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.

Residual Block after Mivacurium with or without Edrophonium Reversal in Adults and Children

1996 ◽  
Vol 84 (2) ◽  
pp. 362-367. ◽  
Author(s):  
David R. Bevan ◽  
Raymond Kahwaji ◽  
John M. Ansermino ◽  
Eleanor Reimer ◽  
Michael F. Smith ◽  
...  
Keyword(s):  
Ulnar Nerve ◽  
Neuromuscular Block ◽  
Saline Group ◽  
Neuromuscular Blocking ◽  
Postanesthesia Care Unit ◽  
Random Allocation ◽  
Train Of Four ◽  
Residual Neuromuscular Block ◽  
Residual Block ◽  
Stimulation Of

Background The rapid recovery from mivacurium- induced neuromuscular block has encouraged omission of its reversal. The purpose of this study was to determine, in children and in adults, whether failure to reverse mivacurium neuromuscular block was associated with residual neuromuscular block on arrival in the postanesthesia care unit. Methods In 50 children, aged 2-12 yr, and 50 adults, aged 20-60 yr, anesthesia was induced and maintained with propofol and fentanyl, and neuromuscular block was achieved by an infusion of mivacurium, to maintain one or two visible responses to train-of-four (TOF) stimulation of the ulnar nerve. At the end of surgery, mivacurium infusion was stopped, and 10 min later, reversal was attempted with saline or 0.5 mg x kg(-1) edrophonium by random allocation. On arrival in the postanesthesia care unit, a blinded observer assessed patients clinically and by stimulation of the ulnar nerve with a Datex electromyogram in the uncalibrated TOF mode. Results Children arrived in the postanesthesia care unit 8.2 +/- 3-4 min after reversal of neuromuscular block and showed no sign of weakness, either clinically or by TOF stimulation. Although TOF ratio was greater in children who had received edrophonium (1.00 +/- 0.05 vs. 0.93 +/- 0.01, P<0.01), TOF was >0.7 in all children. Adults arrived in the postanesthesia care unit 12.9 +/- 5.3 min after reversal of neuromuscular block(P<0.01 vs. children). Six in the saline group demonstrated weakness (two required immediate reversal of neuromuscular block, and TOF was <0.7 in four others), compared with TOF <0.7 in only one of the edrophonium group (P<0.05). Conclusions This study demonstrated that, in adults, failure to reverse mivacurium neuromuscular block was associated with an increased incidence of residual block. Such weakness was not observed in children receiving similar anesthetic and neuromuscular blocking regimens.

scholarly journals Acceleromyography for Use in Scientific and Clinical Practice

2008 ◽  
Vol 108 (6) ◽  
pp. 1117-1140 ◽  
Author(s):  
Casper Claudius ◽  
Jørgen Viby-Mogensen ◽  
David S. Warner ◽  
Mark A. Warner
Keyword(s):  
Clinical Practice ◽  
Upper Airway ◽  
Blocking Agent ◽  
Neuromuscular Blocking ◽  
Good Evidence ◽  
Residual Paralysis ◽  
Response Curves ◽  
Value Recovery ◽  
Airway Function ◽  
Train Of Four

This systematic review describes the evidence on the use of acceleromyography for perioperative neuromuscular monitoring in clinical practice and research. The review documents that although acceleromyography is widely used in research, it cannot be used interchangeably with mechanomyography and electromyography for construction of dose-response curves or for recording different pharmacodynamic variables after injection of a neuromuscular blocking agent. Some studies indicate that it may be beneficial to use a preload to increase the precision of acceleromyography, and to "normalize" the train-of-four ratio to decrease the bias in relation to mechanomyography and electromyography. However, currently the evidence is insufficient to support the routine clinical use of preload and "normalization." In contrast, there is good evidence that acceleromyography improves detection of postoperative residual paralysis. A train-of-four ratio of 1.0 predicts with a high predictive value recovery of pulmonary and upper airway function from neuromuscular blockade.

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.

Preclinical Pharmacology of CW002

2016 ◽  
Vol 125 (4) ◽  
pp. 732-743 ◽  
Author(s):  
Hiroshi Sunaga ◽  
John J. Savarese ◽  
Jeff D. McGilvra ◽  
Paul M. Heerdt ◽  
Matthew R. Belmont ◽  
...  
Keyword(s):  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Blocking Agent ◽  
Neuromuscular Blocking ◽  
Safety And Efficacy ◽  
Circulatory Effects ◽  
Autonomic Changes ◽  
Train Of Four

Abstract Background CW002, a novel nondepolarizing neuromuscular blocking agent of intermediate duration, is degraded in vitro by l-cysteine; CW002-induced neuromuscular blockade (NMB) is antagonized in vivo by exogenous l-cysteine.1 Further, Institutional Animal Care and Use Committee–approved studies of safety and efficacy in eight anesthetized monkeys and six cats are described. Methods Mean arterial pressure, heart rate, twitch, and train-of-four were recorded; estimated dose producing 95% twitch inhibition (ED95) for NMB and twitch recovery intervals from 5 to 95% of baseline were derived. Antagonism of 99 to 100% block in monkeys by l-cysteine (50 mg/kg) was tested after bolus doses of approximately 3.75 to 20 × ED95 and after infusions. Vagal and sympathetic autonomic responses were recorded in cats. Dose ratios for [circulatory (ED20) or autonomic (ED50) changes/ED95 (NMB)] were calculated. Results ED95s of CW002 in monkeys and cats were 0.040 and 0.035 mg/kg; l-cysteine readily antagonized block in monkeys: 5 to 95% twitch recovery intervals were shortened to 1.8 to 3.6 min after 3.75 to 10 × ED95 or infusions versus 11.5 to 13.5 min during spontaneous recovery. ED for 20% decrease of mean arterial pressure (n = 27) was 1.06 mg/kg in monkeys; ED for 20% increase of HR (n = 27) was 2.16 mg/kg. ED50s for vagal and sympathetic inhibition in cats were 0.59 and >>0.80 mg/kg (n = 14 and 15). Dose ratios for [circulatory or autonomic changes/ED95 (NMB)] were all more than 15 × ED95. Conclusions The data further verify the neuromuscular blocking properties of CW002, including rapid reversal by l-cysteine of 100% NMB under several circumstances. A notable lack of autonomic or circulatory effects provided added proof of safety and efficacy.

Dual action of maltoxin, a neuromuscular blocking agent from malt rootlet

1960 ◽  
Vol 198 (5) ◽  
pp. 939-942 ◽  
Author(s):  
Norimoto Urakawa ◽  
Toshio Narahashi ◽  
Takehiko Deguchi ◽  
Yoshio Ohkubo
Keyword(s):  
Mode Of Action ◽  
Neuromuscular Block ◽  
Previous Treatment ◽  
Blocking Agent ◽  
Neuromuscular Blocking ◽  
Sartorius Muscle ◽  
Direct Stimulation ◽  
End Plate ◽  
Muscle Action Potential ◽  
Dual Action

Maltoxin, an amine obtained from brew malt rootlet, causes a neuromuscular block in the frog. Its mode of action on the frog's sartorius muscle has been studied mainly with the aid of intracellular microelectrodes. Maltoxin of 10–5 concentration caused an over-all depolarization of the muscle fibers; therefore, direct and indirect stimulations of the muscle were ineffective in producing muscle action potential. Progressive repolarization took place thereafter and the muscle became excitable by direct stimulation, though indirect stimulation remained ineffective for a long period of time. Small end-plate potentials observed could not be explained in terms of depolarization. It was found that the sensitivity of the end-plate membrane to acetylcholine was effectively depressed by maltoxin, and that this is responsible for the persistent neuromuscular block. The initial over-all depolarization caused by maltoxin was fairly antagonized by a previous treatment with d-tubocurarine. It is concluded that maltoxin has a dual mode of action, having some resemblance to acetylcholine, decamethonium, succinylcholine and nicotine.

scholarly journals Postoperative Neuromuscular Function

1986 ◽  
Vol 14 (1) ◽  
pp. 41-45 ◽  
Author(s):  
G. H. Beemer ◽  
P. Rozental
Keyword(s):  
Recovery Room ◽  
Neuromuscular Transmission ◽  
Blocking Agent ◽  
Neuromuscular Function ◽  
Neuromuscular Blocking ◽  
Neuromuscular Blocking Agent ◽  
Number Of Patients ◽  
Clinical Methods ◽  
Train Of Four ◽  
Bedside Tests

One hundred patients who received a competitive neuromuscular blocking agent during anaesthesia were randomly selected for evaluation of neuromuscular function immediately on their arrival in the recovery room. The anaesthetist was not aware that the patient would be evaluated in the recovery room. Neuromuscular function was assessed by a train-of-four (TOF) ratio, and in conscious and co-operative patients by a series of bedside tests of neuromuscular function. Twenty-one patients had a TOF ratio of less than 0.70 and seven patients a TOF ratio of less than 0.60. Bedside tests of neuromuscular function did not reliably detect this defect in neuromuscular transmission. It is concluded that a relatively large number of patients have a defect in neuromuscular transmission on their arrival in the recovery room, and suggested that this reflects the inadequacy of clinical methods used for the administration and antagonism of competitive neuromuscular blocking agents at this institution.

scholarly journals The tof-guard neuromuscular transmission monitor and its use in horses

1999 ◽  
Vol 29 (1) ◽  
pp. 57-62 ◽  
Author(s):  
Juliana Noda Bechara ◽  
Denise Tabacchi Fantoni ◽  
Paulo Sergio de Moraes Barros ◽  
Elton Rodrigues Migliati ◽  
Marcio Augusto Ferreira ◽  
...  
Keyword(s):  
Surgical Procedure ◽  
Neuromuscular Transmission ◽  
Medical Literature ◽  
Neuromuscular Block ◽  
Blocking Agent ◽  
Neuromuscular Blocking ◽  
Neuromuscular Blocking Agent ◽  
Neuromuscular Transmission Monitor ◽  
To Receive ◽  
Neuromuscular Transmission Monitoring

It has been emphasized in the human medical literature, that when using a neuromuscular blocking agent, it is of vital importance the monitoring of the neuromuscular block and that these agents should never be used without it. The purpose of this study was to evaluate the use of the neuromuscular transmission monitor TOF-Guard in horses. Twelve horses were randomly assigned whether to receive pancuronium or atracurium as the neuromuscular blocking agent. All horses were pre-medicated with romifidine, anaesthesia induced with diazepam and ketamine and maintenance with halothane. Abolition of spontaneous ventilation was accomplished by the administration of atracurium or pancuronium. The time from injection of the muscle relaxant agent to the onset of maximum block (T1=0), recovery of T1 to 25% and the recovery of TOF ratio to 0.7 were recorded, as was the time for recovery of T1 from 25 to 75%. It was concluded that it is very important the neuromuscular transmission monitoring during the use of a nondepolarizing neuromuscular blocking agent, since it provides a safer anaesthetic and surgical procedure with the use of adequate dosages and due to the impossibility of a superficialization of the neuromuscular blockade during a surgical procedure. The TOF-Guard showed to be a good option for neuromuscular monitoring in horses.

First Human Exposure of Org 25969, a Novel Agent to Reverse the Action of Rocuronium Bromide

2005 ◽  
Vol 103 (4) ◽  
pp. 695-703 ◽  
Author(s):  
Francois Gijsenbergh ◽  
Steven Ramael ◽  
Natalie Houwing ◽  
Thijs van Iersel
Keyword(s):  
Side Effects ◽  
The Netherlands ◽  
Adverse Events ◽  
Neuromuscular Block ◽  
Acetylcholinesterase Inhibitors ◽  
Random Order ◽  
Blocking Agent ◽  
Neuromuscular Blocking ◽  
Moderate Intensity ◽  
Rocuronium Bromide

Background Acetylcholinesterase inhibitors are widely used for the reversal of neuromuscular blocking agents. However, acetylcholinesterase inhibitors have several side effects and are not effective during profound block. Org 25969 is a modified gamma-cyclodextrin that encapsulates the neuromuscular blocking agent, rocuronium bromide (Esmeron/Zemuron, NV Organon, Oss, The Netherlands), forming a tightly bound complex with an association constant of approximately 10 m. Chemical encapsulation of rocuronium promotes dissociation of rocuronium from the acetylcholine receptor, thereby reversing the neuromuscular block without the side effects associated with acetylcholinesterase inhibitors. Methods Twenty-nine healthy male volunteers were enrolled to investigate the safety, pharmacokinetics, and efficacy of Org 25969. In part 1, Org 25969 or placebo was administered to 19 subjects during one to three treatment periods each. In part 2, a further 10 subjects received general anesthesia on two separate occasions, using an intubating dose of 0.6 mg/kg rocuronium. Three minutes after rocuronium administration, Org 25969 or placebo was given in random order. Six doses of 0.1-8.0 mg/kg Org 25969 were evaluated. Neuromuscular block was measured using an acceleromyograph, the TOF-Watch-SX (NV Organon, Oss, The Netherlands). Results All adverse events related to Org 25969 treatment were of limited duration and mild intensity, except for a period of paresthesia, seen in one patient receiving 8 mg/kg Org 25969, which was of moderate intensity. No adverse events required any treatment, and all subjects recovered from them. When 8 mg/kg Org 25969 was given, the train-of-four ratio returned to 0.9 within 2 min after its administration. No signs of recurarization were observed. Conclusions Org 25969 was both well tolerated and effective in reversing neuromuscular block induced by rocuronium in 29 human volunteers.

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