Evaluation of Neuromuscular and Cardiovascular Effects of Two Doses of Rapacuronium (ORG 9487) versus Mivacurium and Succinylcholine 

1999 ◽  
Vol 91 (6) ◽  
pp. 1648-1648 ◽  
Author(s):  
Rafael Miguel ◽  
Thomas Witkowski ◽  
Hideo Nagashima ◽  
Robert Fragen ◽  
Richard Bartkowski ◽  
...  
Keyword(s):  
Neuromuscular Blockade ◽  
Cardiovascular Effects ◽  
Rapid Onset ◽  
Neuromuscular Blocking ◽  
Open Label ◽  
Org 9487 ◽  
Train Of Four ◽  
Pressure Changes ◽  
To Receive ◽  
Nondepolarizing Muscle Relaxant

Background This study compares the neuromuscular blocking and cardiovascular effects of rapacuronium (ORG 9487), a new aminosteroid nondepolarizing muscle relaxant, to recommended intubating doses of succinylcholine and mivacurium. Methods Adult patients were randomized in an open-label fashion to receive 1-5 microg/kg fentanyl before 1.5 mg/kg propofol induction followed by 1.5 or 2.5 mg/kg rapacuronium, 1.0 mg/kg succinylcholine, or 0.25 mg/kg mivacurium (i.e., 0.15 mg/kg followed by 0.1 mg/kg 30 s later). Results Patient neuromuscular blockade status was monitored by measuring the train-of-four response to a supramaximal stimulus at the ulnar nerve every 12 s. Percentage of the first twitch of the train-of-four (T1) at 60 s was similar in patients receiving 1.5 mg/kg rapacuronium, 2.5 mg/kg rapacuronium, and succinylcholine and was significantly less than in patients in the mivacurium group (26, 16, and 18%, respectively, vs. 48%; P < 0.01). Times to 80% T1 depression were also similar among patients in the 1.5 mg/kg rapacuronium, 2.5 mg/kg rapacuronium, and succinylcholine groups and significantly longer in the mivacurium group (62, 54, and 54 s, respectively, vs. 112 s; P < 0.01). Clinical duration was longer in all groups compared with the succinylcholine group; however, clinical duration in the 1.5 mg/kg rapacuronium group was shorter compared with the mivacurium group (15 vs. 21 min, respectively; P < 0.01). Heart rate changes were mild in the 1.5 mg/kg rapacuronium, succinylcholine, and mivacurium groups. The patients in the 2.5 mg/kg rapacuronium group had significantly higher heart rates compared with patients in the mivacurium group. No differences were found in blood pressure changes among patients in the four groups. Conclusions Rapacuronium, 1.5 and 2.5 mg/kg, produced neuromuscular blockade as rapidly as succinylcholine and significantly faster than mivacurium. Although succinylcholine continued to show the shortest duration, 1.5 mg/kg rapacuronium used a rapid onset and a relatively short duration and may be considered an alternative to succinylcholine.

Comparison of the Intubation Conditions Provided by Rapacuronium (ORG 9487) or Succinylcholine in Humans during Anesthesia with Fentanyl and Propofol 

1999 ◽  
Vol 91 (5) ◽  
pp. 1311-1311 ◽  
Author(s):  
Neal W. Fleming ◽  
Frances Chung ◽  
Peter S. A. Glass ◽  
John B. Kitts ◽  
Hans Kirkegaard-Nielsen ◽  
...  
Keyword(s):  
Tracheal Intubation ◽  
Short Duration ◽  
Rapid Onset ◽  
Neuromuscular Function ◽  
Neuromuscular Blocking ◽  
Blocking Drug ◽  
Duration Of Action ◽  
Prospective Randomized Clinical Trial ◽  
Org 9487 ◽  
Train Of Four

Background Currently, the only approved muscle relaxant with a rapid onset and short duration of action is succinylcholine, a drug with some undesirable effects. Rapacuronium is an investigational nondepolarizing relaxant that also has a rapid onset and short duration and consequently should be compared with succinylcholine in its ability to facilitate rapid tracheal intubation. Methods This prospective, randomized clinical trial involved 336 patients. Anesthesia was induced with fentanyl and propofol and either 1.5 mg/kg rapacuronium or 1.0 mg/kg succinylcholine. The goal was to accomplish tracheal intubation by 60 s after administration of the neuromuscular blocking drug. Endotracheal intubation was performed, and conditions were graded by a blinded investigator. Recovery of neuromuscular function was assessed by electromyography. Results Intubation conditions were evaluated in 236 patients. Intubation by 60 s after drug administration occurred in 100% of patients with rapacuronium and in 98% with succinylcholine. Intubation conditions were excellent or good in 87% of patients with rapacuronium and in 95% with succinylcholine (P < 0.05). The time (median and range) to the first recovery of the train-of-four response was 8.0 (2.8-20.0) min with rapacuronium and 5.7 (1.8-17.7) min with succinylcholine (P < 0.05). The overall incidence of adverse effects was similar with both drugs. Conclusions A 1.5-mg/kg dose of rapacuronium effectively facilitates rapid tracheal intubation. It can be considered a valid alternative to 1.0 mg/kg succinylcholine for this purpose.

scholarly journals Comparison of Train of Four Measurements with Kinemyography NMT DATEX and Accelerography TOFscan

2021 ◽  
Vol 9 (2) ◽  
pp. 21
Author(s):  
Cyrus Motamed ◽  
Migena Demiri ◽  
Nora Colegrave
Keyword(s):  
Neuromuscular Blockade ◽  
Lower Limit ◽  
Elective Surgery ◽  
Orotracheal Intubation ◽  
Neuromuscular Blocking ◽  
Physical Status Classification ◽  
Train Of Four ◽  
Surgery First ◽  
American Society ◽  
American Society Of Anesthesiologists

Introduction: This study was designed to compare the Datex neuromuscular transmission (NMT) kinemyography (NMTK) device with the TOFscan (TS) accelerometer during the onset and recovery of neuromuscular blockade. Patients and methods: This prospective study included adult patients who were scheduled to undergo elective surgery with general anesthesia and orotracheal intubation. The TS accelerometer was randomly placed at the adductor pollicis on one hand, and the NMTK was placed on the opposite arm. Anesthesia was initiated with remifentanil target-controlled infusion (TCI) and 2.0–3.0 mg/kg of propofol. Thereafter, 0.5 mg/kg of atracurium or 0.6 mg/kg of rocuronium was injected. If needed, additional neuromuscular blocking agents were administered to facilitate surgery. First, we recorded the train of four (TOF) response at the onset of neuromuscular blockade to reach a TOF count of 0. Second, we recorded the TOF response at the recovery of neuromuscular blockade to obtain a T4/T1 90% by both TS and NMTK. Results: There were 32 patients, aged 38–83 years, with the American Society of Anesthesiologists (ASA) Physical Status Classification I–III included and analyzed. Surgery was abdominal, gynecologic, or head and neck. The Bland and Altman analysis for obtaining zero responses during the onset showed a bias (mean) of 2.7 s (delay) of TS in comparison to NMTK, with an upper/lower limit of agreement of [104; −109 s] and a bias of 36 s of TS in comparison to NMTK, with an upper/lower limit of agreement of [−21.8, −23.1 min] during recovery (T4/T1 > 90%). Conclusions: Under the conditions of the present study, the two devices are not interchangeable. Clinical decisions for deep neuromuscular blockade should be made cautiously, as both devices appear less accurate with significant variability.

Use of peripheral nerve stimulators to monitor patients with neuromuscular blockade in the ICU

1996 ◽  
Vol 5 (6) ◽  
pp. 449-454 ◽  
Author(s):  
R Kleinpell ◽  
C Bedrosian ◽  
L McCormick ◽  
M Kremer ◽  
L Bujalski ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Neuromuscular Blockade ◽  
National Sample ◽  
Neuromuscular Blocking ◽  
Nerve Stimulator ◽  
Peripheral Nerve Stimulator ◽  
Number Of Patients ◽  
Train Of Four ◽  
Current Monitoring ◽  
Prolonged Neuromuscular Blockade

BACKGROUND: Neuromuscular blockade is a frequently used therapy in the ICU. However, recent reports of prolonged paralysis and general muscular weakness in patients treated with this procedure have raised concerns about its use in intensive care. OBJECTIVE: The purpose of this study was to assess current monitoring practices of nurses who care for patients treated with neuromuscular blockade. METHODS: In January 1995, questionnaires were mailed to a random national sample of 2000 critical care nurses. Of the 2000 questionnaires mailed, 744 were returned. RESULTS: The number of patients per month who were treated with neuromuscular blockade in ICU settings ranged from 0 to 75 (mean = 6.82, SD = 9.15). For each patient, the average number of days of blockade ranged from less than 1 to 63 (mean = 4.12, SD = 3.36). The most common indications for neuromuscular blockade were to assist in mechanical ventilation, reduce oxygen consumption, and treat agitation. Only 41% of respondents (n = 306) reported using train-of-four stimuli and a peripheral nerve stimulator to monitor patients. Depth of neuromuscular blockade was routinely monitored by using clinical assessment (31%), a peripheral nerve stimulator (16%), or both (52%). CONCLUSIONS: Among the respondents, variations existed in monitoring practices and in the use of peripheral nerve stimulators, including the frequency of monitoring and use of the baseline milliamperage. Appropriate monitoring and titration of neuromuscular blocking agents by ICU nurses may aid in preventing adverse effects, including the potential for prolonged neuromuscular blockade. The existing variations in practice may affect patients' outcomes.

Early Reversal of Rapacuronium with Neostigmine 

1999 ◽  
Vol 91 (1) ◽  
pp. 51-57 ◽  
Author(s):  
Robert Purdy ◽  
David R. Bevan ◽  
Francois Donati ◽  
Lance J. Lichtor
Keyword(s):  
Neuromuscular Block ◽  
Rapid Onset ◽  
Force Of Contraction ◽  
Mean Values ◽  
Neuromuscular Relaxant ◽  
Treatment Groups ◽  
Nitrous Oxide Oxygen ◽  
Train Of Four ◽  
To Receive ◽  
Different Doses

Background Rapacuronium is a rapid-onset, short-acting neuromuscular relaxant. This multiple-center study determined neuromuscular recovery when neostigmine was given 2 or 5 min after rapacuronium. Methods One hundred seventeen patients were randomized to receive two different doses of rapacuronium and to receive neostigmine in two different doses and at two different times. During propofol anesthesia with nitrous oxide, oxygen, and fentanyl, 1.5 or 2.5 mg/kg rapacuronium was given 1 min before tracheal intubation. Neuromuscular block was measured by train-of-four ulnar nerve stimulation every 12 s: The adductor pollicis force of contraction was recorded mechanomyographically. Two or five minutes after rapacuronium was administered, 0.05 or 0.07 mg/kg neostigmine was administered and recovery was compared with that of control patients who received no neostigmine. Results Both doses of rapacuronium produced 100% block in all but one patient, who exhibited 97% block. Neostigmine accelerated recovery in all groups. After 1.5 mg/kg rapacuronium, the time to 25% T1 twitch recovery decreased from a mean of 16 min in control patients to mean values of 8-10 min in the treatment groups: The time to train-of-four ratio of 0.7 decreased from 38 min to 17-19 min. After 2.5 mg/kg rapacuronium, the time to 25% T1 was reduced from 23 min to 11-12 min, and the time to train-of-four ratio of 0.7 decreased from 54 min to 26-32 min. Recovery was not different among the the groups that received different doses and timing of neostigmine. Conclusions Recovery of intense rapacuronium block was accelerated by early neostigmine administration. When given 2 min after rapacuronium, neostigmine was as effective as after 5 min, and 0.05 mg/kg neostigmine was comparable to 0.07 mg/kg neostigmine.

Muscle relaxants in critical illness

2016 ◽  
Author(s):  
Brian J. Pollard
Keyword(s):  
Muscle Relaxant ◽  
Rapid Onset ◽  
Hepatic Disease ◽  
Neuromuscular Blocking ◽  
Nerve Stimulator ◽  
Neurological Assessment ◽  
Onset Of Action ◽  
Increased Risk ◽  
Rapid Reversal ◽  
Train Of Four

The place of neuromuscular blocking agents in the intensive care unit (ICU) has changed markedly over the last 20 years. Originally regarded as a mainstay of the process of ‘sedation’, they are now only used for specific indications. The principal disadvantage is probably the difficulty in neurological assessment when a muscle relaxant is used coupled with the increased risk of awareness, because inadequate sedation will be masked. Of the available agents, the intermediate acting ones are the most popular. The degree of relaxation can be readily controlled and they have few side effects. In the presence of renal and/or hepatic disease atracurium or cisatracurium are preferred. Succinylcholine is only used for securing the airway due to its very rapid onset of action. Rocuronium given in a higher dose also possesses a rapid onset in situations when succinylcholine might be contraindicated. When using a muscle relaxant, its effect should always be monitored with a simple train of four pattern of stimulation from a hand-held nerve stimulator. This will ensure that an adequate and not excessive block is secured. If a more rapid reversal is required then a dose of neostigmine with glycopyrrolate may be used. Alternatively, if rocuronium is the relaxant in use then the new agent sugammadex is effective.

scholarly journals Efficacy, Safety, and Pharmacokinetics of Sugammadex for the Reversal of Rocuronium-induced Meeting Abstracts in Elderly Patients

2011 ◽  
Vol 114 (2) ◽  
pp. 318-329 ◽  
Author(s):  
David L. McDonagh ◽  
Patrick E. Benedict ◽  
Anthony L. Kovac ◽  
David R. Drover ◽  
Neil W. Brister ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Neuromuscular Blockade ◽  
Geometric Mean ◽  
Anesthesia Induction ◽  
Elderly Adult ◽  
Open Label ◽  
Class 1 ◽  
Train Of Four ◽  
Neuromuscular Blockade Reversal ◽  
American Society

Background The management of elderly patients can be challenging for anesthesiologists for many reasons, including altered pharmacokinetics and dynamics. This study compared the efficacy, safety, and pharmacokinetics of sugammadex for moderate rocuronium-induced neuromuscular blockade reversal in adult (aged 18-64 yr) versus elderly adult (aged 65 yr or older) patients. Methods This phase 3a, multicenter, parallel-group, comparative, open-label study enrolled 162 patients aged 18 yr and older, American Society of Anesthesiologists class 1-3, scheduled for surgery with general anesthesia and requiring neuromuscular blockade. After anesthesia induction, patients received rocuronium, 0.6 mg/kg, before tracheal intubation, with maintenance doses of 0.15 mg/kg as required. At the end of surgery, patients received sugammadex, 2.0 mg/kg, at reappearance of the second twitch of the train-of-four (TOF) for reversal. The primary efficacy variable was time from sugammadex administration to recovery of the TOF ratio to 0.9 or greater. Pharmacokinetics and safety were also evaluated. Results Overall, 150 patients were treated and had at least one postbaseline efficacy assessment; 48 were aged 18-64 yr (adult), 62 were aged 65-74 yr (elderly), and 40 were aged 75 yr or older (old-elderly). The geometric mean time (95% confidence interval) from sugammadex administration to recovery of the TOF ratio to 0.9 increased with age, from 2.3 (2.0-2.6) min (adults) to 2.9 (2.7-3.2) min (elderly/old-elderly groups combined). Recovery of the TOF ratio to 0.9 was estimated to be 0.7 min faster in adults compared with patients aged 65 yr or older (P = 0.022). Sugammadex was well tolerated by all patients. Conclusion Sugammadex facilitates rapid reversal from moderate rocuronium-induced neuromuscular blockade in adults of all ages.

Neuromuscular blockade and reversal

2017 ◽  
Author(s):  
Jennifer M. Hunter ◽  
Thomas Fuchs-Buder
Keyword(s):  
Neuromuscular Block ◽  
Neuromuscular Disorders ◽  
Upper Airway ◽  
Blocking Agent ◽  
Rapid Onset ◽  
Neuromuscular Blocking ◽  
Onset Of Action ◽  
Disease States ◽  
Train Of Four ◽  
Residual Block

Over the past 70 years since the introduction of d-tubocurarine, the search for an ideal neuromuscular blocking agent has led to the development of the depolarizing drug, succinylcholine (suxamethonium), with its rapid onset of action and plasma metabolism, and a series of non-depolarizing agents of which there are two groups: benzylisoquinoliniums (e.g. atracurium, cisatracurium and mivacurium) and aminosteroidal agents (e.g. pancuronium, vecuronium and rocuronium). The need to monitor neuromuscular block perioperatively to ensure the appropriate dose of any neuromuscular blocking drug is given has led to the development of several nerve stimulation techniques. Particularly useful clinically are the train-of-four twitch response, double-burst stimulation, and the post-tetanic count. Their benefits and limitations are considered in this chapter. The most suitable equipment to monitor neuromuscular block and the appropriate anatomical sites for stimulation are discussed. To prevent residual block with its pathophysiological consequences such as upper airway and pharyngeal dysfunction and potential respiratory failure at the end of surgery, antagonizing agents are used. These are of two types: anticholinesterases such as neostigmine and edrophonium, and the γ‎-cyclodextrin, sugammadex. The pharmacodynamics and pharmacokinetics of neuromuscular blocking drugs and their antagonists are altered by the extremes of age, obesity, and several disease states including renal and hepatic failure, neuromuscular disorders, and critical illness. The altered response to all these drugs in these pathologies, which is related to their metabolism and excretion, is considered in detail, together with their other side-effects including the particular disadvantages to the use of succinylcholine.

Reversal of Rocuronium-induced Neuromuscular Block by the Selective Relaxant Binding Agent Sugammadex

2006 ◽  
Vol 104 (4) ◽  
pp. 667-674 ◽  
Author(s):  
Iben F. Sorgenfrei ◽  
Kathrine Norrild ◽  
Per Bo Larsen ◽  
Jakob Stensballe ◽  
Doris Østergaard ◽  
...  
Keyword(s):  
Placebo Group ◽  
Renal Excretion ◽  
Neuromuscular Block ◽  
Neuromuscular Blocking ◽  
Dependent Manner ◽  
Binding Agent ◽  
Train Of Four ◽  
Time Required ◽  
To Receive ◽  
Dose Dependent

Background 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. Methods Twenty-seven male surgical patients aged 18-64 yr were randomly assigned to receive placebo or sugammadex (0.5, 1.0, 2.0, 3.0, or 4.0 mg/kg) for reversal of 0.6 mg/kg rocuronium-induced neuromuscular block. Anesthesia was induced and maintained using intravenous fentanyl and propofol. Neuromuscular function was assessed using acceleromyography. Sugammadex or placebo was administered at reappearance of T2 of the train-of-four. The primary efficacy variable was the time required for recovery to a train-of-four ratio of 0.9. Results Sugammadex decreased median recovery time in a dose-dependent manner from 21.0 min in the placebo group to 1.1 min in the group receiving 4.0 mg/kg sugammadex. Doses of sugammadex of 2.0 mg/kg or greater reversed rocuronium-induced neuromuscular block within 3 min. A median of 59-77% of sugammadex was excreted unchanged in the urine within 16 h, mostly in the first 8 h. Sugammadex increased the proportion of the rocuronium dose excreted unchanged in the urine (from a median of 19% in the placebo group to 53% in the 4.0-mg/kg group within 16 h). Sugammadex was safe and well tolerated. No evidence of recurarization was observed in any patient. Conclusion At doses of 2.0 mg/kg or greater, sugammadex safely reversed 0.6 mg/kg rocuronium-induced neuromuscular block in a dose-dependent manner. Sugammadex enhanced renal excretion of rocuronium and was excreted unchanged by the kidneys.

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