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Tsafrir S. Mor - One of the best experts on this subject based on the ideXlab platform.
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Reversal of Succinylcholine Induced Apnea with an Organophosphate Scavenging Recombinant Butyrylcholinesterase
PloS one, 2013Co-Authors: Brian C. Geyer, Katherine E. Larrimore, Jacquelyn Kilbourne, Latha Kannan, Tsafrir S. MorAbstract:Concerns about the safety of paralytics such as Succinylcholine to facilitate endotracheal intubation limit their use in prehospital and emergency department settings. The ability to rapidly reverse paralysis and restore respiratory drive would increase the safety margin of an agent, thus permitting the pursuit of alternative intubation strategies. In particular, patients who carry genetic or acquired deficiency of butyrylcholinesterase, the serum enzyme responsible for Succinylcholine hydrolysis, are susceptible to Succinylcholine-induced apnea, which manifests as paralysis, lasting hours beyond the normally brief half-life of Succinylcholine. We hypothesized that intravenous administration of plant-derived recombinant BChE, which also prevents mortality in nerve agent poisoning, would rapidly reverse the effects of Succinylcholine. Recombinant butyrylcholinesterase was produced in transgenic plants and purified. Further analysis involved murine and guinea pig models of Succinylcholine toxicity. Animals were treated with lethal and sublethal doses of Succinylcholine followed by administration of butyrylcholinesterase or vehicle. In both animal models vital signs and overall survival at specified intervals post Succinylcholine administration were assessed. Purified plant-derived recombinant human butyrylcholinesterase can hydrolyze Succinylcholine in vitro. Challenge of mice with an LD100 of Succinylcholine followed by BChE administration resulted in complete prevention of respiratory inhibition and concomitant mortality. Furthermore, experiments in symptomatic guinea pigs demonstrated extremely rapid Succinylcholine detoxification with complete amelioration of symptoms and no apparent complications. Recombinant plant-derived butyrylcholinesterase was capable of counteracting and reversing apnea in two complementary models of lethal Succinylcholine toxicity, completely preventing mortality. This study of a protein antidote validates the feasibility of protection and treatment of overdose from Succinylcholine as well as other biologically active butyrylcholinesterase substrates.
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reversal of Succinylcholine induced apnea with an organophosphate scavenging recombinant butyrylcholinesterase
PLOS ONE, 2013Co-Authors: Brian C. Geyer, Katherine E. Larrimore, Jacquelyn Kilbourne, Latha Kannan, Tsafrir S. MorAbstract:Background Concerns about the safety of paralytics such as Succinylcholine to facilitate endotracheal intubation limit their use in prehospital and emergency department settings. The ability to rapidly reverse paralysis and restore respiratory drive would increase the safety margin of an agent, thus permitting the pursuit of alternative intubation strategies. In particular, patients who carry genetic or acquired deficiency of butyrylcholinesterase, the serum enzyme responsible for Succinylcholine hydrolysis, are susceptible to Succinylcholine-induced apnea, which manifests as paralysis, lasting hours beyond the normally brief half-life of Succinylcholine. We hypothesized that intravenous administration of plant-derived recombinant BChE, which also prevents mortality in nerve agent poisoning, would rapidly reverse the effects of Succinylcholine.
Martin R Tramer - One of the best experts on this subject based on the ideXlab platform.
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rapid sequence induction with a standard intubation dose of rocuronium after magnesium pretreatment compared with Succinylcholine a randomized clinical trial
Anesthesia & Analgesia, 2020Co-Authors: Martin R Tramer, Christoph Czarnetzki, Eric Albrecht, Philippe Masouye, Moira Baeriswyl, Antoine Poncet, Matthias Robin, Christian KernAbstract:BACKGROUND Succinylcholine remains the muscle relaxant of choice for rapid sequence induction (RSI) but has many adverse effects. High-dose rocuronium bromide may be an alternative to Succinylcholine for RSI but recovery times are nearly doubled compared with a standard intubating dose of rocuronium. Magnesium sulfate significantly shortens the onset time of a standard intubating dose of rocuronium. We set out to investigate whether intravenous (IV) pretreatment with MgSO4 followed by a standard intubating dose of rocuronium achieved superior intubation conditions compared with Succinylcholine. METHODS Adults were randomized to receive a 15-minute IV infusion of MgSO4 (60 mg·kg-1) immediately before RSI with propofol 2 mg·kg-1, sufentanil 0.2 μg·kg-1 and rocuronium 0.6 mg·kg-1, or a matching 15-minute IV infusion of saline immediately before an identical RSI, but with Succinylcholine 1 mg·kg-1. Primary end point was the rate of excellent intubating conditions 60 seconds after administration of the neuromuscular blocking agent and compared between groups using multivariable log-binomial regression model. Secondary end points were blood pressure and heart rate before induction, before and after intubation, and adverse events up to 24 hours postoperatively. RESULTS Among 280 randomized patients, intubating conditions could be analyzed in 259 (133 MgSO4-rocuronium and 126 saline-Succinylcholine). The rate of excellent intubating conditions was 46% with MgSO4-rocuronium and 45% with saline-Succinylcholine. The analysis adjusted for gender and center showed no superiority of MgSO4-rocuronium compared with saline-Succinylcholine (relative risk [RR] 1.06, 95% confidence interval [CI], 0.81-1.39, P = .659). The rate of excellent intubating conditions was higher in women (54% [70 of 130]) compared with men (37% [48 of 129]; adjusted RR 1.42, 95% CI, 1.07-1.91, P = .017). No significant difference between groups was observed for systolic and diastolic blood pressures. Mean heart rate was significantly higher in the MgSO4-rocuronium group. The percentage of patients with at least 1 adverse event was lower with MgSO4-rocuronium (11%) compared with saline-Succinylcholine (28%) (RR 0.38, 95% CI, 0.22-0.66, P < .001). With saline-Succinylcholine, adverse events consisted mainly of postoperative muscle pain (n = 26 [19%]) and signs of histamine release (n = 13 [9%]). With MgSO4-rocuronium, few patients had pain on injection, nausea and vomiting, or skin rash during the MgSO4-infusion (n = 5 [4%]). CONCLUSIONS IV pretreatment with MgSO4 followed by a standard intubating dose of rocuronium did not provide superior intubation conditions to Succinylcholine but had fewer adverse effects.
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prevention of Succinylcholine induced fasciculation and myalgia a meta analysis of randomized trials
Anesthesiology, 2005Co-Authors: Jan-uwe Schreiber, Christopher Lysakowski, Thomas Fuchsbuder, Martin R TramerAbstract:Fifty-two randomized trials (5,318 patients) were included in this meta-analysis. In controls, the incidence of fasciculation was 95%, and the incidence of myalgia at 24 h was 50%. Non-depolarizing muscle relaxants, lidocaine, or magnesium prevented fasciculation (number needed to treat, 1.2-2.5). Best prevention of myalgia was with nonsteroidal antiinflammatory drugs (number needed to treat, 2.5) and with rocuronium or lidocaine (number needed to treat, 3). There was a dose-dependent risk of blurred vision, diplopia, voice disorders, and difficulty in breathing and swallowing (number needed to harm, < 3.5) with muscle relaxants. There was evidence of less myalgia with 1.5 mg/kg succinylchollne (compared with 1 mg/kg). Opioids had no impact. Succinylcholine-induced fasciculation may best be prevented with muscle relaxants, lidocaine, or magnesium. Myalgia may best be prevented with muscle relaxants, lidocaine, or nonsteroidal antiinflammatory drugs. The risk of potentially serious adverse events with muscle relaxants is not negligible. Data that allow for a risk-benefit assessment are lacking for other drugs.
Frederick P. Fuller - One of the best experts on this subject based on the ideXlab platform.
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out of hospital Succinylcholine assisted endotracheal intubation by paramedics
Annals of Emergency Medicine, 2000Co-Authors: Steven A. Pace, Frederick P. FullerAbstract:Abstract Study Objective: To describe the effectiveness and safety of Succinylcholine administration by paramedics to out-of-hospital patients requiring endotracheal intubation. Methods: A consecutive case series was collected by retrospective review of patient care records from a large, private ambulance agency serving an urban and rural county of 600,000 residents over a 40-month period. All patients for whom endotracheal intubation was facilitated by Succinylcholine use were identified. Data were systematically collected on demographics, paramedic diagnosis, intubation attempts, and complications. Results: Succinylcholine was used in 150 patients with a mean age (±SD) of 50±23 years. Paramedic diagnosis was coma in 43% (64/150; 95% confidence interval [CI] 35% to 51%), trauma in 26% (39/150; 95% CI 19% to 33%), and respiratory failure in 31% (47/150; 95% CI 23% to 39%). No patient was in cardiac arrest at the time of Succinylcholine use. The intubation success rate was 92% (138/150; 95% CI 88% to 96%), with success achieved on the first attempt in 82% of patients (123/150; 95% CI 76% to 88%). Four patients who received Succinylcholine developed cardiac arrest, and 3 others had symptomatic bradycardia. Conclusion: The use of Succinylcholine by paramedics to assist intubation appears to aid in intubation of patients who are not in cardiac arrest. However, significant cardiac complications can occur. [Pace SA, Fuller FP. Out-of-hospital Succinylcholine-assisted endotracheal intubation by paramedics. Ann Emerg Med . June 2000;35:568-572.]
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Out-of-hospital Succinylcholine-assisted endotracheal intubation by paramedics ☆ ☆☆
Annals of emergency medicine, 2000Co-Authors: Steven A. Pace, Frederick P. FullerAbstract:Abstract Study Objective: To describe the effectiveness and safety of Succinylcholine administration by paramedics to out-of-hospital patients requiring endotracheal intubation. Methods: A consecutive case series was collected by retrospective review of patient care records from a large, private ambulance agency serving an urban and rural county of 600,000 residents over a 40-month period. All patients for whom endotracheal intubation was facilitated by Succinylcholine use were identified. Data were systematically collected on demographics, paramedic diagnosis, intubation attempts, and complications. Results: Succinylcholine was used in 150 patients with a mean age (±SD) of 50±23 years. Paramedic diagnosis was coma in 43% (64/150; 95% confidence interval [CI] 35% to 51%), trauma in 26% (39/150; 95% CI 19% to 33%), and respiratory failure in 31% (47/150; 95% CI 23% to 39%). No patient was in cardiac arrest at the time of Succinylcholine use. The intubation success rate was 92% (138/150; 95% CI 88% to 96%), with success achieved on the first attempt in 82% of patients (123/150; 95% CI 76% to 88%). Four patients who received Succinylcholine developed cardiac arrest, and 3 others had symptomatic bradycardia. Conclusion: The use of Succinylcholine by paramedics to assist intubation appears to aid in intubation of patients who are not in cardiac arrest. However, significant cardiac complications can occur. [Pace SA, Fuller FP. Out-of-hospital Succinylcholine-assisted endotracheal intubation by paramedics. Ann Emerg Med . June 2000;35:568-572.]
Brian C. Geyer - One of the best experts on this subject based on the ideXlab platform.
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Reversal of Succinylcholine Induced Apnea with an Organophosphate Scavenging Recombinant Butyrylcholinesterase
PloS one, 2013Co-Authors: Brian C. Geyer, Katherine E. Larrimore, Jacquelyn Kilbourne, Latha Kannan, Tsafrir S. MorAbstract:Concerns about the safety of paralytics such as Succinylcholine to facilitate endotracheal intubation limit their use in prehospital and emergency department settings. The ability to rapidly reverse paralysis and restore respiratory drive would increase the safety margin of an agent, thus permitting the pursuit of alternative intubation strategies. In particular, patients who carry genetic or acquired deficiency of butyrylcholinesterase, the serum enzyme responsible for Succinylcholine hydrolysis, are susceptible to Succinylcholine-induced apnea, which manifests as paralysis, lasting hours beyond the normally brief half-life of Succinylcholine. We hypothesized that intravenous administration of plant-derived recombinant BChE, which also prevents mortality in nerve agent poisoning, would rapidly reverse the effects of Succinylcholine. Recombinant butyrylcholinesterase was produced in transgenic plants and purified. Further analysis involved murine and guinea pig models of Succinylcholine toxicity. Animals were treated with lethal and sublethal doses of Succinylcholine followed by administration of butyrylcholinesterase or vehicle. In both animal models vital signs and overall survival at specified intervals post Succinylcholine administration were assessed. Purified plant-derived recombinant human butyrylcholinesterase can hydrolyze Succinylcholine in vitro. Challenge of mice with an LD100 of Succinylcholine followed by BChE administration resulted in complete prevention of respiratory inhibition and concomitant mortality. Furthermore, experiments in symptomatic guinea pigs demonstrated extremely rapid Succinylcholine detoxification with complete amelioration of symptoms and no apparent complications. Recombinant plant-derived butyrylcholinesterase was capable of counteracting and reversing apnea in two complementary models of lethal Succinylcholine toxicity, completely preventing mortality. This study of a protein antidote validates the feasibility of protection and treatment of overdose from Succinylcholine as well as other biologically active butyrylcholinesterase substrates.
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reversal of Succinylcholine induced apnea with an organophosphate scavenging recombinant butyrylcholinesterase
PLOS ONE, 2013Co-Authors: Brian C. Geyer, Katherine E. Larrimore, Jacquelyn Kilbourne, Latha Kannan, Tsafrir S. MorAbstract:Background Concerns about the safety of paralytics such as Succinylcholine to facilitate endotracheal intubation limit their use in prehospital and emergency department settings. The ability to rapidly reverse paralysis and restore respiratory drive would increase the safety margin of an agent, thus permitting the pursuit of alternative intubation strategies. In particular, patients who carry genetic or acquired deficiency of butyrylcholinesterase, the serum enzyme responsible for Succinylcholine hydrolysis, are susceptible to Succinylcholine-induced apnea, which manifests as paralysis, lasting hours beyond the normally brief half-life of Succinylcholine. We hypothesized that intravenous administration of plant-derived recombinant BChE, which also prevents mortality in nerve agent poisoning, would rapidly reverse the effects of Succinylcholine.
Martin Siegemund - One of the best experts on this subject based on the ideXlab platform.
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Succinylcholine versus rocuronium for rapid sequence intubation in intensive care a prospective randomized controlled trial
Critical Care, 2011Co-Authors: Stephan C.u. Marsch, Luzius A Steiner, Evelyne Bucher, Hans Pargger, Timothy Aebi, Martin Schumann, Patrick Hunziker, Martin SiegemundAbstract: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.
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rocuronium versus Succinylcholine for rapid sequence induction of anesthesia and endotracheal intubation a prospective randomized trial in emergent cases
Anesthesia & Analgesia, 2005Co-Authors: Mathias Sluga, Martin Siegemund, Wolfgang Ummenhofer, Wolfgang Studer, Stephan MarschAbstract:When anesthesia is induced with propofol in elective cases, endotracheal intubation conditions are not different between Succinylcholine and rocuronium approximately 60 s after the injection of the neuromuscular relaxant. In the present study, we investigated whether, in emergent cases, endotracheal intubation conditions obtained at the actual moment of intubation under Succinylcholine differ from those obtained 60 s after the injection of rocuronium. One-hundred-eighty adult patients requiring rapid sequence induction of anesthesia for emergent surgery received propofol (1.5 mg/kg) and either rocuronium (0.6 mg/kg; endotracheal intubation 60 s after injection) or Succinylcholine (1 mg/kg; endotracheal intubation as soon as possible). The time from beginning of the induction until completion of the intubation was shorter after the administration of Succinylcholine than after rocuronium (median time 95 s versus 130 s; P < 0.0001). Endotracheal intubation conditions, rated with a 9-point scale, were better after Succinylcholine administration than after rocuronium (8.6 +/- 1.1 versus 8.0 +/- 1.5; P < 0.001). There was no significant difference in patients with poor intubation conditions (7 versus 12) or in patients with failed first intubation attempt (4 versus 5) between the groups. We conclude that during rapid sequence induction of anesthesia in emergent cases, Succinylcholine allows for a more rapid endotracheal intubation sequence and creates superior intubation conditions compared with rocuronium.
