 patients, of whom 26 had displayed successful reversal of the NMB with sugammadex, and failure in five. The mean time to complete moderate NMB reversal was 213 seconds (172-300, median 25-75%). The ED90 of sugammadex calculated by regression was 2.39mg/kg, with a 95% confidence interval of 2.27-2.46 mg/kg. the ED90 of sugammadex in patients with grade III obesity or higher was 2.39mg/kg. determinar a ED90 (dose mínima eficaz em 90% dos pacientes) de sugamadex para a reversão de bloqueio neuromuscular (BNM) moderado induzido pelo rocurônio em pacientes com obesidade grau III submetidos à cirurgia bariátrica. estudo prospectivo com o método de projeção sequencial para cima e para baixo da moeda enviesada. As seguintes doses foram escolhidas: 2,0mg/kg-1, 2,2mg/kg-1, 2,4mg/kg-1, 2,6mg/kg-1, 2,8mg/kg-1. A reversão completa de BNM induzido por rocurônio considerou uma relação T4/T1 ≥0,9 na medida do TOF. Após a indução da anestesia geral e calibração do estimulador de nervo periférico e acelerômetro, rocurônio 0,6mg/kg-1 foi injetado. Infusão contínua de propofol e remifentanil, e bolus intermitente de rocurônio foram injetados durante todo o procedimento. trinta e um pacientes foram

The effects of succinylcholine or low-dose rocuronium to aid endotracheal intubation of adult sows

Science.gov (United States)

Duke-Novakovski, Tanya; Ambros, Barbara; Auckland, Crissie D.; Harding, John C.S.

2012-01-01

This randomized, prospective, blinded study compared the use of succinylcholine or rocuronium to aid endotracheal intubation of 27 adult sows [mean body weight 261 ± 28 (standard deviation) kg]. Preliminary trials allowed development of the intubation technique and skills. The sows were premedicated with azaperone, atropine, and morphine, and anesthesia was induced with thiopental [6 mg/kg body weight (BW)]. Nine sows each received succinylcholine (1.0 mg/kg BW), rocuronium (0.5 mg/kg BW), or saline (15 mL) after induction. Increments of thiopental (1 mg/kg BW) were used if swallowing impaired intubation. Intubation was performed 45 s after injection of the test drug and was timed and scored. The intubation scores were analyzed with Kruskal-Wallis analysis of variance (ANOVA). Time taken for intubation, body weight, and total dose of thiopental were analyzed with ANOVA and Bonferroni’s multiple-comparisons test. No significant differences (at P < 0.05) were found between the groups with regard to intubation score, time taken for intubation, or total thiopental dose. Thus, neuromuscular blocking agents did not aid endotracheal intubation of adult sows anesthetized with thiopental. PMID:22754096

A comparison between succinylcholine and rocuronium on the recovery profile of the laryngeal muscles during intraoperative neuromonitoring of the recurrent laryngeal nerve: A prospective porcine model

Directory of Open Access Journals (Sweden)

I-Cheng Lu

2013-09-01

Full Text Available The use of succinylcholine and rocuronium are reportedly feasible during intraoperative neuromonitoring (IONM of the recurrent laryngeal nerve (RLN in thyroid surgery. This study aimed to investigate and compare the recovery profiles of succinylcholine and rocuronium on the laryngeal muscle during IONM of the RLN in a porcine model. Nine male Duroc-Landrace piglets were anesthetized with thiamylal and underwent tracheal intubation without neuromuscular blocking agents (NMBAs. Needle electrodes were inserted into the vocalis muscles through the cricothyroid ligament. The RLN was exposed and stimulated. Electromyographic (EMG signals were obtained before and after the intravenous administration of a NMBA. The EMG amplitudes were measured before and after (at 1-minute intervals the administration of the study drug until complete recovery. The study NMBA regimen included succinylcholine (1 mg/kg, low-dose rocuronium (0.3 mg/kg, and standard dose rocuronium (0.6 mg/kg. The maximal neuromuscular blockade and 80% recovery (i.e., duration of the control responses were recorded and analyzed. The 80% recovery of the control response for succinylcholine (1 mg/kg was 19.7 ± 1.5 minutes; low-dose rocuronium (0.3 mg/kg, 16.3 ± 2.5 minutes; and standard dose rocuronium (0.6 mg/kg, 29.3 ± 5.7 minutes. Succinylcholine (1 mg/kg and low-dose rocuronium (0.3 mg/kg had significantly shorter durations than standard dose rocuronium (0.6 mg/kg. The EMG signal recovery returned to baseline within 30 minutes in the succinylcholine and low-dose rocuronium groups, but it did not return to baseline until 1 hour after surgery in the rocuronium (0.6 mg/kg group. In this study, succinylcholine (1 mg/kg and low-dose rocuronium (0.3 mg/kg had favorable recovery profiles on the laryngeal muscle. It is recommended that low-dose rocuronium may replace succinylcholine for the induction of general anesthesia during IONM of the RLN in thyroid surgery.

A comparison between succinylcholine and rocuronium on the recovery profile of the laryngeal muscles during intraoperative neuromonitoring of the recurrent laryngeal nerve: a prospective porcine model.

Science.gov (United States)

Lu, I-Cheng; Chang, Pi-Ying; Hsu, Hung-Te; Tseng, Kuang-Yi; Wu, Che-Wei; Lee, Ka-Wo; Ho, Kuen-Yao; Chiang, Feng-Yu

2013-09-01

The use of succinylcholine and rocuronium are reportedly feasible during intraoperative neuromonitoring (IONM) of the recurrent laryngeal nerve (RLN) in thyroid surgery. This study aimed to investigate and compare the recovery profiles of succinylcholine and rocuronium on the laryngeal muscle during IONM of the RLN in a porcine model. Nine male Duroc-Landrace piglets were anesthetized with thiamylal and underwent tracheal intubation without neuromuscular blocking agents (NMBAs). Needle electrodes were inserted into the vocalis muscles through the cricothyroid ligament. The RLN was exposed and stimulated. Electromyographic (EMG) signals were obtained before and after the intravenous administration of a NMBA. The EMG amplitudes were measured before and after (at 1-minute intervals) the administration of the study drug until complete recovery. The study NMBA regimen included succinylcholine (1 mg/kg), low-dose rocuronium (0.3 mg/kg), and standard dose rocuronium (0.6 mg/kg). The maximal neuromuscular blockade and 80% recovery (i.e., duration) of the control responses were recorded and analyzed. The 80% recovery of the control response for succinylcholine (1 mg/kg) was 19.7 ± 1.5 minutes; low-dose rocuronium (0.3 mg/kg), 16.3 ± 2.5 minutes; and standard dose rocuronium (0.6 mg/kg), 29.3 ± 5.7 minutes. Succinylcholine (1 mg/kg) and low-dose rocuronium (0.3 mg/kg) had significantly shorter durations than standard dose rocuronium (0.6 mg/kg). The EMG signal recovery returned to baseline within 30 minutes in the succinylcholine and low-dose rocuronium groups, but it did not return to baseline until 1 hour after surgery in the rocuronium (0.6 mg/kg) group. In this study, succinylcholine (1 mg/kg) and low-dose rocuronium (0.3 mg/kg) had favorable recovery profiles on the laryngeal muscle. It is recommended that low-dose rocuronium may replace succinylcholine for the induction of general anesthesia during IONM of the RLN in thyroid surgery. Copyright © 2013. Published by

Effective method of continuous rocuronium administration based on effect-site concentrations using a pharmacokinetic/pharmacodynamic model during propofol-remifentanil anesthesia.

Science.gov (United States)

Moriyama, Takahiro; Matsunaga, Akira; Nagata, Osamu; Enohata, Kei; Kamikawaji, Tomomi; Uchino, Erika; Kanmura, Yuichi

2015-08-01

Rocuronium bromide (Rb) is a rapid onset, intermediate-acting neuromuscular blocking agent that is suitable for continuous administration. The appropriate rate of rocuronium administration is, however, difficult to determine due to large interindividual differences in sensitivity to rocuronium. The aim of this study was to clarify whether the simulated rocuronium concentration at the time of recovery to %T1 > 0 % after the initial administration of rocuronium is a good indicator of optimal effect-site concentrations during continuous rocuronium administration. Twenty-one patients were anesthetized with propofol. After induction, Rb 0.6 mg/kg was administered intravenously, and nerve stimulation using the single stimulation mode was conducted every 15 s. When %T1 recovered to >0 % after the initial administration of Rb, the effect-site concentration of rocuronium, calculated by pharmacokinetic simulation with Wierda's set of parameters, was recorded and defined as the recovery concentration (Rb r.c.). The administration rate of rocuronium was adjusted to maintain the Rb r.c. during surgery. Rb administration was discontinued just before the end of surgery, and the recovery time until %T1 > 25 % was recorded. Plasma Rb concentrations were measured at 1 and 3 h after the initiation of continuous Rb administration. The mean Rb r.c. was 1.56 ± 0.35 μg/ml, with minimum and maximum values of 1.09 and 2.08 μg/ml, respectively. The %T1 did not increase above 10 % in any of the patients during continuous administration of Rb, and the recovery period to %T1 > 25 % ranged from 9 to 29 min. The effect-site concentrations of Rb calculated with Wierda's parameters significantly correlated with plasma concentrations (P < 0.01) at both 1 and 3 h after the initial administration of Rb. The results suggest that our method may be one of the most reliable protocols for the continuous administration of Rb described to date for maintaining suitable muscle relaxation during surgery

Pharmacodynamic Comparison of Rocuronium Bromide between Patients from the Plateau Area and from the Plain Area.

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Xie, Min; Huang, Jianxin; Li, Peng; Ou, Zhiyan; Hou, Jing

2016-06-23

We aimed to conduct a pharmacodynamic comparison of rocuronium bromide between patients from the plateau area and from the plain area. A total of 104 patients who received laparoscopic cholecystectomy in Sichuan Provincial People's Hospital and Aba Autonomous Prefecture People's Hospital from October 2015 to December 2015 were included in this study. Among them, 46 patients were from the plateau area and 58 were from the plain area. Both groups received total intravenous anesthesia (TIVA) with a dose of 0.6mg/kg rocuronium bromide during induction. In the meantime, neuromuscular block was monitored using a train-of-four (TOF) stimulation mode. The onset time (time to achieve the lowest TOF value after the injection of rocuronium bromide), duration of maximal neuromuscular block (duration of lowest T1 value), time to 25% recovery, time to 75% recovery, recovery index (time from 25% recovery to 75% recovery), time to extubation, length of stay in Post Anesthesia Care Unit (PACU) and muscle strength upon PACU discharge were all recorded. The onset time, time to 25% recovery, time to 75% recovery and time to extubation were all significantly prolonged in patients from the plateau area after receiving one single dose of rocuronium bromide (P0.05). Compared to patients from the plain area, patients from the plateau area showed prolonged onset time of rocuronium bromide, reduced metabolic capabilities and longer duration of muscular relaxation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Sympathetic activity induced by naloxone-precipitated morphine withdrawal is blocked in genetically engineered mice lacking functional CRF1 receptor

International Nuclear Information System (INIS)

García-Carmona, Juan-Antonio; Martínez-Laorden, Elena; Milanés, María-Victoria; Laorden, María-Luisa

2015-01-01

There is large body evidence indicating that stress can lead to cardiovascular disease. However, the exact brain areas and the mechanisms involved remain to be revealed. Here, we performed a series of experiments to characterize the role of CRF1 receptor (CRF1R) in the stress response induced by naloxone-precipitated morphine withdrawal. The experiments were performed in the hypothalamic paraventricular nucleus (PVN) ventrolateral medulla (VLM), brain regions involved in the regulation of cardiovascular activity, and in the right ventricle by using genetically engineered mice lacking functional CRF1R levels (KO). Mice were treated with increasing doses of morphine and withdrawal was precipitated by naloxone administration. Noradrenaline (NA) turnover, c-Fos, expression, PKA and TH phosphorylated at serine 40, was evaluated by high-performance liquid chromatography (HPLC), immunohistochemistry and immunoblotting. Morphine withdrawal induced an enhancement of NA turnover in PVN in parallel with an increase in TH neurons expressing c-Fos in VLM in wild-type mice. In addition we have demonstrated an increase in NA turnover, TH phosphorylated at serine 40 and PKA levels in heart. The main finding of the present study was that NA turnover, TH positive neurons that express c-Fos, TH phosphorylated at serine 40 and PKA expression observed during morphine withdrawal were significantly inhibited in CRF1R KO mice. Our results demonstrate that CRF/CRF1R activation may contribute to the adaptive changes induced by naloxone-precipitated withdrawal in the heart and in the brain areas which modulate the cardiac sympathetic function and suggest that CRF/CRF1R pathways could be contributing to cardiovascular disease associated to opioid addiction. - Highlights: • Naloxone-precipitated morphine withdrawal increases sympathetic activity in the PVN and heart. • Co-localization of TH phosphorylated at serine 40/c-Fos in the VLM after morphine withdrawal • Naloxone

Sympathetic activity induced by naloxone-precipitated morphine withdrawal is blocked in genetically engineered mice lacking functional CRF1 receptor

Energy Technology Data Exchange (ETDEWEB)

García-Carmona, Juan-Antonio; Martínez-Laorden, Elena; Milanés, María-Victoria; Laorden, María-Luisa

2015-02-15

There is large body evidence indicating that stress can lead to cardiovascular disease. However, the exact brain areas and the mechanisms involved remain to be revealed. Here, we performed a series of experiments to characterize the role of CRF1 receptor (CRF1R) in the stress response induced by naloxone-precipitated morphine withdrawal. The experiments were performed in the hypothalamic paraventricular nucleus (PVN) ventrolateral medulla (VLM), brain regions involved in the regulation of cardiovascular activity, and in the right ventricle by using genetically engineered mice lacking functional CRF1R levels (KO). Mice were treated with increasing doses of morphine and withdrawal was precipitated by naloxone administration. Noradrenaline (NA) turnover, c-Fos, expression, PKA and TH phosphorylated at serine 40, was evaluated by high-performance liquid chromatography (HPLC), immunohistochemistry and immunoblotting. Morphine withdrawal induced an enhancement of NA turnover in PVN in parallel with an increase in TH neurons expressing c-Fos in VLM in wild-type mice. In addition we have demonstrated an increase in NA turnover, TH phosphorylated at serine 40 and PKA levels in heart. The main finding of the present study was that NA turnover, TH positive neurons that express c-Fos, TH phosphorylated at serine 40 and PKA expression observed during morphine withdrawal were significantly inhibited in CRF1R KO mice. Our results demonstrate that CRF/CRF1R activation may contribute to the adaptive changes induced by naloxone-precipitated withdrawal in the heart and in the brain areas which modulate the cardiac sympathetic function and suggest that CRF/CRF1R pathways could be contributing to cardiovascular disease associated to opioid addiction. - Highlights: • Naloxone-precipitated morphine withdrawal increases sympathetic activity in the PVN and heart. • Co-localization of TH phosphorylated at serine 40/c-Fos in the VLM after morphine withdrawal • Naloxone

Nicotine Withdrawal Induces Neural Deficits in Reward Processing.

Science.gov (United States)

Oliver, Jason A; Evans, David E; Addicott, Merideth A; Potts, Geoffrey F; Brandon, Thomas H; Drobes, David J

2017-06-01

Nicotine withdrawal reduces neurobiological responses to nonsmoking rewards. Insight into these reward deficits could inform the development of targeted interventions. This study examined the effect of withdrawal on neural and behavioral responses during a reward prediction task. Smokers (N = 48) attended two laboratory sessions following overnight abstinence. Withdrawal was manipulated by having participants smoke three regular nicotine (0.6 mg yield; satiation) or very low nicotine (0.05 mg yield; withdrawal) cigarettes. Electrophysiological recordings of neural activity were obtained while participants completed a reward prediction task that involved viewing four combinations of predictive and reward-determining stimuli: (1) Unexpected Reward; (2) Predicted Reward; (3) Predicted Punishment; (4) Unexpected Punishment. The task evokes a medial frontal negativity that mimics the phasic pattern of dopaminergic firing in ventral tegmental regions associated with reward prediction errors. Nicotine withdrawal decreased the amplitude of the medial frontal negativity equally across all trial types (p nicotine dependence (p Nicotine withdrawal had equivocal impact across trial types, suggesting reward processing deficits are unlikely to stem from changes in phasic dopaminergic activity during prediction errors. Effects on tonic activity may be more pronounced. Pharmacological interventions directly targeting the dopamine system and behavioral interventions designed to increase reward motivation and responsiveness (eg, behavioral activation) may aid in mitigating withdrawal symptoms and potentially improving smoking cessation outcomes. Findings from this study indicate nicotine withdrawal impacts reward processing signals that are observable in smokers' neural activity. This may play a role in the subjective aversive experience of nicotine withdrawal and potentially contribute to smoking relapse. Interventions that address abnormal responding to both pleasant and

Incubation of extinction responding and cue-induced reinstatement, but not context- or drug priming-induced reinstatement, after withdrawal from methamphetamine.

Science.gov (United States)

Adhikary, Sweta; Caprioli, Daniele; Venniro, Marco; Kallenberger, Paige; Shaham, Yavin; Bossert, Jennifer M

2017-07-01

In rats trained to self-administer methamphetamine, extinction responding in the presence of drug-associated contextual and discrete cues progressively increases after withdrawal (incubation of methamphetamine craving). The conditioning factors underlying this incubation are unknown. Here, we studied incubation of methamphetamine craving under different experimental conditions to identify factors contributing to this incubation. We also determined whether the rats' response to methamphetamine priming incubates after withdrawal. We trained rats to self-administer methamphetamine in a distinct context (context A) for 14 days (6 hours/day). Lever presses were paired with a discrete light cue. We then tested groups of rats in context A or a different non-drug context (context B) after 1 day, 1 week or 1 month for extinction responding with or without the discrete cue. Subsequently, we tested the rats for reinstatement of drug seeking induced by exposure to contextual, discrete cue, or drug priming (0, 0.25 and 0.5 mg/kg). Operant responding in the extinction sessions in contexts A or B was higher after 1 week and 1 month of withdrawal than after 1 day; this effect was context-independent. Independent of the withdrawal period, operant responding in the extinction sessions was higher when responding led to contingent delivery of the discrete cue. After extinction, discrete cue-induced reinstatement, but not context- or drug priming-induced reinstatement, progressively increased after withdrawal. Together, incubation of methamphetamine craving, as assessed in extinction tests, is primarily mediated by time-dependent increases in non-reinforced operant responding, and this effect is potentiated by exposure to discrete, but not contextual, cues. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Trajectories of abstinence-induced Internet gaming withdrawal symptoms: A prospective pilot study

Directory of Open Access Journals (Sweden)

Dean Kaptsis

2016-12-01

Full Text Available Internet Gaming Disorder (IGD is positioned in the appendix of the DSM-5 as a condition requiring further study. The IGD criteria refer to withdrawal symptoms, including irritability, anxiety, or sadness, that follow cessation of Internet gaming (APA, 2013. The aim of this study was to prospectively examine the nature of Internet gaming withdrawal symptoms, if they occur, under gaming abstinence conditions. This study employed a repeated-measures protocol to examine the cognitive-affective reactions of participants undertaking an 84-h Internet gaming abstinence period. The sample included individuals who met the IGD criteria as well as those who regularly played Internet games but did not meet the IGD criteria. Outcome variables included affect (positive and negative, psychological distress (depression, anxiety, stress, and Internet gaming withdrawal symptoms (craving/urge, thoughts about gaming, inability to resist gaming. A total of 24 participants (Mage = 24.6 years, SD = 5.8 were recruited from online gaming communities, and completed a series of online surveys before, during, and after abstaining from Massively Multiplayer Online (MMO games. Both the IGD group and the non-IGD group experienced an abstinence-induced decline in withdrawal symptomatology, negative affect, and psychological distress. The IGD group experienced its largest decline in withdrawal symptomatology within the first 24 h of abstinence. These preliminary data suggest that gaming withdrawal symptoms may follow, at least initially, negative linear and quadratic trends. Further prospective work in larger samples involving longer periods of abstinence is required to verify and expand upon these observations.

Trajectories of abstinence-induced Internet gaming withdrawal symptoms: A prospective pilot study.

Science.gov (United States)

Kaptsis, Dean; King, Daniel L; Delfabbro, Paul H; Gradisar, Michael

2016-12-01

Internet Gaming Disorder (IGD) is positioned in the appendix of the DSM-5 as a condition requiring further study. The IGD criteria refer to withdrawal symptoms, including irritability, anxiety, or sadness, that follow cessation of Internet gaming (APA, 2013). The aim of this study was to prospectively examine the nature of Internet gaming withdrawal symptoms, if they occur, under gaming abstinence conditions. This study employed a repeated-measures protocol to examine the cognitive-affective reactions of participants undertaking an 84-h Internet gaming abstinence period. The sample included individuals who met the IGD criteria as well as those who regularly played Internet games but did not meet the IGD criteria. Outcome variables included affect (positive and negative), psychological distress (depression, anxiety, stress), and Internet gaming withdrawal symptoms (craving/urge, thoughts about gaming, inability to resist gaming). A total of 24 participants ( M age  = 24.6 years, SD  = 5.8) were recruited from online gaming communities, and completed a series of online surveys before, during, and after abstaining from Massively Multiplayer Online (MMO) games. Both the IGD group and the non-IGD group experienced an abstinence-induced decline in withdrawal symptomatology, negative affect, and psychological distress. The IGD group experienced its largest decline in withdrawal symptomatology within the first 24 h of abstinence. These preliminary data suggest that gaming withdrawal symptoms may follow, at least initially, negative linear and quadratic trends. Further prospective work in larger samples involving longer periods of abstinence is required to verify and expand upon these observations.

Comparison of rocuronium at two different doses and succinylcholine for endotracheal intubation in adult patients for elective surgeries

Directory of Open Access Journals (Sweden)

S G Chavan

2016-01-01

Conclusion: Rapid sequence induction of anesthesia with propofol and fentanyl, succinylcholine allowed a more rapid endotracheal intubation sequence and created superior intubation conditions than rocuronium. However, the technique of using a large dose of rocuronium to achieve perfect conditions for tracheal intubation may have application whenever succinylcholine is relatively contraindicated.

Should dosing of rocuronium in obese patients be based on ideal or corrected body weight?

DEFF Research Database (Denmark)

Meyhoff, Christian S; Lund, Jørgen; Jenstrup, Morten T

2009-01-01

BACKGROUND: Pharmacokinetic studies in obese patients suggest that dosing of rocuronium should be based on ideal body weight (IBW). This may, however, result in a prolonged onset time or compromised conditions for tracheal intubation. In this study, we compared onset time, conditions for tracheal...... intubation, and duration of action in obese patients when the intubation dose of rocuronium was based on three different weight corrections. METHODS: Fifty-one obese patients, with a median (range) body mass index of 44 (34-72) kg/m2, scheduled for laparoscopic gastric banding or gastric bypass under...... propofol-remifentanil anesthesia were randomized into three groups. The patients received rocuronium (0.6 mg/kg) based on IBW (IBW group, n = 17), IBW plus 20% of excess weight (corrected body weight [CBW]20% group, n = 17), or IBW plus 40% of excess weight (CBW40% group, n = 17). Propofol was administered...

Intubation following high-dose rocuronium in a cat with protracted laryngospasm

Directory of Open Access Journals (Sweden)

Graeme M Doodnaught

2017-10-01

Full Text Available Case summary An 11-year-old spayed female domestic shorthair cat with a history of laryngospasm at induction of general anesthesia presented for dental evaluation and treatment. The cat was premedicated with hydromorphone (0.05 mg/kg and alfaxalone (0.5 mg/kg intravenously, pre-oxygenated for 5 mins (3 l/min, face mask and anesthesia was induced with alfaxalone (to effect intravenously. Lidocaine (0.1 ml, 2% was applied topically to the arytenoid cartilages following loss of jaw tone. Laryngospasm was not noted during or immediately following lidocaine application. However, after waiting 60 s for the onset of effect of the topical lidocaine, laryngospasm was apparent. Orotracheal intubation by direct visualization was unsuccessful after four attempts by three anesthetists (with increasing levels of experience. At this point, a failed intubation was declared and the non-depolarising neuromuscular blocking agent rocuronium (1 mg/kg IV given, resulting in arytenoid abduction and appropriate conditions for intubation. Successful intubation occurred 9 mins after induction of anesthesia. Oxygen was continuously supplemented throughout and arterial hemoglobin saturation with oxygen was never <94%. Relevance and novel information To the authors’ knowledge, this is the first report of the use of high-dose rocuronium to successfully resolve prolonged laryngospasm at induction of general anesthesia in a cat. Despite laryngospasm and a delay in achieving orotracheal intubation, low values for arterial hemoglobin saturation with oxygen (indicative of hypoxemia were not observed, highlighting the benefits of pre-oxygenation and apneic oxygenation. The principles of the Difficult Airway Society 2015 guidelines were followed in managing this difficult intubation.

Recognition and management of iatrogenically induced opioid dependence and withdrawal in children.

Science.gov (United States)

Galinkin, Jeffrey; Koh, Jeffrey Lee

2014-01-01

Opioids are often prescribed to children for pain relief related to procedures, acute injuries, and chronic conditions. Round-the-clock dosing of opioids can produce opioid dependence within 5 days. According to a 2001 Consensus Paper from the American Academy of Pain Medicine, American Pain Society, and American Society of Addiction Medicine, dependence is defined as "a state of adaptation that is manifested by a drug class specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist." Although the experience of many children undergoing iatrogenically induced withdrawal may be mild or goes unreported, there is currently no guidance for recognition or management of withdrawal for this population. Guidance on this subject is available only for adults and primarily for adults with substance use disorders. The guideline will summarize existing literature and provide readers with information currently not available in any single source specific for this vulnerable pediatric population.

PHARMACOKINETICS AND PHARMACOKINETIC DYNAMIC RELATIONSHIP OF ROCURONIUM BROMIDE IN HUMANS

NARCIS (Netherlands)

WIERDA, JMKH; PROOST, JH; SCHIERE, S; HOMMES, FDM

The existing human pharmacokinetic studies have been reviewed and compared with data derived from animals. The earliest study confirms the similarity of rocuronium to vecuronium with respect to the variables derived from the plasma concentration decay curves and the proportion excreted renally.

Stress Sensitization of Ethanol Withdrawal-Induced Reduction in Social Interaction: Inhibition by CRF-1 and Benzodiazepine Receptor Antagonists and a 5-HT1A-Receptor Agonist

OpenAIRE

Breese, George R; Knapp, Darin J; Overstreet, David H

2004-01-01

Repeated withdrawals from chronic ethanol sensitize the withdrawal-induced reduction in social interaction behaviors. This study determined whether stress might substitute for repeated withdrawals to facilitate withdrawal-induced anxiety-like behavior. When two 1-h periods of restraint stress were applied at 1-week intervals to rats fed control diet, social interaction was reduced upon withdrawal from a subsequent 5-day exposure to ethanol diet. Neither this ethanol exposure alone nor exposur...

The predictive ability of six pharmacokinetic models of rocuronium developed using a single bolus: evaluation with bolus and continuous infusion regimen.

Science.gov (United States)

Sasakawa, Tomoki; Masui, Kenichi; Kazama, Tomiei; Iwasaki, Hiroshi

2016-08-01

Rocuronium concentration prediction using pharmacokinetic (PK) models would be useful for controlling rocuronium effects because neuromuscular monitoring throughout anesthesia can be difficult. This study assessed whether six different compartmental PK models developed from data obtained after bolus administration only could predict the measured plasma concentration (Cp) values of rocuronium delivered by bolus followed by continuous infusion. Rocuronium Cp values from 19 healthy subjects who received a bolus dose followed by continuous infusion in a phase III multicenter trial in Japan were used retrospectively as evaluation datasets. Six different compartmental PK models of rocuronium were used to simulate rocuronium Cp time course values, which were compared with measured Cp values. Prediction error (PE) derivatives of median absolute PE (MDAPE), median PE (MDPE), wobble, divergence absolute PE, and divergence PE were used to assess inaccuracy, bias, intra-individual variability, and time-related trends in APE and PE values. MDAPE and MDPE values were acceptable only for the Magorian and Kleijn models. The divergence PE value for the Kleijn model was lower than -10 %/h, indicating unstable prediction over time. The Szenohradszky model had the lowest divergence PE (-2.7 %/h) and wobble (5.4 %) values with negative bias (MDPE = -25.9 %). These three models were developed using the mixed-effects modeling approach. The Magorian model showed the best PE derivatives among the models assessed. A PK model developed from data obtained after single-bolus dosing can predict Cp values during bolus and continuous infusion. Thus, a mixed-effects modeling approach may be preferable in extrapolating such data.

The pharmacokinetics and the pharmacokinetic-dynamic relationship of rocuronium bromide

NARCIS (Netherlands)

Wierda, J.M.K.H.; Proost, J.H.

1995-01-01

Rocuronium is a new non-depolarising agent with an intermediate time-course of neuromuscular blocking action. In healthy patients its time-course as well as its biodisposition largely resembles that of vecuronium. The initial fast rate of block development may be the result of both low potency amd

Comparison of the variability of the onset and recovery from neuromuscular blockade with cisatracurium versus rocuronium in elderly patients under total intravenous anesthesia

Science.gov (United States)

Xiaobo, Feng; Jianjuan, Ke; Yanlin, Wang

2012-01-01

This study was designed to compare the variability of the onset and offset of the effect of two neuromuscular blocking drugs with different elimination pathways in adult and elderly patients during total intravenous anesthesia (TIVA). After Ethics Committee approval and patients' informed consent, the drugs were compared in 40 adult and 40 elderly patients scheduled for elective surgery under TIVA with tracheal intubation who were randomized to receive a single bolus dose of 0.15 mg/kg cisatracurium or 0.9 mg/kg rocuronium. The time of onset of maximum depression, duration of action, and recovery index time were measured and recorded for each patient and variability is reported as means ± standard deviation. Time of onset was significantly shorter for rocuronium than cisatracurium for the adult and elderly groups (P = 0.000), but the variability of cisatracurium was significantly greater compared with rocuronium for the same age groups (93.25 vs 37.01 s in the adult group and 64.56 vs 33.75 s in the elderly group; P = 0.000). The duration of the effect in the elderly group receiving rocuronium was significantly longer than in the elderly group receiving cisatracurium, and the variability of the duration was significantly greater in the rocuronium group than in the cisatracurium group. Mean time of recovery was significantly longer for the elderly group receiving rocuronium than for the elderly group receiving cisatracurium (P = 0.022), and variability was also greater (P = 0.002). Both drugs favored good intubating conditions. In conclusion, cisatracurium showed less variability in these parameters than rocuronium, especially in the elderly, a fact that may be of particular clinical interest. PMID:22584638

Comparison of the variability of the onset and recovery from neuromuscular blockade with cisatracurium versus rocuronium in elderly patients under total intravenous anesthesia

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Feng Xiaobo

2012-07-01

Full Text Available This study was designed to compare the variability of the onset and offset of the effect of two neuromuscular blocking drugs with different elimination pathways in adult and elderly patients during total intravenous anesthesia (TIVA. After Ethics Committee approval and patients’ informed consent, the drugs were compared in 40 adult and 40 elderly patients scheduled for elective surgery under TIVA with tracheal intubation who were randomized to receive a single bolus dose of 0.15 mg/kg cisatracurium or 0.9 mg/kg rocuronium. The time of onset of maximum depression, duration of action, and recovery index time were measured and recorded for each patient and variability is reported as means ± standard deviation. Time of onset was significantly shorter for rocuronium than cisatracurium for the adult and elderly groups (P = 0.000, but the variability of cisatracurium was significantly greater compared with rocuronium for the same age groups (93.25 vs 37.01 s in the adult group and 64.56 vs 33.75 s in the elderly group; P = 0.000. The duration of the effect in the elderly group receiving rocuronium was significantly longer than in the elderly group receiving cisatracurium, and the variability of the duration was significantly greater in the rocuronium group than in the cisatracurium group. Mean time of recovery was significantly longer for the elderly group receiving rocuronium than for the elderly group receiving cisatracurium (P = 0.022, and variability was also greater (P = 0.002. Both drugs favored good intubating conditions. In conclusion, cisatracurium showed less variability in these parameters than rocuronium, especially in the elderly, a fact that may be of particular clinical interest.

Cholecystokinin octapeptide induces endogenous opioid-dependent anxiolytic effects in morphine-withdrawal rats.

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Wen, D; Sun, D; Zang, G; Hao, L; Liu, X; Yu, F; Ma, C; Cong, B

2014-09-26

Cholecystokinin octapeptide (CCK-8), a brain-gut peptide, plays an important role in several opioid addictive behaviors. We previously reported that CCK-8 attenuated the expression and reinstatement of morphine-induced conditioned place preference. The possible effects of CCK-8 on the negative affective components of drug abstinence are not clear. There are no studies evaluating the effect of CCK-8 on emotional symptoms, such as anxiety, in morphine-withdrawal animals. We investigated the effects of CCK-8 on the anxiety-like behavior in morphine-withdrawal rats using an elevated plus-maze. Morphine withdrawal elicited time-dependent anxiety-like behaviors with peak effects on day 10 (5 days after induction of morphine dependence). Treatment with CCK-8 (0.1 and 1 μg, i.c.v.) blocked this anxiety in a dose-dependent fashion. A CCK1 receptor antagonist (L-364,718, 10 μg, i.c.v.) blocked the effect of CCK-8. Mu-opioid receptor antagonism with CTAP (10 μg, i.c.v.) decreased the 'anxiolytic' effect. CCK-8 inhibited anxiety-like behaviors in morphine-withdrawal rats by up-regulating endogenous opioids via the CCK1 receptor in rats. This study clearly identifies a distinct function of CCK-8 and a potential medication target of central CCK1 receptors for drugs aimed at ameliorating drug addiction. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Use of rocuronium and sugammadex under neuromuscular transmission monitoring in a patient with multiple sclerosis

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Chryssoula Staikou

2017-01-01

Full Text Available Multiple sclerosis (MS is a potentially disabling disease characterized by demyelinating lesions in the central nervous system. One of the anesthetic challenges encountered in surgical patients with MS is the management of neuromuscular blockade (NMB and its reversal. We report a case of a 31-year-old female patient suffering from MS, who underwent gynecological surgery under general anesthesia with sevoflurane, fentanyl, and rocuronium which was successfully reversed with sugammadex. Neuromuscular transmission (NMT monitoring was used to guide the intraoperative doses of rocuronium and also the reversal of NMB by the use of sugammadex to ensure a safe tracheal extubation. In addition, delivered volatile was titrated according to anesthetic depth monitoring (Bispectral Index while esophageal temperature was also monitored for the maintenance of normothermia. Postoperatively, a multimodal analgesic scheme offered a high-quality analgesia and sleep, minimization of anxiety, and increased patient satisfaction. At 1-month follow-up, the patient's course was uncomplicated without any MS exacerbation. We consider that the use of rocuronium and sugammadex under NMT monitoring may represent a useful and safe choice in patients with MS.

Rocuronium-induced neuromuscular block and sugammadex in pediatric patient with duchenne muscular dystrophy

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Kim, Ji Eun; Chun, Hea Rim

2017-01-01

Abstract Introduction: Anesthetic management of patients with Duchenne muscular dystrophy (DMD) is complicated because these patients are more sensitive to nondepolarizing neuromuscular blocking agents (NMBAs) and are vulnerable to postoperative complications, such as postoperative residual curarization and respiratory failure. Sugammadex is a new reversal agent for aminosteroidal NMBAs, but its safety in children is controversial. Clinical features: An 11-year-old boy with DMD underwent general anesthesia for a percutaneous nephrolithotomy. We used rocuronium bromide and sugammadex to reverse the deep neuromuscular block. Reversal of neuromuscular block was done 15 minutes after administration of 2 mg/kg of sugammadex. The patient's recovery from anesthesia was uneventful, and he was discharged to the postoperative recovery ward. Conclusion: A delayed recovery was achieved, but no adverse events were observed, such as recurarization or hypersensitivity to sugammadex. We report safe use of 2 mg/kg of sugammadex to reverse a deep neuromuscular block in a child with DMD. PMID:28353578

Safety and Efficacy of Rocuronium With Sugammadex Reversal Versus Succinylcholine in Outpatient Surgery-A Multicenter, Randomized, Safety Assessor-Blinded Trial.

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Soto, Roy; Jahr, Jonathan S; Pavlin, Janet; Sabo, Daniel; Philip, Beverly K; Egan, Talmage D; Rowe, Everton; de Bie, Joris; Woo, Tiffany

Complex surgical procedures are increasingly performed in an outpatient setting, with emphasis on rapid recovery and case turnover. In this study, the combination of rocuronium for neuromuscular blockade (NMB) reversed by single-dose sugammadex was compared with succinylcholine followed by spontaneous recovery in outpatient surgery. This multicenter, randomized, safety assessor-blinded study enrolled adults undergoing a short elective outpatient surgical procedure requiring NMB and tracheal intubation. Patients were randomized to NMB with either rocuronium 0.6 mg/kg for tracheal intubation with incremental doses of rocuronium 0.15 mg/kg and subsequent reversal with sugammadex 4.0 mg/kg at 1-2 posttetanic counts or succinylcholine 1.0 mg/kg for intubation with spontaneous recovery. The primary efficacy end point was the time from sugammadex administration to recovery of the train-of-four ratio to 0.9; for succinylcholine, time from administration to recovery of the first twitch (T1) to 90% was assessed. From 167 patients enrolled, 150 received treatment. The all-subjects-treated population comprised 70 patients in the rocuronium-sugammadex group and 80 in the succinylcholine group. Geometric mean (95% confidence interval) time from the start of sugammadex administration to recovery of the train-of-four ratio to 0.9 was 1.8 (1.6-2.0) minutes. Geometric mean (95% confidence interval) time from succinylcholine administration to recovery of T1 to 90% was 10.8 (10.1-11.5) minutes. Health outcome variables were similar between the groups. Adverse events were reported in 87.1% and 93.8% of patients for rocuronium-sugammadex and succinylcholine, respectively. In conclusion, rocuronium for intubation followed by sugammadex for reversal of NMB offers a viable treatment option in outpatient surgery without prolonging recovery duration or jeopardizing safety.

The CRF1 and the CRF2 receptor mediate recognition memory deficits and vulnerability induced by opiate withdrawal.

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Morisot, Nadège; Contarino, Angelo

2016-06-01

Opiate use disorders are associated with impaired cognitive function and altered stress-responsive systems. The corticotropin-releasing factor (CRF) system mediates stress responses via CRF1 and CRF2 receptors and may be implicated in substance use disorders. However, the specific role for each of the two known CRF receptor subtypes in cognitive impairment induced by opiate administration and withdrawal remains to be elucidated. In the present study, CRF1-/-, CRF2-/- and their respective wild-type mice are injected with escalating doses of morphine and cognitive function assessed by the novel object recognition (NOR) memory task throughout relatively long periods of opiate withdrawal. Early (2 days) phases of opiate withdrawal impair NOR memory in wild-type, CRF1-/- and CRF2-/- mice. However, the duration of opiate withdrawal-induced NOR memory deficits is prolonged in CRF1-/- but shortened in CRF2-/- mice, as compared to their respective wild-type mice, indicating opposite roles for the two CRF receptor subtypes. Nevertheless, following apparent recovery, exposure to an environmental stressor induces the reemergence of NOR memory deficits in long-term opiate-withdrawn wild-type but not CRF1-/- or CRF2-/- mice, indicating an essential role for both CRF receptor subtypes in stress vulnerability. These findings bring initial evidence of a complex physiopathological role for the CRF system in cognitive deficits and the long-lasting vulnerability induced by opiate drugs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rocuronium and sugammadex in a 3 days old neonate for draining an ovarian cyst. Neuromuscular management and review of the literature

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Ricardo Vieira Carlos

2016-08-01

Full Text Available Abstract A case is reported in which a 3-days old neonate with a giant ovarian cyst was scheduled for surgery. The patient received a dose of sugammadex to reverse a rocuronium-induced neuromuscular block. A fast and efficient recovery from neuromuscular block was achieved within 90 s. No adverse events or other safety concerns were observed. Furthermore, a review of the literature on the use of sugammadex in neonates was performed.

Intubation conditions after rocuronium or succinylcholine for rapid sequence induction with alfentanil and propofol in the emergency patient

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Larsen, P B; Hansen, E G; Jacobsen, L S

2005-01-01

Background and objective: Previous studies mainly conducted on elective patients recommend doses of 0.9-1.2 mg kg[-1] rocuronium to obtain comparable intubation conditions with succinylcholine 1.0 mg kg[-1] after 60 s during a rapid-sequence induction. We decided to compare the overall intubating...... conditions of standard doses of rocuronium 0.6 mg kg[-1] and succinylcholine 1.0 mg kg[-1] during a strict rapid-sequence induction regimen including propofol and alfentanil. Methods: Male and female patients (ASA I-III) older than 17 yr scheduled for emergency abdominal or gynaecological surgery...... and with increased risk of pulmonary aspiration of gastric content were randomized to a rapid-sequence induction with succinylcholine 1.0 mg kg[-1] or rocuronium 0.6 mg kg[-1]. Patients with a predicted difficult airway were excluded. A senior anaesthesiologist 'blinded' for the randomization performed...

The administration sequence of propofol and remifentanil does not affect the ED50 and ED95 of rocuronium in rapid sequence induction of anesthesia: a double-blind randomized controlled trial.

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Ozcelik, M; Guclu, C; Bermede, O; Baytas, V; Altay, N; Karahan, M A; Erdogan, B; Can, O

2016-04-01

The topic of drug administration sequence in rapid sequence induction (RSI) is still an object of interest in terms of rocuronium effectiveness. The aim of this prospective, randomized trial was to evaluate the effect of administration sequence of propofol and remifentanil on ED50 and ED95 of rocuronium in a RSI model. Eighty-four patients were randomized into Group Remifentanil (Group R, n = 43), where induction of general anesthesia started with remifentanil (2 µg/kg) and followed by propofol (2 mg/kg) and rocuronium administrations; and Group Propofol (Group P, n = 41), where induction of general anesthesia started with propofol and followed by remifentanil and rocuronium. First patients in each group were paralyzed by 0.8 mg/kg rocuronium. In case of acceptable intubation as evaluated according to the criteria described by Viby-Mogensen et al, rocuronium dose was decreased by 0.1 mg/kg for the next patient; otherwise, rocuronium dose was increased by 0.1 mg/kg. After three crossover points, increments or decrements in rocuronium dosage were set to 0.05 mg/kg. The process was repeated until a total of ten crossover points were obtained. The ED50 and ED95 doses of rocuronium were similar in Group R (0.182 mg/kg, and 0.244 mg/kg, respectively) and Group P (0.121 mg/kg, and 0.243 mg/kg, respectively) according to 95% CI of the estimates. There was no statistically significant difference in terms of clinically acceptable intubation conditions between the two groups (56.1% in Group R vs. 59% in Group P, p = 0.795). The choice of administration sequence of propofol and remifentanil does not have an impact on estimated ED50 and ED95 of rocuronium in providing acceptable intubation conditions in the RSI technique.

Pharmacokinetics of rocuronium after bolus and continuous infusion during halothane anaesthesia

NARCIS (Netherlands)

McCoy, E.P; Mirakhur, R.K; Maddineni, V.R; Wierda, J.MKH; Proost, Hans

We have studied the pharmacokinetics of a single bolus of rocuronium (Org 9426), followed by an infusion, in eight patients during anaesthesia with halothane and nitrous oxide in oxygen. Neuromuscular block was monitored using train-of-four (TOF) stimulation and recording the force of contraction of

Comparing Patient Satisfaction and Intubating Conditions Using Succinylcholine or Low-Dose Rocuronium for Rigid Bronchoscopy: A Randomized Study.

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Ghezel-Ahmadi, Verena; Ghezel-Ahmadi, David; Mangen, Jacques; Bolukbas, Servet; Welker, Andreas; Kuerschner, Veit Christian; Fischer, Andreas; Schirren, Joachim; Beck, Grietje

2015-09-01

Despite its serious side effects, succinylcholine is commonly used for neuromuscular relaxation in short procedures, such as rigid bronchoscopy and tracheobronchial interventions. The application of low-dose rocuronium reversed by low-dose sugammadex might be a modern alternative. The aim of this study was to compare patient satisfaction, incidence of postoperative myalgia (POM) as well as intubating conditions of these two muscle relaxants for rigid bronchoscopy. A single-center, prospective-randomized, blinded study of 95 patients, scheduled for rigid bronchoscopy and tracheobronchial intervention was conducted. The patients were anesthetized with propofol, remifentanil and either low-dose succinylcholine (S) (0.5 mg/kg) or low-dose rocuronium (0.25 mg/kg) with sugammadex (RS) (0.5 mg/kg). All patients were evaluated on the first and second postinterventional day for their satisfaction with the treatment (rigid bronchoscopy) using a Numeric Analog Rating Scale (NAS 0-10) and the presence and severity of POM (NAS 1-4). Intubating conditions were assessed as excellent, good, or poor on the basis of position of vocal cords and reaction to insertion of the rigid bronchoscope. Patients in the S group were less satisfied with the treatment than patients in RS group (72.7 vs. 93.7%, p = 0.007). The incidence of POM on the first day after intervention was significantly higher in the S group then in the RS group (56.9% vs. 4.3%, p rocuronium in 75% of patients. The anesthetic drug costs were significantly higher in the RS group then in the S group (p rocuronium provided better patient satisfaction and less POM. But with the use of low-dose succinylcholine, the intubating conditions are more comfortable, and it is less expensive than rocuronium/sugammadex. Georg Thieme Verlag KG Stuttgart · New York.

The effects of nicardipine or esmolol on the onset time of rocuronium and intubation conditions during rapid sequence induction: a randomized double-blind trial.

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Lee, Ji Heui; Kim, Yunkwang; Lee, Kye Hyeok; Rim, Sung Kyu; Lee, Ji Yeon; Lee, Cheong

2015-06-01

The main aims of rapid sequence induction (RSI) are prompt and adequate muscle relaxation for tracheal intubation and hemodynamic stability during and after intubation. The purpose of the present study was to investigate the effects of nicardipine and esmolol on the action of rocuronium and intubation conditions during RSI. Adult patients (n = 82) were randomly allocated to one of three groups. One minute prior to the induction of sevoflurane-based general anesthesia, patients received 20 μg/kg of nicardipine (N group; n = 27) or 0.5 mg/kg of esmolol (E group; n = 27), or 5 ml of saline (C group; n = 28). Patients were assessed according to intubation conditions, the onset time of rocuronium, mean arterial pressure (MAP), and heart rate (HR) during RSI. The intubation conditions and score were significantly better in the C and N groups than in the E group (P rocuronium was shortened in the N group and prolonged in the E group when compared to the C group (P rocuronium and attenuated changes in MAP after intubation. Esmolol may disturb intubation conditions and the onset of action of rocuronium, despite being effective in alleviating responses of HR after RSI.

Involvement of delta opioid receptors in alcohol withdrawal-induced mechanical allodynia in male C57BL/6 mice.

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Alongkronrusmee, Doungkamol; Chiang, Terrance; van Rijn, Richard M

2016-10-01

As a legal drug, alcohol is commonly abused and it is estimated that 17 million adults in the United States suffer from alcohol use disorder. Heavy alcoholics can experience withdrawal symptoms including anxiety and mechanical allodynia that can facilitate relapse. The molecular mechanisms underlying this phenomenon are not well understood, which stifles development of new therapeutics. Here we investigate whether delta opioid receptors (DORs) play an active role in alcohol withdrawal-induced mechanical allodynia (AWiMA) and if DOR agonists may provide analgesic relief from AWiMA. To study AWiMA, adult male wild-type and DOR knockout C57BL/6 mice were exposed to alcohol by a voluntary drinking model or oral gavage exposure model, which we developed and validated here. We also used the DOR-selective agonist TAN-67 and antagonist naltrindole to examine the involvement of DORs in AWiMA, which was measured using a von Frey model of mechanical allodynia. We created a robust model of alcohol withdrawal-induced anxiety and mechanical allodynia by orally gavaging mice with 3g/kg alcohol for three weeks. AWiMA was exacerbated and prolonged in DOR knockout mice as well as by pharmacological blockade of DORs compared to control mice. However, analgesia induced by TAN-67 was attenuated during withdrawal in alcohol-gavaged mice. DORs appear to play a protective role in the establishment of AWiMA. Our current results indicate that DORs could be targeted to prevent or reduce the development of AWiMA during alcohol use; however, DORs may be a less suitable target to treat AWiMA during active withdrawal. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Improvement of ketamine-induced social withdrawal in rats: the role of 5-HT7 receptors.

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Hołuj, Małgorzata; Popik, Piotr; Nikiforuk, Agnieszka

2015-12-01

Social withdrawal, one of the core negative symptoms of schizophrenia, can be modelled in the social interaction (SI) test in rats using N-methyl-D-aspartate receptor glutamate receptor antagonists. We have recently shown that amisulpride, an antipsychotic with a high affinity for serotonin 5-HT7 receptors, reversed ketamine-induced SI deficits in rats. The aim of the present study was to further elucidate the potential involvement of 5-HT7 receptors in the prosocial action of amisulpride. Acute administration of amisulpride (3 mg/kg) and SB-269970 (1 mg/kg), a 5-HT7 receptor antagonist, reversed ketamine-induced social withdrawal, whereas sulpiride (20 or 30 mg/kg) and haloperidol (0.2 mg/kg) were ineffective. The 5-HT7 receptor agonist AS19 (10 mg/kg) abolished the prosocial efficacy of amisulpride (3 mg/kg). The coadministration of an inactive dose of SB-269970 (0.2 mg/kg) showed the prosocial effects of inactive doses of amisulpride (1 mg/kg) and sulpiride (20 mg/kg). The anxiolytic chlordiazepoxide (2.5 mg/kg) and the antidepressant fluoxetine (2.5 mg/kg) were ineffective in reversing ketamine-induced SI deficits. The present study suggests that the antagonism of 5-HT7 receptors may contribute towards the mechanisms underlying the prosocial action of amisulpride. These results may have therapeutic implications for the treatment of negative symptoms in schizophrenia and other disorders characterized by social withdrawal.

HYPOTHERMIC CARDIOPULMONARY BYPASS INFLUENCES THE CONCENTRATION-RESPONSE RELATIONSHIP AND THE BIODISPOSITION OF ROCURONIUM

NARCIS (Netherlands)

SMEULERS, NJ; WIERDA, JMKH; VANDENBROEK, L; HUET, RCGG; HENNIS, PJ

In 10 patients scheduled for elective coronary artery bypass grafting under midazolam-sufentanil anaesthesia, the influence of hypothermia on the plasma concentration-response and biodisposition of rocuronium were investigated. Neuromuscular function was monitored mechanomyographically. plasma and

Induction of synaptic long-term potentiation after opioid withdrawal.

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Drdla, Ruth; Gassner, Matthias; Gingl, Ewald; Sandkühler, Jürgen

2009-07-10

mu-Opioid receptor (MOR) agonists represent the gold standard for the treatment of severe pain but may paradoxically also enhance pain sensitivity, that is, lead to opioid-induced hyperalgesia (OIH). We show that abrupt withdrawal from MOR agonists induces long-term potentiation (LTP) at the first synapse in pain pathways. Induction of opioid withdrawal LTP requires postsynaptic activation of heterotrimeric guanine nucleotide-binding proteins and N-methyl-d-aspartate receptors and a rise of postsynaptic calcium concentrations. In contrast, the acute depression by opioids is induced presynaptically at these synapses. Withdrawal LTP can be prevented by tapered withdrawal and shares pharmacology and signal transduction pathways with OIH. These findings provide a previously unrecognized target to selectively combat pro-nociceptive effects of opioids without compromising opioid analgesia.

Effects of local low-dose rocuronium on the quality of peribulbar anesthesia for cataract surgery

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Ayman A Abdellatif

2011-01-01

Full Text Available Objectives: Peribulbar anesthesia is associated with delayed and/or incomplete orbital akinesia compared with retrobulbar anesthesia. This study examined the effects of adding rocuronium 5 mg to two different concentrations of lidocaine-bupivacaine mixture on onset time of orbital and eyelid akinesia in patients undergoing cataract surgery. Methods: In a double-blind study, 90 patients were equally randomized to receive a mixture of 0.5 ml normal saline, 4 ml lidocaine 2%, and 4 ml bupivacaine 0.5% (group I, a mixture of rocuronium 0.5 ml (5 mg, 4 ml lidocaine 2%, and 4 ml bupivacaine 0.5% (group II, or a mixture of rocuronium 0.5 ml (5 mg, 4 ml lidocaine 1%, and 4 ml bupivacaine 0.25% (group III. Orbital akinesia was assessed on a 0-8 score (0 = no movement, 8 = normal at 2 min intervals for 10 min. Time to adequate anesthesia was also recorded. Results are presented as mean±SD. Results: Ocular movement score decreased during the assessment period in all groups. However, at 2 min after block administration, the score decreased to 4±2 (95% CI 3,5 in groups II and III compared with 5±2 (95% CI 4,6 in group I (P<0.01. Time to adequate condition to begin surgery was 9.8±2.9 vs. 6.9±4.1 vs. 7.9±3.9 min for groups I, II, and III, respectively (P=0.01. Conclusion: The addition of rocuronium 5 mg to a mixture of lidocaine 2% and bupivacaine 0.5% shortened the onset time of peribulbar anesthesia in patients undergoing cataract surgery without causing adverse effects.

Rapid sequence induction and intubation with rocuronium-sugammadex compared with succinylcholine

DEFF Research Database (Denmark)

Sørensen, M K; Bretlau, C; Gätke, M R

2012-01-01

An unanticipated difficult airway may arise during rapid sequence induction and intubation (RSII). The aim of the trial was to assess how rapidly spontaneous ventilation could be re-established after RSII. We hypothesized that the time period from tracheal intubation to spontaneous ventilation wo...... would be shorter with rocuronium-sugammadex than with succinylcholine....

Effects of rocuronium and vecuronium on initial rundown of endplate potentials in the isolated phrenic nerve diaphragm preparation of rats

OpenAIRE

Li, Jun; Liu, Yong-Qin; Zhang, Han-Ting

2013-01-01

Rocuronium and vecuronium, two non-depolarizing neuromuscular blockers, have been widely used in surgery procedures. However, their electrophysiological properties need to be more widely explored. We examined the effects of rocuronium and vecuronium on initial rundown of endplate potential amplitudes in the non-uniform stretched muscle preparation of the rat isolated phrenic nerve diaphragm. More specifically, the endplate potentials were recorded with one microelectrode from a single endplat...

Sex differences in stress-induced social withdrawal: independence from adult gonadal hormones and inhibition of female phenotype by corncob bedding.

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Trainor, Brian C; Takahashi, Elizabeth Y; Campi, Katharine L; Florez, Stefani A; Greenberg, Gian D; Laman-Maharg, Abigail; Laredo, Sarah A; Orr, Veronica N; Silva, Andrea L; Steinman, Michael Q

2013-03-01

There is compelling evidence for important sex differences in behavioral and hormonal responses to psychosocial stress. Here we examined the effects of gonadal hormones on behavioral responses to social defeat stress in monogamous California mice (Peromyscus californicus). Three episodes of social defeat induced social withdrawal in intact females but not males. Gonadectomy blocked corticosterone responses to defeat in females and sensitized male corticosterone responses. However, gonadectomy had no effects on social interaction behavior, suggesting that social withdrawal is not dependent on gonadal hormones in the adult California mouse. In contrast, defeat reduced exploratory behavior in the open field test for intact but not castrated males. We also examined the effects of social defeat on social interaction behavior when California mice were raised on corncob bedding, which has estrogenic properties. In this dataset of over 300 mice, we observed that social defeat did not induce social withdrawal when females were raised on corncob bedding. This finding suggests that the use of corncob in rodent studies could mask important sex differences in the effects of stress on brain and behavior. Although gonadal hormones do not affect social withdrawal behavior in adults, our data suggest that hormones may act earlier in development to induce a more resilient social phenotype. Copyright © 2013 Elsevier Inc. All rights reserved.

Evaluation of the mydriatic effects of topical administration of rocuronium bromide in Hispaniolan Amazon parrots (Amazona ventralis).

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Petritz, Olivia A; Guzman, David Sanchez-Migallon; Gustavsen, Kate; Wiggans, K Tomo; Kass, Philip H; Houck, Emma; Murphy, Christopher J; Paul-Murphy, Joanne

2016-01-01

OBJECTIVE :To determine the mydriatic effects of topical rocuronium bromide administration in Hispaniolan Amazon parrots (Amazona ventralis) and to identify any adverse effects associated with treatment. Randomized crossover study. 8 healthy adult Hispaniolan Amazon parrots. Rocuronium bromide (20 μL/eye; 10 mg/mL) or saline (20 μL/eye; 0.9% NaCl) solution was administered in both eyes of each bird with a 26-day washout period. The birds were manually restrained in lateral recumbency with the apex of the cornea positioned upward for 2 minutes following administration in each eye. Infrared pupillometry and direct pupillary light reflex measurements were used to evaluate the mydriatic effects. Pupillary measurements were recorded prior to administration and every 20 minutes for 2 hours after administration, then hourly for a total of 7 hours. A brief physical examination was performed, direct pupillary light reflex was tested, and fluorescein staining was performed on each eye of each bird 24 hours after administration. A significant difference in pupillary diameter for the active versus control treatment group was noted from 20 to 360 minutes after drug administration, but not at 420 minutes. Minimal adverse effects were noted. Three birds had transient inferior eyelid paresis noted in both eyes after receiving rocuronium; 24 hours after the treatment, no differences in ocular measurements existed between the active and control treatments. Results suggested that topical rocuronium bromide administration may be safely used for pupillary dilation in Hispaniolan Amazon parrots and could be used for clinical evaluation, fundus imaging, and surgical interventions involving the lens and posterior segment in this species.

The relationship between rate of administration of an intubating dose of rocuronium and time to 50% and 90% block at the adductor pollicis muscle

NARCIS (Netherlands)

De Haes, A; Eleveld, DJ; Wierda, JMKH

2000-01-01

Objective. To determine the relationship between the rate of rocuronium injection and the onset time of neuromuscular block. Methods.After intravenous induction, 60 female patients (ASA I-II) were assigned randomly into 3 groups for rocuronium administration within 1-15, 15-30 or 30-60 seconds.

Analysis of genotoxic activity of ketamine and rocuronium bromide using the somatic mutation and recombination test in Drosophila melanogaster.

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Koksal, Pakize Muge; Gürbüzel, Mehmet

2015-03-01

The present study evaluated the mutagenic and recombinogenic effects of two commonly used anesthetic agents, ketamine and rocuronium bromide, in medicine using the wing somatic mutation and recombination test (SMART) in Drosophila. The standard (ST) cross and the high-bioactivation (HB) cross with high sensitivity to procarcinogens and promutagens were used. The SMART test is based on the loss of heterozygosity, which occurs via various mechanisms, such as chromosome loss and deletion, half-translocation, mitotic recombination, mutation, and non-disjunction. Genetic alterations occurring in the somatic cells of the wing's imaginal discs result in mutant clones in the wing blade. Three-day-old trans-heterozygous larvae with two recessive markers, multiple wing hairs (mwh) and flare (flr(3)), were treated with ketamine and rocuronium bromide. Analysis of the ST cross indicated that ketamine exhibited genotoxicity activity and that this activity was particularly dependent on homologous mitotic recombination at concentrations of 250 μg/ml and above. Rocuronium bromide did not exert mutagenic and/or recombinogenic effects. In the HB cross, ketamine at a concentration of 1000 μg/ml and rocuronium bromide at all concentrations, with the exception of 250 μg/ml (inconclusive), exerted genotoxic effects, which could also be associated with the increase in mitotic recombination. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of rocuronium on the level and mode of pre-synaptic acetylcholine release by facial and somatic nerves, and changes following facial nerve injury in rabbits.

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Tan, Jinghua; Xu, Jing; Xing, Yian; Chen, Lianhua; Li, Shitong

2015-01-01

Muscles innervated by the facial nerve show differential sensitivities to muscle relaxants than muscles innervated by somatic nerves. The evoked electromyography (EEMG) response is also proportionally reduced after facial nerve injury. This forms the theoretical basis for proper utilization of muscle relaxants to balance EEMG monitoring and immobility under general anesthesia. (1) To observe the relationships between the level and mode of acetylcholine (ACh) release and the duration of facial nerve injury, and the influence of rocuronium in an in vitro rabbit model. (2) To explore the pre-synaptic mechanisms of discrepant responses to a muscle relaxant. Quantal and non-quantal ACh release were measured by using intracellular microelectrode recording in the orbicularis oris 1 to 42 days after graded facial nerve injury and in the gastrocnemius with/without rocuronium. Quantal ACh release was significantly decreased by rocuronium in the orbicularis oris and gastrocnemius, but significantly more so in gastrocnemius. Quantal release was reduced after facial nerve injury, which was significantly correlated with the severity of nerve injury in the absence but not in the presence of rocuronium. Non-quantal ACh release was reduced after facial nerve injury, with many relationships observed depending on the extent of the injury. The extent of inhibition of non-quantal release by rocuronium correlated with the grade of facial nerve injury. These findings may explain why EEMG amplitude might be diminished after acute facial nerve injury but relatively preserved after chronic injury and differential responses in sensitivity to rocuronium.

TIME-COURSE OF ACTION AND INTUBATING CONDITIONS FOLLOWING VECURONIUM, ROCURONIUM AND MIVACURIUM

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WIERDA, JMKH; HOMMES, FDM; NAP, HJA; VANDENBROEK, L

The purpose of this study was to compare the time course of action and tracheal intubating conditions of vecuronium, rocuronium, and mivacurium in anaesthetised patients. Anaesthesia consisted of thiopentone, fentanyl, N2O/O-2 and isoflurane. After a 2 x ED(50) dose the first attempt at tracheal

The acute tobacco withdrawal syndrome among black smokers.

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Robinson, Cendrine D; Pickworth, Wallace B; Heishman, Stephen J; Waters, Andrew J

2014-03-01

Black smokers have greater difficulty quitting tobacco than White smokers, but the mechanisms underlying between-race differences in smoking cessation are not clear. One possibility is that Black smokers experience greater acute withdrawal than Whites. We investigated whether Black (n = 104) and White smokers (n = 99) differed in abstinence-induced changes in self-report, physiological, and cognitive performance measures. Smokers not wishing to quit completed two counterbalanced experimental sessions. Before one session, they abstained from smoking for at least 12 hr. They smoked normally before the other session. Black smokers reported smaller abstinence-induced changes on a number of subjective measures including the total score of the 10-item Questionnaire for Smoking Urges (QSU) and the total score of the Wisconsin Smoking Withdrawal Scale (WSWS). However, on most subjective measures, and on all objective measures, there were no between-race differences in abstinence-induced change scores. Moreover, Black participants did not report lower QSU and WSWS ratings at the abstinent session, but they did experience significantly higher QSU and WSWS ratings at the nonabstinent session. Abstinence-induced changes in subjective, physiological, and cognitive measures in White smokers were similar for smokers of nonflavored and menthol-flavored cigarettes. There was no evidence that Black smokers experienced greater acute tobacco withdrawal than Whites. To the contrary, Black participants experienced smaller abstinence-induced changes in self-reported craving and withdrawal on some measures. Racial differences in smoking cessation are unlikely to be explained by acute withdrawal.

Rocuronium and sugammadex in a 3 days old neonate for draining an ovarian cyst. Neuromuscular management and review of the literature

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Ricardo Vieira Carlos

2016-07-01

Full Text Available A case is reported in which a 3-days old neonate with a giant ovarian cyst was scheduled for surgery. The patient received a dose of sugammadex to reverse a rocuronium-induced neuromuscular block. A fast and efficient recovery from neuromuscular block was achieved within 90 s. No adverse events or other safety concerns were observed. Furthermore, a review of the literature on the use of sugammadex in neonates was performed. Resumo: Relato do caso de uma criança recém-nascida de 3 dias de idade com um cisto ovariano gigante programada para a cirurgia. A paciente recebeu uma dose de sugamadex para reverter o bloqueio neuromuscular induzido por rocurônio. Uma recuperação rápida e eficiente do bloqueio neuromuscular foi obtida dentro de 90 segundos. Não foram observados efeitos adversos ou outros problemas de segurança. Além disso, uma revisão da literatura sobre o uso de sugamadex em recém-nascidos foi realizada. Keywords: Neonates, Ovarian cyst, Sugammadex, Rocuronium, Reversal agent, Palavras-chave: Recém-nascidos, Cisto ovariano, Sugammadex, Rocurônio, Agente de reversão

The SLCO1A2 -189_-188InsA polymorphism reduces clearance of rocuronium in patients submitted to elective surgeries.

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Costa, A C C; Coelho, E B; Lanchote, V L; Correia, B V; Abumansur, J T; Lauretti, G R; de Moraes, N V

2017-08-01

Rocuronium (ROC) is a neuromuscular blocker mainly eliminated by biliary excretion dependent on organic anion transporting polypeptide 1A2 (OATP1A2) hepatocellular uptake. However, the influence of SLCO1A2 (gene encoding OATP1A2) genetic polymorphism on ROC pharmacokinetics was never described before. The objective of this work was to evaluate the influence of genetic polymorphisms of SLCO1A2 on the pharmacokinetics of rocuronium (ROC). Patients undergoing elective surgeries under general anesthesia using rocuronium as a neuromuscular blocker were genotyped for SLCO1A2 polymorphisms in the coding region (41A>G, 382A>T, 404A>T, 502C>T, 516A>C, 559G>A, 830C>A, and 833delA) and in the promoter region (-1105G>A, -1032G>A, -715T>C, -361G>A, and -189_-188insA). Rocuronium pharmacokinetic parameters were estimated by non-compartmental analysis. None of the patients had heterozygous or homozygous variant of 404A>T, 382A>T, 502C>T, 833delA, 830C>A, 41A>G, and -715T>C. A linkage disequilibrium was found between -1105G>A and -1032G>A genotypes. Patients genotyped as -A or AA (n = 17) for SLCO1A2 -189_-188InsA showed reduced total clearance of ROC compared to patients genotyped as -/- (n = 13) (151.6 vs 207.1 mL/min, p ≤ 0.05). The pharmacokinetics parameters of ROC were not significantly different between other SLCO1A2 genotypes. SLCO1A2 -189_-188InsA polymorphism is related to the reduced clearance of rocuronium in patients submitted to elective surgeries under general anesthesia. NCT 02399397 ( ClinicalTrials.gov ).

Effect of the addition of rocuronium to 2% lignocaine in peribulbar block for cataract surgery

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Vishalakshi Patil

2017-01-01

Conclusion: The addition of rocuronium 5 mg to a mixture of lidocaine 2% with adrenaline and hyaluronidase 50 IU/ml shortened the onset time of peribulbar anesthesia in patients undergoing cataract surgery without causing adverse effects.

Narp regulates long-term aversive effects of morphine withdrawal

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Reti, Irving M.; Crombag, Hans S.; Takamiya, Kogo; Sutton, Jeffrey M.; Guo, Ning; Dinenna, Megan L.; Huganir, Richard L.; Holland, Peter C.; Baraban, Jay M.

2008-01-01

Although long-lasting effects of drug withdrawal are thought to play a key role in motivating continued drug use, the mechanisms mediating this type of drug-induced plasticity are unclear. As Narp is an immediate early gene product that is secreted at synaptic sites and binds to AMPA receptors, it has been implicated in mediating enduring forms of synaptic plasticity. In previous studies, we found that Narp is selectively induced by morphine withdrawal in the extended amygdala, a group of limbic nuclei that mediate aversive behavioral responses. Accordingly, in this study, we evaluated whether long-term aversive effects of morphine withdrawal are altered in Narp KO mice. We found that acute physical signs of morphine withdrawal are unaffected by Narp deletion. However, Narp KO mice acquire and sustain more aversive responses to the environment conditioned with morphine withdrawal than WT controls. Paradoxically, Narp KO mice undergo accelerated extinction of this heightened aversive response. Taken together, these studies suggest that Narp modulates both acquisition and extinction of aversive responses to morphine withdrawal and, therefore, may regulate plasticity processes underlying drug addiction. PMID:18729628

Effect of the methanolic extracts of different parts of Ferula assa-foetida on naloxone-induced withdrawal behavior in morphine-dependent mice

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Mahnaz Khanavi

2017-08-01

Full Text Available Objective: Ferula assa-foetida, a native species in Iran, is used for treatment of several diseases particularly for neurological disorders in Iranian Traditional Medicine. The aim of this study is to investigate the effect of methanolic roots, fruits, and aerial parts extracts of Ferula assa-foetida on withdrawal syndrome in morphine-dependent mice. Materials and Methods: Aerial parts, roots, and fruits of the plant were separately extracted with 80% MeOH. For induction of dependence, morphine (50, 50 and 75 mg/kg was injected subcutaneously three times daily (10 am, 1 pm and 4 pm for three days and a last dose of morphine (50 mg/kg was administrated on the fourth day. Withdrawal syndrome was induced by injection of naloxone (5 mg/kg, intraperitoneal 2 hr after the final dose of morphine. Different doses of the extracts were administered i.p. 60 minutes before naloxone injection and withdrawal sign was recorded 2 minutes after naloxone injection for a period of 60 minutes.   Results: Pre-treatment of animals with different doses (2.5, 5, 10, 20 mg/kg of methanolic extract of the aerial parts of F. assa-foetida caused a significant decrease in naloxone-induced behavior. Intraperitoneal administration of different doses (10, 15, 20, 25 mg/kg of methanolic extract of the fruit significantly reduced the naloxone-induced withdrawal behavior (p

Optimal dose of combined rocuronium and cisatracurium during minor surgery

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Park, Woo Young; Choi, Jae Chan; Yun, Hey Jeong; Jeon, Yeong Gwan; Park, Gisoon; Choi, Jong Bum

2018-01-01

Abstract Background: Combined rocuronium and cisatracurium have synergistic effects. We investigated whether reduced doses are effective during coadministration, by monitoring neuromuscular relaxation during surgery. Methods: This randomized, controlled clinical trial was registered at http://clinicaltrials.gov (registration number NCT02495038). The participants were 81 patients scheduled for elective mastoidectomy and tympanoplasty. Participants were assigned to groups, including the intubating dose group (Group I, n = 27; combined ED95 rocuronium and ED95 cisatracurium), the small reduction group (Group S, n = 27; dose reduced by 10% of each ED95), or the large reduction group (Group L, n = 27; dose reduced by 20% of each ED95). Drugs were administered to patients and a timer was started using TOF-Watch monitoring. TOF (train-of-four) was monitored at the ulnar nerve, at a setting of 2 Hz/12 s. We recorded the time to TOF ratio = 0 (onset), time to first TOF ratio > 25% (duration 25%), and TOF 25–75% (recovery index) under total intravenous anesthesia. One-way analysis of variance was used for statistical analyses (α = 0.05, β = 0.2). Results: There were no significant demographic differences between groups. Group L had a longer duration to onset (mean ± standard deviation, 399.3 ± 147.8 seconds) and shorter duration 25% (39.4 ± 6.8 minutes) compared to Group I (212.8 ± 56.0 s and 51.3 ± 8.47 minutes, respectively) and Group S (230.7 ± 60.6 s and 47.9 ± 10.7 minutes, respectively). There were no other significant differences between groups. Conclusion: Our findings contribute to determining clinically effective combinations of rocuronium and cisatracurium, as well as to predicting the pharmacokinetic characteristics of the synergistic effects. We suggest that reducing doses of both drugs by approximately 10% of their respective ED95 values is sufficient to maintain neuromuscular

Effect of Morphine Withdrawal Syndrome on Cerebral Ischemia

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Mohammad Allahtavakoli

2011-01-01

Full Text Available Objective(sOpioid abuse is still remained a major mental health problem, a criminal legal issue and may cause ischemic brain changes including stroke and brain edema. In the present study, we investigated whether spontaneously withdrawal syndrome might affect stroke outcomes.Materials and MethodsAddiction was induced by progressive incremental doses of morphine over 7 days. Behavioral signs of withdrawal were observed 24, 48 and 72 hr after morphine deprivation and total withdrawal score was determined. Cerebral ischemia was induced 18-22 hr after the last morphine injection by placing a natural clot into the middle cerebral artery (MCA. Neurological deficits were evaluated at 2, 24 and 48 hr after ischemia induction, and infarct size and brain edema were determined at 48 hr after stroke.ResultsMorphine withdrawal animals showed a significant increase in total withdrawal score and decrease of weight gain during the 72 hr after the last morphine injection. Compared to the addicted and control animals, infarct volume and brain edema were significantly increased in the morphine deprived animals (P< 0.05 at 48 hr after cerebral ischemia. Also, neurological deficits were higher in the morphine-withdrawn rats at 48 hr after stroke (P< 0.05. ConclusionOur data indicates that spontaneous withdrawal syndrome may worsen stroke outcomes. Further investigations are necessary to elucidate mechanisms of opiate withdrawal syndrome on stroke.

Pharmacological activation/inhibition of the cannabinoid system affects alcohol withdrawal-induced neuronal hypersensitivity to excitotoxic insults.

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Marina Rubio

Full Text Available Cessation of chronic ethanol consumption can increase the sensitivity of the brain to excitotoxic damages. Cannabinoids have been proposed as neuroprotectants in different models of neuronal injury, but their effect have never been investigated in a context of excitotoxicity after alcohol cessation. Here we examined the effects of the pharmacological activation/inhibition of the endocannabinoid system in an in vitro model of chronic ethanol exposure and withdrawal followed by an excitotoxic challenge. Ethanol withdrawal increased N-methyl-D-aspartate (NMDA-evoked neuronal death, probably by altering the ratio between GluN2A and GluN2B NMDA receptor subunits. The stimulation of the endocannabinoid system with the cannabinoid agonist HU-210 decreased NMDA-induced neuronal death exclusively in ethanol-withdrawn neurons. This neuroprotection could be explained by a decrease in NMDA-stimulated calcium influx after the administration of HU-210, found exclusively in ethanol-withdrawn neurons. By contrast, the inhibition of the cannabinoid system with the CB1 receptor antagonist rimonabant (SR141716 during ethanol withdrawal increased death of ethanol-withdrawn neurons without any modification of NMDA-stimulated calcium influx. Moreover, chronic administration of rimonabant increased NMDA-stimulated toxicity not only in withdrawn neurons, but also in control neurons. In summary, we show for the first time that the stimulation of the endocannabinoid system is protective against the hyperexcitability developed during alcohol withdrawal. By contrast, the blockade of the endocannabinoid system is highly counterproductive during alcohol withdrawal.

Getting to the Heart of Masculinity Stressors: Masculinity Threats Induce Pronounced Vagal Withdrawal During a Speaking Task.

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Kramer, Brandon L; Himmelstein, Mary S; Springer, Kristen W

2017-12-01

Previous work has found that traditional masculinity ideals and behaviors play a crucial role in higher rates of morbidity and mortality for men. Some studies also suggest that threatening men's masculinity can be stressful. Over time, this stress can weigh on men's cardiovascular and metabolic systems, which may contribute to men's higher rates of cardiometabolic health issues. The purpose of this study is to explore how masculinity threats affect men's heart rate and heart rate variability reactivity (i.e., vagal withdrawal) to masculinity feedback on a social speaking task. Two hundred and eighty-five undergraduate males were randomly assigned to one of six conditions during a laboratory-based speech task. They received one of two feedback types (masculinity or control) and one of three feedback levels (low, high, or dropping) in order to assess whether masculinity threats influence heart rate reactivity and vagal withdrawal patterns during the speech task. Men who receive low masculinity feedback during the speech task experienced more pronounced vagal withdrawal relative to those who received the control. Masculinity threats can induce vagal withdrawal that may accumulate over the life course to contribute to men's relatively worse cardiometabolic health.

Hydrogen sulfide inhibits opioid withdrawal-induced pain sensitization in rats by down-regulation of spinal calcitonin gene-related peptide expression in the spine.

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Yang, Hai-Yu; Wu, Zhi-Yuan; Bian, Jin-Song

2014-09-01

Hyperalgesia often occurs in opioid-induced withdrawal syndrome. In the present study, we found that three hourly injections of DAMGO (a μ-opioid receptor agonist) followed by naloxone administration at the fourth hour significantly decreased rat paw nociceptive threshold, indicating the induction of withdrawal hyperalgesia. Application of NaHS (a hydrogen sulfide donor) together with each injection of DAMGO attenuated naloxone-precipitated withdrawal hyperalgesia. RT-PCR and Western blot analysis showed that NaHS significantly reversed the gene and protein expression of up-regulated spinal calcitonin gene-related peptide (CGRP) in naloxone-treated animals. NaHS also inhibited naloxone-induced cAMP rebound and cAMP response element-binding protein (CREB) phosphorylation in rat spinal cord. In SH-SY5Y neuronal cells, NaHS inhibited forskolin-stimulated cAMP production and adenylate cyclase (AC) activity. Moreover, NaHS pre-treatment suppressed naloxone-stimulated activation of protein kinase C (PKC) α, Raf-1, and extracellular signal-regulated kinase (ERK) 1/2 in rat spinal cord. Our data suggest that H2S prevents the development of opioid withdrawal-induced hyperalgesia via suppression of synthesis of CGRP in spine through inhibition of AC/cAMP and PKC/Raf-1/ERK pathways.

Tolerance and withdrawal from prolonged opioid use in critically ill children.

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Anand, Kanwaljeet J S; Willson, Douglas F; Berger, John; Harrison, Rick; Meert, Kathleen L; Zimmerman, Jerry; Carcillo, Joseph; Newth, Christopher J L; Prodhan, Parthak; Dean, J Michael; Nicholson, Carol

2010-05-01

After prolonged opioid exposure, children develop opioid-induced hyperalgesia, tolerance, and withdrawal. Strategies for prevention and management should be based on the mechanisms of opioid tolerance and withdrawal. Relevant manuscripts published in the English language were searched in Medline by using search terms "opioid," "opiate," "sedation," "analgesia," "child," "infant-newborn," "tolerance," "dependency," "withdrawal," "analgesic," "receptor," and "individual opioid drugs." Clinical and preclinical studies were reviewed for data synthesis. Mechanisms of opioid-induced hyperalgesia and tolerance suggest important drug- and patient-related risk factors that lead to tolerance and withdrawal. Opioid tolerance occurs earlier in the younger age groups, develops commonly during critical illness, and results more frequently from prolonged intravenous infusions of short-acting opioids. Treatment options include slowly tapering opioid doses, switching to longer-acting opioids, or specifically treating the symptoms of opioid withdrawal. Novel therapies may also include blocking the mechanisms of opioid tolerance, which would enhance the safety and effectiveness of opioid analgesia. Opioid tolerance and withdrawal occur frequently in critically ill children. Novel insights into opioid receptor physiology and cellular biochemical changes will inform scientific approaches for the use of opioid analgesia and the prevention of opioid tolerance and withdrawal.

Opioid withdrawal for 4 days prevents synaptic depression induced by low dose of morphine or naloxone in rat hippocampal CA1 area in vivo.

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Dong, Zhifang; Han, Huili; Cao, Jun; Xu, Lin

2010-02-01

The formation of memory is believed to depend on experience- or activity-dependent synaptic plasticity, which is exquisitely sensitive to psychological stress since inescapable stress impairs long-term potentiation (LTP) but facilitates long-term depression (LTD). Our recent studies demonstrated that 4 days of opioid withdrawal enables maximal extents of both hippocampal LTP and drug-reinforced behavior; while elevated-platform stress enables these phenomena at 18 h of opioid withdrawal. Here, we examined the effects of low dose of morphine (0.5 mg kg(-1), i.p.) or the opioid receptor antagonist naloxone (1 mg kg(-1), i.p.) on synaptic efficacy in the hippocampal CA1 region of anesthetized rats. A form of synaptic depression was induced by low dose of morphine or naloxone in rats after 18 h but not 4 days of opioid withdrawal. This synaptic depression was dependent on both N-methyl-D-aspartate receptor and synaptic activity, similar to the hippocampal long-term depression induced by low frequency stimulation. Elevated-platform stress given 2 h before experiment prevented the synaptic depression at 18 h of opioid withdrawal; in contrast, the glucocorticoid receptor (GR) antagonist RU38486 treatment (20 mg kg(-1), s.c., twice per day for first 3 days of withdrawal), or a high dose of morphine reexposure (15 mg kg(-1), s.c., 12 h before experiment), enabled the synaptic depression on 4 days of opioid withdrawal. This temporal shift of synaptic depression by stress or GR blockade supplements our previous findings of potentially correlated temporal shifts of LTP induction and drug-reinforced behavior during opioid withdrawal. Our results therefore support the idea that stress experience during opioid withdrawal may modify hippocampal synaptic plasticity and play important roles in drug-associated memory. (c) 2009 Wiley-Liss, Inc.

Distinct neuronal activation patterns are associated with PCP-induced social withdrawal and its reversal by the endocannabinoid-enhancing drug URB597.

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Matricon, Julien; Seillier, Alexandre; Giuffrida, Andrea

2016-09-01

The fatty acid amide hydrolase inhibitor, URB597, an endocannabinoid enhancing drug, reverses social withdrawal in the sub-chronic PCP rat model of schizophrenia, but reduces social interaction (SI) in controls. To identify the anatomical substrates associated with PCP-induced social withdrawal and the contrasting effects of URB597 on SI in PCP- versus saline-treated rats, we analyzed SI-induced c-Fos expression in 28 brain areas relevant to schizophrenia and/or social behavior following vehicle or URB597 administration. In saline-treated rats, SI was accompanied by changes in c-Fos expression in the infralimbic and orbitofrontal cortices, dorsomedial caudate putamen, ventrolateral nucleus of the septum, dorsolateral periaqueductal gray (dlPAG) and central amygdala. Except for the dlPAG, these changes were not observed in PCP-treated rats or in saline-treated rats receiving URB597. In the dorsomedial part of the bed nucleus of the stria terminalis (dmBNST), SI-induced c-Fos expression was observed only in PCP-treated rats. Interestingly, URB597 in PCP-treated rats restored a similar c-Fos expression pattern as observed in saline-treated rats: activation of the orbitofrontal cortex, inhibition of the central amygdala and suppression of activation of the dmBNST. These data suggest that orbitofrontal cortex, central amygdala and dmBNST play a critical role in the reversal of PCP-induced social withdrawal by URB597. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

Effects of rocuronium bromide on globe position and respiratory function in isoflurane-anesthetized dogs: a comparison between three different dosages.

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Briganti, Angela; Barsotti, Giovanni; Portela, Diego A; Di Nieri, Camilla; Breghi, Gloria

2015-03-01

To evaluate the effect on globe position and respiration of three dosages of intravenous rocuronium in isoflurane-anesthetized dogs. Thirty-two dogs anesthetized for ophthalmic procedures. The dogs were divided into four groups, each of eight animals (G1-G4). G1, G2, G3 received 0.075, 0.05, 0.03 mg/kg of IV rocuronium, respectively; G4 received 0.9% NaCl IV; all the treatments were administered when an end-tidal isoflurane of 1.1-1.2% was reached. Anesthesia was obtained with dexmedetomidine (2.5 mcg/kg IV), methadone (0.1 mg/kg IV), propofol (2 mg/kg IV), and isoflurane in oxygen. Neuromuscular function was assessed with acceleromyography by stimulation of the peroneal nerve using the train-of-four (ToF) and the ToF ratio (ToFR). Monitoring of cardiovascular and respiratory functions was performed. Changes in globe position were recorded. All three dosages of rocuronium produced centralization of the globe. Duration was 24.3 ± 4.2, 23.4 ± 3.6, and 8.7 ± 2.8 min, for G1, G2, and G3, respectively. The control group did not show globe centralization. No significant differences were found among the four groups in cardiovascular and respiratory parameters. Minute volume and ToFR were significantly lower in G1 compared with baseline values. All doses of rocuronium resulted in globe centralization. The higher dose provoked a transient respiratory depression and some degree of skeletal muscular blockade detectable with ToFR. No alterations in respiratory activity were present when 0.05 mg/kg was used. The 0.03 mg/kg dosage could be useful for very short ophthalmic procedures. © 2013 American College of Veterinary Ophthalmologists.

Rocuronium versus dexmedetomidine as an adjuvant to local anesthetics in peribulbar block: A double blind randomized placebo controlled study

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Radwa Hamdi Bakr

2017-07-01

Conclusion: Adding 5 mg rocuronium to local anesthetic mixture provides more rapid onset of corneal and globe akinesia than 50 μg dexmedetomidine. Adding dexmedetomidine decreases IOP and provides sedation.

Chronic ethanol intake induces partial microglial activation that is not reversed by long-term ethanol withdrawal in the rat hippocampal formation.

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Cruz, Catarina; Meireles, Manuela; Silva, Susana M

2017-05-01

Neuroinflammation has been implicated in the pathogenesis of several disorders. Activation of microglia leads to the release of pro-inflammatory mediators and microglial-mediated neuroinflammation has been proposed as one of the alcohol-induced neuropathological mechanisms. The present study aimed to examine the effect of chronic ethanol exposure and long-term withdrawal on microglial activation and neuroinflammation in the hippocampal formation. Male rats were submitted to 6 months of ethanol treatment followed by a 2-month withdrawal period. Stereological methods were applied to estimate the total number of microglia and activated microglia detected by CD11b immunohistochemistry in the hippocampal formation. The expression levels of the pro-inflammatory cytokines TNF-α, COX-2 and IL-15 were measured by qRT-PCR. Alcohol consumption was associated with an increase in the total number of activated microglia but morphological assessment indicated that microglia did not exhibit a full activation phenotype. These data were supported by functional evidence since chronic alcohol consumption produced no changes in the expression of TNF-α or COX-2. The levels of IL-15 a cytokine whose expression is increased upon activation of both astrocytes and microglia, was induced by chronic alcohol treatment. Importantly, the partial activation of microglia induced by ethanol was not reversed by long-term withdrawal. This study suggests that chronic alcohol exposure induces a microglial phenotype consistent with partial activation without significant increase in classical cytokine markers of neuroinflammation in the hippocampal formation. Furthermore, long-term cessation of alcohol intake is not sufficient to alter the microglial partial activation phenotype induced by ethanol. Copyright © 2017 Elsevier B.V. All rights reserved.

CLINICAL-PHARMACOLOGY OF ROCURONIUM (ORG-9426) - STUDY OF THE TIME-COURSE OF ACTION, DOSE REQUIREMENT, REVERSIBILITY, AND PHARMACOKINETICS

NARCIS (Netherlands)

VANDENBROEK, L; WIERDA, JMKH; SMEULERS, NJ; VANSANTEN, GJ; LECLERCQ, MGL; HENNIS, PJ

1994-01-01

Study Objective: To evaluate the time course of action, dose requirement, reversibility, and pharmacokinetics of rocuronium (Org 9426) under 3 anesthetic techniques (nitrous oxide-fentanyl supplemented with propofol halothane, or isoflurane). Design: Prospective, randomized study. Setting: Operating

Reversal of prolonged rocuronium neuromuscular blockade with sugammadex in an obstetric patient with transverse myelitis.

LENUS (Irish Health Repository)

Weekes, G

2010-07-01

A 38-year-old wheelchair-bound primigravida with transverse myelitis presented at 38 weeks of gestation for elective caesarean section. Transverse myelitis, which is characterised by bilateral inflammation of the spinal cord and myelin destruction, is associated with myopathy, autonomic dysreflexia and pulmonary aspiration. Regional anaesthesia was contraindicated in this case as the patient had undergone two previous lumbar spinal fusion procedures. Rocuronium 1.2 mg\\/kg was used to facilitate rapid intubating conditions. The caesarean section proceeded uneventfully, but even after administration of neostigmine the patient exhibited prolonged neuromuscular blockade. After 3 h and 15 min sugammadex was obtained to reverse neuromuscular blockade; the drug was not stocked in our hospital. Sugammadex 4 mg\\/kg resulted in complete reversal of blockade after 2 min. We believe that myopathy associated with transverse myelitis led to the prolonged duration of action of rocuronium. Sugammadex is a relatively new drug with few reported side effects. In this case it was used to reverse neuromuscular blockade and prevented prolonged postoperative ventilatory support.

Reversal of prolonged rocuronium neuromuscular blockade with sugammadex in an obstetric patient with transverse myelitis.

LENUS (Irish Health Repository)

Weekes, G

2012-02-01

A 38-year-old wheelchair-bound primigravida with transverse myelitis presented at 38 weeks of gestation for elective caesarean section. Transverse myelitis, which is characterised by bilateral inflammation of the spinal cord and myelin destruction, is associated with myopathy, autonomic dysreflexia and pulmonary aspiration. Regional anaesthesia was contraindicated in this case as the patient had undergone two previous lumbar spinal fusion procedures. Rocuronium 1.2 mg\\/kg was used to facilitate rapid intubating conditions. The caesarean section proceeded uneventfully, but even after administration of neostigmine the patient exhibited prolonged neuromuscular blockade. After 3 h and 15 min sugammadex was obtained to reverse neuromuscular blockade; the drug was not stocked in our hospital. Sugammadex 4 mg\\/kg resulted in complete reversal of blockade after 2 min. We believe that myopathy associated with transverse myelitis led to the prolonged duration of action of rocuronium. Sugammadex is a relatively new drug with few reported side effects. In this case it was used to reverse neuromuscular blockade and prevented prolonged postoperative ventilatory support.

Modeling of fluid injection and withdrawal induced fault activation using discrete element based hydro-mechanical and dynamic coupled simulator

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Yoon, Jeoung Seok; Zang, Arno; Zimmermann, Günter; Stephansson, Ove

2016-04-01

Operation of fluid injection into and withdrawal from the subsurface for various purposes has been known to induce earthquakes. Such operations include hydraulic fracturing for shale gas extraction, hydraulic stimulation for Enhanced Geothermal System development and waste water disposal. Among these, several damaging earthquakes have been reported in the USA in particular in the areas of high-rate massive amount of wastewater injection [1] mostly with natural fault systems. Oil and gas production have been known to induce earthquake where pore fluid pressure decreases in some cases by several tens of Mega Pascal. One recent seismic event occurred in November 2013 near Azle, Texas where a series of earthquakes began along a mapped ancient fault system [2]. It was studied that a combination of brine production and waste water injection near the fault generated subsurface pressures sufficient to induced earthquakes on near-critically stressed faults. This numerical study aims at investigating the occurrence mechanisms of such earthquakes induced by fluid injection [3] and withdrawal by using hydro-geomechanical coupled dynamic simulator (Itasca's Particle Flow Code 2D). Generic models are setup to investigate the sensitivity of several parameters which include fault orientation, frictional properties, distance from the injection well to the fault, amount of fluid withdrawal around the injection well, to the response of the fault systems and the activation magnitude. Fault slip movement over time in relation to the diffusion of pore pressure is analyzed in detail. Moreover, correlations between the spatial distribution of pore pressure change and the locations of induced seismic events and fault slip rate are investigated. References [1] Keranen KM, Weingarten M, Albers GA, Bekins BA, Ge S, 2014. Sharp increase in central Oklahoma seismicity since 2008 induced by massive wastewater injection, Science 345, 448, DOI: 10.1126/science.1255802. [2] Hornbach MJ, DeShon HR

Quantifying the Clinical Significance of Cannabis Withdrawal

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Allsop, David J.; Copeland, Jan; Norberg, Melissa M.; Fu, Shanlin; Molnar, Anna; Lewis, John; Budney, Alan J.

2012-01-01

Background and Aims Questions over the clinical significance of cannabis withdrawal have hindered its inclusion as a discrete cannabis induced psychiatric condition in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV). This study aims to quantify functional impairment to normal daily activities from cannabis withdrawal, and looks at the factors predicting functional impairment. In addition the study tests the influence of functional impairment from cannabis withdrawal on cannabis use during and after an abstinence attempt. Methods and Results A volunteer sample of 49 non-treatment seeking cannabis users who met DSM-IV criteria for dependence provided daily withdrawal-related functional impairment scores during a one-week baseline phase and two weeks of monitored abstinence from cannabis with a one month follow up. Functional impairment from withdrawal symptoms was strongly associated with symptom severity (p = 0.0001). Participants with more severe cannabis dependence before the abstinence attempt reported greater functional impairment from cannabis withdrawal (p = 0.03). Relapse to cannabis use during the abstinence period was associated with greater functional impairment from a subset of withdrawal symptoms in high dependence users. Higher levels of functional impairment during the abstinence attempt predicted higher levels of cannabis use at one month follow up (p = 0.001). Conclusions Cannabis withdrawal is clinically significant because it is associated with functional impairment to normal daily activities, as well as relapse to cannabis use. Sample size in the relapse group was small and the use of a non-treatment seeking population requires findings to be replicated in clinical samples. Tailoring treatments to target withdrawal symptoms contributing to functional impairment during a quit attempt may improve treatment outcomes. PMID:23049760

Quantifying the clinical significance of cannabis withdrawal.

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David J Allsop

Full Text Available Questions over the clinical significance of cannabis withdrawal have hindered its inclusion as a discrete cannabis induced psychiatric condition in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV. This study aims to quantify functional impairment to normal daily activities from cannabis withdrawal, and looks at the factors predicting functional impairment. In addition the study tests the influence of functional impairment from cannabis withdrawal on cannabis use during and after an abstinence attempt.A volunteer sample of 49 non-treatment seeking cannabis users who met DSM-IV criteria for dependence provided daily withdrawal-related functional impairment scores during a one-week baseline phase and two weeks of monitored abstinence from cannabis with a one month follow up. Functional impairment from withdrawal symptoms was strongly associated with symptom severity (p=0.0001. Participants with more severe cannabis dependence before the abstinence attempt reported greater functional impairment from cannabis withdrawal (p=0.03. Relapse to cannabis use during the abstinence period was associated with greater functional impairment from a subset of withdrawal symptoms in high dependence users. Higher levels of functional impairment during the abstinence attempt predicted higher levels of cannabis use at one month follow up (p=0.001.Cannabis withdrawal is clinically significant because it is associated with functional impairment to normal daily activities, as well as relapse to cannabis use. Sample size in the relapse group was small and the use of a non-treatment seeking population requires findings to be replicated in clinical samples. Tailoring treatments to target withdrawal symptoms contributing to functional impairment during a quit attempt may improve treatment outcomes.

Blocking of beta-2 adrenergic receptors hastens recovery from hypoglycemia-associated social withdrawal.

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Park, Min Jung; Guest, Christopher B; Barnes, Meredith B; Martin, Jonathan; Ahmad, Uzma; York, Jason M; Freund, Gregory G

2008-11-01

Hypoglycemia is associated with a variety of adverse behaviors including fatigue, confusion and social withdrawal. While these clinical symptoms are well characterized, the mechanism of their cause is not understood. Here we investigated how insulin-induced hypoglycemia causes social withdrawal. Male 8-12-week-old C57BL/6J mice were injected intraperitoneally (IP) with or without and/or insulin, norepinephrine (NE) and epinephrine (Epi), terbutaline and butoxamine with subsequent measurement of blood glucose, social withdrawal and plasma catecholamines. Insulin generated (0.75h post-injection) significant hypoglycemia with blood glucose nadirs of 64+/-4 and 48+/-5mg/dl for 0.8 and 1.2units/kg of insulin, respectively. Insulin (0.8 or 1.2units/kg) caused near total social withdrawal at 0.75h with full recovery not occurring until 4h (0.8units/kg) or 8h (1.2units/kg) post-insulin injection. Insulin also caused a marked elevation in plasma catecholamines. Basal 12h fasting NE and Epi were 287+/-38 and 350+/-47pg/ml, respectively. Insulin at 0.8units/kg increased plasma NE and Epi to 994+/-73 and 1842+/-473pg/ml, respectively. Administration of exogenous NE or Epi caused social withdrawal similar in magnitude to insulin. Importantly, administration of the beta-2 adrenergic receptor agonist terbutaline also caused social withdrawal while administration of the beta-2 adrenergic receptor antagonist butoxamine blocked NE-induced social withdrawal. Finally, butoxamine blocked insulin-induced social withdrawal. These data demonstrate that hypoglycemia-associated social withdrawal is dependent on catecholamines via a beta-2 receptor-mediated pathway.

Modulation of histone deacetylase attenuates naloxone-precipitated opioid withdrawal syndrome.

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Rehni, Ashish K; Singh, Nirmal; Rachamalla, Mahesh; Tikoo, Kulbhushan

2012-06-01

The present study has been designed to investigate the effect of selective inhibitors of histone deacetylase and/or N-acetyl-Asp-Glu-Val-Asp-al (Ac-DEVD-CHO), a selective interleukin-1β converting enzyme inhibitor, on the development of naloxone-induced opioid withdrawal syndrome both in vitro and in vivo and the effect of histone deacetylase inhibition on histone H3 acetylation in brain. Sub-acute morphine administration followed by a single injection of naloxone (8 mg/kg, i.p.) was used to precipitate opioid withdrawal syndrome in mice. Behavioral observations were made immediately after naloxone treatment. Withdrawal syndrome was quantitatively assessed in terms of withdrawal severity score and frequency of jumping, rearing, fore paw licking and circling. Separately naloxone-induced contraction in morphine-dependent isolated rat ileum was employed as an in vitro model. An isobolographic study design was employed to assess potential synergistic activity between trichostatin A and Ac-DEVD-CHO. Brain histone acetylation status was examined by western blotting. Injection of naloxone precipitated a severe form of abstinence syndrome in morphine-dependent mice along with strong contracture in isolated rat ileum. Administration of tributyrin (1.5, 3 and 6 g/kg, p.o.), trichostatin A (0.3, 1.0 and 3.0 mg/kg, p.o.) and Ac-DEVD-CHO (0.3, 1.0 and 3.0 mg/kg, p.o.) markedly and dose dependently attenuated naloxone-induced morphine withdrawal syndrome in vivo as well as in vitro in rat ileum. Trichostatin A was also observed to exert a synergistic interaction with Ac-DEVD-CHO. Western blot analysis revealed that multiple administration with the effective dose of tributyrin or trichostatin A in the in vivo experiments induced hyperacetylation of histone H3 in the mouse brain. Thus, it is proposed that histone deacetylase activation linked mechanism might be involved in the development of opioid dependence and the precipitation of its withdrawal syndrome.

Nature cures nature: Hypericum perforatum attenuates physical withdrawal signs in opium dependent rats.

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Khan, Munasib; Subhan, Fazal; Khan, Arif-Ullah; Abbas, Muzaffar; Ali, Gowhar; Rauf, Khalid; Gilani, Anwarul Hassan

2014-05-01

Hypericum perforatum Linn. (Hypericaceae) (St. John's wort) attenuates opium withdrawal signs. To explore the therapeutic potential of Hypericum perforatum in the management of opium-induced withdrawal syndrome. The effect of the Hypericum perforatum hydro-ethanol extract was investigated for potential to reverse naloxone (0.25 mg/kg)-induced opium withdrawal physical signs. Rats received opium extract (80-650 mg/kg) twice daily for 8 days along with Hypericum perforatum (20 mg/kg, orally) twice daily in chronic treatment and the same single dose 1 h before induction of withdrawal syndrome in the acute treated group. Hypericum perforatum reduced stereotype jumps and wet dog shake number in the chronic treatment compared to the saline control group (F(2, 24) = 3.968, p opium withdrawal syndrome possibly through direct or indirect interaction with opioid receptors. Further study is needed to clarify its mechanism.

Generalised pustular psoriasis induced by cyclosporin a withdrawal responding to the tumour necrosis factor alpha inhibitor etanercept.

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Kamarashev, J; Lor, P; Forster, A; Heinzerling, L; Burg, G; Nestle, F O

2002-01-01

We report a 50-year-old male patient with a 15-year history of psoriasis including mutilating psoriatic arthritis, in whom the withdrawal of cyclosporin A induced a generalised pustular exacerbation and a aggravation of the joint condition. Two weekly injections of 25 mg of the tumour necrosis factor alpha inhibitor etanercept led to a rapid improvement of his psoriatic arthritis, as well as regression of the pustular eruption, while residual erythema was still present. The clinical response was reflected by an increase in circulating interleukin (IL) 10 and a decrease in IL-6 and IL-8 serum levels during treatment. We conclude that etanercept may be a safe and effective therapy not only in severe psoriatic arthritis, but also in cases of pustular rebound after withdrawal of immunosuppressive agents. Copyright 2002 S. Karger AG, Basel

Dose requirements of alfentanil to eliminate autonomic responses during rapid-sequence induction with thiopental 4 mg/kg and rocuronium 0.6 mg/kg.

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Abou-Arab, Mohammad H; Rostrup, Morten; Heier, Tom

2016-12-01

Opioids are integral part of anesthesia induction, but information on optimal dosing is limited. We aimed to determine doses of alfentanil needed to eliminate increases in 5 autonomic response variables (plasma concentrations of epinephrine, norepinephrine and vasopressin, arterial blood pressure [ABP], and heart rate) during rapid-sequence induction of anesthesia with thiopental 4 mg/kg and rocuronium 0.6 mg/kg. Prospective, randomized, observer-blinded, interventional clinical study. Large academic institution. Eighty-four healthy patients, aged 18 to 55 years, received 1 of 7 assessor-blinded doses of alfentanil (0, 10, 20, 30, 40, 50, and 60 μg/kg) together with thiopental 4 mg/kg and rocuronium 0.6 mg/kg, administered in rapid succession (15 seconds). Laryngoscopy was initiated 40 seconds after rocuronium, and tracheal intubation was concluded within 15 seconds thereafter. An indwelling radial artery catheter was used for hemodynamic monitoring and blood sampling. Relationships between alfentanil dose and response variables were tested with linear regression, and the influence of covariates (sex, body weight, and age) was determined. Alfentanil dose needed to prevent increases in ABP >10% above baseline with 95% probability was estimated with logistic regression. Significant relationships were determined between alfentanil dose and response variables. Clinically interesting influence of covariates was not found. Alfentanil 55 μg/kg was needed to prevent increases in ABP postintubation >10% above baseline with 95% probability. One individual needed a bolus of vasopressor postintubation. Optimal control of autonomic responses during rapid-sequence induction was achieved with clinically relevant doses of alfentanil in healthy patients anesthetized with thiopental 4 mg/kg and rocuronium 0.6 mg/kg. Copyright © 2016 Elsevier Inc. All rights reserved.

Peptidase inhibitors reduce opiate narcotic withdrawal signs, including seizure activity, in the rat.

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Pinsky, C; Dua, A K; LaBella, F S

1982-07-15

Narcotic withdrawal was precipitated by administration of naloxone in a low dose at 2 h after the final dose of morphine in a 9-day dependency-inducing schedule. Withdrawal was characterized by leaps, increased nocifensor activity and by cerebral cortical epileptiform activity, the latter not generally reported to be prominent in narcotic withdrawal. Single large doses of morphine did not provoke epileptiform activity at 2 h postinjection but did induce an acute opioid dependency wherein a moderately high dose of naloxone, ineffective in non-dependent rats, provoked upward leaping and electrocortical epileptiform activity. Pretreatment of the 9-day dependent rats with peptidase inhibitors, administered intracerebroventricularly, significantly reduced withdrawal severity including the epileptiform activity. We propose that peptidase inhibitors protect certain species of endogenous opioids and/or other neuropeptides that tend to suppress expression of the narcotic withdrawal syndrome. Furthermore, our findings suggest that epileptiform activity is a nascent form of cerebral activity hitherto largely unnoticed in narcotic withdrawal and that neuropeptides may be involved in certain epileptic states.

Cardiac adverse effects of naloxone-precipitated morphine withdrawal on right ventricle: Role of corticotropin-releasing factor (CRF) 1 receptor

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Navarro-Zaragoza, J.; Martínez-Laorden, E.; Mora, L.; Hidalgo, J.; Milanés, M.V.; Laorden, M.L., E-mail: laorden@um.es

2014-02-15

Opioid addiction is associated with cardiovascular disease. However, mechanisms linking opioid addiction and cardiovascular disease remain unclear. This study investigated the role of corticotropin-releasing factor (CRF) 1 receptor in mediating somatic signs and the behavioural states produced during withdrawal from morphine dependence. Furthermore, it studied the efficacy of CRF1 receptor antagonist, CP-154,526 to prevent the cardiac sympathetic activity induced by morphine withdrawal. In addition, tyrosine hydroxylase (TH) phosphorylation pathways were evaluated. Like stress, morphine withdrawal induced an increase in the hypothalamic–pituitary–adrenal (HPA) axis activity and an enhancement of noradrenaline (NA) turnover. Pre-treatment with CRF1 receptor antagonist significantly reduced morphine withdrawal-induced increases in plasma adrenocorticotropic hormone (ACTH) levels, NA turnover and TH phosphorylation at Ser31 in the right ventricle. In addition, CP-154,526 reduced the phosphorylation of extracellular signal-regulated kinase (ERK) after naloxone-precipitated morphine withdrawal. In addition, CP-154,526 attenuated the increases in body weight loss during morphine treatment and suppressed some of morphine withdrawal signs. Altogether, these results support the idea that cardiac sympathetic pathways are activated in response to naloxone-precipitated morphine withdrawal suggesting that treatment with a CRF1 receptor antagonist before morphine withdrawal would prevent the development of stress-induced behavioural and autonomic dysfunction in opioid addicts. - Highlights: • Morphine withdrawal caused an increase in myocardial sympathetic activity. • ERK regulates TH phosphorylation after naloxone-induced morphine withdrawal. • CRF1R is involved in cardiac adaptive changes during morphine dependence.

Cardiac adverse effects of naloxone-precipitated morphine withdrawal on right ventricle: Role of corticotropin-releasing factor (CRF) 1 receptor

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Navarro-Zaragoza, J.; Martínez-Laorden, E.; Mora, L.; Hidalgo, J.; Milanés, M.V.; Laorden, M.L.

2014-01-01

Opioid addiction is associated with cardiovascular disease. However, mechanisms linking opioid addiction and cardiovascular disease remain unclear. This study investigated the role of corticotropin-releasing factor (CRF) 1 receptor in mediating somatic signs and the behavioural states produced during withdrawal from morphine dependence. Furthermore, it studied the efficacy of CRF1 receptor antagonist, CP-154,526 to prevent the cardiac sympathetic activity induced by morphine withdrawal. In addition, tyrosine hydroxylase (TH) phosphorylation pathways were evaluated. Like stress, morphine withdrawal induced an increase in the hypothalamic–pituitary–adrenal (HPA) axis activity and an enhancement of noradrenaline (NA) turnover. Pre-treatment with CRF1 receptor antagonist significantly reduced morphine withdrawal-induced increases in plasma adrenocorticotropic hormone (ACTH) levels, NA turnover and TH phosphorylation at Ser31 in the right ventricle. In addition, CP-154,526 reduced the phosphorylation of extracellular signal-regulated kinase (ERK) after naloxone-precipitated morphine withdrawal. In addition, CP-154,526 attenuated the increases in body weight loss during morphine treatment and suppressed some of morphine withdrawal signs. Altogether, these results support the idea that cardiac sympathetic pathways are activated in response to naloxone-precipitated morphine withdrawal suggesting that treatment with a CRF1 receptor antagonist before morphine withdrawal would prevent the development of stress-induced behavioural and autonomic dysfunction in opioid addicts. - Highlights: • Morphine withdrawal caused an increase in myocardial sympathetic activity. • ERK regulates TH phosphorylation after naloxone-induced morphine withdrawal. • CRF1R is involved in cardiac adaptive changes during morphine dependence

Stress and Withdrawal from Chronic Ethanol Induce Selective Changes in Neuroimmune mRNAs in Differing Brain Sites

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Darin J. Knapp

2016-07-01

Full Text Available Stress is a strong risk factor in alcoholic relapse and may exert effects that mimic aspects of chronic alcohol exposure on neurobiological systems. With the neuroimmune system becoming a prominent focus in the study of the neurobiological consequences of stress, as well as chronic alcohol exposure proving to be a valuable focus in this regard, the present study sought to compare the effects of stress and chronic ethanol exposure on induction of components of the neuroimmune system. Rats were exposed to either 1 h exposure to a mild stressor (restraint or exposure to withdrawal from 15 days of chronic alcohol exposure (i.e., withdrawal from chronic ethanol, WCE and assessed for neuroimmune mRNAs in brain. Restraint stress alone elevated chemokine (C–C motif ligand 2 (CCL2, interleukin-1-beta (IL-1β, tumor necrosis factor alpha (TNFα and toll-like receptor 4 (TLR4 mRNAs in the cerebral cortex within 4 h with a return to a control level by 24 h. These increases were not accompanied by an increase in corresponding proteins. Withdrawal from WCE also elevated cytokines, but did so to varying degrees across different cytokines and brain regions. In the cortex, stress and WCE induced CCL2, TNFα, IL-1β, and TLR4 mRNAs. In the hypothalamus, only WCE induced cytokines (CCL2 and IL-1β while in the hippocampus, WCE strongly induced CCL2 while stress and WCE induced IL-1β. In the amygdala, only WCE induced CCL2. Finally—based on the previously demonstrated role of corticotropin-releasing factor 1 (CRF1 receptor inhibition in blocking WCE-induced cytokine mRNAs—the CRF1 receptor antagonist CP154,526 was administered to a subgroup of stressed rats and found to be inactive against induction of CCL2, TNFα, or IL-1β mRNAs. These differential results suggest that stress and WCE manifest broad neuroimmune effects in brain depending on the cytokine and brain region, and that CRF inhibition may not be a relevant mechanism in non-alcohol exposed animals

Tolerance and withdrawal to anticonvulsant action of clonazepam: role of nitric oxide.

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Gupta, N; Bhargava, V K; Pandhi, P

2000-05-01

The use of clonazepam in the long-term treatment of epilepsy is greatly inhibited by its capacity to induce tolerance and dependence. A means of preventing or minimizing the tolerance and dependence inducing properties is required. Here the role of nitric oxide in preventing the development of tolerance and withdrawal hyperexcitability was studied. In Wistar rats, clonazepam at a dose of 0.25 mg/kg i.p. twice daily produced tolerance to its anticonvulsant action in 28 days. After sudden cessation of therapy it produced hyperexcitability. Tolerance was shown by a decrease in seizure threshold to near control value while withdrawal hyperexcitability was evidenced by a significant decrease in seizure threshold below the control value. L-Arginine (a donor of nitric oxide) and N omega-nitro-L-arginine (an inhibitor of nitric oxide synthase) were given in doses of 150 mg/kg and 8 mg/kg, respectively on day 1, 3, 7, 14, 21 and 28 with clonazepam. Withdrawal hyperexcitability was seen on day 1, 2 and 4 after cessation of drug therapy. Electroshock was used as a model of epilepsy and seizure thresholds were determined by an up and down method of Kimball et al. L-Arginine was found to inhibit the development tolerance as well as withdrawal hyperexcitability when administered with clonazepam while N omega-L-arginine did not prevent either the development of tolerance or withdrawal hyperexcitability in the electroshock model. In the PTZ model, however, L-arginine had no effect on the anticonvulsant action and withdrawal hyperexcitability while inhibition of nitric oxide synthesis prevented withdrawal hyperexcitability in PTZ-induced seizures.

Dose-response and concentration-response relation of rocuronium infusion during propofol nitrous oxide and isoflurane nitrous oxide anaesthesia

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Kansanaho, M; Olkkola, KT; Wierda, JMKH

The dose-response and concentration-response relation of rocuronium infusion was studied in 20 adult surgical patients during proporfol-nitrous oxide and isoflurane (1 MAC) -nitrous oxide anaesthesia. Neuromuscular block was kept constant, initially at 90% and then at 50% with a closed-loop feedback

Opioid antagonists with minimal sedation for opioid withdrawal.

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Gowing, Linda; Ali, Robert; White, Jason M

2017-05-29

without indicating the level of care provided.The included studies were heterogeneous in terms of the type of opioid antagonist treatment regimen, the comparator, the outcome measures assessed, and the means of assessing outcomes. As a result, the validity of any estimates of overall effect is doubtful, therefore we did not calculate pooled results for any of the analyses.The quality of the evidence for treatment with an opioid antagonist-adrenergic agonist combination versus an alpha 2 -adrenergic agonist is very low. Two studies reported data on peak withdrawal severity, and four studies reported data on the average severity over the period of withdrawal. Peak withdrawal induced by opioid antagonists in combination with an adrenergic agonist appears to be more severe than withdrawal managed with clonidine or lofexidine alone, but the average severity over the withdrawal period is less. In some situations antagonist-induced withdrawal may be associated with significantly higher rates of treatment completion compared to withdrawal managed with adrenergic agonists. However, this result was not consistent across studies, and the extent of any benefit is highly uncertain.We could not extract any data on the occurrence of adverse events, but two studies reported delirium or confusion following the first dose of naltrexone. Delirium may be more likely with higher initial doses and with naltrexone rather than naloxone (which has a shorter half-life), but we could not confirm this from the available evidence.Insufficient data were available to make any conclusions on the best duration of treatment. Using opioid antagonists plus alpha 2 -adrenergic agonists is a feasible approach for managing opioid withdrawal. However, it is unclear whether this approach reduces the duration of withdrawal or facilitates transfer to naltrexone treatment to a greater extent than withdrawal managed primarily with an adrenergic agonist.A high level of monitoring and support is desirable for several

Effect of Potassium Channel Modulators on Morphine Withdrawal in Mice

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Vikas Seth

2010-01-01

Full Text Available The present study was conducted to investigate the effect of potassium channel openers and blockers on morphine withdrawal syndrome. Mice were rendered dependent on morphine by subcutaneous injection of morphine; four hours later, withdrawal was induced by using an opioid antagonist, naloxone. Mice were observed for 30 minutes for the withdrawal signs ie, the characteristic jumping, hyperactivity, urination and diarrhea. ATP-dependent potassium (K + ATP channel modulators were injected intraperitoneally (i.p. 30 minutes before the naloxone. It was found that a K + ATP channel opener, minoxidil (12.5–50 mg/kg i.p., suppressed the morphine withdrawal significantly. On the other hand, the K + ATP channel blocker glibenclamide (12.5–50 mg/kg i.p. caused a significant facilitation of the withdrawal. Glibenclamide was also found to abolish the minoxidil's inhibitory effect on morphine withdrawal. The study concludes that K + ATP channels play an important role in the genesis of morphine withdrawal and K + ATP channel openers could be useful in the management of opioid withdrawal. As morphine opens K + ATP channels in neurons, the channel openers possibly act by mimicking the effects of morphine on neuronal K + currents.

Pioglitazone attenuates the opioid withdrawal and vulnerability to relapse to heroin seeking in rodents.

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de Guglielmo, Giordano; Kallupi, Marsida; Scuppa, Giulia; Demopulos, Gregory; Gaitanaris, George; Ciccocioppo, Roberto

2017-01-01

Relapse to opioids is often driven by the avoidance of the aversive states of opioid withdrawal. We recently demonstrated that activation of peroxisome proliferator-activated receptor gamma (PPARγ) by pioglitazone reduces the motivation for heroin and attenuates its rewarding properties. However, the role of PPARγ in withdrawal and other forms of relapse to heroin is unknown. To further address this issue, we investigated the role of PPARγ on the development and expression of morphine withdrawal in mice and the effect of pioglitazone on several forms of heroin relapse in rats. We induced physical dependence to morphine in mice by injecting morphine twice daily for 6 days. Withdrawal syndrome was precipitated on day 6 with an injection of naloxone. In addition, different groups of rats were trained to self-administer heroin and, after the extinction, the relapse was elicited by cues, priming, or stress. The effect of different doses of pioglitazone was tested on these different paradigms. Data show that chronic and acute administration of pioglitazone attenuates morphine withdrawal symptoms, and these effects are mediated by activation of PPARγ receptors. Activation of PPARγ by pioglitazone also abolishes yohimbine-induced reinstatement of heroin seeking and reduces heroin-induced reinstatement, while it does not affect cue-induced relapse. These findings provide new insights on the role of PPARγ on opioid dependence and suggest that pioglitazone may be useful for the treatment of opioid withdrawal in opioid-addicted individuals.

Opioid withdrawal increases transient receptor potential vanilloid 1 activity in a protein kinase A-dependent manner.

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Spahn, Viola; Fischer, Oliver; Endres-Becker, Jeannette; Schäfer, Michael; Stein, Christoph; Zöllner, Christian

2013-04-01

Hyperalgesia is a cardinal symptom of opioid withdrawal. The transient receptor potential vanilloid 1 (TRPV1) is a ligand-gated ion channel expressed on sensory neurons responding to noxious heat, protons, and chemical stimuli such as capsaicin. TRPV1 can be inhibited via μ-opioid receptor (MOR)-mediated reduced activity of adenylyl cyclases (ACs) and decreased cyclic adenosine monophosphate (cAMP) levels. In contrast, opioid withdrawal following chronic activation of MOR uncovers AC superactivation and subsequent increases in cAMP and protein kinase A (PKA) activity. Here we investigated (1) whether an increase in cAMP during opioid withdrawal increases the activity of TRPV1 and (2) how opioid withdrawal modulates capsaicin-induced nocifensive behavior in rats. We applied whole-cell patch clamp, microfluorimetry, cAMP assays, radioligand binding, site-directed mutagenesis, and behavioral experiments. Opioid withdrawal significantly increased cAMP levels and capsaicin-induced TRPV1 activity in both transfected human embryonic kidney 293 cells and dissociated dorsal root ganglion (DRG) neurons. Inhibition of AC and PKA, as well as mutations of the PKA phosphorylation sites threonine 144 and serine 774, prevented the enhanced TRPV1 activity. Finally, capsaicin-induced nocifensive behavior was increased during opioid withdrawal in vivo. In summary, our results demonstrate an increased activity of TRPV1 in DRG neurons as a new mechanism contributing to opioid withdrawal-induced hyperalgesia. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Remifentanil-induced tolerance, withdrawal or hyperalgesia in infants: a randomized controlled trial. RAPIP trial: remifentanil-based analgesia and sedation of paediatric intensive care patients.

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Welzing, Lars; Link, Florian; Junghaenel, Shino; Oberthuer, Andre; Harnischmacher, Urs; Stuetzer, Hartmut; Roth, Bernhard

2013-01-01

Short-acting opioids like remifentanil are suspected of an increased risk for tolerance, withdrawal and opioid-induced hyperalgesia (OIH). These potential adverse effects have never been investigated in neonates. To compare remifentanil and fentanyl concerning the incidence of tolerance, withdrawal and OIH. 23 mechanically ventilated infants received up to 96 h either a remifentanil- or fentanyl-based analgesia and sedation regimen with low-dose midazolam. We compared the required opioid doses and the number of opioid dose adjustments. Following extubation, withdrawal symptoms were assessed by a modification of the Finnegan score. OIH was evaluated by the CHIPPS scale and by testing the threshold of the flexion withdrawal reflex with calibrated von Frey filaments. Remifentanil had to be increased by 24% and fentanyl by 47% to keep the infants adequately sedated during mechanical ventilation. Following extubation, infants revealed no pronounced opioid withdrawal and low average Finnegan scores in both groups. Only 1 infant of the fentanyl group and 1 infant of the remifentanil group required methadone for treatment of withdrawal symptoms. Infants also revealed no signs of OIH and low CHIPPS scores in both groups. The median threshold of the flexion withdrawal reflex was 4.5 g (IQR = 2.3) in the fentanyl group and 2.7 g (IQR = 3.3) in the remifentanil group (p = 0.312), which is within the physiologic range of healthy infants. Remifentanil does not seem to be associated with an increased risk for tolerance, withdrawal or OIH. Copyright © 2013 S. Karger AG, Basel.

Opioid withdrawal syndrome: emerging concepts and novel therapeutic targets.

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Rehni, Ashish K; Jaggi, Amteshwar S; Singh, Nirmal

2013-02-01

Opioid withdrawal syndrome is a debilitating manifestation of opioid dependence and responds poorly to the available clinical therapies. Studies from various in vivo and in vitro animal models of opioid withdrawal syndrome have led to understanding of its pathobiology which includes complex interrelated pathways leading to adenylyl cyclase superactivation based central excitation. Advancements in the elucidation of opioid withdrawal syndrome mechanisms have revealed a number of key targets that have been hypothesized to modulate clinical status. The present review discusses the neurobiology of opioid withdrawal syndrome and its therapeutic target recptors like calcitonin gene related peptide receptors (CGRP), N-methyl-D-aspartate (NMDA) receptors, gamma aminobutyric acid receptors (GABA), G-proteingated inwardly rectifying potassium (GIRK) channels and calcium channels. The present review further details the potential role of second messengers like calcium (Ca2+) / calmodulin-dependent protein kinase (CaMKII), nitric oxide synthase, cytokines, arachidonic acid metabolites, corticotropin releasing factor, fos and src kinases in causing opioid withdrawal syndrome. The exploitation of these targets may provide effective therapeutic agents for the management of opioid dependence-induced abstinence syndrome.

Three suspected cases of sugammadex-induced anaphylactic shock.

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Takazawa, Tomonori; Tomita, Yukinari; Yoshida, Nagahide; Tomioka, Akihiro; Horiuchi, Tatsuo; Nagata, Chie; Orihara, Masaki; Yamada, Makiko Hardy; Saito, Shigeru

2014-01-01

Sugammadex has a unique mechanism of action and is widely used because of its safety and efficacy. A few recent reports have described allergic reactions to clinical doses of sugammadex. We hereby describe another series of cases of possible anaphylaxis to sugammadex. We present three suspected cases of sugammadex-induced anaphylactic shock, including a 13-year-old boy who underwent laparoscopic appendectomy, a 75-year-old woman who underwent left knee arthroplasty, and a 34-year-old man who underwent left pansinectomy for sinobronchitis. All three patients received general anesthesia with rocuronium and their tracheas were intubated. Shortly after injection of sugammadex for reversal of rocuronium, all of them experienced a decrease in blood pressure along with mucocutaneous erythema. In the most severe case, reintubation after extubation was required due to difficulty in manual ventilation. All patients recovered with anti-allergic therapy. On later investigation, all three patients had a positive skin reaction to sugammadex. Our results suggest that physicians using sugammadex should be aware of the possibility of sugammadex-induced anaphylaxis.

Sex differences in effects of dopamine D1 receptors on social withdrawal.

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Campi, Katharine L; Greenberg, Gian D; Kapoor, Amita; Ziegler, Toni E; Trainor, Brian C

2014-02-01

Dopamine signaling in the nucleus accumbens (NAc) plays a critical role in the regulation of motivational states. Recent studies in male rodents show that social defeat stress increases the activity of ventral tegmental dopamine neurons projecting to the NAc, and that this increased activity is necessary for stress-induced social withdrawal. Domestic female mice are not similarly aggressive, which has hindered complementary studies in females. Using the monogamous California mouse (Peromyscus californicus), we found that social defeat increased total dopamine, DOPAC, and HVA content in the NAc in both males and females. These results are generally consistent with previous studies in Mus, and suggest defeat stress also increases NAc dopamine signaling in females. However, these results do not explain our previous observations that defeat stress induces social withdrawal in female but not male California mice. Pharmacological manipulations provided more insights. When 500 ng of the D1 agonist SKF38393 was infused in the NAc shell of females that were naïve to defeat, social interaction behavior was reduced. This same dose of SKF38393 had no effect in males, suggesting that D1 receptor activation is sufficient to induce social withdrawal in females but not males. Intra-accumbens infusion of the D1 antagonist SCH23390 increased social approach behavior in females exposed to defeat but not in females naïve to defeat. This result suggests that D1 receptors are necessary for defeat-induced social withdrawal. Overall, our results suggest that sex differences in molecular pathways that are regulated by D1 receptors contribute to sex differences in social withdrawal behavior. Copyright © 2013 Elsevier Ltd. All rights reserved.

Phenolic Compounds Protect Cultured Hippocampal Neurons against Ethanol-Withdrawal Induced Oxidative Stress

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Marianna E. Jung

2009-04-01

Full Text Available Ethanol withdrawal is linked to elevated oxidative damage to neurons. Here we report our findings on the contribution of phenolic antioxidants (17β-estradiol, p-octyl-phenol and 2,6-di-tert-butyl-4-methylphenol to counterbalance sudden ethanol withdrawal-initiated oxidative events in hippocampus-derived cultured HT-22 cells. We showed that ethanol withdrawal for 4 h after 24-h ethanol treatment provoked greater levels of oxidative damage than the preceding ethanol exposure. Phenolic antioxidant treatment either during ethanol exposure or ethanol withdrawal only, however, dose-dependently reversed cellular oxidative damage, as demonstrated by the significantly enhanced cell viability, reduced malondialdehyde production and protein carbonylation, compared to untreated cells. Interestingly, the antioxidant treatment schedule had no significant impact on the observed neuroprotection. In addition, the efficacy of the three phenolic compounds was practically equipotent in protecting HT-22 cells in spite of predictions based on an in silico study and a cell free assay of lipid peroxidation. This finding implies that free-radical scavenging may not be the sole factor responsible for the observed neuroprotection and warrants further studies to establish, whether the HT-22 line is indeed a suitable model for in vitro screening of antioxidants against EW-related neuronal damage.

Trajectories of abstinence-induced Internet gaming withdrawal symptoms: A prospective pilot study

OpenAIRE

Dean Kaptsis; Daniel L. King; Paul H. Delfabbro; Michael Gradisar

2016-01-01

Internet Gaming Disorder (IGD) is positioned in the appendix of the DSM-5 as a condition requiring further study. The IGD criteria refer to withdrawal symptoms, including irritability, anxiety, or sadness, that follow cessation of Internet gaming (APA, 2013). The aim of this study was to prospectively examine the nature of Internet gaming withdrawal symptoms, if they occur, under gaming abstinence conditions. This study employed a repeated-measures protocol to examine the cognitive-affective ...

Heavy Alcohol Consumption Effects on Blood Pressure and on Kidney Structure Persist After Long-Term Withdrawal

Directory of Open Access Journals (Sweden)

Sandra Leal

2017-11-01

Full Text Available Background/Aims: Heavy ethanol consumption is a risk factor for hypertension and prompts organ damage. There is no information regarding the impact of long-term heavy ethanol consumption on kidney structure and function linking to their hypertensive effects nor the repercussions after withdrawal. Methods: Rats were exposed to ethanol for 24 weeks and, afterwards, a group was assigned to withdrawal for 8 weeks. Blood pressure (BP was measured and serum biochemical parameters were quantified. Glomerular volume density, areal density of glomerular tuft and renal corpuscles were determined. Angiotensin II type 1 receptor (AT1R protein expression was evaluated. Results: Twenty-four weeks of ethanol consumption causes atrophy of renal corpuscles and glomeruli and reduces the volume of glomeruli. Glomerular changes induced by ethanol consumption were still evident after withdrawal. Renal AT1R levels were increased in ethanol-treated rats and returned to control levels during withdrawal. Ethanol consumption also induced an increase in BP, uric acid and albumin levels. Upon withdrawal, systolic and mean arterial pressures decreased, but were still higher than in controls rats. Conclusion: Ethanol consumption induces changes in glomerular morphology associated with increased BP and AT1R expression. Long-term withdrawal was inefficient to restore the structural integrity of renal corpuscles and in lowering systolic pressure.

Administration of memantine during ethanol withdrawal in neonatal rats: effects on long-term ethanol-induced motor incoordination and cerebellar Purkinje cell loss.

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Idrus, Nirelia M; McGough, Nancy N H; Riley, Edward P; Thomas, Jennifer D

2011-02-01

Alcohol consumption during pregnancy can damage the developing fetus, illustrated by central nervous system dysfunction and deficits in motor and cognitive abilities. Binge drinking has been associated with an increased risk of fetal alcohol spectrum disorders, likely due to increased episodes of ethanol withdrawal. We hypothesized that overactivity of the N-methyl-D-aspartate (NMDA) receptor during ethanol withdrawal leads to excitotoxic cell death in the developing brain. Consistent with this, administration of NMDA receptor antagonists (e.g., MK-801) during withdrawal can attenuate ethanol's teratogenic effects. The aim of this study was to determine whether administration of memantine, an NMDA receptor antagonist, during ethanol withdrawal could effectively attenuate ethanol-related deficits, without the adverse side effects associated with other NMDA receptor antagonists. Sprague-Dawley pups were exposed to 6.0 g/kg ethanol or isocaloric maltose solution via intubation on postnatal day 6, a period of brain development equivalent to a portion of the 3rd trimester. Twenty-four and 36 hours after ethanol, subjects were injected with 0, 10, or 15 mg/kg memantine, totaling doses of 0, 20, or 30 mg/kg. Motor coordination was tested on a parallel bar task and the total number of cerebellar Purkinje cells was estimated using unbiased stereology. Alcohol exposure induced significant parallel bar motor incoordination and reduced Purkinje cell number. Memantine administration significantly attenuated both ethanol-associated motor deficits and cerebellar cell loss in a dose-dependent manner. Memantine was neuroprotective when administered during ethanol withdrawal. These data provide further support that ethanol withdrawal contributes to fetal alcohol spectrum disorders. Copyright © 2010 by the Research Society on Alcoholism.

Low efficacy of non-opioid drugs in opioid withdrawal symptoms.

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Hermann, Derik; Klages, Eckard; Welzel, Helga; Mann, Karl; Croissant, Bernhard

2005-06-01

Opioid withdrawal, stress or cues associated with opioid consumption can induce opioid craving. If opioids are not available, opioid-dependent patients usually search for alternative drugs. Because several non-opioid drugs stimulate the endogenous opioidergic system, this concept may explain their frequent use by opioid-dependent patients. We hypothesized that non-opioid drugs alleviate opioid withdrawal symptoms and are therefore consumed by opioid addicts. We asked 89 opioid-dependent patients participating in an out-patient opioid maintenance program to estimate the potential of several non-opioid drugs in being able to alleviate opioid withdrawal. We applied a five-point Lickert scale (1 = very good reduction of opioid withdrawal; 5 = no reduction of opioid withdrawal). Patients could also indicate a worsening of opioid withdrawal. Values (mean +/- SD) were: for benzodiazepines, 3.2 +/- 1.1; tricyclic antidepressants, 3.6 +/- 1.1; cannabis, 3.6 +/- 1.0; alcohol, 4.1 +/- 1.1; cocaine, 4.2 +/- 1.1; amphetamine, 4.4 +/- 0.9; nicotine, 4.7 +/- 0.7; and caffeine, 4.9 +/- 0.5. A worsening of opioid withdrawal was reported by 62% of the patients for cocaine, 62% for amphetamine, 50% for caffeine, 37.5% for cannabis, 27% for nicotine, 26% for alcohol, 8% for tricyclic antidepressants and 3% for benzodiazepines. Our study shows a low efficacy of non-opioid drugs in alleviating opioid withdrawal symptoms. The data basis of this study was good and the sample was suitable to be asked for estimations of drug-drug interactions. Of the patients, 26 - 62% even reported a worsening of opioid withdrawal for cannabis, alcohol, cocaine and amphetamine. Only benzodiazepines and tricyclic antidepressants were reported to have a moderate positive effect on opioid withdrawal.

[An examination of the determinants of social withdrawal and affinity for social withdrawal].

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Watanabe, Asami; Matsui, Yutaka; Takatsuka, Yusuke

2010-12-01

This study examined the determinants of social withdrawal using data from a survey by the Tokyo Metropolitan Government Office for Youth Affairs and Public Safety (2008). In addition, this study identified young people who showed an affinity for social withdrawal although they were not in a state of withdrawal, and examined the determinants of an affinity for social withdrawal. The results of stepwise discriminant analysis showed that factors such as social phobia, depression, violence, and emotional bonds with family differentiated between the general youth group and the social withdrawal group and the "affinity group". Social phobia, violence, and refusal to be interfered in self-decision making differentiated between the social withdrawal group and the "affinity group". This study shows that an "affinity group" should be cared as well as an actual withdrawal group.

Pseudopheochromocytoma induced by anxiolytic withdrawal.

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Páll, Alida; Becs, Gergely; Erdei, Annamária; Sira, Lívia; Czifra, Arpád; Barna, Sándor; Kovács, Péter; Páll, Dénes; Pfliegler, György; Paragh, György; Szabó, Zoltán

2014-10-08

Symptomatic paroxysmal hypertension without significantly elevated catecholamine concentrations and with no evidence of an underlying adrenal tumor is known as pseudopheochromocytoma. We describe the case of a female patient with paroxysmal hypertensive crises accompanied by headache, vertigo, tachycardia, nausea and altered mental status. Previously, she was treated for a longer period with alprazolam due to panic disorder. Causes of secondary hypertension were excluded. Neurological triggers (intracranial tumor, cerebral vascular lesions, hemorrhage, and epilepsy) could not be detected. Setting of the diagnosis of pseudopheochromocytoma treatment was initiated with alpha- and beta-blockers resulting in reduced frequency of symptoms. Alprazolam was restarted at a daily dose of 1 mg. The patient's clinical condition improved rapidly and the dosage of alpha- and beta-blockers could be decreased. We conclude that the withdrawal of an anxiolytic therapeutic regimen may generate sympathetic overdrive resulting in life-threatening paroxysmal malignant hypertension and secondary encephalopathy. We emphasize that pseudopheochromocytoma can be diagnosed only after exclusion of the secondary causes of hypertension. We highlight the importance of a psychopharmacological approach to this clinical entity.

Half dose sugammadex combined with neostigmine is non-inferior to full dose sugammadex for reversal of rocuronium-induced deep neuromuscular blockade: a cost-saving strategy.

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Aouad, Marie T; Alfahel, Waseem S; Kaddoum, Roland N; Siddik-Sayyid, Sahar M

2017-04-11

Sugammadex reverses the effect of rocuronium more rapidly and effectively than neostigmine, at all levels of neuromuscular blockade (NMB). However, its cost is prohibitive. The combination of half dose sugammadex with neostigmine would be non-inferior to full dose sugammadex for the reversal of deep NMB. This approach would reduce the cost of sugammadex while preserving its efficacy. Patients were randomly allocated to receive sugammadex 4 mg/kg (Group S) or sugammadex 2 mg/kg with neostigmine 50 μg/kg and glycopyrrolate 10 μg/kg (Group NS) for reversal of rocuronium deep NMB. The primary outcome was the percentage of patients who recovered to 90% Train of Four (TOF) ratio within 5 min. The non-inferiority margin was set at 10%. Twenty eight patients were enrolled in each group. The number of patients who reached 90% TOF ratio within 5 min was 27 out of 28 (96%) in group S versus 25 out of 28 (89%) in group NS by intention-to-treat (difference: 7%, 95% CI of the difference: -9% to 24%). The number of patients who reached 90% TOF ratio within 5 min was 26 out of 26 (100%) in group S versus 23 out of 25 (92%) in group NS by per-protocol (difference: 8%, 95% CI of the difference: -6% to 25%). Sugammadex 2 mg/kg with neostigmine 50 μg/kg was at worst 9% and 6% less effective than sugammadex 4 mg/kg by intention-to-treat and by per-protocol analysis respectively. Hence, the combination is non-inferior to the recommended dose of sugammadex. Clinicaltrials.gov NCT 02375217 , registered on February 11, 2015.

Food withdrawal lowers energy expenditure and induces inactivity in long-chain fatty acid oxidation-deficient mouse models.

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Diekman, Eugene F; van Weeghel, Michel; Wanders, Ronald J A; Visser, Gepke; Houten, Sander M

2014-07-01

Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is an inherited disorder of mitochondrial long-chain fatty acid β-oxidation (FAO). Patients with VLCAD deficiency may present with hypoglycemia, hepatomegaly, cardiomyopathy, and myopathy. Although several mouse models have been developed to aid in the study of the pathogenesis of long-chain FAO defects, the muscular phenotype is underexposed. To address the muscular phenotype, we used a newly developed mouse model on a mixed genetic background with a more severe defect in FAO (LCAD(-/-); VLCAD(+/-)) in addition to a validated mouse model (LCAD(-/-); VLCAD(+/+)) and compared them with wild-type (WT) mice. We found that both mouse models show a 20% reduction in energy expenditure (EE) and a 3-fold decrease in locomotor activity in the unfed state. In addition, we found a 1.7°C drop in body temperature in unfed LCAD(-/-); VLCAD(+/+) mice compared with WT body temperature. We conclude that food withdrawal-induced inactivity, hypothermia, and reduction in EE are novel phenotypes associated with FAO deficiency in mice. Unexpectedly, inactivity was not explained by rhabdomyolysis, but rather reflected the overall reduced capacity of these mice to generate heat. We suggest that mice are partly protected against the negative consequence of an FAO defect.-Diekman, E. F., van Weeghel, M., Wanders, R. J. A., Visser, G., Houten, S. M. Food withdrawal lowers energy expenditure and induces inactivity in long-chain fatty acid oxidation-deficient mouse models. © FASEB.

Treatment for amphetamine withdrawal.

Science.gov (United States)

Shoptaw, Steven J; Kao, Uyen; Heinzerling, Keith; Ling, Walter

2009-04-15

Few studies examined treatments for amphetamine withdrawal, although it is a common problem among amphetamine users. Its symptoms, in particular intense craving, may be a critical factor leading to relapse to amphetamine use. In clinical practice, medications for cocaine withdrawal are commonly used to manage amphetamine withdrawal although the pharmacodynamic and pharmacokinetic properties of these two illicit substances are different. To assess the effectiveness of pharmacological alone or in combination with psychosocial treatment for amphetamine withdrawals on discontinuation rates, global state, withdrawal symptoms, craving, and other outcomes. MEDLINE (1966 - 2008), CINAHL (1982 - 2008), PsycINFO (1806 - 2008), CENTRAL (Cochrane Library 2008 issue 2), references of obtained articles. All randomised controlled and clinical trials evaluating pharmacological and or psychosocial treatments (alone or combined) for people with amphetamine withdrawal symptoms. Two authors evaluated and extracted data independently. The data were extracted from intention-to-treat analyses. The Relative Risk (RR) with the 95% confidence interval (95% CI) was used to assess dichotomous outcomes. The Weighted Mean Difference (WMD) with 95% CI was used to assess continuous outcomes. Four randomised controlled trials (involving 125 participants) met the inclusion criteria for the review. Two studies found that amineptine significantly reduced discontinuation rates and improved overall clinical presentation, but did not reduce withdrawal symptoms or craving compared to placebo. The benefits of mirtazapine over placebo for reducing amphetamine withdrawal symptoms were not as clear. One study suggested that mirtazapine may reduce hyperarousal and anxiety symptoms associated with amphetamine withdrawal. A more recent study failed to find any benefit of mirtazapine over placebo on retention or on amphetamine withdrawal symptoms. No medication is effective for treatment of amphetamine

Opiate and opioid withdrawal

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... opiate withdrawal; Oxycontin - opiate withdrawal; Hydrocodone - opiate withdrawal; Detox - opiates; Detoxification - opiates ... facilities set up to help people with detoxification (detox). In a regular hospital, if symptoms are severe. ...

Tobacco withdrawal symptoms mediate motivation to reinstate smoking during abstinence.

Science.gov (United States)

Aguirre, Claudia G; Madrid, Jillian; Leventhal, Adam M

2015-08-01

Withdrawal-based theories of addiction hypothesize that motivation to reinstate drug use following acute abstinence is mediated by withdrawal symptoms. Experimental tests of this hypothesis in the tobacco literature are scant and may be subject to methodological limitations. This study utilized a robust within-subject laboratory experimental design to investigate the extent to which composite tobacco withdrawal symptomatology level and 3 unique withdrawal components (i.e., low positive affect, negative affect, and urge to smoke) mediated the effect of smoking abstinence on motivation to reinstate smoking. Smokers (≥10 cigarettes per day; N = 286) attended 2 counterbalanced sessions at which abstinence duration was differentially manipulated (1 hr vs. 17 hr). At both sessions, participants reported current withdrawal symptoms and subsequently completed a task in which they were monetarily rewarded proportional to the length of time they delayed initiating smoking, with shorter latency reflecting stronger motivation to reinstate smoking. Abstinence reduced latency to smoking initiation and positive affect and increased composite withdrawal symptom level, urge, and negative affect. Abstinence-induced reductions in latency to initiating smoking were mediated by each withdrawal component, with stronger effects operating through urge. Combined analyses suggested that urge, negative affect, and low positive affect operate through empirically unique mediational pathways. Secondary analyses suggested similar effects on smoking quantity, few differences among specific urge and affect subtypes, and that dependence amplifies some abstinence effects. This study provides the first experimental evidence that within-person variation in abstinence impacts motivation to reinstate drug use through withdrawal. Urge, negative affect, and low positive affect may reflect unique withdrawal-mediated mechanisms underlying tobacco addiction. (c) 2015 APA, all rights reserved).

Palonosetron and hydroxyzine pre-treatment reduces the objective signs of experimentally-induced acute opioid withdrawal in humans: a double-blinded, randomized, placebo-controlled crossover study.

Science.gov (United States)

Erlendson, Matthew J; D'Arcy, Nicole; Encisco, Ellen M; Yu, Jeffrey J; Rincon-Cruz, Lorena; Peltz, Gary; Clark, J David; Chu, Larry F

2017-01-01

Treatments for reducing opioid withdrawal are limited and prone to problematic side effects. Laboratory studies, clinical observations, and limited human trial data suggest 5-HT3-receptor antagonists and antihistamines may be effective. This double-blind, crossover, placebo-controlled study employing an acute physical dependence model evaluated whether (i) treatment with a 5-HT3-receptor antagonist (palonosetron) would reduce opioid withdrawal symptoms, and (ii) co-administration of an antihistamine (hydroxyzine) would enhance any treatment effect. At timepoint T = 0, healthy (non-opioid dependent, non-substance abuser) male volunteers (N = 10) were pre-treated with either a) placebo, b) palonosetron IV (0.75 mg), or c) palonosetron IV (0.75 mg) and hydroxyzine PO (100 mg) in a crossover study design. This was followed at T = 30 by intravenous morphine (10 mg/70kg). At T = 165, 10 mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T = 170, 180, respectively). Baseline measurements were recorded at T = -30 and T = -15. Comparison of average baseline OOWS scores with OOWS scores obtained 15 minutes after naloxone was significant (p = 0.0001). Scores from 15 minutes post-naloxone infusion showed significant differences in OOWS scores between treatment groups: placebo, 3.7 ± 2.4; palonosetron, 1.5 ± 0.97; and palonosetron with hydroxyzine, 0.2 ± 0.1333. Pretreatment with palonosetron significantly reduced many signs of experimentally-induced opioid withdrawal. Co-administration with hydroxyzine further reduced opioid withdrawal severity. These results suggest that 5-HT3 receptor antagonists, alone or in combination with an antihistamine, may be useful in the treatment of opioid withdrawal.

Sex differences in stress-induced social withdrawal: role of brain derived neurotrophic factor in the bed nucleus of the stria terminalis.

Science.gov (United States)

Greenberg, Gian D; Laman-Maharg, Abigail; Campi, Katharine L; Voigt, Heather; Orr, Veronica N; Schaal, Leslie; Trainor, Brian C

2013-01-01

Depression and anxiety disorders are more common in women than men, and little is known about the neurobiological mechanisms that contribute to this disparity. Recent data suggest that stress-induced changes in neurotrophins have opposing effects on behavior by acting in different brain networks. Social defeat has been an important approach for understanding neurotrophin action, but low female aggression levels in rats and mice have limited the application of these methods primarily to males. We examined the effects of social defeat in monogamous California mice (Peromyscus californicus), a species in which both males and females defend territories. We demonstrate that defeat stress increases mature brain-derived neurotrophic factor (BDNF) protein but not mRNA in the bed nucleus of the stria terminalis (BNST) in females but not males. Changes in BDNF protein were limited to anterior subregions of the BNST, and there were no changes in the adjacent nucleus accumbens (NAc). The effects of defeat on social withdrawal behavior and BDNF were reversed by chronic, low doses of the antidepressant sertraline. However, higher doses of sertraline restored social withdrawal and elevated BDNF levels. Acute treatment with a low dose of sertraline failed to reverse the effects of defeat. Infusions of the selective tyrosine-related kinase B receptor (TrkB) antagonist ANA-12 into the anterior BNST specifically increased social interaction in stressed females but had no effect on behavior in females naïve to defeat. These results suggest that stress-induced increases in BDNF in the anterior BNST contribute to the exaggerated social withdrawal phenotype observed in females.

Rocuronium blockade reversal with sugammadex vs. neostigmine

DEFF Research Database (Denmark)

Wu, Xinmin; Oerding, Helle; Liu, Jin

2014-01-01

BACKGROUND: This study compared efficacy and safety of the selective relaxant binding agent sugammadex (2 mg/kg) with neostigmine (50 μg/kg) for neuromuscular blockade (NMB) reversal in Chinese and Caucasian subjects. METHODS: This was a randomized, active-controlled, multicenter, safety-assessor......BACKGROUND: This study compared efficacy and safety of the selective relaxant binding agent sugammadex (2 mg/kg) with neostigmine (50 μg/kg) for neuromuscular blockade (NMB) reversal in Chinese and Caucasian subjects. METHODS: This was a randomized, active-controlled, multicenter, safety...... twitch reappearance, after last rocuronium dose, subjects received sugammadex 2 mg/kg or neostigmine 50 μg/kg plus atropine 10-20 μg/kg, according to randomization. Primary efficacy variable was time from sugammadex/neostigmine to recovery of the train-of-four (TOF) ratio to 0.9. RESULTS: Overall, 230...... Chinese subjects (sugammadex, n = 119, neostigmine, n = 111); and 59 Caucasian subjects (sugammadex, n = 29, neostigmine, n = 30) had evaluable data. Geometric mean (95% CI) time to recovery to TOF ratio 0.9 was 1.6 (1.5-1.7) min with sugammadex vs 9.1 (8.0-10.3) min with neostigmine in Chinese subjects...

Evaluation of Ashwagandha in alcohol withdrawal syndrome

Directory of Open Access Journals (Sweden)

Ruby B

2012-10-01

Full Text Available Objective: To evaluate the effect of Ashwagandha (ASW in attenuation of alcohol withdrawal in ethanol withdrawal mice model. Methods: Alcohol dependence was induced in mice by the oral, once-daily administration of 10% v/v ethanol (2 g/kg for one week. Once the animals were withdrawn from alcohol, the efficacy of ASW (200mg/kg and 500mg/kg in comparison with diazepam (1 mg/kg in the attenuation of withdrawal was studied using, pentylenetetrazole (PTZ kindling test for seizure threshold, forced swim test (FST for depression and locomotor activity (LCA in open field test (OFT. 6 hours after the last ethanol administration, seizure threshold was measured in all the groups by administering the convulsant drug, PTZ with a subconvulsive dose of 30 mg/kg i.p. In FST, mice were forced to swim and the total duration of immobility (seconds was measured during the last 4 min of a single 6-min test session. In OFT, number of crossings of the lines marked on the floor was recorded for a period of 5 min. Results: Compared to ethanol group, ASW (500 mg/Kg has suppressed the PTZ kindling seizures in ethanol withdrawal animals [0% convulsion], FST has shown decreased immobility time and OFT has exhibited increase in the number of line crossing activity by mice which may be the consequence of anxiolytic activity of ASW similar to that of diazepam. Conclusions: The present study provides satisfactory evidence to use ASW as a safe and reliable alternative to diazepam in alcohol withdrawal conditions.

Reduction of opioid withdrawal and potentiation of acute opioid analgesia by systemic AV411 (ibudilast).

Science.gov (United States)

Hutchinson, Mark R; Lewis, Susannah S; Coats, Benjamen D; Skyba, David A; Crysdale, Nicole Y; Berkelhammer, Debra L; Brzeski, Anita; Northcutt, Alexis; Vietz, Christine M; Judd, Charles M; Maier, Steven F; Watkins, Linda R; Johnson, Kirk W

2009-02-01

Morphine-induced glial proinflammatory responses have been documented to contribute to tolerance to opioid analgesia. Here, we examined whether drugs previously shown to suppress glial proinflammatory responses can alter other clinically relevant opioid effects; namely, withdrawal or acute analgesia. AV411 (ibudilast) and minocycline, drugs with distinct mechanisms of action that result in attenuation of glial proinflammatory responses, each reduced naloxone-precipitated withdrawal. Analysis of brain nuclei associated with opioid withdrawal revealed that morphine altered expression of glial activation markers, cytokines, chemokines, and a neurotrophic factor. AV411 attenuated many of these morphine-induced effects. AV411 also protected against spontaneous withdrawal-induced hyperactivity and weight loss recorded across a 12-day timecourse. Notably, in the spontaneous withdrawal study, AV411 treatment was delayed relative to the start of the morphine regimen so to also test whether AV411 could still be effective in the face of established morphine dependence, which it was. AV411 did not simply attenuate all opioid effects, as co-administering AV411 with morphine or oxycodone caused three-to-five-fold increases in acute analgesic potency, as revealed by leftward shifts in the analgesic dose response curves. Timecourse analyses revealed that plasma morphine levels were not altered by AV411, suggestive that potentiated analgesia was not simply due to prolongation of morphine exposure or increased plasma concentrations. These data support and extend similar potentiation of acute opioid analgesia by minocycline, again providing converging lines of evidence of glial involvement. Hence, suppression of glial proinflammatory responses can significantly reduce opioid withdrawal, while improving analgesia.

Chronic agmatine treatment prevents behavioral manifestations of nicotine withdrawal in mice.

Science.gov (United States)

Kotagale, Nandkishor R; Chopde, Chandrabhan T; Umekar, Milind J; Taksande, Brijesh G

2015-05-05

Smoking cessation exhibits an aversive withdrawal syndrome characterized by both increases in somatic signs and affective behaviors including anxiety and depression. In present study, abrupt withdrawal of daily nicotine injections (2mg/kg, s.c., four times daily, for 10 days) significantly increased somatic signs viz. rearing, grooming, jumping, genital licking, leg licking, head shakes with associated depression (increased immobility in forced swim test) as well as anxiety (decreased the number of entries and time spent in open arm in elevated plus maze) in nicotine dependent animals. The peak effect was observed at 24h time point of nicotine withdrawal. Repeated administration of agmatine (40-80µg/mouse, i.c.v.) before the first daily dose of nicotine from day 5 to 10 attenuated the elevated scores of somatic signs and abolished the depression and anxiety like behavior induced by nicotine withdrawal in dependent animals. However, in separate groups, its acute administration 30min before behavior analysis of nicotine withdrawal was ineffective. This result clearly shows the role of agmatine in development of nicotine dependence and its withdrawal. In extension to behavioral experiments, brain agmatine analyses, carried out at 24h time point of nicotine withdrawal demonstrated marked decrease in basal brain agmatine concentration as compared to control animals. Taken together, these data support the role of agmatine as common biological substrate for somatic signs and affective symptoms of nicotine withdrawal. This data may project therapies based on agmatine in anxiety, depression and mood changes associated with tobacco withdrawal. Copyright © 2015 Elsevier B.V. All rights reserved.

Sugammadex versus two doses of neostigmine for reversal of rocuronium in gastric sleeve surgery

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Abdulhamid Alsaeed

2017-01-01

Patients and Methods: A total of 110 patients with body mass index> 40 underwent elective gastric sleeve surgery were enrolled in this study. Exclusion criteria included patients with co-existing muscular and cardiovascular diseases. Patients were randomly allocated to one of the following groups: group A (SUG, Group B (NEO 2.5 mg, and Group C (NEO 5 mg. General anesthesia was induced in the three groups using propofol 2.0 mg/kg of corrected body weight (CBW and fentanyl 3 mcg/kg of CBW. Anesthesia was maintained with O2/air/desflurane 1 minimum alveolar concentration. Remifentanil infusion started at 0.05–0.2 mcg/kg/min. Tracheal intubation was facilitated with rocuronium 1.2 mg/kg of CBW guided with PNS. When the train of four (TOF reached zero, intubation was performed using a GlideScope. At the end of surgery, TOF ratio and posttetanic counts were recorded. SUG 2 mg/kg of CBW (Group A, NEO 2.5 mg (Group B, and NEO 5 mg (Group C were administered according to the random envelope. The time to achieve 90% of TOF was recorded in seconds using a timer. ANOVA for repeated measurements was used for statistical analyses. P 90%, the recovery pattern of both was similar.

Depression of home cage wheel running is an objective measure of spontaneous morphine withdrawal in rats with and without persistent pain

Science.gov (United States)

Kandasamy, Ram; Lee, Andrea T.; Morgan, Michael M.

2017-01-01

Opioid withdrawal in humans is often subtle and almost always spontaneous. In contrast, most preclinical studies precipitate withdrawal by administration of an opioid receptor antagonist such as naloxone. These animal studies rely on measurement of physiological symptoms (e.g., wet dog shakes) in the period immediately following naloxone administration. To more closely model the human condition, we tested the hypothesis that depression of home cage wheel running will provide an objective method to measure the magnitude and duration of spontaneous morphine withdrawal. Rats were allowed access to a running wheel in their home cage for 8 days prior to implantation of two 75 mg morphine or placebo pellets. The pellets were removed 3 or 5 days later to induce spontaneous withdrawal. In normal pain-free rats, removal of the morphine pellets depressed wheel running for 48 hours compared to rats that had placebo pellets removed. Morphine withdrawal-induced depression of wheel running was greatly enhanced in rats with persistent inflammatory pain induced by injection of Complete Freund’s Adjuvant (CFA) into the hindpaw. Removal of the morphine pellets following 3 days of treatment depressed wheel running in these rats for over 6 days. These data demonstrate that home cage wheel running provides an objective and more clinically relevant method to assess spontaneous morphine withdrawal compared to precipitated withdrawal in laboratory rats. Moreover, the enhanced withdrawal in rats with persistent inflammatory pain suggests that pain patients may be especially susceptible to opioid withdrawal. PMID:28366799

Title: Sex differences in stress-induced social withdrawal: role of brain derived neurotrophic factor in the bed nucleus of the stria terminalis

Directory of Open Access Journals (Sweden)

Gian David Greenberg

2014-01-01

Full Text Available Depression and anxiety disorders are more common in women than men, and little is known about the neurobiological mechanisms that contribute to this disparity. Recent data suggest that stress-induced changes in neurotrophins have opposing effects on behavior by acting in different brain networks. Social defeat has been an important approach for understanding neurotrophin action, but low female aggression levels in rats and mice have limited the application of these methods primarily to males. We examined the effects of social defeat in monogamous California mice (Peromyscus californicus, a species in which both males and females defend territories. We demonstrate that defeat stress increases mature brain-derived neurotrophic factor (BDNF protein but not mRNA in the bed nucleus of the stria terminalis (BNST in females but not males. Changes in BDNF protein were limited to anterior subregions of the BNST, and there were no changes in the adjacent nucleus accumbens (NAc. The effects of defeat on social withdrawal behavior and BDNF were reversed by chronic, low doses of the antidepressant sertraline. However, higher doses of sertraline restored social withdrawal and elevated BDNF levels. Acute treatment with a low dose of sertraline failed to reverse the effects of defeat. Infusions of the selective tyrosine-related kinase B receptor (TrkB antagonist ANA-12 into the anterior BNST specifically increased social interaction in stressed females but had no effect on behavior in females naïve to defeat. These results suggest that stress-induced increases in BDNF in the anterior BNST contribute to the exaggerated social withdrawal phenotype observed in females.

A Case Report of Severe Delirium after Amantadine Withdrawal

Directory of Open Access Journals (Sweden)

Franz Marxreiter

2017-03-01

Full Text Available Amantadine is frequently used in addition to dopaminergic substances like dopamine agonists or L-Dopa in advanced Parkinson disease (PD. However, adverse effects like hallucinations limit its use. PD patients developing severe psychotic symptoms upon treatment with either dopaminergic substances and/or amantadine need to stop intake of any psychotropic substance. Here, we report the case of a 71-year-old PD patient without previously known cognitive impairment. He presented with drug-induced psychotic symptoms due to changes in his therapeutic regimen (increase in COMT inhibitors, newly introduced MAO B inhibitors. Also, amantadine had been part of his long-term medication for more than 2 years. The severity of his psychotic symptoms required a L-Dopa monotherapy. After changing his medication, the patient developed severe delirium that resolved rapidly after i.v. amantadine infusion, suggesting an amantadine withdrawal syndrome. Amantadine withdrawal syndrome is a rare adverse event that may present even in PD patients without cognitive impairment. This case report highlights the need for a gradual withdrawal of amantadine even if acute and severe psychotic symptoms are present. Moreover, this is the first report of a cognitively unimpaired patient developing an amantadine withdrawal syndrome.

Intubating conditions and side effects of propofol, remifentanil and sevoflurane compared with propofol, remifentanil and rocuronium: a randomised, prospective, clinical trial

Science.gov (United States)

2014-01-01

Background Tracheal intubation without muscle relaxants is usually performed with remifentanil and propofol or sevoflurane. Remifentanil 1.0 to 4.0 μg·kg-1 and propofol 2.0-3.0 mg·kg-1 or sevoflurane up to 8.0 Vol% provide acceptable, i.e. excellent or good intubating conditions. We hypothesized that sevoflurane 1.0 MAC would provide acceptable intubating conditions when combined with propofol and remifentanil. Methods Eighty-three patients to be intubated were randomised to two groups. The SEVO group received propofol 1.5 mg kg-1, remifentanil 0.30 μg kg min-1 and sevoflurane 1.0 MAC; the MR group received the same doses of propofol and remifentanil plus rocuronium 0.45 mg kg-1. We evaluated intubation and extubation conditions, mean arterial pressure (MAP), heart rate (HR) and bispectral index (BIS). The vocal cords were examined for injury by videolaryngoscopy before and 24 hours after surgery. Results Acceptable intubating conditions were seen more frequently with rocuronium than with sevoflurane: 97% versus 82%; p = 0.03; the subscore for vocal cords was comparable: 100% versus 98%. MAP before intubation decreased significantly compared with the MAP at baseline to the same extent in both groups; ephedrine IV was given in 15 (SEVO) versus 16 (MR) patients; p = 0.93. BIS at tracheal intubation was 27 (13-65) in the SEVO group, 29 (14-62) in the MR group; p = 0.07. Vocal cord injuries (oedema, haematoma) were similar: 4 patients in each group. Conclusions Overall intubating conditions were better when rocuronium was used; the subscore for vocal cords was comparable. The incidence of side effects was the same in the two groups. Trial registration ClinicalTrials.Gov: NCT 01591031. PMID:24860256

In vivo and in vitro attenuation of naloxone-precipitated experimental opioid withdrawal syndrome by insulin and selective KATP channel modulator.

Science.gov (United States)

Singh, Prabhat; Sharma, Bhupesh; Gupta, Surbhi; Sharma, B M

2015-01-01

Opiate exposure for longer duration develops state of dependence in humans and animals, which is revealed by signs and symptoms of withdrawal precipitated by opioid receptor antagonists. The sudden withdrawal of opioids produces a withdrawal syndrome in opioid-dependent subjects. Insulin and ATP-sensitive potassium (KATP) channel-mediated glucose homeostasis have been shown to modulate morphine withdrawal. Present study has been structured to investigate the role of insulin and pharmacological modulator of KATP channel (gliclazide) in experimental morphine withdrawal syndrome, both invivo and invitro. In this study, naloxone-precipitated morphine withdrawal syndrome in mice (invivo) as well as in rat ileum (invitro) were utilized to assess opioid withdrawal phenomenon. Morphine withdrawal syndromes like jumping and rearing frequency, forepaw licking, circling, fore paw tremor, wet dog shake, sneezing, overall morphine withdrawal severity (OMWS), serum glucose, brain malondialdehyde (MDA), glutathione (GSH), nitrite/nitrate, and calcium (Ca(+2)) were assessed. Naloxone has significantly increased morphine withdrawal syndrome, both invivo and invitro. Insulin and gliclazide have significantly attenuated, naloxone induced behavioral changes like jumping and rearing frequency, forepaw licking, wet dog shake, sneezing, straightening, circling, OMWS, and various biochemical impairments such as serum glucose, brain MDA, GSH, nitrite/nitrate, and Ca(+2) in morphine-dependent animals (invivo). In vitro, insulin and gliclazide have significantly reduced naloxone-induced contraction in morphine-withdrawn rat ileum preparation. Insulin and gliclazide (KATP channel blocker) have attenuated naloxone-precipitated morphine withdrawal syndrome, both invivo and invitro. Thus, insulin and KATP channel modulation may provide new avenues for research in morphine withdrawal.

Withdrawal: Expanding a Key Addiction Construct.

Science.gov (United States)

Piper, Megan E

2015-12-01

Withdrawal is an essential component of classical addiction theory; it is a vital manifestation of dependence and motivates relapse. However, the traditional conceptualization of withdrawal as a cohesive collection of symptoms that emerge during drug deprivation and decline with either the passage of time or reinstatement of drug use, may be inadequate to explain scientific findings or fit with modern theories of addiction. This article expands the current understanding of tobacco withdrawal by examining: (1) withdrawal variability; (2) underlying causes of withdrawal variability, including biological and person factors, environmental influences, and the influence of highly routinized behavioral patterns; (3) new withdrawal symptoms that allow for enhanced characterization of the withdrawal experience; and (4) withdrawal-related cognitive processes. These topics provide guidance regarding the optimal assessment of withdrawal and illustrate the potential impact modern withdrawal conceptualization and assessment could have on identifying treatment targets. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Anterior Cingulate Cortex Contributes to Alcohol Withdrawal- Induced and Socially Transferred Hyperalgesia.

Science.gov (United States)

Smith, Monique L; Walcott, Andre T; Heinricher, Mary M; Ryabinin, Andrey E

2017-01-01

Pain is often described as a "biopsychosocial" process, yet social influences on pain and underlying neural mechanisms are only now receiving significant experimental attention. Expression of pain by one individual can be communicated to nearby individuals by auditory, visual, and olfactory cues. Conversely, the perception of another's pain can lead to physiological and behavioral changes in the observer, which can include induction of hyperalgesia in "bystanders" exposed to "primary" conspecifics in which hyperalgesia has been induced directly. The current studies were designed to investigate the neural mechanisms responsible for the social transfer of hyperalgesia in bystander mice housed and tested with primary mice in which hyperalgesia was induced using withdrawal (WD) from voluntary alcohol consumption. Male C57BL/6J mice undergoing WD from a two-bottle choice voluntary alcohol-drinking procedure served as the primary mice. Mice housed in the same room served as bystanders. Naïve, water-drinking controls were housed in a separate room. Immunohistochemical mapping identified significantly enhanced Fos immunoreactivity (Fos-ir) in the anterior cingulate cortex (ACC) and insula (INS) of bystander mice compared to naïve controls, and in the dorsal medial hypothalamus (DMH) of primary mice. Chemogenetic inactivation of the ACC but not primary somatosensory cortex reversed the expression of hyperalgesia in both primary and bystander mice. These studies point to an overlapping neural substrate for expression of socially transferred hyperalgesia and that expressed during alcohol WD.

Time-dependent negative reinforcement of ethanol intake by alleviation of acute withdrawal.

Science.gov (United States)

Cunningham, Christopher L; Fidler, Tara L; Murphy, Kevin V; Mulgrew, Jennifer A; Smitasin, Phoebe J

2013-02-01

Drinking to alleviate the symptoms of acute withdrawal is included in diagnostic criteria for alcoholism, but the contribution of acute withdrawal relief to high alcohol intake has been difficult to model in animals. Ethanol dependence was induced by passive intragastric ethanol infusions in C57BL/6J (B6) and DBA/2J (D2) mice; nondependent control animals received water infusions. Mice were then allowed to self-administer ethanol or water intragastrically. The time course of acute withdrawal was similar to that produced by chronic ethanol vapor exposure in mice, reaching a peak at 7 to 9 hours and returning to baseline within 24 hours; withdrawal severity was greater in D2 than in B6 mice (experiment 1). Postwithdrawal delays in initial ethanol access (1, 3, or 5 days) reduced the enhancement in later ethanol intake normally seen in D2 (but not B6) mice allowed to self-infuse ethanol during acute withdrawal (experiment 2). The postwithdrawal enhancement of ethanol intake persisted over a 5-day abstinence period in D2 mice (experiment 3). D2 mice allowed to drink ethanol during acute withdrawal drank more ethanol and self-infused more ethanol than nondependent mice (experiment 4). Alcohol access during acute withdrawal increased later alcohol intake in a time-dependent manner, an effect that may be related to a genetic difference in sensitivity to acute withdrawal. This promising model of negative reinforcement encourages additional research on the mechanisms underlying acute withdrawal relief and its role in determining risk for alcoholism. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Neonatal opioid withdrawal syndrome.

Science.gov (United States)

Sutter, Mary Beth; Leeman, Lawrence; Hsi, Andrew

2014-06-01

Neonatal opioid withdrawal syndrome is common due to the current opioid addiction epidemic. Infants born to women covertly abusing prescription opioids may not be identified as at risk until withdrawal signs present. Buprenorphine is a newer treatment for maternal opioid addiction and appears to result in a milder withdrawal syndrome than methadone. Initial treatment is with nonpharmacological measures including decreasing stimuli, however pharmacological treatment is commonly required. Opioid monotherapy is preferred, with phenobarbital or clonidine uncommonly needed as adjunctive therapy. Rooming-in and breastfeeding may decease the severity of withdrawal. Limited evidence is available regarding long-term effects of perinatal opioid exposure. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparison of the effect of rocuronium dosing based on corrected or lean body weight on rapid sequence induction and neuromuscular blockade duration in obese female patients

Science.gov (United States)

Sakızcı-Uyar, Bahar; Çelik, Şeref; Postacı, Aysun; Bayraktar, Yeşim; Dikmen, Bayazit; Özkoçak-Turan, Işıl; Saçan, Özlem

2016-01-01

Objectives: To compare onset time, duration of action, and tracheal intubation conditions in obese patients when the intubation dose of rocuronium was based on corrected body weight (CBW) versus lean body weight (LBW) for rapid sequence induction. Methods: This prospective study was carried out at Numune Education and Research Hospital, Ankara, Turkey between August 2013 and May 2014. Forty female obese patients scheduled for laparoscopic surgery under general anesthesia were randomized into 2 groups. Group CBW (n=20) received 1.2 mg/kg rocuronium based on CBW, and group LBW (n=20) received 1.2 mg/kg rocuronium based on LBW. Endotracheal intubation was performed 60 seconds after injection of muscle relaxant, and intubating conditions were evaluated. Neuromuscular transmission was monitored using acceleromyography of the adductor pollicis. Onset time, defined as time to depression of the twitch tension to 95% of its control value, and duration of action, defined as time to achieve one response to train-of-four stimulation (T1) were recorded. Results: No significant differences were observed between the groups in intubation conditions or onset time (50-60 seconds median, 30-30 interquartile range [IQR]). Duration of action was significantly longer in the CBW group (60 minutes median, 12 IQR) than the LBW group (35 minutes median, 16 IQR; procuronium based on LBW provides excellent or good tracheal intubating conditions within 60 seconds after administration and does not lead to prolonged duration of action. PMID:26739976

Control rod withdrawal monitoring device

International Nuclear Information System (INIS)

Ebisuya, Mitsuo.

1984-01-01

Purpose: To prevent the power ramp even if a plurality of control rods are subjected to withdrawal operation at a time, by reducing the reactivity applied to the reactor. Constitution: The control rod withdrawal monitoring device is adapted to monitor and control the withdrawal of the control rods depending on the reactor power and the monitoring region thereof is divided into a control rod group monitoring region a transition region and a control group monitoring not interfere region. In a case if the distance between a plurality of control rods for which the withdrawal positions are selected is less than a limiting value, the coordinate for the control rods, distance between the control rods and that the control rod distance is shorter are displayed on a display panel, and the withdrawal for the control rods are blocked. Accordingly, even if a plurality of control rods are subjected successively to the withdrawal operation contrary to the control rod withdrawal sequence upon high power operation of the reactor, the power ramp can be prevented. (Kawakami, Y.)

Expression of brain-derived neurotrophic factors, neurotrophin-3, and neurotrophin-4 in the nucleus accumbens during heroin dependency and withdrawal.

Science.gov (United States)

Li, Yixin; Xia, Baijuan; Li, Rongrong; Yin, Dan; Wang, Yanlin; Liang, Wenmei

2017-08-02

Neurotrophins, brain-derived neurotrophic factors (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), have been implicated in the modulation of heroin dependency. This study was designed to explore the expression alterations of BDNF, NT-3, and NT-4 in the context of heroin dependence and withdrawal in the rat nucleus accumbens (NAc). Heroin dependence was induced by a progressive intraperitoneal treatment of heroin. The results showed that the expression levels of BDNF and NT-4 were significantly decreased in the NAc of rats with heroin addiction in comparison with the control group, whereas there was a significant increase in BDNF and NT-4 expressions in the groups of rats with both naloxone-induced and spontaneous withdrawal. Moreover, NT-3 expression was markedly increased in the NAc of rats with heroin addiction and spontaneous withdrawal in comparison with the control group, but decreased in the NAc of rats with naloxone-induced withdrawal. These results indicated that chronic administration of heroin results in the alterations of BDNF, NT-3, and NT-4 expressions in the rat NAc. BDNF, NT-3, and NT-4 may play a critical role in the development of heroin dependency and withdrawal.

Long Withdrawal of Methylphenidate Induces a Differential Response of the Dopaminergic System and Increases Sensitivity to Cocaine in the Prefrontal Cortex of Spontaneously Hypertensive Rats.

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Maurício dos Santos Pereira

Full Text Available Methylphenidate (MPD is one of the most prescribed drugs for alleviating the symptoms of Attention Deficit/Hyperactivity Disorder (ADHD. However, changes in the molecular mechanisms related to MPD withdrawal and susceptibility to consumption of other psychostimulants in normal individuals or individuals with ADHD phenotype are not completely understood. The aims of the present study were: (i to characterize the molecular differences in the prefrontal dopaminergic system of SHR and Wistar strains, (ii to establish the neurochemical consequences of short- (24 hours and long-term (10 days MPD withdrawal after a subchronic treatment (30 days with Ritalin® (Methylphenidate Hydrochloride; 2.5 mg/kg orally, (iii to investigate the dopaminergic synaptic functionality after a cocaine challenge in adult MPD-withdrawn SHR and Wistar rats. Our results indicate that SHR rats present reduced [3H]-Dopamine uptake and cAMP accumulation in the prefrontal cortex (PFC and are not responsive to dopaminergic stimuli in when compared to Wistar rats. After a 24-hour withdrawal of MPD, SHR did not present any alterations in [3H]-Dopamine Uptake, [3H]-SCH 23390 binding and cAMP production; nonetheless, after a 10-day MPD withdrawal, the results showed a significant increase of [3H]-Dopamine uptake, of the quantity of [3H]-SCH 23390 binding sites and of cAMP levels in these animals. Finally, SHR that underwent a 10-day MPD withdrawal and were challenged with cocaine (10 mg/kg i.p. presented reduced [3H]-Dopamine uptake and increased cAMP production. Wistar rats were affected by the 10-day withdrawal of MPD in [3H]-dopamine uptake but not in cAMP accumulation; in addition, cocaine was unable to induce significant modifications in [3H]-dopamine uptake and in cAMP levels after the 10-day withdrawal of MPD. These results indicate a mechanism that could explain the high comorbidity between ADHD adolescent patients under methylphenidate treatment and substance abuse in adult

Geraniin attenuates Naloxone-Precipitated Morphine Withdrawal and Morphine-Induced Tolerance in Mice

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Ella Anle Kasanga

2017-06-01

Conclusion: Geraniin does not produce any tolerant effects like morphine and also reduced the signs associated with naloxone-precipitated morphine withdrawal in mice. [J Complement Med Res 2017; 6(2.000: 199-205

The Effect of Nicotine Administration on Physical and Psychological Signs of Withdrawal Syndrome Induced by Single or Frequent Doses of Morphine in Rats

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Mohammad Allahtavakoli

2012-07-01

Full Text Available Introduction. Morphine addiction and morphine withdrawal syndrome are the two main problems of today’s human society. The present study has investigated the effects of nicotine on the strength of physical and psychological dependency in single and repeated doses morphine administrated rats. Materials and methods. Male Wistar rats were subjected to morphine consumption with single or frequent dose protocols. In the single dose protocol, rats received only one dose of morphine and 24hrs later they also received one dose of nicotine 30 min prior to injection of naloxone. In the repeated dose protocol, rats received incremental doses of morphine for 7 days and 24hr after the last dose (the 8th day were given naloxone. However, the nicotine regimen of this group was injected 15 min before the morphine injection, for 4 days, from the 4th to the 7th day. Five minutes after naloxone injection, each rat′s behavior was captured for 30 min, and then physical and psychological signs of withdrawal syndrome were recorded. Data were analyzed by ANOVA followed by Tukey tests and p<0.05 was considered as significant difference. Findings. Results showed that the injection of frequent and single doses of morphine lead to morphine dependency. In single dose protocol, nicotine consumption attenuated the signs of withdrawal syndrome, especially weight of excrement and total withdrawal score. In frequent dose protocol, in addition to these effects, nicotine induced weight loss and place aversion. Conclusion. The inhibitory effects of nicotine on signs of withdrawal syndrome may involve a dopaminergic portion of the central nervous system and is mediated by central nicotinic receptors. There is also a cross-dependence between nicotine and morphine.

Why glucocorticoid withdrawal may sometimes be as dangerous as the treatment itself

DEFF Research Database (Denmark)

Dinsen, Stina; Baslund, Bo; Klose, Marianne

2013-01-01

Glucocorticoid therapy is widely used, but withdrawal from glucocorticoids comes with a potential life-threatening risk of adrenal insufficiency. Recent case reports document that adrenal crisis after glucocorticoid withdrawal remains a serious problem in clinical practice. Partly due...... to difficulties in inter-study comparison the true prevalence of glucocorticoid-induced adrenal insufficiency is unknown, but it might be somewhere between 46 and 100% 24h after glucocorticoid withdrawal, 26-49% after approximately one week, and some patients show prolonged suppression lasting months to years....... Adrenal insufficiency might therefore be underdiagnosed in clinical practice. Clinical data do not permit accurate estimates of a lower limit of glucocorticoid dose and duration of treatment, where adrenal insufficiency will not occur. Due to individual variation, neither the glucocorticoid dose nor...

Effect of Short-term Forced Exercise on Naloxone Induced Withdrawal Symptoms in Morphine Addicted Male Rats

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KH Saadipour

2008-01-01

Full Text Available ABSTRACT: Introduction & Objective: Opioid dependence has been causing limitation in usage of morphine and other opioid drugs in pain control. The aim of this study was to assess the effect of short-term forced exercise on withdrawal syndrome in morphine addicted male rats. Materials & Methods: This experimental study was done in the physiology research center of Ahwas Jondishapour University of Medical Sciences. Twenty four young male Wistar rats, weighing 200-300gr, were randomly divided into four groups: no addiction and no exercise, no addiction and exercise, addiction and no exercise and addiction and exercise. The exercise groups underwent treadmill forced exercise for ten days. The first five days morphine was administrated (ip twice daily with increasing dose (5، 10، 20، 40, 50 mg/kg to addicted groups. Also single dose (50mg/kg of morphine was administrated to them on the 10th day of exercise. After administration of naloxone hydrochloride the withdrawal symptoms were evaluated for 5 minutes. The findings of this study were analyzed by SPSS software and One- way ANOVA (Tukey test. Results: The findings of this study showed that the withdrawal symptoms was elevated in exercise and addicted groups in comparison with control group (p<0.05 , p<0.01. However, most of withdrawal symptoms decreased in addicted and exercise group in comparison with addicted and no exercise group (p<0.01, p<0.001. Conclusion: The exercise could increase endogenous opioid and withdrawal symptoms in animals but reduce withdrawal symptoms in addicted and exercise groups compared to addicted and no exercise group. Its mechanism might be related to down regulation and low sensitivity of opioid receptors

Conditioned flavor avoidance as a measure of withdrawal in rats chronically exposed to a caffeine solution.

Science.gov (United States)

Dreumont-Boudreau, Sarah E; Dingle, Rachel N; Alcolado, Gillian M; Lolordo, Vincent M

2008-09-03

Rats were given 21 days of chronic oral caffeine. A novel flavor (Maintenance CS) was then paired with the continuation of caffeine, and a second flavor (Withdrawal CS) was paired with caffeine removal. Rats avoided the Withdrawal CS, and drank more of the Maintenance CS in a two-bottle test, suggesting that removing caffeine had induced withdrawal. The value of the Maintenance CS was investigated by comparing it to a novel flavor paired with water (Neutral CS). In a series of two-bottle tests, the Maintenance and Neutral CSs were equivalent when pitted against each other, and both were preferred to the Withdrawal CS. These results demonstrate that conditioned flavor avoidance is a useful procedure in assessing caffeine withdrawal, and by inference dependence, produced by chronic oral consumption.

Phenobarbital influence on neuromuscular block produced by rocuronium in rats Influência do fenobarbital no bloqueio neuromuscular produzido pelo rocurônio em ratos

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Angélica de Fátima de Assunção Braga

2008-08-01

Full Text Available PURPOSE: To evaluate in vitro and in vivo neuromuscular blockade produced by rocuronium in rats treated with Phenobarbital and to determine cytochrome P450 and cytochrome b5 concentrations in hepatic microsomes. METHODS: Thirty rats were included in the study and distributed into 6 groups of 5 animals each. Rats were treated for seven days with phenobarbital (20 mg/kg and the following parameters were evaluated: 1 the amplitude of muscle response in the preparation of rats exposed to phenobarbital; 2 rocuronium effect on rat preparation exposed or not to phenobarbital; 3 concentrations of cytochrome P450 and cytochrome b5 in hepatic microsomes isolated from rats exposed or not to phenobarbital. The concentration and dose of rocuronium used in vitro and in vivo experiments were 4 µg/mL and 0,6 mg/kg, respectively. RESULTS: Phenobarbital in vitro and in vivo did not alter the amplitude of muscle response. The neuromuscular blockade in vitro produced by rocuronium was significantly different (p=0.019 between exposed (20% and not exposed (60% rats; the blockade in vivo was significantly greater (p=0.0081 in treated rats (93.4%. The enzymatic concentrations were significantly greater in rats exposed to phenobarbital. CONCLUSIONS: Phenobarbital alone did not compromise neuromuscular transmission. It produced enzymatic induction, and neuromuscular blockade in vivo produced by rocuronium was potentiated by phenobarbital.OBJETIVO: Avaliar in vitro e in vivo o bloqueio neuromuscular produzido pelo rocurônio em ratos tratados com fenobarbital e determinar as concentrações de citocromo P450 e b5 em microssomos hepáticos. MÉTODOS: Trinta ratos foram incluídos no estudo e distribuídos em seis grupos de cinco animais cada. Ratos foram tratados por sete dias com fenobarbital (20 mg/kg e avaliou-se: 1 amplitude das respostas musculares em preparação de ratos expostos ao fenobarbital; 2 o efeito do rocurônio em preparações de ratos expostos ou n

Alcohol Withdrawal and Brain Injuries: Beyond Classical Mechanisms

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Marianna E. Jung

2010-07-01

Full Text Available Unmanaged sudden withdrawal from the excessive consumption of alcohol (ethanol adversely alters neuronal integrity in vulnerable brain regions such as the cerebellum, hippocampus, or cortex. In addition to well known hyperexcitatory neurotransmissions, ethanol withdrawal (EW provokes the intense generation of reactive oxygen species (ROS and the activation of stress-responding protein kinases, which are the focus of this review article. EW also inflicts mitochondrial membranes/membrane potential, perturbs redox balance, and suppresses mitochondrial enzymes, all of which impair a fundamental function of mitochondria. Moreover, EW acts as an age-provoking stressor. The vulnerable age to EW stress is not necessarily the oldest age and varies depending upon the target molecule of EW. A major female sex steroid, 17β-estradiol (E2, interferes with the EW-induced alteration of oxidative signaling pathways and thereby protects neurons, mitochondria, and behaviors. The current review attempts to provide integrated information at the levels of oxidative signaling mechanisms by which EW provokes brain injuries and E2 protects against it. Unmanaged sudden withdrawal from the excessive consumption of alcohol (ethanol adversely alters neuronal integrity in vulnerable brain regions such as the cerebellum, hippocampus, or cortex. In addition to well known hyperexcitatory neurotransmissions, ethanol withdrawal (EW provokes the intense generation of reactive oxygen species (ROS and the activation of stress-responding protein kinases, which are the focus of this review article. EW also inflicts mitochondrial membranes/membrane potential, perturbs redox balance, and suppresses mitochondrial enzymes, all of which impair a fundamental function of mitochondria. Moreover, EW acts as an age-provoking stressor. The vulnerable age to EW stress is not necessarily the oldest age and varies depending upon the target molecule of EW. A major female sex steroid, 17�

Withdrawal symptoms in children after long-term administration of sedatives and/or analgesics: A literature review. "Assessment remains troublesome"

NARCIS (Netherlands)

E. Ista (Erwin); M. van Dijk (Monique); C. Gamel (Claudia); D. Tibboel (Dick); M. de Hoog (Matthijs)

2007-01-01

textabstractBackground: Prolonged administration of benzodiazepines and/or opioids to children in a pediatric intensive care unit (PICU) may induce physiological dependence and withdrawal symptoms. Objective: We reviewed the literature for relevant contributions on the nature of these withdrawal

Rocuronium blockade reversal with sugammadex vs. neostigmine: randomized study in Chinese and Caucasian subjects.

Science.gov (United States)

Wu, Xinmin; Oerding, Helle; Liu, Jin; Vanacker, Bernard; Yao, Shanglong; Dahl, Vegard; Xiong, Lize; Claudius, Casper; Yue, Yun; Huang, Yuguang; Abels, Esther; Rietbergen, Henk; Woo, Tiffany

2014-01-01

This study compared efficacy and safety of the selective relaxant binding agent sugammadex (2 mg/kg) with neostigmine (50 μg/kg) for neuromuscular blockade (NMB) reversal in Chinese and Caucasian subjects. This was a randomized, active-controlled, multicenter, safety-assessor-blinded study (NCT00825812) in American Society of Anesthesiologists Class 1-3 subjects undergoing surgery with propofol anesthesia. Rocuronium 0.6 mg/kg was administered for endotracheal intubation, with 0.1-0.2 mg/kg maintenance doses given as required. NMB was monitored using TOF-Watch(®) SX. At second twitch reappearance, after last rocuronium dose, subjects received sugammadex 2 mg/kg or neostigmine 50 μg/kg plus atropine 10-20 μg/kg, according to randomization. Primary efficacy variable was time from sugammadex/neostigmine to recovery of the train-of-four (TOF) ratio to 0.9. Overall, 230 Chinese subjects (sugammadex, n = 119, neostigmine, n = 111); and 59 Caucasian subjects (sugammadex, n = 29, neostigmine, n = 30) had evaluable data. Geometric mean (95% CI) time to recovery to TOF ratio 0.9 was 1.6 (1.5-1.7) min with sugammadex vs 9.1 (8.0-10.3) min with neostigmine in Chinese subjects. Corresponding times for Caucasian subjects were 1.4 (1.3-1.5) min and 6.7 (5.5-8.0) min, respectively. Sugammadex 2 mg/kg was generally well tolerated, with no serious adverse events reported. There was no residual NMB or recurrence of NMB. Both Chinese and Caucasian subjects recovered from NMB significantly faster after sugammadex 2 mg/kg vs neostigmine 50 μg/kg, with a ~5.7 times (p sugammadex vs neostigmine in Chinese subjects. Sugammadex was generally well tolerated. ClinicalTrials.gov Identifier: NCT00825812.

Tobacco Withdrawal Amongst African American, Hispanic, and White Smokers.

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Bello, Mariel S; Pang, Raina D; Cropsey, Karen L; Zvolensky, Michael J; Reitzel, Lorraine R; Huh, Jimi; Leventhal, Adam M

2016-06-01

Persistent tobacco use among racial and ethnic minority populations in the United States is a critical public health concern. Yet, potential sources of racial/ethnic disparities in tobacco use remain unclear. The present study examined racial/ethnic differences in tobacco withdrawal-a clinically-relevant underpinning of tobacco use that has received sparse attention in the disparities literature-utilizing a controlled laboratory design. Daily smokers (non-Hispanic African American [n = 178], non-Hispanic white [n = 118], and Hispanic [n = 28]) attended two counterbalanced sessions (non-abstinent vs. 16-hour abstinent). At both sessions, self-report measures of urge, nicotine withdrawal, and affect were administered and performance on an objective behavioral task that assessed motivation to reinstate smoking was recorded. Abstinence-induced changes (abstinent scores vs. non-abstinent scores) were analyzed as a function of race/ethnicity. Non-Hispanic African American smokers reported greater abstinence-induced declines in several positive affect states in comparison to other racial/ethnic groups. Relative to Hispanic smokers, non-Hispanic African American and non-Hispanic white smokers displayed larger abstinence-provoked increases in urges to smoke. No racial/ethnic differences were detected for a composite measure of nicotine withdrawal symptomatology, negative affect states, and motivation to reinstate smoking behavior. These results suggest qualitative differences in the expression of some components of tobacco withdrawal across three racial/ethnic groups. This research helps shed light on bio-behavioral sources of tobacco-related health disparities, informs the application of smoking cessation interventions across racial/ethnic groups, and may ultimately aid the overall effort towards reducing the public health burden of tobacco addiction in minority populations. The current study provides some initial evidence that there may be qualitative differences in the

Sugammadex in patients with chronic renal failure: two case reports

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Gwi Eun Yeo

2016-04-01

Full Text Available Rocuronium is a non-depolarizing aminosteroidal neuromuscular blocking agent that is widely used in general anesthesia. Its effects may be prolonged in patients with renal disease, especially renal failure, due to reduced clearance of the drug. Sugammadex, a modified γ-cyclodextrin, is known to be a highly effective reversal agent for rocuronium-induced muscle relaxation. However, the administration of sugammadex for reversal of rocuronium-induced neuromuscular block in patients with renal disease is controversial. Recently, we administered rocuronium for neuromuscular blockade during the surgery of two patients with chronic renal failure, instead of cisatracurium, a benzylisoquinoline compound. Therefore, we had to administer sugammadex to ensure maximum alleviation of residual neuromuscular blockade risk after surgery. Although the effect of rocuronium was prolonged during surgery, sugammadex quickly and completely restored the response of train-of-four stimulation postoperatively. There were no residual neuromuscular block signs or symptoms observed in these patients throughout the postoperative period. In this report, we share our experience with these cases, and discuss the effectiveness and safety of sugammadex in the context of chronic renal failure.   Keywords: Neuromuscular blockade; Neuromuscular monitoring; Renal failure; Residual neuromuscular blockade; Rocuronium; Sugammadex

‌‌The effect of nicotine administration on physical and psychological signs of withdrawal syndrome induced by single or frequent doses of morphine in rats

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Ali Shamsizadeh

2012-07-01

Full Text Available Introduction: Morphine addiction and morphine withdrawal syndrome are the two main problems of today’s human society. The present study has investigated the effects of nicotine on the strength of physical and psychological dependency in single and repeated doses morphine administrated rats. Methods: Male Wistar rats were subjected to morphine consumption with single or frequent dose protocols. In the single dose protocol, rats received only one dose of morphine and 24hrs later they also received one dose of nicotine 30 min prior to injection of naloxone. In the repeated dose protocol, rats received incremental doses of morphine for 7 days and 24hr after the last dose (the 8th day were given naloxone. However, the nicotine regimen of this group was injected 15 min before the morphine injection, for 4 days, from the 4th to the 7th day. Five minutes after naloxone injection, each rat′s behavior was captured for 30 min, and then physical and psychological signs of withdrawal syndrome were recorded. Data were analyzed by ANOVA followed by Tukey tests and p<0.05 was considered as significant difference. Results: Results showed that the injection of frequent and single doses of morphine lead to morphine dependency. In single dose protocol, nicotine consumption attenuated the signs of withdrawal syndrome, especially weight of excrement and total withdrawal score. In frequent dose protocol, in addition to these effects, nicotine induced weight loss and place aversion. Discussion: The inhibitory effects of nicotine on signs of withdrawal syndrome may involve a dopaminergic portion of the central nervous system and is mediated by central nicotinic receptors. There is also a cross-dependence between nicotine and morphine.

Precipitated withdrawal counters the adverse effects of subchronic cannabinoid administration on male rat sexual behavior.

Science.gov (United States)

Riebe, Caitlin J; Lee, Tiffany T; Hill, Matthew N; Gorzalka, Boris B

2010-03-26

In the present study, sexual behavior of male rats was assessed following prolonged treatment with the CB(1) receptor agonist, HU-210 (0.1mg/mg/day for 10 days) under conditions of drug maintenance, spontaneous withdrawal and precipitated withdrawal (induced via administration of the CB(1) receptor antagonist AM251; 1mg/kg). Following subchronic cannabinoid treatment, sexual activity in male rats was impaired under both the drug maintenance and spontaneous withdrawal conditions, as revealed by a reduction in frequency of both intromissions and ejaculations. Notably, the induction of precipitated drug withdrawal reversed the negative effects of subchronic HU-210 treatment on sexual activity as seen by a reversal of the suppression of ejaculations. These data illustrate that, contrary to expectations, the impairments in male sexual activity following protracted cannabinoid administration are not due to drug withdrawal, per se, but are likely mediated by neuroadaptive changes provoked by repeated drug exposure. 2010 Elsevier Ireland Ltd. All rights reserved.

A critical period of progesterone withdrawal precedes menstruation in macaques

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Slayden, Ov D; Brenner, Robert M

2006-01-01

Macaques are menstruating nonhuman primates that provide important animal models for studies of hormonal regulation in the uterus. In women and macaques the decline of progesterone (P) at the end of the cycle triggers endometrial expression of a variety of matrix metalloproteinase (MMP) enzymes that participate in tissue breakdown and menstrual sloughing. To determine the minimal duration of P withdrawal required to induce menses, we assessed the effects of adding P back at various time points after P withdrawal on both frank bleeding patterns and endometrial MMP expression. Artificial menstrual cycles were induced by treating the animals sequentially with implants releasing estradiol (E2) and progesterone (P). To assess bleeding patterns, P implants were removed at the end of a cycle and then added back at 12, 24, 30, 36, 40, 48, 60, or 72 hours (h) after the initial P withdrawal. Observational analysis of frank bleeding patterns showed that P replacement at 12 and 24 h blocked menses, replacement at 36 h reduced menses but replacement after 36 h failed to block menses. These data indicate that in macaques, a critical period of P withdrawal exists and lasts approximately 36 h. In other similarly cycled animals, we withdrew P and then added P back either during (12–24 h) or after (48 h) the critical period, removed the uterus 24 h after P add back and evaluated endometrial MMP expression. Immunocytochemistry showed that replacement of P during the critical period suppressed MMP-1, -2 and -3 expression along with menses, but replacement of P at 48 h, which failed to suppress mense, suppressed MMP-1 and MMP-3 but did not block MMP-2. We concluded that upregulation of MMPs is essential to menses induction, but that after the critical period, menses will occur even if some MMPs are experimentally blocked. PMID:17118170

Is this ?complicated? opioid withdrawal?

OpenAIRE

Parkar, S.R.; Seethalakshmi, R; Adarkar, S; Kharawala, S

2006-01-01

Seven patients with opioid dependence admitted in the de-addiction centre for detoxification developed convulsions and delirium during the withdrawal phase. After ruling out all other possible causes of these complications, opioid withdrawal seemed to emerge as the most likely explanation. The unpredictability of the course of opioid dependence and withdrawal needs to be considered when treating patients with opioid dependence.

Cerebral blood flow and oxygen consumption during ethanol withdrawal in the rat.

Science.gov (United States)

Hemmingsen, R; Barry, D I; Hertz, M M; Klinken, L

1979-09-14

The ethanol withdrawal syndrome in man and animals is characterized by signs of CNS hyperactivity although a direct measurement of a physiological variable reflecting this CNS hyperactivity has never been performed in untreated man or in animals. We induced ethanol dependence in the rat by means of intragastric intubation with a 20% w/v ethanol solution, thus keeping the animals in a state of continuous severe intoxication for 3--4 days; during the subsequent state of withdrawal characterized by tremor, rigidity, stereotyped movements and general seizures a 25% increase in cerebral oxygen consumption (CMRO2) could be measured; this increase was not due to catecholamines originating from adrenal medulla as adrenomedullectomized animals showed a similar increase in CMRO2 (28%); the withdrawing animals showed a corresponding cerebral blood flow (CBF) increase. The elevated CMRO2 and CBF could be reduced to normal by administration of a beta-adrenergic receptor blocker (propranolol 2 mg/kg i.v.), and hence the increased CMRO2 during ethanol withdrawal could be related to catecholaminergic systems in the brain, e.g. the noradrenergic locus coeruleus system which is anatomically well suited as a general activating system. This interpretation is supported by the earlier neurochemical finding of an increased cerebral noradrenaline turnover during ethanol withdrawal. The exact mechanism underlying the increased cerebral oxygen consumption during ethanol withdrawal and the effect of propranolol on cerebral function during this condition remains to be clarified.

Betaxolol, a selective beta(1)-adrenergic receptor antagonist, diminishes anxiety-like behavior during early withdrawal from chronic cocaine administration in rats.

Science.gov (United States)

Rudoy, C A; Van Bockstaele, E J

2007-06-30

Anxiety has been indicated as one of the main symptoms of the cocaine withdrawal syndrome in human addicts and severe anxiety during withdrawal may potentially contribute to relapse. As alterations in noradrenergic transmission in limbic areas underlie withdrawal symptomatology for many drugs of abuse, the present study sought to determine the effect of cocaine withdrawal on beta-adrenergic receptor (beta(1) and beta(2)) expression in the amygdala. Male Sprague Dawley rats were administered intraperitoneal (i.p.) injections of cocaine (20 mg/kg) once daily for 14 days. Two days following the last cocaine injection, amygdala brain regions were micro-dissected and processed for Western blot analysis. Results showed that beta(1)-adrenergic receptor, but not beta(2)-adrenergic receptor expression was significantly increased in amygdala extracts of cocaine-withdrawn animals as compared to controls. This finding motivated further studies aimed at determining whether treatment with betaxolol, a highly selective beta(1)-adrenergic receptor antagonist, could ameliorate cocaine withdrawal-induced anxiety. In these studies, betaxolol (5 mg/kg via i.p. injection) was administered at 24 and then 44 h following the final chronic cocaine administration. Anxiety-like behavior was evaluated using the elevated plus maze test approximately 2 h following the last betaxolol injection. Following behavioral testing, betaxolol effects on beta(1)-adrenergic receptor protein expression were examined by Western blotting in amygdala extracts from rats undergoing cocaine withdrawal. Animals treated with betaxolol during cocaine withdrawal exhibited a significant attenuation of anxiety-like behavior characterized by increased time spent in the open arms and increased entries into the open arms compared to animals treated with only saline during cocaine withdrawal. In contrast, betaxolol did not produce anxiolytic-like effects in control animals treated chronically with saline. Furthermore

Effects of the BDNF Val66Met Polymorphism on Anxiety-Like Behavior Following Nicotine Withdrawal in Mice.

Science.gov (United States)

Lee, Bridgin G; Anastasia, Agustin; Hempstead, Barbara L; Lee, Francis S; Blendy, Julie A

2015-12-01

Nicotine withdrawal is characterized by both affective and cognitive symptoms. Identifying genetic polymorphisms that could affect the symptoms associated with nicotine withdrawal are important in predicting withdrawal sensitivity and identifying personalized cessation therapies. In the current study we used a mouse model of a non-synonymous single nucleotide polymorphism in the translated region of the brain-derived neurotrophic factor (BDNF) gene that substitutes a valine (Val) for a methionine (Met) amino acid (Val66Met) to examine the relationship between the Val66Met single nucleotide polymorphism and nicotine dependence. This study measured proBDNF and the BDNF prodomain levels following nicotine and nicotine withdrawal and examined a mouse model of a common polymorphism in this protein (BDNF(Met/Met)) in three behavioral paradigms: novelty-induced hypophagia, marble burying, and the open-field test. Using the BDNF knock-in mouse containing the BDNF Val66Met polymorphism we found: (1) blunted anxiety-like behavior in BDNF(Met/Met) mice following withdrawal in three behavioral paradigms: novelty-induced hypophagia, marble burying, and the open-field test; (2) the anxiolytic effects of chronic nicotine are absent in BDNF(Met/Met) mice; and (3) an increase in BDNF prodomain in BDNF(Met/Met) mice following nicotine withdrawal. Our study is the first to examine the effect of the BDNF Val66Met polymorphism on the affective symptoms of withdrawal from nicotine in mice. In these mice, a single-nucleotide polymorphism in the translated region of the BDNF gene can result in a blunted withdrawal, as measured by decreased anxiety-like behavior. The significant increase in the BDNF prodomain in BDNF(Met/Met) mice following nicotine cessation suggests a possible role of this ligand in the circuitry remodeling after withdrawal. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For

The pathogenesis of propranolol-withdrawal syndrome in essential hypertension.

Science.gov (United States)

Kristensen, B O; Steiness, E; Weeke, J

1979-12-01

1. In hypertension, the beta-adrenoreceptor-blocker-withdrawal syndrome comprises tachycardia, sweating, tremor and general malaise, symptoms resembling thyrotoxicosis. 2. The effect of abrupt cessation of propranolol on serum concentrations of thyroxine (T4) and triiodothyronine (T3) was therefore investigated in five patients with uncomplicated essential hypertension, treated with propranolol in doses from 160 to 480 mg/day. 3. Four of the five patients developed one or more of the above-mentioned symptoms within 2-6 days after withdrawal of propranolol. 4. A mean relative increase in serum free T3 of 51% (range 22-74%) was found in these four patients on the day of onset of symptoms. 5. The increase in free T3 in the five patients correlated positively with total serum propranolol on the last day the drug was given (r = 0.91, 2P = 0.03). 6. As an increase in T3 was found only in patients suffering the withdrawal syndrome, and was maximal the day the symptoms appeared, despite a variation in time of onset from 2 to 6 days, it is suggested that the beta-adrenoreceptor-blocker-withdrawal syndrome, at least partially, is caused by rebound increased production of T3, induced by the well-known inhibition of the monodeiodination of T4 to T3 during beta-adrenoreceptor blockade. 7. This assumption may explain the clinical symptoms and the reported transient increased beta-adrenoreceptor sensitivity with unchanged serum concentrations of catecholamines.

19 CFR 144.38 - Withdrawal for consumption.

Science.gov (United States)

2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Withdrawal for consumption. 144.38 Section 144.38... Withdrawal for consumption. (a) Form. Withdrawals for consumption of merchandise in bonded warehouses shall... considered a withdrawal for consumption pursuant to § 181.53 of this chapter. (c) Information to be shown on...

Changes in the female arcuate nucleus morphology and neurochemistry after chronic ethanol consumption and long-term withdrawal.

Science.gov (United States)

Rebouças, Elce C C; Leal, Sandra; Silva, Susana M; Sá, Susana I

2016-11-01

Ethanol is a macronutrient whose intake is a form of ingestive behavior, sharing physiological mechanisms with food intake. Chronic ethanol consumption is detrimental to the brain, inducing gender-dependent neuronal damage. The hypothalamic arcuate nucleus (ARN) is a modulator of food intake that expresses feeding-regulatory neuropeptides, such as alpha melanocyte-stimulating hormone (α-MSH) and neuropeptide Y (NPY). Despite its involvement in pathways associated with eating disorders and ethanol abuse, the impact of ethanol consumption and withdrawal in the ARN structure and neurochemistry in females is unknown. We used female rat models of 20% ethanol consumption for six months and of subsequent ethanol withdrawal for two months. Food intake and body weights were measured. ARN morphology was stereologically analyzed to estimate its volume, total number of neurons and total number of neurons expressing NPY, α-MSH, tyrosine hydroxylase (TH) and estrogen receptor alpha (ERα). Ethanol decreased energy intake and body weights. However, it did not change the ARN morphology or the expression of NPY, α-MSH and TH, while increasing ERα expression. Withdrawal induced a significant volume and neuron loss that was accompanied by an increase in NPY expression without affecting α-MSH and TH expression. These findings indicate that the female ARN is more vulnerable to withdrawal than to excess alcohol. The data also support the hypothesis that the same pathways that regulate the expression of NPY and α-MSH in long-term ethanol intake may regulate food intake. The present model of long-term ethanol intake and withdrawal induces new physiological conditions with adaptive responses. Copyright © 2016 Elsevier B.V. All rights reserved.

Neuromuscular transmission: new concepts and agents.

NARCIS (Netherlands)

Boer, H.D. de

2009-01-01

Sugammadex is the first selective relaxant binding agent which was originally designed to reverse the steroidal NMB drug rocuronium. The results of recent studies demonstrate that sugammadex is effective for reversal of rocuronium and vecuronium-induced neuromuscular block without apparent

Rocuronium blockade reversal with sugammadex vs. neostigmine: randomized study in Chinese and Caucasian subjects

Science.gov (United States)

2014-01-01

Background This study compared efficacy and safety of the selective relaxant binding agent sugammadex (2 mg/kg) with neostigmine (50 μg/kg) for neuromuscular blockade (NMB) reversal in Chinese and Caucasian subjects. Methods This was a randomized, active-controlled, multicenter, safety-assessor-blinded study (NCT00825812) in American Society of Anesthesiologists Class 1-3 subjects undergoing surgery with propofol anesthesia. Rocuronium 0.6 mg/kg was administered for endotracheal intubation, with 0.1–0.2 mg/kg maintenance doses given as required. NMB was monitored using TOF-Watch® SX. At second twitch reappearance, after last rocuronium dose, subjects received sugammadex 2 mg/kg or neostigmine 50 μg/kg plus atropine 10–20 μg/kg, according to randomization. Primary efficacy variable was time from sugammadex/neostigmine to recovery of the train-of-four (TOF) ratio to 0.9. Results Overall, 230 Chinese subjects (sugammadex, n = 119, neostigmine, n = 111); and 59 Caucasian subjects (sugammadex, n = 29, neostigmine, n = 30) had evaluable data. Geometric mean (95% CI) time to recovery to TOF ratio 0.9 was 1.6 (1.5–1.7) min with sugammadex vs 9.1 (8.0–10.3) min with neostigmine in Chinese subjects. Corresponding times for Caucasian subjects were 1.4 (1.3–1.5) min and 6.7 (5.5–8.0) min, respectively. Sugammadex 2 mg/kg was generally well tolerated, with no serious adverse events reported. There was no residual NMB or recurrence of NMB. Conclusion Both Chinese and Caucasian subjects recovered from NMB significantly faster after sugammadex 2 mg/kg vs neostigmine 50 μg/kg, with a ~5.7 times (p < 0.0001) faster recovery with sugammadex vs neostigmine in Chinese subjects. Sugammadex was generally well tolerated. Trial registration ClinicalTrials.gov Identifier: NCT00825812. PMID:25187755

Betaxolol, a selective β1-adrenergic receptor antagonist, diminishes anxiety-like behavior during early withdrawal from chronic cocaine administration in rats

Science.gov (United States)

Rudoy, C.A.; Van Bockstaele, E.J.

2007-01-01

Background Anxiety has been indicated as one of the main symptoms of the cocaine withdrawal syndrome in human addicts and severe anxiety during withdrawal may potentially contribute to relapse. As alterations in noradrenergic transmission in limbic areas underlie withdrawal symptomatology for many drugs of abuse, the present study sought to determine the effect of cocaine withdrawal on β-adrenergic receptor (β1 and β2) expression in the amygdala. Methods Male Sprague Dawley rats were administered intraperitoneal (i.p.) injections of cocaine (20 mg/kg) once daily for 14 days. Two days following the last cocaine injection, amygdala brain regions were micro-dissected and processed for Western blot analysis. Results showed that β1–adrenergic receptor, but not β2–adrenergic receptor expression was significantly increased in amygdala extracts of cocaine-withdrawn animals as compared to controls. This finding motivated further studies aimed at determining whether treatment with betaxolol, a highly selective β1–adrenergic receptor antagonist, could ameliorate cocaine withdrawal-induced anxiety. In these studies, betaxolol (5 mg/kg via i.p. injection) was administered at 24 and then 44 hours following the final chronic cocaine administration. Anxiety-like behavior was evaluated using the elevated plus maze test approximately 2 hours following the last betaxolol injection. Following behavioral testing, betaxolol effects on β1-adrenergic receptor protein expression were examined by Western blotting in amygdala extracts from rats undergoing cocaine withdrawal. Results Animals treated with betaxolol during cocaine withdrawal exhibited a significant attenuation of anxiety-like behavior characterized by increased time spent in the open arms and increased entries into the open arms compared to animals treated with only saline during cocaine withdrawal. In contrast, betaxolol did not produce anxiolytic-like effects in control animals treated chronically with saline

A clinical trial to determine if corelease of morphine and naltrexone from crushed extended-release capsules induces withdrawal in opioid-dependent patients: a descriptive analysis of six patients.

Science.gov (United States)

Setnik, Beatrice; Roland, Carl L; Goli, Veeraindar; Sommerville, Kenneth; Webster, Lynn

2013-01-01

To evaluate whether intact or crushed doses of an extended-release formulation of morphine sulfate surrounding an inner core of sequestered naltrexone (MSN) induces signs and symptoms of withdrawal in opioid-dependent patients. Randomized, double-blind, two-way crossover study. Single center. Fourteen patients with chronic moderate-to-severe noncancer pain receiving opioids were enrolled into the study; six completed the maintenance and treatment phases prior to early study discontinuation for issues with manufacturing; eight discontinued: adverse effects (4), noncompliance (1), patient decision (1), study termination (2). Patients were titrated to a stable dose of MSN (ranging from 30/1.2 to 100/4.0 mg of morphine/naltrexone) that was used in the single-dose crossover evaluation of crushed and intact MSN. Clinical Opiate Withdrawal Scale (COWS). Clinically significant withdrawal (COWS ≥ 13) was observed with rapid onset (≤0.8 hours postdose) in three patients (50 percent) following treatment with crushed MSN at the highest doses administered of ≥60/2.4 mg. Although naltrexone exposure was negligible following exposure to intact MSN, increasing plasma levels of naltrexone and 6-β-naltrexol were associated with COWS score ≥13 in patients who received crushed MSN. COWS ≥ 13 was observed in one patient receiving intact MSN without quantifiable naltrexone concentrations. Crushing the MSN capsule may precipitate moderate-to-severe signs and symptoms of opioid withdrawal in opioid-dependent individuals. The negligible exposure to naltrexone following exposure to intact MSN supports that intact capsules may be taken safely without precipitating withdrawal in opioid-dependent individuals.

Anxiety does not contribute to social withdrawal in the subchronic phencyclidine rat model of schizophrenia.

Science.gov (United States)

Seillier, Alexandre; Giuffrida, Andrea

2017-10-01

Social withdrawal should not be considered a direct measure of the negative symptoms of schizophrenia as it may result not only from asociality (primary negative symptom) but also from other altered processes such as anxiety. To understand the contribution of these two factors to social deficit, we investigated whether the social withdrawal observed in the subchronic phencyclidine (PCP) rat model of schizophrenia could be attributed to increased anxiety. Compared to saline controls, PCP-treated rats (5 mg/kg, twice daily for 7 days, followed by a washout period) spent significantly less time in social interaction, but did not show anxiety-like behaviors in different relevant behavioral paradigms. In addition, their social deficit was not affected by a behavioral procedure known to reduce anxiety-like behavior (repeated exposure to the same partner) nor by systemic administration of the classical anxiolytic diazepam. In contrast, PCP-induced social withdrawal was reversed by the cannabinoid agonist CP55,940, a drug with known anxiogenic properties. Furthermore, when using the social approach task, PCP-treated animals performed similarly to control animals treated with diazepam, but not to those treated with the anxiogenic compound pentylenetetrazole. Taken together, our results indicate that PCP-induced social withdrawal cannot be attributed to increased anxiety. These data are discussed in the context of primary versus secondary negative symptoms and the deficit syndrome of schizophrenia.

Anticonvulsants for alcohol withdrawal.

Science.gov (United States)

Minozzi, Silvia; Amato, Laura; Vecchi, Simona; Davoli, Marina

2010-03-17

Alcohol abuse and dependence represents a most serious health problem worldwide with major social, interpersonal and legal interpolations. Besides benzodiazepines, anticonvulsants are often used for the treatment of alcohol withdrawal symptoms. Anticonvulsants drugs are indicated for the treatment of alcohol withdrawal syndrome, alone or in combination with benzodiazepine treatments. In spite of the wide use, the exact role of the anticonvulsants for the treatment of alcohol withdrawal has not yet bee adequately assessed. To evaluate the effectiveness and safety of anticonvulsants in the treatment of alcohol withdrawal. We searched Cochrane Drugs and Alcohol Group' Register of Trials (December 2009), PubMed, EMBASE, CINAHL (1966 to December 2009), EconLIT (1969 to December 2009). Parallel searches on web sites of health technology assessment and related agencies, and their databases. Randomized controlled trials (RCTs) examining the effectiveness, safety and overall risk-benefit of anticonvulsants in comparison with a placebo or other pharmacological treatment. All patients were included regardless of age, gender, nationality, and outpatient or inpatient therapy. Two authors independently screened and extracted data from studies. Fifty-six studies, with a total of 4076 participants, met the inclusion criteria. Comparing anticonvulsants with placebo, no statistically significant differences for the six outcomes considered.Comparing anticonvulsant versus other drug, 19 outcomes considered, results favour anticonvulsants only in the comparison carbamazepine versus benzodiazepine (oxazepam and lorazepam) for alcohol withdrawal symptoms (CIWA-Ar score): 3 studies, 262 participants, MD -1.04 (-1.89 to -0.20), none of the other comparisons reached statistical significance.Comparing different anticonvulsants no statistically significant differences in the two outcomes considered.Comparing anticonvulsants plus other drugs versus other drugs (3 outcomes considered), results

An Emerging New Paradigm in Opioid Withdrawal: A Critical Role for Glia-Neuron Signaling in the Periaqueductal Gray

Directory of Open Access Journals (Sweden)

Handong Ouyang

2012-01-01

Full Text Available The chronic use of opiates (i.e., narcotics such as the natural derivatives of opium including morphine or codeine or opioids (i.e., semisynthetic derivatives of opium and other molecules that activate opioid receptors induces dependence, which is associated with various specific behavioral and somatic signs after their withdrawal or after the administration of an opioid antagonist. Among the brain regions implicated in opiate dependence and withdrawal, the periaqueductal gray area (PAG appears to be critical in regulating the complex signs and symptoms of opioid withdrawal. Numerous neurochemical mechanisms in the PAG have been identified that may contribute to the opioid withdrawal syndrome. Accumulating evidence suggests that glial activation leading to the release of proinflammatory molecules acting on neurons is important in the complex syndrome of opioid dependence and withdrawal. This paper focuses on the recent advances in our understanding of the vital role that glia-neuron interactions play in opioid dependence and withdrawal within the PAG. We summarize those neurochemical mechanisms associated with opioid withdrawal including the recently defined importance of TNFα release from activated glial cells that communicate with TNF receptors on PAG neurons.

Perinatal risk factors and social withdrawal behaviour.

Science.gov (United States)

Guedeney, Antoine; Marchand-Martin, Laetitia; Cote, Sylvana J; Larroque, Béatrice

2012-04-01

The objectives of the study were (1) to assess prevalence of social withdrawal behaviour in infants aged 12 months included in the French Perinatal Risk Factor Study Eden; (2) To study the correlation between relational withdrawal and several perinatal and parental factors assessed in the EDEN study. A longitudinal study using the ADBB scale was conducted within the Eden Cohort in the year 2008. 1,586 infants were included in the study. Fourteen percent of the children who had an ADBB assessment had a score at 5 and over on the ADBB, a scale designed to assess social withdrawal behaviour at age 0-24 months. Social withdrawal at 12 months was associated with low birth weight, low gestational age and with intra uterine growth retardation. Social withdrawal was independently associated with several maternal and paternal risk factors. The level of social withdrawal behaviour increased with a score of maternal difficulties. This study on a large longitudinally followed volunteer sample demonstrate a clear association of social withdrawal behaviour at age one with low birth weight and preterm birth, possibly mediated by parental vulnerabilities. Social withdrawal behaviour seems to be an important alarm signal to detect early on particularly in premature and small for date babies. © Springer-Verlag 2012

Clinical management of alcohol withdrawal: A systematic review

Directory of Open Access Journals (Sweden)

Shivanand Kattimani

2013-01-01

Full Text Available Alcohol withdrawal is commonly encountered in general hospital settings. It forms a major part of referrals received by a consultation-liaison psychiatrist. This article aims to review the evidence base for appropriate clinical management of the alcohol withdrawal syndrome. We searched Pubmed for articles published in English on pharmacological management of alcohol withdrawal in humans with no limit on the date of publication. Articles not relevant to clinical management were excluded based on the titles and abstract available. Full-text articles were obtained from this list and the cross-references. There were four meta-analyses, 9 systematic reviews, 26 review articles and other type of publications like textbooks. Alcohol withdrawal syndrome is a clinical diagnosis. It may vary in severity. Complicated alcohol withdrawal presents with hallucinations, seizures or delirium tremens. Benzodiazepines have the best evidence base in the treatment of alcohol withdrawal, followed by anticonvulsants. Clinical institutes withdrawal assessment-alcohol revised is useful with pitfalls in patients with medical comorbidities. Evidence favors an approach of symptom-monitored loading for severe withdrawals where an initial dose is guided by risk factors for complicated withdrawals and further dosing may be guided by withdrawal severity. Supportive care and use of vitamins is also discussed.

Development of Ethanol Withdrawal-Related Sensitization and Relapse Drinking in Mice Selected for High or Low Ethanol Preference

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Lopez, Marcelo F.; Grahame, Nicholas J.; Becker, Howard C.

2010-01-01

Background Previous studies have shown that high alcohol consumption is associated with low withdrawal susceptiblility, while at the same time, other studies have shown that exposure to ethanol vapor increases alcohol drinking in rats and mice. In the present studies, we sought to shed light on this seeming contradiction by using mice selectively bred for High- (HAP) and Low- (LAP) Alcohol Preference, first, assessing these lines for differences in signs of ethanol withdrawal and second, for differences in the efficacy of intermittent alcohol vapor exposure on elevating subsequent ethanol intake. Methods Experiment 1 examined whether these lines of mice differed in ethanol withdrawal-induced CNS hyperexcitability and the development of sensitization to this effect following intermittent ethanol vapor exposure. Adult HAP and LAP lines (replicates 1 and 2), and the C3H/HeNcr inbred strain (included as a control genotype for comparison purposes) received intermittent exposure to ethanol vapor and were evaluated for ethanol withdrawal-induced seizures assessed by scoring handling-induced convulsions (HIC). Experiment 2 examined the influence of chronic intermittent ethanol exposure on voluntary ethanol drinking. Adult male and female HAP-2 and LAP-2 mice, along with male C57BL/6J (included as comparative controls) were trained to drink 10% ethanol using a limited access (2 hr/day) 2-bottle choice paradigm. After stable baseline daily intake was established, mice received chronic intermittent ethanol vapor exposure in inhalation chambers. Ethanol intake sessions resumed 72 hr after final ethanol (or air) exposure for 5 consecutive days. Results Following chronic ethanol treatment, LAP mice exhibited overall greater withdrawal seizure activity compared to HAP mice. In Experiment 2, chronic ethanol exposure/withdrawal resulted in a significant increase in ethanol intake in male C57BL/6J, and modestly elevated intake in HAP-2 male mice. Ethanol intake for male control mice

Selegiline prevents long-term changes in dopamine efflux and stress immobility during the second and third weeks of abstinence following opiate withdrawal.

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Grasing, K; Ghosh, S

1998-08-01

Selegiline is an irreversible inhibitor of monoamine oxidase B with trophic and neuroprotective effects. Because of evidence for decreased dopaminergic function during the withdrawal syndromes associated with opiates and other medications with potential for abuse, we investigated effects of treatment with selegiline on in vitro measures of dopamine efflux following opiate withdrawal. Treatment with 2.0 mg/kg/day of selegiline did not modify the severity of opiate withdrawal, as assessed by weight loss over the first 3 days of abstinence. Opiate withdrawal increased immobility in response to a forced warm water swim test performed during the second and third weeks of abstinence following the onset of withdrawal. Brain slices obtained from the nucleus accumbens of opiate-withdrawn animals immediately following swim stress testing displayed diminished efflux of tritiated dopamine after two in vitro exposures to cocaine or amphetamine. Cocaine increases neurotransmitter efflux through blockade of dopamine reuptake, while amphetamine augments efflux by stimulating release of dopamine from intracellular storage vesicles. Although slices from opiate withdrawal subjects showed decreases in efflux after in vitro treatment with these agents, no differences were observed after exposure to 4-aminopyridine, which increases neurotransmitter release by prolonging action potential duration. These findings indicate mechanisms of action that are specific for catecholamine neurotransmitter systems are important for demonstrating long-term changes in dopaminergic function following opiate withdrawal. Selegiline prevented decreases in the efflux of tritiated dopamine in slices obtained from opiate-withdrawn subjects. In addition, selegiline decreased withdrawal-induced immobility during warm water swim testing. In conclusion, treatment with selegiline can prevent long-term changes in stress-induced immobility and deficits in presynaptic dopaminergic function that occur following the

Phosphodiesterase 2A Inhibitor TAK-915 Ameliorates Cognitive Impairments and Social Withdrawal in N-Methyl-d-Aspartate Receptor Antagonist-Induced Rat Models of Schizophrenia.

Science.gov (United States)

Nakashima, Masato; Imada, Haruka; Shiraishi, Eri; Ito, Yuki; Suzuki, Noriko; Miyamoto, Maki; Taniguchi, Takahiko; Iwashita, Hiroki

2018-04-01

The pathophysiology of schizophrenia has been associated with glutamatergic dysfunction. Modulation of the glutamatergic signaling pathway, including N -methyl-d-aspartate (NMDA) receptors, can provide a new therapeutic target for schizophrenia. Phosphodiesterase 2A (PDE2A) is highly expressed in the forebrain, and is a dual substrate enzyme that hydrolyzes both cAMP and cGMP, which play pivotal roles as intracellular second messengers downstream of NMDA receptors. Here we characterize the in vivo pharmacological profile of a selective and brain-penetrant PDE2A inhibitor, ( N -{(1 S )-1-[3-fluoro-4-(trifluoromethoxy)phenyl]-2-methoxyethyl}-7-methoxy-2-oxo-2,3-dihydropyrido[2,3- b ]pyrazine-4(1 H )-carboxamide) (TAK-915) as a novel treatment of schizophrenia. Oral administration of TAK-915 at 3 and 10 mg/kg significantly increased cGMP levels in the frontal cortex, hippocampus, and striatum of rats. TAK-915 at 10 mg/kg significantly upregulated the phosphorylation of α -amino-3-hydroxy-5-methylisoxazole-4-proprionic acid receptor subunit GluR1 in the rat hippocampus. TAK-915 at 3 and 10 mg/kg significantly attenuated episodic memory deficits induced by the NMDA receptor antagonist (+)-MK-801 hydrogen maleate (MK-801) in the rat passive avoidance test. TAK-915 at 10 mg/kg significantly attenuated working memory deficits induced by MK-801 in the rat radial arm maze test. Additionally, TAK-915 at 10 mg/kg prevented subchronic phencyclidine-induced social withdrawal in social interaction in rats. In contrast, TAK-915 did not produce antipsychotic-like activity; TAK-915 had little effect on MK-801- or methamphetamine-induced hyperlocomotion in rats. These results suggest that TAK-915 has a potential to ameliorate cognitive impairments and social withdrawal in schizophrenia. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Prediction of withdrawal symptoms during opioid detoxification

NARCIS (Netherlands)

Dijkstra, Boukje A G; Krabbe, Paul F M; De Jong, Cor A J; van der Staak, Cees P F

2008-01-01

OBJECTIVE: The severity of self-reported withdrawal symptoms varies during detoxification of opioid-dependent patients. The aim of this study is to identify subgroups of withdrawal symptoms within the detoxification trajectory and to predict the severity of withdrawal symptoms on the basis of

Prediction of withdrawal symptoms during opioid detoxification

NARCIS (Netherlands)

Dijkstra, B.A.G.; Krabbe, P.F.M.; Jong, C.A.J. de; Staak, C.P.F. van der

2008-01-01

Objective: The severity of self-reported withdrawal symptoms varies during detoxification of opioid-dependent patients. The aim of this study is to identify subgroups of withdrawal symptoms within the detoxification trajectory and to predict the severity of withdrawal symptoms on the basis of

Adolescent Mice Are Resilient to Alcohol Withdrawal-Induced Anxiety and Changes in Indices of Glutamate Function within the Nucleus Accumbens.

Science.gov (United States)

Lee, Kaziya M; Coelho, Michal A; McGregor, Hadley A; Solton, Noah R; Cohen, Matan; Szumlinski, Karen K

2016-01-01

Binge-drinking is the most prevalent form of alcohol abuse and while an early life history of binge-drinking is a significant risk factor for subsequent alcoholism and co-morbid affective disorders, relatively little is known regarding the biobehavioral impact of binge-drinking during the sensitive neurodevelopmental period of adolescence. In adult mice, a month-long history of binge-drinking elicits a hyper-glutamatergic state within the nucleus accumbens (Acb), coinciding with hyper-anxiety. Herein, we employed a murine model of binge-drinking to determine whether or not: (1) withdrawal-induced changes in brain and behavior differ between adult and adolescent bingers; and (2) increased behavioral signs of negative affect and changes in Acb expression of glutamate-related proteins would be apparent in adult mice with less chronic binge-drinking experience (14 days, approximating the duration of mouse adolescence). Adult and adolescent male C57BL/6J mice were subjected to a 14-day binge-drinking protocol (5, 10, 20 and 40% alcohol (v/v) for 2 h/day), while age-matched controls received water. At 24 h withdrawal, half of the animals from each group were assayed for negative affect, while tissue was sampled from the shell (AcbSh) and core (AcbC) subregions of the remaining mice for immunoblotting analyses. Adult bingers exhibited hyper-anxiety when tested for defensive marble burying. Additionally, adult bingers showed increased mGlu1, mGlu5, and GluN2b expression in the AcbSh and PKCε and CAMKII in the AcbC. Compared to adults, adolescent mice exhibited higher alcohol intake and blood alcohol concentrations (BACs); however, adolescent bingers did not show increased anxiety in the marble-burying test. Furthermore, adolescent bingers also failed to exhibit the same alcohol-induced changes in mGlu and kinase protein expression seen in the adult bingers. Irrespective of age, bingers exhibited behavioral hyperactivity in the forced swim test (FST) compared to water

Adolescent mice are resilient to alcohol withdrawal-induced anxiety and changes in indices of glutamate function within the nucleus accumbens

Directory of Open Access Journals (Sweden)

Kaziya M Lee

2016-11-01

Full Text Available Binge-drinking is the most prevalent form of alcohol abuse and while an early life history of binge-drinking is a significant risk factor for subsequent alcoholism and co-morbid affective disorders, relatively little is known regarding the biobehavioral impact of binge-drinking during the sensitive neurodevelopmental period of adolescence. In adult mice, a month-long history of binge-drinking elicits a hyper-glutamatergic state within the nucleus accumbens (Acb, coinciding with hyper-anxiety. Herein, we employed a murine model of binge-drinking to determine whether or not: 1 withdrawal-induced changes in brain and behavior differ between adult and adolescent bingers and 2 increased behavioral signs of negative affect and changes in Acb expression of glutamate-related proteins would be apparent in adult mice with less chronic binge-drinking experience (14 days, approximating the duration of mouse adolescence. Adult and adolescent male C57BL/6J mice were subjected to a 14-day binge-drinking protocol (5, 10, 20 and 40% alcohol (v/v for 2 h/day, while age-matched controls received water. At 24 h withdrawal, half of the animals from each group were assayed for negative affect, while tissue was sampled from the shell (AcbSh and core (AcbC subregions of the remaining mice for immunoblotting analyses. Adult bingers exhibited hyper-anxiety when tested for defensive marble burying. Additionally, adult bingers showed increased mGlu1, mGlu5, and GluN2b expression in the AcbSh and PKCε and CAMKII in the AcbC. Compared to adults, adolescent mice exhibited higher alcohol intake and blood alcohol concentrations; however, adolescent bingers did not show increased anxiety in the marble-burying test. Furthermore, adolescent bingers also failed to exhibit the same alcohol-induced changes in mGlu and kinase protein expression seen in the adult bingers. Irrespective of age, bingers exhibited behavioral hyperactivity in the forced swim test compared to water drinkers

Control rod excess withdrawal prevention device

International Nuclear Information System (INIS)

Takayama, Yoshihito.

1992-01-01

Excess withdrawal of a control rod of a BWR type reactor is prevented. That is, the device comprises (1) a speed detector for detecting the driving speed of a control rod, (2) a judging circuit for outputting an abnormal signal if the driving speed is greater than a predetermined level and (3) a direction control valve compulsory closing circuit for controlling the driving direction of inserting and withdrawing a control rod based on an abnormal signal. With such a constitution, when the with drawing speed of a control rod is greater than a predetermined level, it is detected by the speed detector and the judging circuit. Then, all of the direction control valve are closed by way of the direction control valve compulsory closing circuit. As a result, the operation of the control rod is stopped compulsorily and the withdrawing speed of the control rod can be lowered to a speed corresponding to that upon gravitational withdrawal. Accordingly, excess withdrawal can be prevented. (I.S)

19 CFR 144.37 - Withdrawal for exportation.

Science.gov (United States)

2010-04-01

...) Class 9 warehouse withdrawals for exportation—(1) Applicability of sales ticket procedure. Merchandise... be eligible for withdrawal under the sales ticket procedure specified in this paragraph. (2) Sales ticket content and handling. Sales ticket withdrawals must be made only under a blanket permit to...

5 CFR 362.207 - Withdrawal and readmission.

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Withdrawal and readmission. 362.207... PRESIDENTIAL MANAGEMENT FELLOWS PROGRAM Program Administration § 362.207 Withdrawal and readmission. (a...) An agency must notify OPM when a Fellow or Senior Fellow withdraws from the Program. (b) Readmission...

Tobacco withdrawal among opioid-dependent smokers.

Science.gov (United States)

Streck, Joanna M; Heil, Sarah H; Higgins, Stephen T; Bunn, Janice Y; Sigmon, Stacey C

2018-04-01

Prevalence of cigarette smoking among opioid-dependent individuals is 6-fold that of the general U.S. adult population and their quit rates are notoriously poor. One possible reason for the modest cessation outcomes in opioid-dependent smokers may be that they experience more severe tobacco withdrawal upon quitting. In this secondary analysis, we evaluated tobacco withdrawal in opioid-dependent (OD) smokers versus smokers without co-occurring substance use disorders (SUDs). Participants were 47 methadone- or buprenorphine-maintained smokers and 25 non-SUD smokers who completed 1 of several 2-week studies involving daily visits for biochemical monitoring, delivery of financial incentives contingent on smoking abstinence, and assessment of withdrawal via the Minnesota Nicotine Withdrawal Scale (MNWS). Prior to quitting smoking, OD smokers presented with higher baseline withdrawal scores than non-SUD smokers (1.7 ± 0.2 vs. 0.7 ± 0.2, respectively; F [1, 63] = 7.31, p non-SUD smokers, suggesting that elevated withdrawal severity following quitting may not be a major factor contributing to the poor cessation outcomes consistently observed among OD smokers. Further scientific efforts are needed to improve our understanding of the high smoking rates and modest cessation outcomes in this challenging population. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Water withdrawals in Florida, 2012

Science.gov (United States)

Marella, Richard L.

2015-09-01

In 2012, the total amount of water withdrawn in Florida was estimated to be 14,237 million gallons per day (Mgal/d). Saline water accounted for 7,855 Mgal/d (55 percent), and freshwater accounted for 6,383 Mgal/d (45 percent). Groundwater accounted for 4,167 Mgal/d (65 percent) of freshwater withdrawals, and surface water accounted for the remaining 2,216 Mgal/d (35 percent). Surface water accounted for nearly all (99.9 percent) saline-water withdrawals. Freshwater withdrawals were greatest in Palm Beach County (682 Mgal/d), and saline-water withdrawals were greatest in Pasco County (1,822 Mgal/d). Fresh groundwater provided drinking water (through either public supply or private domestic wells) for 17.699 million residents (93 percent of Florida’s population), and fresh surface water provided drinking water for 1.375 million residents (7 percent). The statewide public-supply gross per capita water use for 2012 was estimated at 136 gallons per day.

The benzodiazepine withdrawal syndrome and its management.

OpenAIRE

Onyett, S R

1989-01-01

The literature on benzodiazepine dependence and withdrawal is reviewed with an emphasis on social and psychological considerations. The problems of when to prescribe, identifying withdrawal symptoms, effective communication with the patient, the structure of withdrawal programmes, and the use of drugs, psychological approaches and other services are discussed.

47 CFR 1.8 - Withdrawal of papers.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false Withdrawal of papers. 1.8 Section 1.8 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND PROCEDURE General Rules of Practice and Procedure General § 1.8 Withdrawal of papers. The granting of a request to dismiss or withdraw an...

29 CFR 102.104 - Withdrawal of petition.

Science.gov (United States)

2010-07-01

... 29 Labor 2 2010-07-01 2010-07-01 false Withdrawal of petition. 102.104 Section 102.104 Labor... Orders and Advisory Opinions Regarding Board Jurisdiction § 102.104 Withdrawal of petition. The petitioner may withdraw his petition at any time prior to issuance of the Board's advisory opinion. ...

Crosstalk between G protein-coupled receptors (GPCRs and tyrosine kinase receptor (TXR in the heart after morphine withdrawal

Directory of Open Access Journals (Sweden)

Pilar eAlmela

2013-12-01

Full Text Available G protein-coupled receptors (GPCRs comprise a large family of membrane receptors involved in signal transduction. These receptors are linked to a variety of physiological and biological processes such as regulation of neurotransmission, growth and cell differentiation among others. Some of the effects of GPCRs are known to be mediated by the activation of mitogen-activated extracellular kinase (MAPK pathways. Cross-talk among various signal pathways plays an important role in activation of intracellular and intranuclear signal transduction cascades. Naloxone-induced morphine withdrawal leads to an up-regulation of adenyl cyclase-mediated signalling, resulting in high expression of protein kinase (PK A. In addition, there is also an increased expression of extracellular signal regulated kinase (ERK, one member of MAPK. For this reason, the crosstalk between these GPCRs and receptors with tyrosine kinase activity (TKR can be considered a possible mechanism for adaptive changes that occurs after morphine withdrawal. Morphine withdrawal activates ERK1/2 and phosphorylated tyrosine hydroxylase (TH at Ser31 in the right and left ventricle. When N-(2-guanidinoethyl-5-isoquinolinesulfonamide (HA-1004, a PKA inhibitor was infused, the ability of morphine withdrawal to activate ERK, which phosphorylates TH at Ser31, was reduced. The present finding demonstrated that the enhancement of ERK1/2 expression and the phosphorylation state of TH at Ser31 during morphine withdrawal are dependent on PKA and suggest cross-talk between PKA and ERK1/2 transduction pathway mediating morphine withdrawal-induced activation of TH. Increasing understanding of the mechanisms that interconnect the two pathway regulated by GPCRs and TKRs may facilitate the design of new therapeutic strategies.

19 CFR 144.36 - Withdrawal for transportation.

Science.gov (United States)

2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Withdrawal for transportation. 144.36 Section 144... § 144.36 Withdrawal for transportation. (a) Time limit. Merchandise may be withdrawn from warehouse for transportation to another port of entry if withdrawal for consumption or exportation can be accomplished at the...

The Successful Treatment of Opioid Withdrawal-Induced Refractory Muscle Spasms with 5-HTP in a Patient Intolerant to Clonidine.

Science.gov (United States)

Dais, Jennifer; Khosia, Ankur; Doulatram, Gulshan

2015-01-01

Instituting drug holidays for chronic opioid using patients is becoming commonplace for pain practitioners initiating procedures such as intrathecal pump or spinal cord stimulator trials. As such, pain practitioners need to be adept in their management of acute opioid withdrawal. Successfully weaning an opioid dependent patient off of chronic opioids requires a thorough knowledge of the available adjuvants to assist in this process. However, that selection can become exhausted by adjuvant side effects or by ineffective attenuation of opioid withdrawal symptoms. In that case, novel drugs, or novel application of currently available medications must be sought after to assist in the drug holiday. We present a case in which refractory muscle spasms secondary to opioid withdrawal were successfully treated with an over-the-counter supplement that is not typically used for the attenuation of opioid withdrawal symptoms. In a patient intolerant to the side effects of clonidine, we were able to successfully wean chronic opiates by treating refractory muscle spasms with the serotonin precursor, 5-hydroxytryptophan (5-HTP). We hypothesize that our success with this medication gives further credence to the role of serotonin in opioid withdrawal somatic symptomatology, and supports the need for future research to clarify the role of serotonin precursors or serotonin modulating drugs as potential alternatives in those unable to follow standard treatment protocols.

Psychosis following Tramadol Withdrawal

OpenAIRE

Rajabizadeh, Ghodratolah; Kheradmand, Ali; Nasirian, Mansoureh

2009-01-01

Background: Tramadol is a centrally acting opioid analgesic used to treat moderate to sever pain. It has more advantage and less opioid adverse effects than conventional opioid analgesia. Case Report: This article reports a patient with tramadol dependency that had psychosis after tramadol withdrawal. Conclusion: By the increase of tramadol usage for relief of chronic pain, tramadol abuse and dependency is increased. Some of tramadol withdrawal symptoms are not related to opioid, for example ...

Activation of Peripheral κ-Opioid Receptors Normalizes Caffeine Effects Modified in Nicotine-Dependent Rats during Nicotine Withdrawal.

Science.gov (United States)

Sudakov, S K; Bogdanova, N G

2016-10-01

The study examined the effect of peripheral (intragastric) ICI-204,448, an agonist of gastric κ-opioid receptors, on the psychostimulating and anxiolytic effects of caffeine in nicotinedependent rats at the stage of nicotine withdrawal. In these rats, the effects of caffeine (10 mg/kg) were perverted. In nicotine-dependent rats, caffeine produced an anxiolytic effect accompanied by pronounced stimulation of motor activity, in contrast to anxiogenic effect induced by caffeine in intact rats without nicotine dependence. During nicotine withdrawal, nicotine-dependent rats demonstrated enhanced sensitivity to nicotine. Intragastric administration of κ-opioid receptor agonist ICI-204,448 normalized the effect of caffeine in nicotinedependent rats. We have previously demonstrated that activation of peripheral κ-opioid receptors inhibited central κ-opioid activity and eliminated manifestations of nicotine withdrawal syndrome in nicotine-dependent rats, e.g. metabolism activation, stimulation of motor activity, and enhancement of food consumption. In its turn, inhibition of central κ-opioid structures activates the brain adenosine system, which can attenuate the caffeine-induced effects in nicotine-dependent rats.

Predictors of withdrawal: possible precursors of avoidant personality disorder.

Science.gov (United States)

Eggum, Natalie D; Eisenberg, Nancy; Spinrad, Tracy L; Valiente, Carlos; Edwards, Alison; Kupfer, Anne S; Reiser, Mark

2009-01-01

Relations of avoidant personality disorder (AvPD) with shyness and inhibition suggest that a precursor of AvPD is withdrawal. Using a sample of 4.5- to 7-year-olds studied four times, 2 years apart, four and three classes of children differing in trajectories of mother- and teacher-reported withdrawal, respectively, were identified. Mothers and teachers generally did not agree on children's trajectories but the pattern of findings in the two contexts did not differ markedly. The mother-identified high and declining withdrawal class, in comparison with less withdrawn classes, and the teacher-identified high and declining class compared with low withdrawal classes, were associated with relatively high levels of anger and low levels of attentional control and resiliency. The mother-identified moderate and increasing withdrawal class was distinguished from less problematic withdrawal classes by higher anger, lower resiliency, and sometimes, lower attentional control. The teacher-identified low and increasing withdrawal class was distinguished from less problematic withdrawal classes by lower resiliency and lower attentional control. Findings are discussed in terms of the developmental precursors to social withdrawal and avoidant behavior.

An Emerging New Paradigm in Opioid Withdrawal: A Critical Role for Glia-Neuron Signaling in the Periaqueductal Gray

OpenAIRE

Ouyang, Handong; Liu, Shue; Zeng, Weian; Levitt, Roy C.; Candiotti, Keith A.; Hao, Shuanglin

2012-01-01

The chronic use of opiates (i.e., narcotics such as the natural derivatives of opium including morphine or codeine) or opioids (i.e., semisynthetic derivatives of opium and other molecules that activate opioid receptors) induces dependence, which is associated with various specific behavioral and somatic signs after their withdrawal or after the administration of an opioid antagonist. Among the brain regions implicated in opiate dependence and withdrawal, the periaqueductal gray area (PAG) ap...

Buprenorphine for managing opioid withdrawal.

Science.gov (United States)

Gowing, Linda; Ali, Robert; White, Jason M; Mbewe, Dalitso

2017-02-21

Managed withdrawal is a necessary step prior to drug-free treatment or as the endpoint of substitution treatment. To assess the effects of buprenorphine versus tapered doses of methadone, alpha 2 -adrenergic agonists, symptomatic medications or placebo, or different buprenorphine regimens for managing opioid withdrawal, in terms of the intensity of the withdrawal syndrome experienced, duration and completion of treatment, and adverse effects. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 11, 2016), MEDLINE (1946 to December week 1, 2016), Embase (to 22 December 2016), PsycINFO (1806 to December week 3, 2016), and the Web of Science (to 22 December 2016) and handsearched the reference lists of articles. Randomised controlled trials of interventions using buprenorphine to modify the signs and symptoms of withdrawal in participants who were primarily opioid dependent. Comparison interventions involved reducing doses of methadone, alpha 2 -adrenergic agonists (clonidine or lofexidine), symptomatic medications or placebo, and different buprenorphine-based regimens. We used standard methodological procedures expected by Cochrane. We included 27 studies involving 3048 participants. The main comparators were clonidine or lofexidine (14 studies). Six studies compared buprenorphine versus methadone, and seven compared different rates of buprenorphine dose reduction. We assessed 12 studies as being at high risk of bias in at least one of seven domains of methodological quality. Six of these studies compared buprenorphine with clonidine or lofexidine and two with methadone; the other four studies compared different rates of buprenorphine dose reduction.For the comparison of buprenorphine and methadone in tapered doses, meta-analysis was not possible for the outcomes of intensity of withdrawal or adverse effects. However, information reported by the individual studies was suggestive of buprenorphine and methadone having similar capacity to

20 CFR 408.355 - Can you withdraw your application?

Science.gov (United States)

2010-04-01

... Section 408.355 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Filing Applications Withdrawal of Application § 408.355 Can you withdraw your application? (a) Request for withdrawal filed before a determination is made. You may withdraw your application...

21 CFR 514.7 - Withdrawal of applications without prejudice.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Withdrawal of applications without prejudice. 514... Withdrawal of applications without prejudice. The sponsor may withdraw his pending application from.... Such withdrawal may be made without prejudice to a future filing. Upon resubmission, the time...

Administration of memantine during withdrawal mitigates overactivity and spatial learning impairments associated with neonatal alcohol exposure in rats.

Science.gov (United States)

Idrus, Nirelia M; McGough, Nancy N H; Riley, Edward P; Thomas, Jennifer D

2014-02-01

Prenatal alcohol exposure can disrupt central nervous system development, manifesting as behavioral deficits that include motor, emotional, and cognitive dysfunction. Both clinical and animal studies have reported binge drinking during development to be highly correlated with an increased risk of fetal alcohol spectrum disorders (FASD). We hypothesized that binge drinking may be especially damaging because it is associated with episodes of alcohol withdrawal. Specifically, we have been investigating the possibility that NMDA receptor-mediated excitotoxicity occurs during alcohol withdrawal and contributes to developmental alcohol-related neuropathology. Consistent with this hypothesis, administration of the NMDA receptor antagonists MK-801 or eliprodil during withdrawal attenuates behavioral alterations associated with early alcohol exposure. In this study, we investigated the effects of memantine, a clinically used NMDA receptor antagonist, on minimizing ethanol-induced overactivity and spatial learning deficits. Sprague-Dawley pups were exposed to 6.0 g/kg ethanol via intubation on postnatal day (PD) 6, a period of brain development that models late gestation in humans. Controls were intubated with a calorically matched maltose solution. During withdrawal, 24 and 36 hours after ethanol exposure, subjects were injected with a total of either 0, 20, or 30 mg/kg memantine. The subjects' locomotor levels were recorded in open field activity monitors on PDs 18 to 21 and on a serial spatial discrimination reversal learning task on PDs 40 to 43. Alcohol exposure induced overactivity and impaired performance in spatial learning. Memantine administration significantly attenuated the ethanol-associated behavioral alterations in a dose-dependent manner. Thus, memantine may be neuroprotective when administered during ethanol withdrawal. These data have important implications for the treatment of EtOH's neurotoxic effects and provide further support that ethanol withdrawal

Methyl Parathion Masks Withdrawal from Physical Dependence on Morphine

Directory of Open Access Journals (Sweden)

Robin W. Rockhold

2002-10-01

Full Text Available Abstract: The cholinergic system has been proposed to participate in the development of dependence on opioids. The present study examined effects of dermal pretreatment with methyl parathion (MP, an acetylcholinesterase inhibitor, on the development of physical dependence on morphine. Opioid dependence was induced by continuous intracerebroventricular (i.c.v. infusion of morphine (26 nmol/μl/h for 3 days in adult male Sprague-Dawley rats. Each rat received two doses of MP, 12.5 mg/kg, dermally, initially, 3 days prior to initiation of i.c.v. morphine infusion and again on the first day of infusion. Withdrawal was precipitated after 3 days of infusion by administering an opioid antagonist, naloxone (48 nmol/5 μl, i.c.v.. Twelve of 23 MP-treated rats exhibited signs of acetylcholinesterase inhibitor intoxication (mild tremors and showed reduced spontaneous locomotor activity (tested by an open field test, prior to naloxone. The brain cholinesterase activity in these 12 rats was 13% of levels in control rats. Eleven rats that did not show toxic signs, exhibited cholinesterase activities that were 20% of control (not significant versus toxic group. The group that showed signs of MP intoxication exhibited a significantly lower incidence of opioid withdrawal jumping, rearing and wet dog shakes compared with the non-toxic group. No differences between quantal withdrawal signs (ptosis, penis-licking, and vocalization were noted between the two groups. The results suggest that toxic inhibition of acetylcholinesterase non-specifically reduces locomotor activity and may obscure certain behavioral signs of withdrawal from opioid dependence. This indicates that caution should be used in interpreting a direct involvement of acetylcholinesterase inhibition in preventing opioid dependence.

Nicotine withdrawal and stress-induced changes in pain sensitivity: a cross-sectional investigation between abstinent smokers and nonsmokers.

Science.gov (United States)

Nakajima, Motohiro; Al'Absi, Mustafa

2014-10-01

Chronic smoking has been linked with alterations in endogenous pain regulation. These alterations may be pronounced when individuals quit smoking because nicotine withdrawal produces a variety of psychological and physiological symptoms. Smokers interested in quitting (n = 98) and nonsmokers (n = 37) completed a laboratory session including cold pressor test (CPT) and heat thermal pain. Smokers set a quit date and completed the session after 48 h of abstinence. Participants completed the pain assessments once after rest and once after stress. Cardiovascular and nicotine withdrawal measures were collected. Smokers showed blunted cardiovascular responses to stress relative to nonsmokers. Only nonsmokers had greater pain tolerance to CPT after stress than after rest. Lower systolic blood pressure was related to lower pain tolerance. These findings suggest that smoking withdrawal is associated with blunted stress response and increased pain sensitivity. Copyright © 2014 Society for Psychophysiological Research.

Determinants of early withdrawal and of early withdrawal by reason of disability from the Irish labour force in the third age

OpenAIRE

Lawless, Martin

2015-01-01

III – Abstract: Determinants of early withdrawal and early withdrawal by reason of disability from the Irish labour force in the Third Age.Background. This study examines the relationship between early withdrawal and early withdrawal through disability from the Irish labour force in the Third Age. The relationship between unemployment or early retirement and ill health has been determined by a number of studies and, while unemployment through ill health or occupational disability may lead to ...

20 CFR 404.640 - Withdrawal of an application.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Withdrawal of an application. 404.640 Section 404.640 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Filing of Applications and Other Forms Withdrawal of Application § 404.640 Withdrawal of...

20 CFR 416.355 - Withdrawal of an application.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Withdrawal of an application. 416.355 Section 416.355 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL SECURITY INCOME FOR THE AGED, BLIND, AND DISABLED Filing of Applications Withdrawal of Application § 416.355 Withdrawal of an...

Withdrawal symptoms in internet gaming disorder: A systematic review.

Science.gov (United States)

Kaptsis, Dean; King, Daniel L; Delfabbro, Paul H; Gradisar, Michael

2016-02-01

Internet gaming disorder (IGD) is currently positioned in the appendix of the DSM-5 as a condition requiring further study. The aim of this review was to examine the state of current knowledge of gaming withdrawal symptomatology, given the importance of withdrawal in positioning the disorder as a behavioral addiction. A total of 34 studies, including 10 qualitative studies, 17 research reports on psychometric instruments, and 7 treatment studies, were evaluated. The results indicated that the available evidence on Internet gaming withdrawal is very underdeveloped. Internet gaming withdrawal is most consistently referred to as 'irritability' and 'restlessness' following cessation of the activity. There exists a concerning paucity of qualitative studies that provide detailed clinical descriptions of symptoms arising from cessation of internet gaming. This has arguably compromised efforts to quantify withdrawal symptoms in empirical studies of gaming populations. Treatment studies have not reported on the natural course of withdrawal and/or withdrawal symptom trajectory following intervention. It is concluded that many more qualitative clinical studies are needed, and should be prioritised, to develop our understanding of gaming withdrawal. This should improve clinical descriptions of problematic internet gaming and in turn improve the quantification of IGD withdrawal and thus treatments for harmful internet gaming. Copyright © 2015 Elsevier Ltd. All rights reserved.

SSRI and SNRI withdrawal symptoms reported on an internet forum.

Science.gov (United States)

Stockmann, Tom; Odegbaro, Dolapo; Timimi, Sami; Moncrieff, Joanna

2018-05-09

Antidepressant withdrawal symptoms are well-recognised, but their potential duration remains uncertain. We aimed to describe the characteristics of withdrawal associated with two popular classes of antidepressants, including duration. We analysed the content of a sample of posts on an antidepressant withdrawal website. We compared the characteristics of withdrawal associated with SSRIs and SNRIs, including time of onset, duration and nature of symptoms. 110 posts about SSRI withdrawal, and 63 concerning SNRI withdrawal, were analysed. The mean duration of withdrawal symptoms was significantly longer with SSRIs than SNRIs: 90.5 weeks (standard deviation, SD, 150.0) and 50.8 weeks (SD 76.0) respectively; p = 0.043). Neurological symptoms, such as 'brain zaps,' were more common among SNRI users (p = 0.023). Psychosexual/genitourinary symptoms may be more common among SSRI users (p = 0.054). The website aims to help people with antidepressant withdrawal, and is therefore likely to attract people who have difficulties. Length of prior use of antidepressants was long, with a mean of 252.2 weeks (SD 250.8). People accessing antidepressant withdrawal websites report experiencing protracted withdrawal symptoms. There are some differences in the characteristics of withdrawal associated with different classes of antidepressants.

The Non-Proliferation Treaty and the Withdrawal Clause

International Nuclear Information System (INIS)

Boutherin, Gregory

2008-01-01

Like any international agreement, the NPT includes a withdrawal clause. The North Korean withdrawal, which was announced in 1993 and became effective in 2003, shows how difficult it is to preserve this possibility, while guaranteeing compliance with signed agreements. To achieve this target, two conditions are required: first, enhancing the means by which the reasons for withdrawals can be made clear and second, to allow the Security Council to draw all the consequences of withdrawals that could imply that a treaty has been violated

Altered brain serotonergic neurotransmission following caffeine withdrawal produces behavioral deficits in rats.

Science.gov (United States)

Khaliq, Saima; Haider, Saida; Naqvi, Faizan; Perveen, Tahira; Saleem, Sadia; Haleem, Darakhshan Jabeen

2012-01-01

Caffeine administration has been shown to enhance performance and memory in rodents and humans while its withdrawal on the other hand produces neurobehavioral deficits which are thought to be mediated by alterations in monoamines neurotransmission. A role of decreased brain 5-HT (5-hydroxytryptamine, serotonin) levels has been implicated in impaired cognitive performance and depression. Memory functions of rats were assessed by Water Maze (WM) and immobility time by Forced Swim Test (FST). The results of this study showed that repeated caffeine administration for 6 days at 30 mg/kg dose significantly increases brain 5-HT (pcaffeine. Withdrawal of caffeine however produced memory deficits and significantly increases the immobility time of rats in FST. The results of this study are linked with caffeine induced alterations in serotonergic neurotransmission and its role in memory and depression.

Withdrawal-oriented therapy for smokers.

Science.gov (United States)

Hajek, P

1989-06-01

The treatment approach of the Maudsley Hospital Smokers Clinic is described. It stems from the notion that smokers seeking help are dependent on nicotine, and that withdrawal discomfort is a major block to their success in quitting. Accordingly, therapy focuses on helping clients overcome nicotine deprivation. It uses nicotine replacement and a special format of group treatment. Details are given of preparation of clients, use of nicotine chewing gum, use of group-oriented groupwork, use of information about withdrawal, and training in withdrawal-oriented therapy. Data are presented concerning characteristics of the clientele, treatment adherence, and treatment results. A number of controversial issues are addressed, such as the optimal duration of treatment, timing of the quit date, the value of educational input, and the value of individualization of treatment goals.

Management of precipitated opiate withdrawal syndrome induced by nalmefene mistakenly prescribed in opiate-dependent patients: a review for clinicians.

Science.gov (United States)

Franchitto, Nicolas; Jullian, Benedicte; Salles, Juliette; Pelissier, Fanny; Rolland, Benjamin

2017-06-01

Nalmefene, a long-acting µ-opioid antagonist approved to treat alcohol use disorder, is occasionally mistakenly prescribed to opiate-dependent or opioid-treated patients. We review recent literature on drug-drug interactions between nalmefene and opioids that lead to precipitated opioid withdrawal, and focus on its management and planning for care at discharge. Areas covered: This article provides a brief and comprehensive review of management of precipitated opioid withdrawal syndrome when nalmefene is associated with an opioid, whether misused or legally prescribed. Expert opinion: When treating an opiate-dependent patient with co-occurring alcohol use disorder, both conditions need to be a focus of clinical attention. New drugs for alcohol use disorder have been approved, but must be given cautiously and with a full understanding of their potential drug-drug interactions with opioid medications. Opiate-dependent patients should be intensively monitored for risk factors of alcohol use disorder and should be continuously motivated for treatment maintenance. When nalmefene is administered to opiate-dependent patients, acute opioid withdrawal syndrome may occur. Management of precipitated acute opioid withdrawal may include short or long-acting µ-opioid agonists during hospitalization, in addition to supportive treatment. The best management of polydrug abusers is based on a multidisciplinary approach, which should be pursued and improved through continuing medical education.

Water Withdrawals, Use, and Trends in Florida, 2005

Science.gov (United States)

Marella, Richard L.

2009-01-01

In 2005, the total amount of water withdrawals in Florida was estimated at 18,359 million gallons per day (Mgal/d). Saline water accounted for 11,486 Mgal/d (63 percent), and freshwater accounted for 6,873 Mgal/d (37 percent). Groundwater accounted for 4,247 Mgal/d (62 percent) of freshwater withdrawals, and surface water accounted for the remaining 2,626 Mgal/d (38 percent). Surface water accounted for nearly all (99.9 percent) saline-water withdrawals. An additional 660 Mgal/d of reclaimed wastewater was used in Florida during 2005. The largest amount of freshwater was withdrawn from Palm Beach County, and the largest amount of saline water was withdrawn from Pasco County. Fresh groundwater provided drinking water (public supplied and self-supplied) for 16.19 million people (90 percent of Florida's population), and fresh surface water provided drinking water for 1.73 million people (10 percent). The majority of groundwater withdrawals (nearly 60 percent) in 2005 was obtained from the Floridan aquifer system which is present throughout the entire State. The majority of fresh surface-water withdrawals (59 percent) came from the southern Florida hydrologic unit subregion and is associated with Lake Okeechobee and the canals in the Everglades Agricultural Area of Glades, Hendry, and Palm Beach Counties, as well as the Caloosahatchee River and its tributaries in the agricultural areas of Collier, Glades, Hendry, and Lee Counties. Overall, agricultural irrigation accounted for 40 percent of the total freshwater withdrawals (ground and surface), followed by public supply with 37 percent. Public supply accounted for 52 percent of groundwater withdrawals, followed by agricultural self-supplied (31 percent), ommercial-industrial-mining self-supplied (8.5 percent), recreational irrigation and domestic self-supplied (4 percent each), and power generation (0.5 percent). Agricultural self-supplied accounted for 56 percent of fresh surface-water withdrawals, followed by power

Acupuncture Attenuates Anxiety-Like Behavior by Normalizing Amygdaloid Catecholamines during Ethanol Withdrawal in Rats

Directory of Open Access Journals (Sweden)

Zheng Lin Zhao

2011-01-01

Full Text Available Previously, we demonstrated acupuncture at acupoint HT7 (Shen-Men attenuated ethanol withdrawal syndrome by normalizing the dopamine release in nucleus accumbens shell. In the present study, we investigated the effect of acupuncture on anxiety-like behavior in rats and its relevant mechanism by studying neuro-endocrine parameters during ethanol withdrawal. Rats were treated with 3 g kg−1day−1 of ethanol (20%, w/v or saline by intraperitoneal injections for 28 days. The rats undergoing ethanol withdrawal exhibited anxiety-like behavior 72 h after the last dose of ethanol characterized by the decrease of time spent in the open arms of the elevated plus maze compared with the saline-treated rats (P < .05. Radioimmunoassay exhibited there were notably increased concentrations of plasma corticosterone in ethanol-withdrawn rats compared with saline-treated rats (P < .05. Additionally, high performance liquid chromatography analysis also showed the levels of norepinephrine and 3-methoxy-4-hydroxy-phenylglycol were markedly increased while the levels of dopamine and 3,4-dihydroxyphenylacetic acid were significantly decreased in the central nucleus of the amygdala of ethanol-withdrawn rats compared with saline-treated rats (P < .01. Acupuncture groups were treated with acupuncture at acupoint HT7 or PC6 (Nei-Guan. Acupuncture at HT7 but not PC6 greatly attenuated the anxiety-like behavior during ethanol withdrawal as evidenced by significant increases in the percentage of time spent in open arms (P < .05. In the meantime, acupuncture at HT7 also markedly inhibited the alterations of neuro-endocrine parameters induced by ethanol withdrawal (P < .05. These results suggest that acupuncture may attenuate anxiety-like behavior during ethanol withdrawal through regulation of neuro-endocrine system.

Opiate Withdrawal Complicated by Tetany and Cardiac Arrest

Directory of Open Access Journals (Sweden)

Irfanali R. Kugasia

2014-01-01

Full Text Available Patients with symptoms of opiate withdrawal, after the administration of opiate antagonist by paramedics, are a common presentation in the emergency department of hospitals. Though most of opiate withdrawal symptoms are benign, rarely they can become life threatening. This case highlights how a benign opiate withdrawal symptom of hyperventilation led to severe respiratory alkalosis that degenerated into tetany and cardiac arrest. Though this patient was successfully resuscitated, it is imperative that severe withdrawal symptoms are timely identified and immediate steps are taken to prevent catastrophes. An easier way to reverse the severe opiate withdrawal symptom would be with either low dose methadone or partial opiate agonists like buprenorphine. However, if severe acid-base disorder is identified, it would be safer to electively intubate these patients for better control of their respiratory and acid-base status.

The alcohol withdrawal syndrome.

LENUS (Irish Health Repository)

McKeon, A

2008-08-01

The alcohol withdrawal syndrome (AWS) is a common management problem in hospital practice for neurologists, psychiatrists and general physicians alike. Although some patients have mild symptoms and may even be managed in the outpatient setting, others have more severe symptoms or a history of adverse outcomes that requires close inpatient supervision and benzodiazepine therapy. Many patients with AWS have multiple management issues (withdrawal symptoms, delirium tremens, the Wernicke-Korsakoff syndrome, seizures, depression, polysubstance abuse, electrolyte disturbances and liver disease), which requires a coordinated, multidisciplinary approach. Although AWS may be complex, careful evaluation and available treatments should ensure safe detoxification for most patients.

42 CFR 457.170 - Withdrawal process.

Science.gov (United States)

2010-10-01

... 42 Public Health 4 2010-10-01 2010-10-01 false Withdrawal process. 457.170 Section 457.170 Public... Plans for Child Health Insurance Programs and Outreach Strategies § 457.170 Withdrawal process. (a... amendment, or any portion of a proposed State plan or plan amendment, at any time during the review process...

Mitragynine attenuates withdrawal syndrome in morphine-withdrawn zebrafish.

Directory of Open Access Journals (Sweden)

Beng-Siang Khor

Full Text Available A major obstacle in treating drug addiction is the severity of opiate withdrawal syndrome, which can lead to unwanted relapse. Mitragynine is the major alkaloid compound found in leaves of Mitragyna speciosa, a plant widely used by opiate addicts to mitigate the harshness of drug withdrawal. A series of experiments was conducted to investigate the effect of mitragynine on anxiety behavior, cortisol level and expression of stress pathway related genes in zebrafish undergoing morphine withdrawal phase. Adult zebrafish were subjected to two weeks chronic morphine exposure at 1.5 mg/L, followed by withdrawal for 24 hours prior to tests. Using the novel tank diving tests, we first showed that morphine-withdrawn zebrafish display anxiety-related swimming behaviors such as decreased exploratory behavior and increased erratic movement. Morphine withdrawal also elevated whole-body cortisol levels, which confirms the phenotypic stress-like behaviors. Exposing morphine-withdrawn fish to mitragynine however attenuates majority of the stress-related swimming behaviors and concomitantly lower whole-body cortisol level. Using real-time PCR gene expression analysis, we also showed that mitragynine reduces the mRNA expression of corticotropin releasing factor receptors and prodynorphin in zebrafish brain during morphine withdrawal phase, revealing for the first time a possible link between mitragynine's ability to attenuate anxiety during opiate withdrawal with the stress-related corticotropin pathway.

Withdrawing to a Virtual World: Associations between Subtypes of Withdrawal, Media Use, and Maladjustment in Emerging Adults

Science.gov (United States)

Nelson, Larry J.; Coyne, Sarah M.; Howard, Emily; Clifford, Brandon N.

2016-01-01

An approach-avoidance model of social withdrawal (Asendorpf, 1990) identifies 3 types of social withdrawal including shyness, unsociability, and avoidance. Each appears to be uniquely associated with varying indicators of maladjustment in emerging adulthood (Nelson, 2013) but little, if any, work has been done to see how they might be linked to…

An overview of research on social withdrawal in childhood

OpenAIRE

野村, あすか; NOMURA, Asuka

2013-01-01

In recent years, “HIKIKOMORI” in adolescence or adulthood has grown into a serious problem in Japan and the need for early intervention and support has been emphasized. Among the risk factors of “HIKIKOMORI” is social withdrawal in childhood. With this in mind, I reviewed previous studies on the social withdrawal in children living abroad. The review commences with an examination of definitions of social withdrawal, which showed that in some foreign countries, social withdrawal refers to the ...

Why withdrawal from the European Union is undemocratic

DEFF Research Database (Denmark)

Olsen, Tore Vincents; Rostbøll, Christian F.

2017-01-01

The Lisbon Treaty from 2009 introduced the possibility for individual member states to withdraw from the European Union (EU) on the basis of a unilateral decision. In June 2016 the UK decided to leave the EU invoking article 50 of the treaty. But is withdrawal democratically legitimate? In fact......, the all affected principle suggests that it is undemocratic for subunits to leave larger political units when it adversely affects other citizens without including them in the decision. However, it is unclear what the currency of this affectedness is and, hence, why withdrawal would be undemocratic. We...... argue that it is the effect of withdrawal on the status of citizens as free and equal that is decisive and that explains why unilateral withdrawal of subunits from larger units is democratically illegitimate. Moreover, on the ‘all affected status principle’ that we develop, even multilaterally agreed...

Pathophysiology of metabolic syndrome: The onset of natural recovery on withdrawal of a high-carbohydrate, high-fat diet.

Science.gov (United States)

Hazarika, Ankita; Kalita, Himadri; Chandra Boruah, Dulal; Chandra Kalita, Mohan; Devi, Rajlakshmi

2016-10-01

Chronic consumption of high-carbohydrate, high-fat (HCHF) diet induces metabolic syndrome (MetS) and markedly impairs the ultra-structure of organs. To our knowledge, no scientific study has yet to report the effect of withdrawal of an HCHF diet on MetS-associated ultra-structural abnormalities in affected organs and tissues. Therefore, the aim of this study was to investigate the effects of subchronic withdrawal of the HCHF diet, specifically with a pathophysiological approach. Wister albino rats (N = 72) were divided into three groups: Groups A and B were fed a standard basal diet and an HCHF diet, respectively, for 16 wk. Group C was on an HCHF diet for the initial 12 wk and then returned to basal diet for 4 wk. Histopathological changes in the heart, lungs, liver, spleen, pancreas, small intestine, kidney, white adipose tissue (WAT), skeletal muscle, and hippocampus of the brain were monitored at 4, 8, 12, and 16 wk. Lipid droplets (LDs) in liver, fibrosis in the pancreas, abnormalities in the glomerulus of the kidney, and an increase in the size of adipocytes were observed in groups B and C at week 12. Withdrawal of the HCHF diet in group C showed the onset of regenerative features at the ultra-structural level. HCHF diet-fed rats in group B had higher body weights; raised lipid profiles, blood glucose levels, and insulin resistance than basal diet-fed rats in group A and HCHF to basal diet-fed rats in group C at week 16. An HCHF diet induces ultra-structural abnormalities, which are significantly reversed by subchronic withdrawal of a MetS-inducing HCHF diet, indicating the onset of natural recovery at the ultra-structural level of affected organs. Copyright © 2016 Elsevier Inc. All rights reserved.

Regulation of glutamate transporter 1 (GLT-1) gene expression by cocaine self-administration and withdrawal.

Science.gov (United States)

Kim, Ronald; Sepulveda-Orengo, Marian T; Healey, Kati L; Williams, Emily A; Reissner, Kathryn J

2018-01-01

Downregulation of the astroglial glutamate transporter GLT-1 is observed in the nucleus accumbens (NAc) following administration of multiple drugs of abuse. The decrease in GLT-1 protein expression following cocaine self-administration is dependent on both the amount of cocaine self-administered and the length of withdrawal, with longer access to cocaine and longer withdrawal periods leading to greater decreases in GLT-1 protein. However, the mechanism(s) by which cocaine downregulates GLT-1 protein remains unknown. We used qRT-PCR to examine gene expression of GLT-1 splice isoforms (GLT-1A, GLT-1B) in the NAc, prelimbic cortex (PL) and basolateral amygdala (BLA) of rats, following two widely used models of cocaine self-administration: short-access (ShA) self-administration, and the long-access (LgA) self-administration/incubation model. While downregulation of GLT-1 protein is observed following ShA cocaine self-administration and extinction, this model did not lead to a change in GLT-1A or GLT-1B gene expression in any brain region examined. Forced abstinence following ShA cocaine self-administration also was without effect. In contrast, LgA cocaine self-administration and prolonged abstinence significantly decreased GLT-1A gene expression in the NAc and BLA, and significantly decreased GLT-1B gene expression in the PL. No change was observed in NAc GLT-1A gene expression one day after LgA cocaine self-administration, indicating withdrawal-induced decreases in GLT-1A mRNA. In addition, LgA cocaine self-administration and withdrawal induced hypermethylation of the GLT-1 gene in the NAc. These results indicate that a decrease in NAc GLT-1 mRNA is only observed after extended access to cocaine combined with protracted abstinence, and that epigenetic mechanisms likely contribute to this effect. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cytoplasmic sequestration of cyclin D1 associated with cell cycle withdrawal of neuroblastoma cells

International Nuclear Information System (INIS)

Sumrejkanchanakij, Piyamas; Eto, Kazuhiro; Ikeda, Masa-Aki

2006-01-01

The regulation of D-type cyclin-dependent kinase activity is critical for neuronal differentiation and apoptosis. We recently showed that cyclin D1 is sequestered in the cytoplasm and that its nuclear localization induces apoptosis in postmitotic primary neurons. Here, we further investigated the role of the subcellular localization of cyclin D1 in cell cycle withdrawal during the differentiation of N1E-115 neuroblastoma cells. We show that cyclin D1 became predominantly cytoplasmic after differentiation. Targeting cyclin D1 expression to the nucleus induced phosphorylation of Rb and cdk2 kinase activity. Furthermore, cyclin D1 nuclear localization promoted differentiated N1E-115 cells to reenter the cell cycle, a process that was inhibited by p16 INK4a , a specific inhibitor of D-type cyclin activity. These results indicate that cytoplasmic sequestration of cyclin D1 plays a role in neuronal cell cycle withdrawal, and suggests that the abrogation of machinery involved in monitoring aberrant nuclear cyclin D1 activity contributes to neuronal tumorigenesis

Enhanced striatial 3H-spiroperidol binding induced by chronic haloperidol treatment inhibited by peptides administered during the withdrawal phase

International Nuclear Information System (INIS)

Bhargava, H.N.

1984-01-01

Chronic intragastric administration of haloperidol (1.5 mg/kg/day) for 21 days followed by a 3-day withdrawal period resulted in the development of enhanced locomotor activity response to apomorphine, and an increase in the number of binding sites for 3 H-spiroperidol in the striatal membranes of the rat brain. Subcutaneous administration of Pro-Leu-Gly-NH 2 or cyclo-(Leu-Gly) in doses of 2 mg/kg/day given for 3-days after termination of haloperidol treatment inhibited the enhanced response to apomorphine, as well as the increases in the number of 3 H-spiroperidol binding sites in the striatum. If indeed, the supersensitivity of striatal dopamine receptors is one of the mechanisms in the development of tardive dyskinesia symptoms, the present results suggest that the above peptides may be helpful in ameliorating some of the symptoms of tardive dyskinesia induced by neuroleptic drugs. 31 references, 3 figures

15 CFR 10.13 - Withdrawal of a published standard.

Science.gov (United States)

2010-01-01

...) Before withdrawing a standard published under these procedures, the Director will review the relative... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Withdrawal of a published standard. 10... DEVELOPMENT OF VOLUNTARY PRODUCT STANDARDS § 10.13 Withdrawal of a published standard. (a) Standards published...

Demand-Withdraw Patterns in Marital Conflict in the Home.

Science.gov (United States)

Papp, Lauren M; Kouros, Chrystyna D; Cummings, E Mark

2009-06-01

The present study extended laboratory-based findings of demand-withdraw communication into marital conflict in the home and further explored its linkages with spousal depression. U.S. couples (N = 116) provided diary reports of marital conflict and rated depressive symptoms. Hierarchical linear modeling results indicated that husband demand-wife withdraw and wife demand-husband withdraw occurred in the home at equal frequency, and both were more likely to occur when discussing topics that concerned the marital relationship. For both patterns, conflict initiator was positively linked to the demander role. Accounting for marital satisfaction, both demand-withdraw patterns predicted negative emotions and tactics during marital interactions and lower levels of conflict resolution. Spousal depression was linked to increased likelihood of husband demand-wife withdraw.

75 FR 7526 - Withdrawal of Regulatory Guide

Science.gov (United States)

2010-02-19

...'s Electronic Reading Room at http://www.nrc.gov/reading-rm/doc-collections . Regulatory guides are... NUCLEAR REGULATORY COMMISSION [NRC-2010-0052] Withdrawal of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Withdrawal of Regulatory Guide 1.56, ``Maintenance of Water Purity in Boiling...

Extinction Training Regulates Neuroadaptive Responses to Withdrawal from Chronic Cocaine Self-Administration

OpenAIRE

Self, David W.; Choi, Kwang-Ho; Simmons, Diana; Walker, John R.; Smagula, Cynthia S.

2004-01-01

Cocaine produces multiple neuroadaptations with chronic repeated use. Many of these neuroadaptations can be reversed or normalized by extinction training during withdrawal from chronic cocaine self-administration in rats. This article reviews our past and present studies on extinction-induced modulation of the neuroadaptive response to chronic cocaine in the mesolimbic dopamine system, and the role of this modulation in addictive behavior in rats. Extinction training normalizes tyrosine hydro...

Acupuncture for alcohol withdrawal: a randomized controlled trial.

Science.gov (United States)

Trümpler, François; Oez, Suzan; Stähli, Peter; Brenner, Hans Dieter; Jüni, Peter

2003-01-01

Previous trials on acupuncture in alcohol addiction were in outpatients and focused on relapse prevention. Rates of dropout were high and interpretation of results difficult. We compared auricular laser and needle acupuncture with sham laser stimulation in reducing the duration of alcohol withdrawal. Inpatients undergoing alcohol withdrawal were randomly allocated to laser acupuncture (n = 17), needle acupuncture (n = 15) or sham laser stimulation (n = 16). Attempts were made to blind patients, therapists and outcome assessors, but this was not feasible for needle acupuncture. The duration of withdrawal symptoms (as assessed using a nurse-rated scale) was the primary outcome; the duration of sedative prescription was the secondary outcome. Patients randomized to laser and sham laser had identical withdrawal symptom durations (median 4 days). Patients randomized to needle stimulation had a shorter duration of withdrawal symptoms (median 3 days; P = 0.019 versus sham intervention), and tended to have a shorter duration of sedative use, but these differences diminished after adjustment for baseline differences. The data from this pilot trial do not suggest a relevant benefit of auricular laser acupuncture for alcohol withdrawal. A larger trial including adequate sham interventions is needed, however, to reliably determine the effectiveness of any type of auricular acupuncture in this condition.

45 CFR 400.301 - Withdrawal from the refugee program.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 2 2010-10-01 2010-10-01 false Withdrawal from the refugee program. 400.301... Waivers and Withdrawals § 400.301 Withdrawal from the refugee program. (a) In the event that a State... assistance, social services, preventive health, and an unaccompanied minors program if appropriate. A State...

Water withdrawals, use, and trends in Florida, 2010

Science.gov (United States)

Marella, Richard L.

2014-01-01

In 2010, the total amount of water withdrawn in Florida was estimated to be 14,988 million gallons per day (Mgal/d). Saline water accounted for 8,589 Mgal/d (57 percent) and freshwater accounted for 6,399 Mgal/d (43 percent). Groundwater accounted for 4,166 Mgal/d (65 percent) of freshwater withdrawals, and surface water accounted for the remaining 2,233 Mgal/d (35 percent). Surface water accounted for nearly all (99.9 percent) saline-water withdrawals. An additional 659 Mgal/d of reclaimed wastewater was used in Florida during 2010. Freshwater withdrawals were greatest in Palm Beach County (707 Mgal/d), and saline-water withdrawals were greatest in Hillsborough County (1,715 Mgal/d). Fresh groundwater provided drinking water (public supplied and self-supplied) for 17.33 million people (92 percent of Florida’s population), and fresh surface water provided drinking water for 1.47 million people (8 percent). The statewide public-supply gross per capita use for 2010 was 134 gallons per day, whereas the statewide public-supply domestic per capita use was 85 gallons per day. The majority of groundwater withdrawals (almost 62 percent) in 2010 were obtained from the Floridan aquifer system, which is present throughout most of the State. The majority of fresh surface-water withdrawals (56 percent) came from the southern Florida hydrologic unit subregion and is associated with Lake Okeechobee and the canals in the Everglades Agricultural Area of Glades, Hendry, and Palm Beach Counties, as well as the Caloosahatchee River and its tributaries in the agricultural areas of Collier, Glades, Hendry, and Lee Counties. Overall, agricultural irrigation accounted for 40 percent of the total freshwater withdrawals (ground and surface), followed by public supply with 35 percent. Public supply accounted for 48 percent of groundwater withdrawals, followed by agricultural self-supplied (34 percent), commercial-industrial-mining self-supplied (7 percent), recreational

A psychometric validation of the Short Alcohol Withdrawal Scale (SAWS)

DEFF Research Database (Denmark)

Elholm, Bjarne; Larsen, Klaus; Hornnes, Nete

2010-01-01

The study aimed to evaluate psychometrically a Danish translation of the Short Alcohol Withdrawal Scale (SAWS) in an outpatient setting in patients with Alcohol Dependence (AD) and Alcohol Withdrawal Symptoms/Syndrome (AWS).......The study aimed to evaluate psychometrically a Danish translation of the Short Alcohol Withdrawal Scale (SAWS) in an outpatient setting in patients with Alcohol Dependence (AD) and Alcohol Withdrawal Symptoms/Syndrome (AWS)....

[Treatment of gamma-hydroxybutyrate withdrawal].

Science.gov (United States)

Strand, Niels August Willer; Petersen, Tonny Studsgaard; Nielsen, Lars Martin; Boegevig, Soren

2017-12-11

Gamma-hydroxybutyrate (GHB) is a drug of abuse, for which physical addiction develops quickly. GHB withdrawal can develop into a life-threatening condition and has previously been treated mainly with benzodiazepines. These have not always proven effective, leading to long hospitalizations in intensive care units. Based on successful Dutch treatment results for using GHB to treat GHB withdrawal symptoms, we propose to implement a similar method in Denmark. The method requires an interdisciplinary effort for which The Danish Poison Information Centre should be consulted for expertise.

21 CFR 171.7 - Withdrawal of petition without prejudice.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Withdrawal of petition without prejudice. 171.7... Withdrawal of petition without prejudice. (a) In some cases the Commissioner will notify the petitioner that... clarification or the obtaining of additional data. This withdrawal will be without prejudice to a future filing...

21 CFR 571.7 - Withdrawal of petition without prejudice.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Withdrawal of petition without prejudice. 571.7... Withdrawal of petition without prejudice. (a) In some cases the Commissioner will notify the petitioner that... clarification or the obtaining of additional data. This withdrawal will be without prejudice to a future filing...

Withdrawal-Related Changes in Delay Discounting Predict Short-Term Smoking Abstinence.

Science.gov (United States)

Miglin, Rickie; Kable, Joseph W; Bowers, Maureen E; Ashare, Rebecca L

2017-06-01

Impulsive decision making is associated with smoking behavior and reflects preferences for smaller, immediate rewards and intolerance of temporal delays. Nicotine withdrawal may alter impulsive decision making and time perception. However, little is known about whether withdrawal-related changes in decision making and time perception predict smoking relapse. Forty-five smokers (14 female) completed two laboratory sessions, one following 24-hour abstinence and one smoking-as-usual (order counterbalanced; biochemically verified abstinence). During each visit, participants completed measures of time perception, decision making (ie, discount rates), craving, and withdrawal. Following the second laboratory session, subjects underwent a well-validated model of short-term abstinence (quit week) with small monetary incentives for each day of biochemically confirmed abstinence. Smokers significantly overestimated time during abstinence, compared to smoking-as-usual (p = .021), but there were no abstinence effects on discount rates (p = .6). During the quit week, subjects were abstinent for 3.5 days (SD = 2.15) and smoked a total of 12.9 cigarettes (SD = 15.8). Importantly, higher discount rates (ie, preferences for immediate rewards) during abstinence (abstinence minus smoking difference score) predicted greater number of days abstinent (p = .01) and fewer cigarettes smoked during the quit week (p = .02). Withdrawal-related change in time reproduction did not predict relapse (p = .2). These data suggest that individuals who have a greater preference for immediate rewards during abstinence (vs. smoking-as-usual) may be more successful at maintaining short-term abstinence when provided with frequent (eg, daily) versus less frequent incentive schedules (eg, 1 month). Abstinence-induced changes in decision making may be important for identifying smokers who may benefit from interventions that incentivize abstinence such as contingency management (CM). The present results

A case of rhabdomyolysis associated with severe opioid withdrawal.

Science.gov (United States)

Gangahar, Deepali

2015-08-01

While the risk of opioid overdose is widely accepted, the dangers of opioid withdrawal are far less clearly defined. The purpose of this publication is to provide evidence against the erroneous clinical dictum that opioid withdrawal is never life-threatening. This case report (N = 1) illustrates an unfortunate, common scenario of a man abusing prescription opioids and heroin. His attempt at self-detoxification with buprenorphine-naloxone resulted in life-threatening opioid withdrawal. A detailed account of each day of his withdrawal period was documented by patient and family report and review of all medical records. The patient was contacted three months after hospitalization to verify information and determine progress in treatment and abstinence from drugs and alcohol. A review of the literature was completed on severe cases of precipitated and spontaneous opioid withdrawal followed by a discussion of the significance as it relates to this case. Given the widespread use of prescription opioids and opioid maintenance treatment, physicians should be aware of the complications of acute opioid withdrawal and should be equipped to treat these complications. © American Academy of Addiction Psychiatry.

Cocaine craving during protracted withdrawal requires PKCε priming within vmPFC.

Science.gov (United States)

Miller, Bailey W; Wroten, Melissa G; Sacramento, Arianne D; Silva, Hannah E; Shin, Christina B; Vieira, Philip A; Ben-Shahar, Osnat; Kippin, Tod E; Szumlinski, Karen K

2017-05-01

In individuals with a history of drug taking, the capacity of drug-associated cues to elicit indices of drug craving intensifies or incubates with the passage of time during drug abstinence. This incubation of cocaine craving, as well as difficulties with learning to suppress drug-seeking behavior during protracted withdrawal, are associated with a time-dependent deregulation of ventromedial prefrontal cortex (vmPFC) function. As the molecular bases for cocaine-related vmPFC deregulation remain elusive, the present study assayed the consequences of extended access to intravenous cocaine (6 hours/day; 0.25 mg/infusion for 10 day) on the activational state of protein kinase C epsilon (PKCε), an enzyme highly implicated in drug-induced neuroplasticity. The opportunity to engage in cocaine seeking during cocaine abstinence time-dependently altered PKCε phosphorylation within vmPFC, with reduced and increased p-PKCε expression observed in early (3 days) and protracted (30 days) withdrawal, respectively. This effect was more robust within the ventromedial versus dorsomedial PFC, was not observed in comparable cocaine-experienced rats not tested for drug-seeking behavior and was distinct from the rise in phosphorylated extracellular signal-regulated kinase observed in cocaine-seeking rats. Further, the impact of inhibiting PKCε translocation within the vmPFC using TAT infusion proteins upon cue-elicited responding was determined and inhibition coinciding with the period of testing attenuated cocaine-seeking behavior, with an effect also apparent the next day. In contrast, inhibitor pretreatment prior to testing during early withdrawal was without effect. Thus, a history of excessive cocaine taking influences the cue reactivity of important intracellular signaling molecules within the vmPFC, with PKCε playing a critical role in the manifestation of cue-elicited cocaine seeking during protracted drug withdrawal. © 2016 Society for the Study of Addiction.

Impact of high- versus low-dose neuromuscular blocking agent administration on unplanned 30-day readmission rates in retroperitoneal laparoscopic surgery.

Directory of Open Access Journals (Sweden)

Martijn Boon

Full Text Available Recent data shows that a neuromuscular block (NMB induced by administration of high doses of rocuronium improves surgical conditions in certain procedures. However, there are limited data on the effect such practices on postoperative outcomes. We performed a retrospective analysis to compare unplanned 30-day readmissions in patients that received high-dose versus low-dose rocuronium administration during general anesthesia for laparoscopic retroperitoneal surgery. This retrospective cohort study was performed in the Netherlands in an academic hospital where routine high-dose rocuronium NMB has been practiced since July 2015. Charts of patients receiving anesthesia between January 2014 and December 2016 were searched for surgical cases receiving high-dose rocuronium and matched with respect to procedure, age, sex and ASA classification to patients receiving low-dose rocuronium. The primary post-operative outcome was unplanned 30-day readmission rate. There were 130 patients in each cohort. Patients in the high- and low-dose rocuronium cohorts received 217 ± 49 versus 37 ± 5 mg rocuronium, respectively. In the high-dose rocuronium group neuromuscular activity was consistently monitored; matched patients were unreliably monitored. All patients receiving high-dose rocuronium were reversed with sugammadex, while just 33% of matched patients were reversed with sugammadex and 20% with neostigmine; the remaining patients were not reversed. Unplanned 30-day readmission rate was significantly lower in the high-dose compared to the low-dose rocuronium cohort (3.8% vs. 12.7%; p = 0.03; odds ratio = 0.33, 95% C.I. 0.12-0.95. This small retrospective study demonstrates a lower incidence of unplanned readmissions within 30-days following laparoscopic retroperitoneal surgery with high-dose relaxant anesthesia and sugammadex reversal in comparison to low-dose relaxant anesthesia. Further prospective studies are needed in larger samples to corroborate our

Impact of high- versus low-dose neuromuscular blocking agent administration on unplanned 30-day readmission rates in retroperitoneal laparoscopic surgery.

Science.gov (United States)

Boon, Martijn; Martini, Chris; Yang, H Keri; Sen, Shuvayu S; Bevers, Rob; Warlé, Michiel; Aarts, Leon; Niesters, Marieke; Dahan, Albert

2018-01-01

Recent data shows that a neuromuscular block (NMB) induced by administration of high doses of rocuronium improves surgical conditions in certain procedures. However, there are limited data on the effect such practices on postoperative outcomes. We performed a retrospective analysis to compare unplanned 30-day readmissions in patients that received high-dose versus low-dose rocuronium administration during general anesthesia for laparoscopic retroperitoneal surgery. This retrospective cohort study was performed in the Netherlands in an academic hospital where routine high-dose rocuronium NMB has been practiced since July 2015. Charts of patients receiving anesthesia between January 2014 and December 2016 were searched for surgical cases receiving high-dose rocuronium and matched with respect to procedure, age, sex and ASA classification to patients receiving low-dose rocuronium. The primary post-operative outcome was unplanned 30-day readmission rate. There were 130 patients in each cohort. Patients in the high- and low-dose rocuronium cohorts received 217 ± 49 versus 37 ± 5 mg rocuronium, respectively. In the high-dose rocuronium group neuromuscular activity was consistently monitored; matched patients were unreliably monitored. All patients receiving high-dose rocuronium were reversed with sugammadex, while just 33% of matched patients were reversed with sugammadex and 20% with neostigmine; the remaining patients were not reversed. Unplanned 30-day readmission rate was significantly lower in the high-dose compared to the low-dose rocuronium cohort (3.8% vs. 12.7%; p = 0.03; odds ratio = 0.33, 95% C.I. 0.12-0.95). This small retrospective study demonstrates a lower incidence of unplanned readmissions within 30-days following laparoscopic retroperitoneal surgery with high-dose relaxant anesthesia and sugammadex reversal in comparison to low-dose relaxant anesthesia. Further prospective studies are needed in larger samples to corroborate our findings and

49 CFR 450.16 - Withdrawal of delegation.

Science.gov (United States)

2010-10-01

... 49 Transportation 6 2010-10-01 2010-10-01 false Withdrawal of delegation. 450.16 Section 450.16... SECURITY SAFETY APPROVAL OF CARGO CONTAINERS GENERAL Procedure for Delegation to Approval Authorities § 450.16 Withdrawal of delegation. (a) The Chief, Office of Operating and Environmental Standards (CG-522...

20 CFR 410.690 - Withdrawal of charges.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Withdrawal of charges. 410.690 Section 410.690 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL COAL MINE HEALTH AND SAFETY ACT OF 1969... Review, Finality of Decisions, and Representation of Parties § 410.690 Withdrawal of charges. If an...

CONSUMER'S RIGHT TO WITHDRAW

Directory of Open Access Journals (Sweden)

ANCA NICOLETA GHEORGHE

2013-05-01

Full Text Available The right of withdrawal (of a contract belongs to the consumer, and is an essential means for the improvement of regulations that protect the consumer.. Right of withdrawal is not a recent creation and is not even specific to the consumer field. He was previously recognized in civil and commercial law (without special regulation. The right to withdraw may even have as ground the parties will. Thus, based on the contractual freedom, the parties may agree that one of them has the right to terminate the contract unilaterally The possibility of unilateral denunciation of the contract, gives the consumer, added protection by being able to reflect the decision and to check how the trader fulfil its obligations. In this context, through its effects, the right of denunciation, forces the professional parties to conduct themselves as fair as possible to the consumer and to execute the contract properly. In the study of the consumer protection, the time of conclusion is essential because in this stage is manifested, the inequality between the consumer and professional. Thus, the lack of information, the major of products and activities, commercial practices, influence the formation of consumer will, preventing the expression of a freely and knowingly consent.

Neural mechanisms underlying morphine withdrawal in addicted patients: a review

Directory of Open Access Journals (Sweden)

Nima Babhadiashar

2015-06-01

Full Text Available Morphine is one of the most potent alkaloid in opium, which has substantial medical uses and needs and it is the first active principle purified from herbal source. Morphine has commonly been used for relief of moderate to severe pain as it acts directly on the central nervous system; nonetheless, its chronic abuse increases tolerance and physical dependence, which is commonly known as opiate addiction. Morphine withdrawal syndrome is physiological and behavioral symptoms that stem from prolonged exposure to morphine. A majority of brain regions are hypofunctional over prolonged abstinence and acute morphine withdrawal. Furthermore, several neural mechanisms are likely to contribute to morphine withdrawal. The present review summarizes the literature pertaining to neural mechanisms underlying morphine withdrawal. Despite the fact that morphine withdrawal is a complex process, it is suggested that neural mechanisms play key roles in morphine withdrawal.

Effects of chronic alcohol consumption, withdrawal and nerve growth factor on neuropeptide Y expression and cholinergic innervation of the rat dentate hilus.

Science.gov (United States)

Pereira, Pedro A; Rocha, João P; Cardoso, Armando; Vilela, Manuel; Sousa, Sérgio; Madeira, M Dulce

2016-05-01

Several studies have demonstrated the vulnerability of the hippocampal formation (HF) to chronic alcohol consumption and withdrawal. Among the brain systems that appear to be particularly vulnerable to the effects of these conditions are the neuropeptide Y (NPY)-ergic and the cholinergic systems. Because these two systems seem to closely interact in the HF, we sought to study the effects of chronic alcohol consumption (6months) and subsequent withdrawal (2months) on the expression of NPY and on the cholinergic innervation of the rat dentate hilus. As such, we have estimated the areal density and the somatic volume of NPY-immunoreactive neurons, and the density of the cholinergic varicosities. In addition, because alcohol consumption and withdrawal are associated with impaired nerve growth factor (NGF) trophic support and the administration of exogenous NGF alters the effects of those conditions on various cholinergic markers, we have also estimated the same morphological parameters in withdrawn rats infused intracerebroventricularly with NGF. NPY expression increased after withdrawal and returned to control values after NGF treatment. Conversely, the somatic volume of these neurons did not differ among all groups. On other hand, the expression of vesicular acetylcholine transporter (VAChT) was reduced by 24% in ethanol-treated rats and by 46% in withdrawn rats. The administration of NGF to withdrawn rats increased the VAChT expression to values above control levels. These results show that the effects of prolonged alcohol intake and protracted withdrawal on the hilar NPY expression differ from those induced by shorter exposures to ethanol and by abrupt withdrawal. They also suggest that the normalizing effect of NGF on NPY expression might rely on the NGF-induced improvement of cholinergic neurotransmission in the dentate hilus. Copyright © 2016 Elsevier Inc. All rights reserved.

Antibiotic-induced immediate type hypersensitivity is a risk factor for positive allergy skin tests for neuromuscular blocking agents.

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Hagau, Natalia; Gherman, Nadia; Cocis, Mihaela; Petrisor, Cristina

2016-01-01

Skin tests for neuromuscular blocking agents (NMBAs) are not currently recommended for the general population undergoing general anaesthesia. In a previous study we have reported a high incidence of positive allergy tests for NMBAs in patients with a positive history of non-anaesthetic drug allergy, a larger prospective study being needed to confirm those preliminary results. The objective of this study was to compare the skin tests results for patients with a positive history of antibiotic-induced immediate type hypersensitivity reactions to those of controls without drug allergies. Ninety eight patients with previous antibiotic hypersensitivity and 72 controls were prospectively included. Skin tests were performed for atracurium, pancuronium, rocuronium, and suxamethonium. We found 65 positive skin tests from the 392 tests performed in patients with a positive history of antibiotic hypersensitivity (1 6.58%) and 23 positive skin tests from the 288 performed in controls (7.98%), the two incidences showing significant statistical difference (p = 0.0011). The relative risk for having a positive skin test for NMBAs for patients versus controls was 1.77 (1.15-2.76). For atracurium, skin tests were more often positive in patients with a positive history of antibiotic hypersensitivity versus controls (p = 0.02). For pancuronium, rocuronium and suxamethonium the statistical difference was not attained (p-values 0.08 for pancuronium, 0.23 for rocuronium, and 0.26 for suxamethonium). Patients with a positive history of antibiotic hypersensitivity seem to have a higher incidence of positive skin tests for NMBAs. They might represent a group at higher risk for developing intraoperative anaphylaxis compared to the general population. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Two-day thionamide withdrawal prior to radioiodine uptake sufficiently increases uptake and does not exacerbate hyperthyroidism compared to 7-day withdrawal in Graves' disease

International Nuclear Information System (INIS)

Kubota, Sumihisa; Ohye, Hidemi; Yano, Genichiro; Nishihara, Eijun; Kudo, Takumi; Ito, Mitsuru; Fukata, Shuji; Amino, Nobuyuki; Kuma, Kanji; Miyauchi, Akira

2006-01-01

The appropriate period of antithyroid drug (ATD) discontinuation before radioiodine therapy is the most critical problem in Graves' disease patients under going treatment with ATD. To determine the optimal period that does not alter the outcome of radioiodine therapy or exacerbate hyperthyroidism, we compared serum FT4 levels at radioiodine uptake (RAIU) and therapy outcomes between a 2-day withdrawal group and 7-day withdrawal group. We prospectively recruited 43 patients for the 2-day withdrawal protocol and retrospectively reviewed 49 patients treated with radioiodine following the protocol of 7-day withdrawal. There was no significant difference in RAIU between the 2 groups. The mean serum FT4 level measured on the first day of 24-h RAIU of the 7-day group was significantly higher than that in the 2-day group. There were no significant differences in the outcomes at each point (6 months, 1 year, and 2 years after therapy) between the 2 groups. Our results indicated that withdrawal of ATD for 2 days is superior to 7 days in that 2 days discontinuation did not exacerbate hyperthyroidism. In order to prevent serum thyroid hormone increase after ATD withdrawal and radioiodine therapy, a 2-day ATD withdrawal period before radioiodine therapy may be useful for high-risk patients such as the elderly and patients with cardiac complications. We believe that the 2-day ATD withdrawal method may be useful for patients undergoing treatment with ATD who are to undergo radioiodine therapy. (author)

Acute coronary ischemia during alcohol withdrawal: a case report

Directory of Open Access Journals (Sweden)

Sriram Ganeshalingam

2011-08-01

Full Text Available Abstract Introduction The potential of alcohol withdrawal to cause acute coronary events is an area that needs the urgent attention of clinicians and researchers. Case presentation We report the case of a 52-year-old heavy-alcohol-using Sri Lankan man who developed electocardiogram changes suggestive of an acute coronary event during alcohol withdrawal. Despite the patient being asymptomatic, subsequent echocardiogram showed evidence of ischemic myocardial dysfunction. We review the literature on precipitation of myocardial ischemia during alcohol withdrawal and propose possible mechanisms. Conclusions Alcohol withdrawal is a commonly observed phenomenon in hospitals. However, the number of cases reported in the literature of acute coronary events occurring during withdrawal is few. Many cases of acute ischemia or sudden cardiac deaths may be attributed to other well known complications of delirium tremens. This is an area needing the urgent attention of clinicians and epidemiologists.

Corticotropin-releasing factor (CRF) and α 2 adrenergic receptors mediate heroin withdrawal-potentiated startle in rats.

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Park, Paula E; Vendruscolo, Leandro F; Schlosburg, Joel E; Edwards, Scott; Schulteis, Gery; Koob, George F

2013-09-01

Anxiety is one of the early symptoms of opioid withdrawal and contributes to continued drug use and relapse. The acoustic startle response (ASR) is a component of anxiety that has been shown to increase during opioid withdrawal in both humans and animals. We investigated the role of corticotropin-releasing factor (CRF) and norepinephrine (NE), two key mediators of the brain stress system, on acute heroin withdrawal-potentiated ASR. Rats injected with heroin (2 mg/kg s.c.) displayed an increased ASR when tested 4 h after heroin treatment. A similar increase in ASR was found in rats 10-20 h into withdrawal from extended access (12 h) to i.v. heroin self-administration, a model that captures several aspects of heroin addiction in humans. Both the α 2 adrenergic receptor agonist clonidine (10 μg/kg s.c.) and CRF1 receptor antagonist N,N-bis(2-methoxyethyl)-3-(4-methoxy-2-methylphenyl)-2,5-dimethyl-pyrazolo[1,5-a] pyrimidin-7-amine (MPZP; 20 mg/kg s.c.) blocked heroin withdrawal-potentiated startle. To investigate the relationship between CRF1 and α 2 adrenergic receptors in the potentiation of the ASR, we tested the effect of MPZP on yohimbine (1.25 mg/kg s.c.)-potentiated startle and clonidine on CRF (2 μg i.c.v.)-potentiated startle. Clonidine blocked CRF-potentiated startle, whereas MPZP partially attenuated but did not reverse yohimbine-potentiated startle, suggesting that CRF may drive NE release to potentiate startle. These results suggest that CRF1 and α 2 receptors play an important role in the heightened anxiety-like behaviour observed during acute withdrawal from heroin, possibly via CRF inducing the release of NE in stress-related brain regions.

Attenuation of Morphine Withdrawal Syndrome by Various Dosages of Curcumin in Comparison with Clonidine in Mouse: Possible Mechanism

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Majid Motaghinejad

2015-03-01

Full Text Available Background: Herbal medical compounds and their major constituent have been used in the management and treatment of opioid withdrawal syndrome and pain. This study was carried out to clarify the effect of curcumin, the major compound of turmeric, on morphine withdrawal syndrome in mouse model and its possible mechanisms of pain relieving activity by assessing in writhing test as a model of visceral pain. Methods: Due to two separate protocols (withdrawal syndrome and pain, 144 male albino mice were divided in two major groups. In withdrawal syndrome group, test effect of various dosages of curcumin (10, 20, and 40 mg/kg was assessed on withdrawal signs and compared with positive and negative control and standard treatment (clonidine 0.4 mg/kg groups. In pain groups, to determine the mechanism of pain relieving activity of curcumin, various dosages of curcumin (10, 20, and 40 mg/kg in three separated groups, were used against acetic acid induced writhing (which is a constriction test. The most effective dose (40 mg/kg was used in writhing test and compared with groups pretreated with antagonist of major neurotransmitters involved in pain; and compared with group pretreated with vehicle (DMSO, 0.05% as control. Results: Curcumin attenuates withdrawal syndrome in a dose dependent manner in comparison with the dependent positive control group (P<0.05. It also indicated that pretreatment with naloxone and cyproheptadine significantly attenuate antinociception effect of curcumin (P<0.05. Conclusion: This study advocate that antinociception of curcumin was mediated by opioidergic and adrenergic system.

TRACY transient experiment databook. 2) ramp withdrawal experiment

International Nuclear Information System (INIS)

Nakajima, Ken; Yamane, Yuichi; Ogawa, Kazuhiko; Aizawa, Eiju; Yanagisawa, Hiroshi; Miyoshi, Yoshinori

2002-03-01

This is a databook of TRACY ''ramp withdrawal'' experiments. TRACY is a reactor to perform supercritical experiments using low-enriched uranyl nitrate aqueous solution. The excess reactivity of TRACY is 3$ at maximum, and it is inserted by feeding the solution to a core tank or by withdrawing a control rod, which is called as the transient rod, from the core. In the ramp withdrawal experiment, the supercritical experiment is initiated by withdrawing the transient rod from the core in a constant speed using a motor drive system. The data in the present databook consist of datasheets and graphs. Experimental conditions and typical values of measured parameters are tabulated in the datasheet. In the graph, power and temperature profiles are plotted. Those data are useful for the investigation of criticality accidents with fissile solutions, and for validation of criticality accident analysis codes. (author)

Cannabis Withdrawal in Adults With Attention-Deficit/Hyperactivity Disorder.

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Chauchard, Emeline; Hartwell, Karen J; McRae-Clark, Aimee L; Sherman, Brian J; Gorelick, David A

2018-02-22

Cannabis withdrawal has not been studied in adults with attention-deficit/hyperactivity disorder (ADHD) who have high rates of cannabis use. We aimed to describe cannabis withdrawal, motivations to quit, and strategies to quit cannabis use in cannabis-dependent adults with ADHD. Twenty-three adults with ADHD enrolled in a controlled clinical trial of pharmacotherapy (atomoxetine) for cannabis dependence (DSM-IV criteria) completed the Marijuana Quit Questionnaire (MJQQ) to provide information on their "most serious" quit attempt made without formal treatment. The study was conducted between November 2005 and June 2008. Participants were predominantly male (82.6%, n = 19), with a mean (SD) age of 27.4 (8.5) years (range, 18-53) at the start of their index quit attempt. The most common motive for quitting cannabis was "to save money" (87%, n = 20); the most common strategy to maintain abstinence was "stopped associating with people who smoke marijuana" (43%, n = 10). Almost all (96%, n = 22) subjects reported ≥ 1 cannabis withdrawal symptom; 7 (30%) met DSM-5 diagnostic criteria for cannabis withdrawal syndrome. Participants with comorbid ADHD and cannabis dependence reported withdrawal symptoms similar to other samples of non-treatment-seeking cannabis-dependent adults with no psychiatric comorbidity. These findings suggest that ADHD does not influence cannabis withdrawal in the way that it does tobacco (nicotine) withdrawal. Data used in this secondary analysis came from ClinicalTrials.gov identifier: NCT00360269. © Copyright 2018 Physicians Postgraduate Press, Inc.

Two case reports of oral ulcers with lamotrigine several weeks after oxcarbazepine withdrawal.

Science.gov (United States)

O'Neill, Amy; de Leon, Jose

2007-05-01

To report two cases of mouth ulcers in lamotrigine patients after oxcarbazepine withdrawal. The first patient was a 35-year-old woman with bipolar disorder II (BD II) started on lamotrigine and tapered off oxcarbazepine while an inpatient. The second patient was a 36-year-old man with BD II. He was discharged on lamotrigine and oxcarbazepine with the recommendation of a slow withdrawal of oxcarbazepine. Many weeks after hospital discharge and after a stable lamotrigine dose had been established, both patients developed painful mouth ulcers that were diagnosed during outpatient visits. The first patient developed ulcers 39 days after oxcarbazepine was stopped and the ulcers resolved 4 days after lamotrigine discontinuation. The second patient was taking 1200 mg/day of oxcarbazepine and after leaving hospital decreased this to 600 mg/day. Twenty-two days after the oxcarbazepine decrease, he developed oral ulcers that resolved with oxcarbazepine and lamotrigine discontinuation. Lamotrigine is mainly metabolized by glucuronidation, specifically by the uridine 5'-diphosphate glucuronosyltransferases 1A4 (UGT1A4). Carbamazepine is a UGT1A4 inducer. These two cases suggest that oxcarbazepine may also induce lamotrigine metabolism. The discontinuation or dosage decrease of carbamazepine or oxcarbazepine may be associated with a slow increase of lamotrigine levels over several weeks and thus increase risk of lamotrigine toxicity that may manifest as oral ulcers. Hospital psychiatrists need to be aware that discontinuation of inducers may take several weeks to manifest as side effects.

40 CFR 97.86 - Withdrawal from NOX Budget Trading Program.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Withdrawal from NOX Budget Trading... PROGRAMS (CONTINUED) FEDERAL NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS Individual Unit Opt-ins. § 97.86 Withdrawal from NOX Budget Trading Program. (a) Requesting withdrawal. To...

42 CFR 8.6 - Withdrawal of approval of accreditation bodies.

Science.gov (United States)

2010-10-01

... PROVISIONS CERTIFICATION OF OPIOID TREATMENT PROGRAMS Accreditation § 8.6 Withdrawal of approval of... 42 Public Health 1 2010-10-01 2010-10-01 false Withdrawal of approval of accreditation bodies. 8.6... to establish that the problems that were grounds for withdrawal of approval have been resolved. (2...

Neurobiology of opioid withdrawal: Role of the endothelin system.

Science.gov (United States)

Bhalla, Shaifali; Andurkar, Shridhar V; Gulati, Anil

2016-08-15

Morphine and oxycodone are potent opioid analgesics most commonly used for the management of moderate to severe acute and chronic pain. Their clinical utility is limited by undesired side effects like analgesic tolerance, dependence, and withdrawal. We have previously demonstrated that endothelin-A (ETA) receptor antagonists potentiate opioid analgesia and eliminate analgesic tolerance. Mechanistically, G proteins and regulatory proteins such as β-arrestins have shown to play an important role in mediating opioid tolerance, dependence, and withdrawal. Recently, the involvement of central ET mechanisms in opioid withdrawal was investigated. ETA receptor antagonist was shown to block majority of the signs and symptoms associated with opioid withdrawal. This review focuses on ET as one of the potential novel strategies to manage the challenge of opioid withdrawal. An overview of additional players in this process (G proteins and β-arrestin2), and the possible therapeutic implications of these findings are presented. Copyright © 2016 Elsevier Inc. All rights reserved.

Social Withdrawal, Friendship, and Depressed Mood in Adolescents

NARCIS (Netherlands)

Aleva, A.E.|info:eu-repo/dai/nl/141299789; van Beek, Y.|info:eu-repo/dai/nl/107292300

2017-01-01

Social withdrawal in children may develop into a depressed mood in early adolescence , through experiences of problematic peer relationships, while friendship may function as a buffer (Rubin, Coplan, & Bowker, 2009). Our study examines the predictive relation between social withdrawal and depressive

Adolescent anabolic/androgenic steroids: Aggression and anxiety during exposure predict behavioral responding during withdrawal in Syrian hamsters (Mesocricetus auratus).

Science.gov (United States)

Ricci, Lesley A; Morrison, Thomas R; Melloni, Richard H

2013-11-01

In the U.S. and worldwide anabolic/androgenic steroid use remains high in the adolescent population. This is concerning given that anabolic/androgenic steroid use is associated with a higher incidence of aggressive behavior during exposure and anxiety during withdrawal. This study uses pubertal Syrian hamsters (Mesocricetus auratus) to investigate the hypothesis that an inverse behavioral relationship exists between anabolic/androgenic steroid-induced aggression and anxiety across adolescent exposure and withdrawal. In the first experiment, we examined aggression and anxiety during adolescent anabolic/androgenic steroid exposure and withdrawal. Adolescent anabolic/androgenic steroid administration produced significant increases in aggression and decreases in anxiety during the exposure period followed by significant decreases in aggression and increases in anxiety during anabolic/androgenic steroid withdrawal. In a second experiment, anabolic/androgenic steroid exposed animals were separated into groups based on their aggressive response during the exposure period and then tested for anxiety during exposure and then for both aggression and anxiety during withdrawal. Data were analyzed using a within-subjects repeated measures predictive analysis. Linear regression analysis revealed that the difference in aggressive responding between the anabolic/androgenic steroid exposure and withdrawal periods was a significant predictor of differences in anxiety for both days of testing. Moreover, the combined data suggest that the decrease in aggressive behavior from exposure to withdrawal predicts an increase in anxiety-like responding within these same animals during this time span. Together these findings indicate that early anabolic/androgenic steroid exposure has potent aggression- and anxiety-eliciting effects and that these behavioral changes occur alongside a predictive relationship that exists between these two behaviors over time. © 2013.

Prolonged social withdrawal disorder: a hikikomori case in Spain.

Science.gov (United States)

Ovejero, Santiago; Caro-Cañizares, Irene; de León-Martínez, Victoria; Baca-Garcia, Enrique

2014-09-01

The Japanese term hikikomori means literally 'to be confined'. Social withdrawal can be present in severe psychiatric disorders; however, in Japan, hikikomori is a defined nosologic entity. There have been only a few reported cases in occidental culture. We present a case report of a Spanish man with prolonged social withdrawal lasting for 4 years. This is a case of prolonged social withdrawal not bound to culture, as well as the second case of hikikomori reported in Spain. We propose prolonged social withdrawal disorder as a disorder not linked to culture, in contrast to hikikomori. Further documentation of this disorder is still needed to encompass all cases reported in Japan and around the world. © The Author(s) 2013.

Alcohol withdrawal delirium manifested by manic symptoms in an elderly patient.

Science.gov (United States)

Chan, Hung-Yu; Lee, Kuan-I

2015-03-01

Alcohol withdrawal syndrome is a commonly seen problem in psychiatric practice. Alcohol withdrawal delirium is associated with significant morbidity and mortality. Withdrawal symptoms usually include tremulousness, psychotic and perceptual symptoms, seizures, and consciousness disturbance. Herein, we report a case involving a 63-year-old man who had alcohol withdrawal delirium that was manifested mainly by manic symptoms. © 2014 The Authors. Psychogeriatrics © 2014 Japanese Psychogeriatric Society.

Dipeptidyl-peptidase IV (DPP-IV) inhibitor delays tolerance to anxiolytic effect of ethanol and withdrawal-induced anxiety in rats.

Science.gov (United States)

Sharma, Ajaykumar N; Pise, Ashish; Sharma, Jay N; Shukla, Praveen

2015-06-01

Dipeptidyl-peptidase IV (DPP-IV) is an enzyme responsible for the metabolism of endogenous gut-derived hormone, glucagon-like peptide-1 (GLP-1). DPP-IV is known for its role in energy homeostasis and pharmacological blockade of this enzyme is a recently approved clinical strategy for the management of type II diabetes. Accumulating evidences suggest that enzyme DPP-IV can affect spectrum of central nervous system (CNS) functions. However, little is known about the role of this enzyme in ethanol-mediated neurobehavioral complications. The objective of the present study was to examine the impact of DPP-IV inhibitor, sitagliptin on the development of tolerance to anxiolytic effect of ethanol and anxiety associated with ethanol withdrawal in rats. A dose-response study revealed that sitaglitpin (20 mg/kg, p.o.) per se exhibit anxiolytic effect in the elevated plus maze (EPM) test in rats. Tolerance to anxiolytic effect of ethanol (2 g/kg, i.p.; 8 % w/v) was observed from 7(th) day of ethanol-diet (6 % v/v) consumption. In contrast, tolerance to anxiolytic effect of ethanol was delayed in rats that were treated daily with sitagliptin (20 mg/kg, p.o.) as tolerance was observed from 13(th)day since commencement of ethanol-diet consumption. Discontinuation of rats from ethanol-diet after 15-days of ethanol consumption resulted in withdrawal anxiety between 8 h and 12 h post-abstinence. However, rats on 15-day ethanol-diet with concomitant sitagliptin (20 mg/kg, p.o.) treatment exhibited delay in appearance (24 h post-withdrawal) of withdrawal anxiety. In summary, DPP-IV inhibitors may prove as an attractive research strategy against ethanol tolerance and dependence.

Acceleromyography and mechanomyography for establishing potency of neuromuscular blocking agents: a randomized-controlled trial

DEFF Research Database (Denmark)

Claudius, C; Viby-Mogensen, J; Skovgaard, Lene Theil

2009-01-01

) for this purpose. The aim of this study was to compare AMG and MMG for establishing dose-response relationship and potency, using rocuronium as an example. METHODS: We included 40 adult patients in this randomized-controlled single-dose response study. Anaesthesia was induced and maintained with propofol...... and opioid. Neuromuscular blockade was induced with rocuronium 100, 150, 200 or 250 microg/kg. Neuromuscular monitoring was performed with AMG (TOF-Watch SX) with pre-load (Hand Adapter) at one arm and MMG (modified TOF-Watch SX) on the other, using 0.1 Hz single twitch stimulation. Dose...

Social Withdrawal and Maladjustment in a Very Group-Oriented Society

Science.gov (United States)

Valdivia, Ibis Alvarez; Schneider, Barry H.; Chavez, Kenia Lorenzo; Chen, Xinyin

2005-01-01

Elementary-school children in Cuba and Canada participated in measures of loneliness, sociometric status, friendship, aggression, and social withdrawal. Withdrawal was associated with loneliness in the Cuban data from both cohorts, Grade 4 and Grade 6. In the Canadian data, withdrawal was only linked to loneliness in Grade 6. In contrast with…

Sugammadex: A Review of Neuromuscular Blockade Reversal.

Science.gov (United States)

Keating, Gillian M

2016-07-01

Sugammadex (Bridion(®)) is a modified γ-cyclodextrin that reverses the effect of the steroidal nondepolarizing neuromuscular blocking agents rocuronium and vecuronium. Intravenous sugammadex resulted in rapid, predictable recovery from moderate and deep neuromuscular blockade in patients undergoing surgery who received rocuronium or vecuronium. Recovery from moderate neuromuscular blockade was significantly faster with sugammadex 2 mg/kg than with neostigmine, and recovery from deep neuromuscular blockade was significantly faster with sugammadex 4 mg/kg than with neostigmine or spontaneous recovery. In addition, recovery from neuromuscular blockade was significantly faster when sugammadex 16 mg/kg was administered 3 min after rocuronium than when patients spontaneously recovered from succinylcholine. Sugammadex also demonstrated efficacy in various special patient populations, including patients with pulmonary disease, cardiac disease, hepatic dysfunction or myasthenia gravis and morbidly obese patients. Intravenous sugammadex was generally well tolerated. In conclusion, sugammadex is an important option for the rapid reversal of rocuronium- or vecuronium-induced neuromuscular blockade.

Demand-Withdraw Patterns in Marital Conflict in the Home

OpenAIRE

Papp, Lauren M.; Kouros, Chrystyna D.; Cummings, E. Mark

2009-01-01

The present study extended laboratory-based findings of demand-withdraw communication into marital conflict in the home and further explored its linkages with spousal depression. U.S. couples (N = 116) provided diary reports of marital conflict and rated depressive symptoms. Hierarchical linear modeling results indicated that husband demand-wife withdraw and wife demand-husband withdraw occurred in the home at equal frequency, and both were more likely to occur when discussing topics that con...

Rats that binge eat fat-rich food do not show somatic signs or anxiety associated with opiate-like withdrawal: implications for nutrient-specific food addiction behaviors.

Science.gov (United States)

Bocarsly, Miriam E; Berner, Laura A; Hoebel, Bartley G; Avena, Nicole M

2011-10-24

Previous studies suggest that binge eating sugar leads to behavioral and neurochemical changes similar to those seen with drug addiction, including signs of opiate-like withdrawal. Studies are emerging that show multiple neurochemical and behavioral indices of addiction when animals overeat a fat-rich diet. The goal of the present study was to utilize liquid and solid diets high in sugar and fat content to determine whether opiate-like withdrawal is seen after binge consumption of these diets in Sprague-Dawley rats. Control groups were given ad libitum access to the sweet-fat food or standard chow. All rats were then given a battery of tests to measure signs of opiate-like withdrawal, which included somatic signs of distress, elevated plus-maze anxiety, and locomotor hypoactivity. Neither naloxone-precipitated (3 mg/kg) nor deprivation-induced withdrawal was observed in rats that were maintained on a nutritionally complete pelleted sweet-fat diet or a sweet, high-fat diet supplemented with standard rodent chow. Naloxone-precipitated withdrawal was also not seen in rats fed a liquid sweet-fat food. Further, body weight reduction to 85%, which is known to potentiate the reinforcing effects of substances of abuse, did not affect naloxone-precipitated signs of opiate-like withdrawal. Thus, unlike previous findings reported regarding rats with binge access to a sucrose solution, rats that binge eat sweet-fat combinations do not show signs of opiate-like withdrawal under the conditions tested. These data support the idea that excessive consumption of different nutrients can induce behaviors associated with addiction in different ways, and that the behaviors that could characterize "food addiction" may be subtyped based on the nutritional composition of the food consumed. Copyright © 2011 Elsevier Inc. All rights reserved.

Ethical Analysis of Withdrawing Total Artificial Heart Support.

Science.gov (United States)

DeMartino, Erin S; Wordingham, Sara E; Stulak, John M; Boilson, Barry A; Fuechtmann, Kayla R; Singh, Nausheen; Sulmasy, Daniel P; Pajaro, Octavio E; Mueller, Paul S

2017-05-01

To describe the characteristics of patients who undergo withdrawal of total artificial heart support and to explore the ethical aspects of withdrawing this life-sustaining treatment. We retrospectively reviewed the medical records of all adult recipients of a total artificial heart at Mayo Clinic from the program's inception in 2007 through June 30, 2015. Management of other life-sustaining therapies, approach to end-of-life decision making, engagement of ethics and palliative care consultation, and causes of death were analyzed. Of 47 total artificial heart recipients, 14 patients or their surrogates (30%) requested withdrawal of total artificial heart support. No request was denied by treatment teams. All 14 patients were supported with at least 1 other life-sustaining therapy. Only 1 patient was able to participate in decision making. It is widely held to be ethically permissible to withdraw a life-sustaining treatment when the treatment no longer meets the patient's health care-related goals (ie, the burdens outweigh the benefits). These data suggest that some patients, surrogates, physicians, and other care providers believe that this principle extends to the withdrawal of total artificial heart support. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Alcohol Withdrawal Mimicking Organophosphate Poisoning

Directory of Open Access Journals (Sweden)

Nezihat Rana Disel

2014-02-01

Full Text Available Organophosphates, which can cause occupational poisoning due to inappropriate personal protective measures, are widely used insecticides in agricultural regions of southern Turkey. Therefore, the classical clinical findings of this cholinergic poisoning are myosis, excessive secretions, bradicardia and fasciculations are easy to be recognized by local medical stuff. Diseases and conditions related to alcoholism such as mental and social impairments, coma, toxicity, withdrawal, and delirium are frequent causes of emergency visits of chronic alcoholic patients. Here we present a case diagnosed and treated as organophosphate poisoning although it was an alcohol withdrawal in the beginning and became delirium tremens, due to similar symptoms.

Sedative-hypnotic drug withdrawal syndrome: recognition and treatment [digest].

Science.gov (United States)

Santos, Cynthia; Olmedo, Ruben E; Kim, Jeremy

2017-03-22

Sedative-hypnotic drugs include gamma-Aminobutyric acid (GABA)ergic agents such as benzodiazepines, barbiturates, gamma-Hydroxybutyric acid [GHB], gamma-Butyrolactone [GBL], baclofen, and ethanol. Chronic use of these substances can cause tolerance, and abrupt cessation or a reduction in the quantity of the drug can precipitate a life-threatening withdrawal syndrome. Benzodiazepines, phenobarbital, propofol, and other GABA agonists or analogues can effectively control symptoms of withdrawal from GABAergic agents. Managing withdrawal symptoms requires a patient-specific approach that takes into account the physiologic pathways of the particular drugs used as well as the patient's age and comorbidities. Adjunctive therapies include alpha agonists, beta blockers, anticonvulsants, and antipsychotics. Newer pharmacological therapies offer promise in managing withdrawal symptoms. [Points & Pearls is a digest of Emergency Medicine Practice].

Caffeine Withdrawal and Dependence: A Convenience Survey Among Addiction Professionals.

Science.gov (United States)

Budney, Alan J; Brown, Pamela C; Griffiths, Roland R; Hughes, John R; Juliano, Laura M

2013-06-01

Caffeine withdrawal was included in the research appendix of the DSM-IV to encourage additional research to assist with determining its status for the next version of the manual. Caffeine dependence was not included because of a lack of empirical research at the time of publication. This study assessed the beliefs of addiction professionals about the clinical importance of caffeine withdrawal and dependence. A 6-item survey was developed and delivered electronically to the members of six professional organizations that focus on addiction. Open-ended comments were also solicited. Five hundred members responded. The majority (95%) thought that cessation of caffeine could produce a withdrawal syndrome, and that caffeine withdrawal can have clinical importance (73%); however, only half (48%) thought that caffeine withdrawal should be included in the Diagnostic and Statistical Manual of Mental Disorders (DSM). A majority (58%) believed that some people develop caffeine dependence; however, only 44% indicated that it should be in the DSM. Comments suggested that trepidation about inclusion of caffeine diagnoses was due to the concerns about the field of psychiatry being criticized for including common disorders with a relatively low clinical severity. Others, however, expressed an urgent need to take caffeine-related problems more seriously. The majority of addiction professionals believe that caffeine withdrawal and dependence disorders exist and are clinically important; however, these professionals are divided in whether caffeine withdrawal and dependence should be included in DSM. Wider dissemination of the extant literature on caffeine withdrawal and additional research on caffeine dependence will be needed to provide additional guidance to policymakers and healthcare workers.

[Alcohol withdrawal syndrome dynamics during treatment with nooclerin (deanoli aceglumas)].

Science.gov (United States)

Agibalova, T V; Buzik, O Zh; Rychkova, O V; Smyshlyaev, A V; Rumbesht, V V

2018-01-01

To study the efficacy of nooclerin (deanoli aceglumas) in alcohol withdrawal syndrome assessed by clinical and biochemical characteristics. A multicenter, open, randomized, comparative study of nooclerin in the complex treatment of alcohol withdrawal syndrome included 90 patients. The patients were randomized into nooclerin group (n=55) and control group (n=35). Nooclerin reduced alcohol withdrawal symptoms more significantly throughout the whole study period. There were significant between-group differences on the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar) and the Multidimensional Fatigue Inventory (МFI-20). However, patients exhibited no excessive activity. No adverse side-effects were observed.

The relative potency of inverse opioid agonists and a neutral opioid antagonist in precipitated withdrawal and antagonism of analgesia and toxicity.

Science.gov (United States)

Sirohi, Sunil; Dighe, Shveta V; Madia, Priyanka A; Yoburn, Byron C

2009-08-01

Opioid antagonists can be classified as inverse agonists and neutral antagonists. In the opioid-dependent state, neutral antagonists are significantly less potent in precipitating withdrawal than inverse agonists. Consequently, neutral opioid antagonists may offer advantages over inverse agonists in the management of opioid overdose. In this study, the relative potency of three opioid antagonists to block opioid analgesia and toxicity and precipitate withdrawal was examined. First, the potency of two opioid inverse agonists (naltrexone and naloxone) and a neutral antagonist (6beta-naltrexol) to antagonize fentanyl-induced analgesia and lethality was determined. The order of potency to block analgesia was naltrexone > naloxone > 6beta-naltrexol (17, 4, 1), which was similar to that to block lethality (13, 2, 1). Next, the antagonists were compared using withdrawal jumping in fentanyl-dependent mice. The order of potency to precipitate withdrawal jumping was naltrexone > naloxone 6beta-naltrexol (1107, 415, 1). The relative potencies to precipitate withdrawal for the inverse agonists compared with the neutral antagonist were dramatically different from that for antagonism of analgesia and lethality. Finally, the effect of 6beta-naltrexol pretreatment on naloxone-precipitated jumping was determined in morphine and fentanyl-dependent mice. 6beta-Naltrexol pretreatment decreased naloxone precipitated withdrawal, indicating that 6beta-naltrexol is a neutral antagonist. These data demonstrate that inverse agonists and neutral antagonists have generally comparable potencies to block opioid analgesia and lethality, whereas the neutral opioid antagonist is substantially less potent in precipitating opioid withdrawal. These results support suggestions that neutral antagonists may have advantages over inverse agonists in the management of opioid overdose.

Evidence for a causative role of N-methyl-D-aspartate receptors in an in vitro model of alcohol withdrawal hyperexcitability.

Science.gov (United States)

Thomas, M P; Monaghan, D T; Morrisett, R A

1998-10-01

Synaptic mechanisms underlying hyperexcitability due to withdrawal from chronic ethanol exposure were investigated in a hippocampal explant model system using electrophysiological techniques. Whole-cell voltage clamp recordings from CA1 pyramidal cells demonstrated that acute ethanol exposure inhibited N-methyl-D-aspartate receptor (NMDAR)-mediated excitatory postsynaptic currents by over 40%. Chronic ethanol exposure for 6 to 11 days at 35 or 75 mM induced no differences from control explants in the fast component of the population synaptic response (non-NMDAR-mediated). Prolonged field potential recordings (to 10 hr) were used to monitor the withdrawal process in vitro. Ethanol-exposed explants from both 35 and 75 mM groups displayed an increase (60% and 89%, respectively) in the NMDAR-mediated component of synaptic transmission on withdrawal from chronic exposure. Prolonged tonic-clonic electrographic seizure activity was consistently observed after ethanol withdrawal only after the increase in NMDAR function. This hyperexcitability was inhibited by the NMDAR antagonist D-2-amino-5-phosphonovaleric acid and returned once the NMDAR component was reestablished after antagonist washout. In situ hybridization studies suggest that expression of NR2B subunit mRNA may be enhanced in explants after chronic ethanol exposure. No lasting differences were observed in the NMDAR component after acute in vitro ethanol exposure and withdrawal. These data suggest that the occurance of ethanol withdrawal hyperexcitability in this system may be directly dependent on alterations in NMDAR function after chronic exposure. Since this region and others that contain ethanol sensitive NMDARs may serve as epileptic foci, long term alterations in NMDAR function may be expected to generate paroxysmal depolarizing shifts underlying ictal events after withdrawal from ethanol exposure.

USA Withdrawal from Paris Agreement – What Next?

OpenAIRE

Sergey Chestnoy; Dinara Gershinkova

2017-01-01

In June 2017, President Trump announced the USA’s withdrawal from the Paris Climate Accord, which had been ratified for less than a year, thanks in large part to the USA. That drastic shift followed the change in residency at the White House. Withdrawing from the Paris Accord presents an interesting topic for analysis. There’s the practical side of the withdrawal procedure as set out in Article 28 of the agreement, not to mention the consequences of US non-participation in address...

Cocaine withdrawal causes delayed dysregulation of stress genes in the hippocampus.

Directory of Open Access Journals (Sweden)

M Julia García-Fuster

Full Text Available Relapse, even following an extended period of withdrawal, is a major challenge in substance abuse management. Delayed neurobiological effects of the drug during prolonged withdrawal likely contribute to sustained vulnerability to relapse. Stress is a major trigger of relapse, and the hippocampus regulates the magnitude and duration of stress responses. Recent work has implicated hippocampal plasticity in various aspects of substance abuse. We asked whether changes in stress regulatory mechanisms in the hippocampus may participate in the neuroadaptations that occur during prolonged withdrawal. We therefore examined changes in the rat stress system during the course of withdrawal from extended daily access (5-hours of cocaine self-administration, an animal model of addiction. Tissue was collected at 1, 14 and 28 days of withdrawal. Plasma corticosterone levels were determined and corticosteroid receptors (GR, MR, MR/GR mRNA ratios and expression of other stress-related molecules (HSP90AA1 and HSP90AB1 mRNA were measured in hippocampal subfields using in situ hybridization. Results showed a delayed emergence of dysregulation of stress genes in the posterior hippocampus following 28 days of cocaine withdrawal. This included increased GR mRNA in DG and CA3, increased MR and HSP90AA1 mRNA in DG, and decreased MR/GR mRNA ratio in DG and CA1. Corticosterone levels progressively decreased during the course of withdrawal, were normalized following 28 days of withdrawal, and were correlated negatively with GR and positively with MR/GR mRNA ratio in DG. These results suggest a role for the posterior hippocampus in the neuroadaptations that occur during prolonged withdrawal, and point to a signaling partner of GR, HSP90AA1, as a novel dysregulated target during cocaine withdrawal. These delayed neurobiological effects of extended cocaine exposure likely contribute to sustained vulnerability to relapse.

Environmental enrichment may protect against neural and behavioural damage caused by withdrawal from chronic alcohol intake.

Science.gov (United States)

Nobre, Manoel Jorge

2016-12-01

Exposure to stress and prolonged exposure to alcohol leads to neuronal damages in several brain regions, being the medial prefrontal cortex (mPFC) one of the most affected. These changes presumably reduce the ability of the organism to cope with these stimuli and may underlie a series of maladaptive behaviours among which include drug addiction and withdrawal. Drug-addicted individuals show a pattern of behavior similar to patients with lesions of the mPFC. This impairment in the decision-making could be one of the mechanisms responsible for the transition from the casual to compulsive drug use. The environmental enrichment (EE) has a protective effect on the neural and cognitive impairments induced by psychoactive drugs, including ethyl alcohol. The present study aims to determine the influence of withdrawal from intermittent long-term alcohol exposure on alcohol preference, emotional reactivity and neural aspects of early isolated or grouped reared rats kept under standard or complex environments and the influence of social isolation on these measures, as well. Our results point out new insights on this matter showing that the EE can attenuate the adverse effects of withdrawal and social isolation on rat's behavior. This effect is probably due to its protective action on the mPFC integrity, including the cingulate area 1 (Cg1), and the prelimbic (PrL) and infralimbic cortex (IL), what could account for the absence of changes in the emotional reactivity in EE alcohol withdrawal rats. We argue that morphological changes at these cortical levels can afford the emotional, cognitive and behavioural dysregulations verified following withdrawal from chronic alcohol intake. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

Ketogenic Diet suppresses Alcohol Withdrawal Syndrome in Rats

DEFF Research Database (Denmark)

Dencker, Ditte; Molander, Anna; Thomsen, Morgane

2018-01-01

, we investigated the potential therapeutic benefit of a ketogenic diet in managing alcohol withdrawal symptoms during detoxification. METHODS: Male Sprague Dawley rats fed either ketogenic or regular diets were administered ethanol or water orally, twice daily for 6 days while the diet conditions were...... maintained. Abstinence symptoms were rated 6, 24, 48, and 72 hours after the last alcohol administration. RESULTS: Maintenance on a ketogenic diet caused a significant decrease in the alcohol withdrawal symptoms 'rigidity' and 'irritability'. CONCLUSION: Our preclinical pilot study suggests that a ketogenic...... diet may be a novel approach for treating alcohol withdrawal symptoms in humans. This article is protected by copyright. All rights reserved....

Emergence of dormant conditioned incentive approach by conditioned withdrawal in nicotine addiction.

Science.gov (United States)

Scott, Daniel; Hiroi, Noboru

2010-10-15

Nicotine is one of the determinants for the development of persistent smoking, and this maladaptive behavior is characterized by many symptoms, including withdrawal and nicotine seeking. The process by which withdrawal affects nicotine seeking is poorly understood. The impact of a withdrawal-associated cue on nicotine (.2 mg/kg)-conditioned place preference was assessed in male C57BL/6J mice (n = 8-17/group). To establish a cue selectively associated with withdrawal distinct from those associated with nicotine, a tone was paired with withdrawal in their home cages; mice were chronically exposed to nicotine (200 μg/mL for 15 days) from drinking water in their home cages and received the nicotinic acetylcholine receptor antagonist mecamylamine (2.5 mg/kg) to precipitate withdrawal in the presence of a tone. The effect of the withdrawal-associated tone on nicotine-conditioned place preference was then evaluated in the place-conditioning apparatus after a delay, when nicotine-conditioned place preference spontaneously disappeared. A cue associated with precipitated withdrawal reactivated the dormant effect of nicotine-associated cues on conditioned place preference. This effect occurred during continuous exposure to nicotine but not during abstinence. A conditioned withdrawal cue could directly amplify the incentive properties of cues associated with nicotine. This observation extends the contemporary incentive account of the role of withdrawal in addiction to cue-cue interaction. Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Time-course of the DSM-5 cannabis withdrawal symptoms in poly-substance abusers

DEFF Research Database (Denmark)

Hesse, Morten; Thylstrup, Birgitte

2013-01-01

Background Evidence is accumulating that a cannabis withdrawal syndrome is common, of clinical significance, and has a clear time course. Up till now, very limited data exist on the cannabis withdrawal symptoms in patients with co-morbid substance use disorders, other than cannabis use and tobacco...... the DSM-5 Withdrawal Symptom Check List with withdrawal symptoms from all classes of substances, with no indication that the described symptoms should be attributed to withdrawal. Self-reported time since last use of cannabis was used as a predictor of cannabis withdrawal severity. Results...... With the exception of loss of appetite, time since last use of cannabis was associated with all types of withdrawal symptoms listed in the DSM-5. Only four of 19 symptoms intended to measure withdrawal from other substances were related to time since last use of cannabis, including vivid, unpleasant dreams...

A double blind, within subject comparison of spontaneous opioid withdrawal from buprenorphine versus morphine.

Science.gov (United States)

Tompkins, D Andrew; Smith, Michael T; Mintzer, Miriam Z; Campbell, Claudia M; Strain, Eric C

2014-02-01

Preliminary evidence suggests that there is minimal withdrawal after the cessation of chronically administered buprenorphine and that opioid withdrawal symptoms are delayed compared with those of other opioids. The present study compared the time course and magnitude of buprenorphine withdrawal with a prototypical μ-opioid agonist, morphine. Healthy, out-of-treatment opioid-dependent residential volunteers (N = 7) were stabilized on either buprenorphine (32 mg/day i.m.) or morphine (120 mg/day i.m.) administered in four divided doses for 9 days. They then underwent an 18-day period of spontaneous withdrawal, during which four double-blind i.m. placebo injections were administered daily. Stabilization and spontaneous withdrawal were assessed for the second opioid using the same time course. Opioid withdrawal measures were collected eight times daily. Morphine withdrawal symptoms were significantly (P withdrawal as measured by mean peak ratings of Clinical Opiate Withdrawal Scale (COWS), Subjective Opiate Withdrawal Scale (SOWS), all subscales of the Profile of Mood States (POMS), sick and pain (0-100) Visual Analog Scales, systolic and diastolic blood pressure, heart rate, respiratory rate, and pupil dilation. Peak ratings on COWS and SOWS occurred on day 2 of morphine withdrawal and were significantly greater than on day 2 of buprenorphine withdrawal. Subjective reports of morphine withdrawal resolved on average by day 7. There was minimal evidence of buprenorphine withdrawal on any measure. In conclusion, spontaneous withdrawal from high-dose buprenorphine appears subjectively and objectively milder compared with that of morphine for at least 18 days after drug cessation.

The Study of the Role of Contributor Factors in Addiction Withdrawal

Directory of Open Access Journals (Sweden)

Omar Kianipour

2012-08-01

Full Text Available Introduction: The present paper investigated the factors contributing to addiction withdrawal so as to it would be possible to set preventive and rehabilitative programs for addicts. Method: The study was ex-post facto and causal-comparative one. Population included all addicts referred to addiction withdrawal centers of Kahnouj city and the sample was selected of addicts of Yaran addiction withdrawal Center by voluntary sampling. Bar-on emotional intelligence inventory, family boundary questionnaire and demographic information were administered among selected sample. Results: The results showed that normal family boundaries, higher emotional intelligence and opium use in comparison of crack and crystal glass are effective on addiction withdrawal. But disengaged family boundaries, crack and crystal glass use can be led to addiction recursion. Age, addiction duration, marital status, and education level are not effective on addiction withdrawal. Conclusion: Altogether, the results represented the role and importance of variables namely: family, emotional intelligence, and the kind of used material in addiction withdrawal.

20 CFR 410.232 - Withdrawal of a claim.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Withdrawal of a claim. 410.232 Section 410.232 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL COAL MINE HEALTH AND SAFETY ACT OF 1969... Claims and Evidence § 410.232 Withdrawal of a claim. (a) Before adjudication of claim. A claimant (or an...

12 CFR 563g.11 - Withdrawal or abandonment.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Withdrawal or abandonment. 563g.11 Section 563g.11 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY SECURITIES OFFERINGS § 563g.11 Withdrawal or abandonment. (a) Any offering circular, amendment, or exhibit may be withdrawn...

27 CFR 19.997 - Withdrawal of fuel alcohol.

Science.gov (United States)

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Withdrawal of fuel alcohol. 19.997 Section 19.997 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU... and Transfers § 19.997 Withdrawal of fuel alcohol. For each shipment or other removal of fuel alcohol...

Supersensitive Kappa Opioid Receptors Promotes Ethanol Withdrawal-Related Behaviors and Reduce Dopamine Signaling in the Nucleus Accumbens.

Science.gov (United States)

Rose, Jamie H; Karkhanis, Anushree N; Chen, Rong; Gioia, Dominic; Lopez, Marcelo F; Becker, Howard C; McCool, Brian A; Jones, Sara R

2016-05-01

Chronic ethanol exposure reduces dopamine transmission in the nucleus accumbens, which may contribute to the negative affective symptoms associated with ethanol withdrawal. Kappa opioid receptors have been implicated in withdrawal-induced excessive drinking and anxiety-like behaviors and are known to inhibit dopamine release in the nucleus accumbens. The effects of chronic ethanol exposure on kappa opioid receptor-mediated changes in dopamine transmission at the level of the dopamine terminal and withdrawal-related behaviors were examined. Five weeks of chronic intermittent ethanol exposure in male C57BL/6 mice were used to examine the role of kappa opioid receptors in chronic ethanol-induced increases in ethanol intake and marble burying, a measure of anxiety/compulsive-like behavior. Drinking and marble burying were evaluated before and after chronic intermittent ethanol exposure, with and without kappa opioid receptor blockade by nor-binaltorphimine (10mg/kg i.p.). Functional alterations in kappa opioid receptors were assessed using fast scan cyclic voltammetry in brain slices containing the nucleus accumbens. Chronic intermittent ethanol-exposed mice showed increased ethanol drinking and marble burying compared with controls, which was attenuated with kappa opioid receptor blockade. Chronic intermittent ethanol-induced increases in behavior were replicated with kappa opioid receptor activation in naïve mice. Fast scan cyclic voltammetry revealed that chronic intermittent ethanol reduced accumbal dopamine release and increased uptake rates, promoting a hypodopaminergic state of this region. Kappa opioid receptor activation with U50,488H concentration-dependently decreased dopamine release in both groups; however, this effect was greater in chronic intermittent ethanol-treated mice, indicating kappa opioid receptor supersensitivity in this group. These data suggest that the chronic intermittent ethanol-induced increase in ethanol intake and anxiety

Psychosocial withdrawal characteristics of nicotine compared with alcohol and caffeine.

Science.gov (United States)

Miyata, Hisatsugu; Hironaka, Naoyuki; Takada, Kohji; Miyasato, Katsumasa; Nakamura, Koichi; Yanagita, Tomoji

2008-10-01

The purpose of the present study was to observe the psychosocial characteristics of withdrawal from cigarette smoking in comparison with those from caffeine (CAF) and alcoholic (ALC) beverage withdrawal. Twenty-seven healthy volunteers at a medial level of dependence on both cigarettes (nicotine, NCT) and either CAF or ALC, as judged by the DSM-IV-TR criteria for substance dependence, participated in this study. The participants were required to abstain from smoking and either CAF or ALC for 7 days, each one after another, with a 7-day interval. The order of abstinence was counterbalanced among the participants. Psychosocial parameters, including a desire for substances, social activity function, well-being, withdrawal symptoms, and vital signs, were assessed during the withdrawal periods. The study protocol was approved by the Jikei University Review Board. The results indicated that there were no differences in the maximum level of desire for a substance and the influence on social activity function between NCT and other substances during the withdrawal periods. As for withdrawal symptoms, NCT caused a more intensive degree of irritability than CAF or ALC, and a more intensive degree of difficulty concentrating and restlessness than did withdrawal from ALC. However, the subjective well-being questionnaire indicated no differences in these symptoms between NCT and other substances. The present results suggest that there are no significant differences in psychosocial manifestations regarding the difficulty in abstaining from NCT, CAF, and ALC.

Non-analgesic effects of opioids: management of opioid-induced constipation by peripheral opioid receptor antagonists: prevention or withdrawal?

Science.gov (United States)

Holzer, Peter

2012-01-01

The therapeutic action of opioid analgesics is compromised by peripheral adverse effects among which opioid-induced constipation (OIC) is the most disabling, with a prevalence reported to vary between 15 and 90 %. Although OIC is usually treated with laxatives, there is insufficient clinical evidence that laxatives are efficacious in this indication. In contrast, there is ample evidence from double- blind, randomized and placebo-controlled trials that peripheral opioid receptor antagonists (PORAs) counteract OIC. This specific treatment modality is currently based on subcutaneous methylnaltrexone for the interruption of OIC in patients with advanced illness, and a fixed combination of oral prolonged-release naloxone with prolonged-release oxycodone for the prevention of OIC in the treatment of non-cancer and cancer pain. Both drugs counteract OIC while the analgesic effect of opioids remains unabated. The clinical studies show that more than 50 % of the patients with constipation under opioid therapy may benefit from the use of PORAs, while PORA-resistant patients are likely to suffer from non-opioid-induced constipation, the prevalence of which increases with age. While the addition of naloxone to oxycodone seems to act by preventing OIC, the intermittent dosing of methylnaltrexone every other day seems to stimulate defaecation by provoking an intestinal withdrawal response. The availability of PORAs provides a novel opportunity to specifically control OIC and other peripheral adverse effects of opioid analgesics (e.g., urinary retention and pruritus). The continuous dosing of a PORA has the advantage of few adverse effects, while intermittent dosing of a PORA can be associated with abdominal cramp-like pain.

The Treatment of Clozapine-Withdrawal Delirium with Electroconvulsive Therapy

Directory of Open Access Journals (Sweden)

Anish Modak

2017-01-01

Full Text Available Clozapine, a commonly used atypical antipsychotic, can precipitate a severe withdrawal syndrome. In this report, we describe a case of delirium with catatonic features emerging after the immediate cessation of clozapine subsequent to concerns of developing neuroleptic malignant syndrome. After multiple treatments were found to be inefficacious, electroconvulsive therapy (ECT was initiated, resulting in significant improvement. A literature search revealed six previous cases of clozapine-withdrawal syndromes of varied symptomatology treated with ECT. To our knowledge, the present case represents the first reported clozapine-withdrawal delirium treated successfully with ECT.

Youth social withdrawal behavior (hikikomori): A systematic review of qualitative and quantitative studies.

Science.gov (United States)

Li, Tim M H; Wong, Paul W C

2015-07-01

Acute and/or severe social withdrawal behavior among youth was seen as a culture-bound psychiatric syndrome in Japan, but more youth social withdrawal cases in different countries have been discovered recently. However, due to the lack of a formal definition and diagnostic tool for youth social withdrawal, cross-cultural observational and intervention studies are limited. We aimed to consolidate existing knowledge in order to understand youth social withdrawal from diverse perspectives and suggest different interventions for different trajectories of youth social withdrawal. This review examined the current available scientific information on youth social withdrawal in the academic databases: ProQuest, ScienceDirect, Web of Science and PubMed. We included quantitative and qualitative studies of socially withdrawn youths published in English and academic peer-reviewed journals. We synthesized the information into the following categories: (1) definitions of youth social withdrawal, (2) developmental theories, (3) factors associated with youth social withdrawal and (4) interventions for socially withdrawn youths. Accordingly, there are diverse and controversial definitions for youth social withdrawal. Studies of youth social withdrawal are based on models that lead to quite different conclusions. Researchers with an attachment perspective view youth social withdrawal as a negative phenomenon, whereas those who adopt Erikson's developmental theory view it more positively as a process of seeking self-knowledge. Different interventions for socially withdrawn youths have been developed, mainly in Japan, but evidence-based practice is almost non-existent. We propose a theoretical framework that views youth social withdrawal as resulting from the interplay between psychological, social and behavioral factors. Future validation of the framework will help drive forward advances in theory and interventions for youth social withdrawal as an emerging issue in developed

Smartphone Restriction and its Effect on Subjective Withdrawal Related Scores

OpenAIRE

Aarestad, Sarah Helene; Eide, Tine Almenning

2017-01-01

Smartphone overuse is associated with a number of negative consequences for the individual and the environment. In the right end of the distribution of smartphone usage, concepts such as smartphone addiction seem warranted. An area that so far lacks research concerns the effect of smartphone restriction generally and specifically on subjective withdrawal related scores across different degrees of smartphone usage. The present study examined withdrawal related scores on the Smartphone Withdraw...

Tramadol Induced Adrenal Insufficiency: Histological, Immunohistochemical, Ultrastructural, and Biochemical Genetic Experimental Study.

Science.gov (United States)

Abdelaleem, Shereen Abdelhakim; Hassan, Osama A; Ahmed, Rasha F; Zenhom, Nagwa M; Rifaai, Rehab A; El-Tahawy, Nashwa F

2017-01-01

Tramadol is a synthetic, centrally acting analgesic. It is the most consumed narcotic drug that is prescribed in the world. Tramadol abuse has dramatically increased in Egypt. Long term use of tramadol can induce endocrinopathy. So, the aim of this study was to analyze the adrenal insufficiency induced by long term use of tramadol in experimental animals and also to assess its withdrawal effects through histopathological and biochemical genetic study. Forty male albino rats were used in this study. The rats were divided into 4 groups (control group, tramadol-treated group, and withdrawal groups). Tramadol was given to albino rats at a dose of 80 mg/kg body weight for 3 months and after withdrawal periods (7-15 days) rats were sacrificed. Long term use of tramadol induced severe histopathological changes in adrenal glands. Tramadol decreased the levels of serum cortisol and DHEAS hormones. In addition, it increased the level of adrenal MDA and decreased the genetic expression of glutathione peroxidase and thioredoxin reductase in adrenal gland tissues. All these changes started to return to normal after withdrawal of tramadol. Thus, it was confirmed that long term use of tramadol can induce severe adrenal insufficiency.

The use of sugammadex in a patient with Kennedy′s disease under general anesthesia

Directory of Open Access Journals (Sweden)

Risa Takeuchi

2014-01-01

Full Text Available Kennedy′s disease (KD, also known as spinal and bulbar muscular atrophy, is a rare, X-linked recessive, neurodegenerative disorder of the lower motor neurons characterized by progressive bulbar and appendicle muscular atrophy. Here we report a case of a 62-year-old male patient with KD, weighing 70 kg and 173 cm tall, was scheduled for frontal sinusectomy due to sinusitis. General anesthesia was induced through propofol 80 mg, remifentanil 0.25 μg/kg/min and 40 mg rocuronium. We were successfully able to use a sugammadex on a patient suffering from KD in order to reverse rocuronium-induced neuromuscular blockade.

Cannabis withdrawal in chronic, frequent cannabis smokers during sustained abstinence within a closed residential environment.

Science.gov (United States)

Lee, Dayong; Schroeder, Jennifer R; Karschner, Erin L; Goodwin, Robert S; Hirvonen, Jussi; Gorelick, David A; Huestis, Marilyn A

2014-01-01

Chronic, frequent cannabis smokers may experience residual and offset effects, withdrawal, and craving when abstaining from the drug. We characterized the prevalence, duration, and intensity of these effects in chronic frequent cannabis smokers during abstinence on a closed research unit. Non-treatment-seeking participants (N = 29 on admission, 66% and 34% remaining after 2 and 4 weeks) provided subjective effects data. A battery of five instruments was computer-administered daily to measure psychological, sensory, and physical symptoms associated with cannabinoid intoxication and withdrawal. Plasma and oral fluid specimens were concurrently collected and analyzed for cannabinoids. Outcome variables were evaluated as change from admission (Day 0) with regression models. Most abstinence effects, including irritability and anxiety were greatest on Days 0-3 and decreased thereafter. Cannabis craving significantly decreased over time, whereas decreased appetite began to normalize on Day 4. Strange dreams and difficulty getting to sleep increased over time, suggesting intrinsic sleep problems in chronic cannabis smokers. Symptoms likely induced by residual drug effects were at maximum intensity on admission and positively correlated with plasma and oral fluid cannabinoid concentrations on admission but not afterward; these symptoms showed overall prevalence higher than cannabis withdrawal symptoms. The combined influence of residual/offset drug effects, withdrawal, and craving was observed in chronic cannabis smokers during monitored abstinence. Abstinence symptoms were generally more intense in the initial phase, implying importance of early intervention in cannabis quit attempts. Sleep disturbance persisting for an extended period suggests that hypnotic medications could be beneficial in treating cannabis dependence. © American Academy of Addiction Psychiatry.

5 CFR 831.1207 - Withdrawal of disability retirement applications.

Science.gov (United States)

2010-01-01

... type. (d) OPM also considers a disability retirement application to be withdrawn when the agency... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Withdrawal of disability retirement...) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT Disability Retirement § 831.1207 Withdrawal of...

Opioid withdrawal signs and symptoms in children: frequency and determinants.

Science.gov (United States)

Fisher, Deborah; Grap, Mary Jo; Younger, Janet B; Ameringer, Suzanne; Elswick, R K

2013-01-01

The purpose of this study was to, in a pediatric population, describe the frequency of opioid withdrawal signs and symptoms and to identify factors associated with these opioid withdrawal signs and symptoms. Opioids are used routinely in the pediatric intensive care population for analgesia, sedation, blunting of physiologic responses to stress, and safety. In children, physical dependence may occur in as little as 2-3 days of continuous opioid therapy. Once the child no longer needs the opioid, the medications are reduced over time. A prospective, descriptive study was conducted. The sample of 26 was drawn from all patients, ages 2 weeks to 21 years admitted to the Children's Hospital of Richmond pediatric intensive care unit (PICU) and who have received continuous infusion or scheduled opioids for at least 5 days. Data collected included: opioid withdrawal score (WAT-1), opioid taper rate (total dose of opioid per day in morphine equivalents per kilogram [MEK]), pretaper peak MEK, pretaper cumulative MEK, number of days of opioid exposure prior to taper, and age. Out of 26 enrolled participants, only 9 (45%) had opioid withdrawal on any given day. In addition, there was limited variability in WAT-1 scores. The most common symptoms notes were diarrhea, vomit, sweat, and fever. For optimal opioid withdrawal assessments, clinicians should use a validated instrument such as the WAT-1 to measure for signs and symptoms of opioid withdrawal. Further research is indicated to examine risk factors for opioid withdrawal in children. Copyright © 2013 Elsevier Inc. All rights reserved.

U.S. withdrawal from the Paris Agreement: Reasons, impacts, and China's response

OpenAIRE

Hai-Bin Zhang; Han-Cheng Dai; Hua-Xia Lai; Wen-Tao Wang

2017-01-01

Applying qualitative and quantitative methods, this article explains the driving forces behind U.S. President Donald Trump's decision to withdraw from the Paris Agreement, assesses the impacts of this withdrawal on the compliance prospects of the agreement, and proposes how China should respond. The withdrawal undercuts the foundation of global climate governance and upsets the process of climate cooperation, and the impacts are manifold. The withdrawal undermines the universality of the Pari...

Phenobarbital compared to benzodiazepines in alcohol withdrawal treatment

DEFF Research Database (Denmark)

Askgaard, Gro; Hallas, Jesper; Fink-Jensen, Anders

2016-01-01

BACKGROUND: Long-acting benzodiazepines such as chlordiazepoxide are recommended as first-line treatment for alcohol withdrawal. These drugs are known for their abuse liability and might increase alcohol consumption among problem drinkers. Phenobarbital could be an alternative treatment option......, possibly with the drawback of a more pronounced acute toxicity. We evaluated if phenobarbital compared to chlordiazepoxide decreased the risk of subsequent use of benzodiazepines, alcohol recidivism and mortality. METHODS: The study was a register-based cohort study of patients admitted for alcohol...... withdrawal 1998-2013 and treated with either phenobarbital or chlordiazepoxide. Patients were followed for one year. We calculated hazard ratios (HR) for benzodiazepine use, alcohol recidivism and mortality associated with alcohol withdrawal treatment, while adjusting for confounders. RESULTS: A total...

75 FR 12804 - Withdrawal of Regulatory Guide 8.6

Science.gov (United States)

2010-03-17

... ``Regulatory Guides'' in the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/doc-collections... NUCLEAR REGULATORY COMMISSION [NRC-2010-0103] Withdrawal of Regulatory Guide 8.6 AGENCY: Nuclear Regulatory Commission. ACTION: Withdrawal of Regulatory Guide 8.6, ``Standard Test Procedure for Geiger-M...

40 CFR 180.8 - Withdrawal of petitions without prejudice.

Science.gov (United States)

2010-07-01

... prejudice. 180.8 Section 180.8 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... § 180.8 Withdrawal of petitions without prejudice. In some cases the Administrator will notify the... clarification or the obtaining of additional data. This withdrawal may be without prejudice to a future filing...

Caffeine withdrawal symptoms and self-administration following caffeine deprivation.

Science.gov (United States)

Mitchell, S H; de Wit, H; Zacny, J P

1995-08-01

This study examined the effects of complete or partial caffeine deprivation on withdrawal symptomatology and self-administration of coffee in caffeine-dependent coffee drinkers. Nine habitual coffee drinkers abstained from dietary sources of caffeine for 33.5 h. Caffeine deprivation was manipulated by administering capsules containing 0%, 50%, or 100% of each subject's daily caffeine intake (complete, partial, and no deprivation conditions). Caffeine withdrawal symptomatology was measured using self-report questionnaires. Caffeine self-administration was measured using: i) the amount of coffee subjects earned on a series of concurrent random-ratio schedules that yielded coffee and money reinforcers; ii) the amount of earned coffee they consumed. Saliva samples revealed that subjects complied with the caffeine abstinence instructions. Caffeine withdrawal symptoms occurred reliably following complete caffeine deprivation, though not in the partial deprivation condition. Caffeine self-administration was not related to deprivation condition. We conclude that caffeine withdrawal symptomatology is not necessarily associated with increased caffeine consumption.

Steroid withdrawal in renal transplant patients: the Irish experience.

LENUS (Irish Health Repository)

Phelan, P J

2012-02-01

BACKGROUND: Steroid therapy is associated with significant morbidity in renal transplant recipients. However, there is concern that steroid withdrawal will adversely affect outcome. METHODS: We report on 241 renal transplant recipients on different doses of corticosteroids at 3 months (zero, <\\/= 5 mg\\/day, > 5 mg\\/day). Parameters analysed included blood pressure, lipid profile, weight change, new onset diabetes after transplantation (NODAT), allograft survival and acute rejection. RESULTS: Elimination of corticosteroids had no impact on allograft survival at 1 year. There were no cases of NODAT in the steroid withdrawal group compared with over 7% in each of the steroid groups. There were no significant improvements in weight gain, blood pressure control or total cholesterol with withdrawal of steroids before 3 months. CONCLUSIONS: In renal transplant patients treated with tacrolimus and mycophenolate, early withdrawal of steroids does not appear to adversely affect allograft outcome at 1 year. It may result in less NODAT.

Steroid withdrawal in renal transplant patients: the Irish experience.

LENUS (Irish Health Repository)

Phelan, P J

2010-10-29

BACKGROUND: Steroid therapy is associated with significant morbidity in renal transplant recipients. However, there is concern that steroid withdrawal will adversely affect outcome. METHODS: We report on 241 renal transplant recipients on different doses of corticosteroids at 3 months (zero, ≤5 mg\\/day, >5 mg\\/day). Parameters analysed included blood pressure, lipid profile, weight change, new onset diabetes after transplantation (NODAT), allograft survival and acute rejection. RESULTS: Elimination of corticosteroids had no impact on allograft survival at 1 year. There were no cases of NODAT in the steroid withdrawal group compared with over 7% in each of the steroid groups. There were no significant improvements in weight gain, blood pressure control or total cholesterol with withdrawal of steroids before 3 months. CONCLUSIONS: In renal transplant patients treated with tacrolimus and mycophenolate, early withdrawal of steroids does not appear to adversely affect allograft outcome at 1 year. It may result in less NODAT.

Determination of Screw and Nail Withdrawal Resistance of Some Important Wood Species

Directory of Open Access Journals (Sweden)

Alper Aytekin

2008-04-01

Full Text Available In this study, screw and nail withdrawal resistance of fir (Abies nordmanniana, oak (Quercus robur L. black pine (Pinus nigra Arnold and Stone pine (Pinus pinea L. wood were determined and compared. The data represent the testing of withdrawal resistance of three types of screws as smart, serrated and conventional and common nails. The specimens were prepared according to TS 6094 standards. The dimensions of the specimens were 5x5x15cm and for all of the directions. Moreover, the specimens were conditioned at ambient room temperature and 65±2% relative humidity. The screws and nails were installed according to ASTM-D 1761 standards. Nail dimensions were 2.5mm diameter and 50 mm length, conventional screws were 4x50mm, serrated screws were 4x45mm and smart screws were 4x50mm. Results show that the maximum screw withdrawal resistance value was found in Stone pine for the serrated screw. There were no significant differences between Stone pine and oak regarding screw withdrawal resistance values. Conventional screw yielded the maximum screw withdrawal resistance value in oak, followed by Stone pine, black pine and fir. Oak wood showed the maximum screw withdrawal resistance value for the smart screw, followed by Stone pine, black pine, and fir. Oak wood showed higher nail withdrawal resistances than softwood species. It was also determined that oak shows the maximum nail withdrawal resistance in all types. The nail withdrawal resistances at the longitudinal direction are lower with respect to radial and tangential directions.

Apoptosis following interleukin-2 withdrawal from T cells: evidence for a regulatory role of CD18 (beta 2-integrin) molecules

DEFF Research Database (Denmark)

Röpke, C; Gladstone, P; Nielsen, M

1996-01-01

, these findings suggest that CD18 molecules (beta 2-integrins) play a regulatory role in the apoptotic response following cytokine withdrawal, and that the regulation is mediated, at least partly, through T-T cell interactions. Thus, apoptotic death following IL-2 deprivation appears to be under "social" control...... activated T cells. Thus, removal of IL-2 from proliferating T cells not only induces growth arrest, but triggers a massive cell death due to apoptosis. While the apoptotic response involves a series of well-described events, it remains less clear how apoptosis is regulated following IL-2 withdrawal. Here...... molecules (CD28, CD29, CD49d, CD80, CD86) did not. Secondly, IL-2 withdrawal resulted in a retarded apoptotic response in LFA-1 (CD11a/CD18) negative T cells obtained from a leukocyte adhesion deficiency (LAD) patient, as compared to LFA-1 positive T cell lines. Thirdly, co-culture of LFA-1 positive...

A genetic perspective on the proposed inclusion of cannabis withdrawal in the DSM-5

Science.gov (United States)

Verweij, K.J.H.; Agrawal, A.; Nat, N.O.; Creemers, H.E.; Huizink, A.C.; Martin, N.G.; Lynskey, M.T.

2013-01-01

Background Various studies support the inclusion of cannabis withdrawal to the diagnosis of cannabis use disorders in the upcoming DSM-5. The aims of the current study were to (1) estimate the prevalence of DSM-5 cannabis withdrawal (Criterion B), (2) estimate the role of genetic and environmental influences on individual differences in cannabis withdrawal, and (3) determine the extent to which genetic and environmental influences on cannabis withdrawal overlap with those on DSM-IV defined abuse/dependence. Methods The sample included 2276 lifetime cannabis-using adult Australian twins. Cannabis withdrawal was defined in accordance with Criterion B of the proposed DSM-5 revisions. Cannabis abuse/dependence was defined as endorsing one or more DSM-IV criteria of abuse or three or more dependence criteria. The classical twin model was used to estimate the genetic and environmental influences on variation in cannabis withdrawal, as well as its covariation with abuse/dependence. Results Of all cannabis users 11.9% met criteria for cannabis withdrawal. Around 50% of between-individual variation in withdrawal could be attributed to additive genetic variation, and the rest of the variation was mostly due to non-shared environmental influences. Importantly, the genetic influences on cannabis withdrawal almost completely (99%) overlapped with those on abuse/dependence. Conclusions We showed that cannabis withdrawal symptoms exist among cannabis users, and that cannabis withdrawal is moderately heritable. Genetic influences on cannabis withdrawal are the same as those influencing abuse/dependence. These results add to the wealth of literature that recommends the addition of cannabis withdrawal to the diagnosis of DSM-5 cannabis use disorders. PMID:23194657