Good Clinical Research Practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents

Purpose:The interaction between mivacurium and inhaled anesthetics is known, with the exception of xenon. We compared the pharmacodynamics of mivacurium during xenon anesthesia vs total iv anesthesia with propofol.Methods: This randomized controlled trial was carried out in the Aachen University Hospital. Forty-two adult patients ASA I or II, aged 18 to 60 yr, were randomized to receive either xenon or propofol anesthesia. Anesthesia was induced with propofol and remifentanil in both groups (each n = 21). The xenon group received xenon via facemask until an end-expiratory concentration of 60% was reached for one minute. Meanwhile, the acceleromyograph was calibrated and a train-of-four stimulation of the adductor pollicis muscle was started. After stabilization of the signal for five minutes, a single bolus of 0.16 mg·kg -1 mivacurium was injected. Anesthesia was maintained with xenon and remifentanil or with propofol and remifentanil.Results: There were no significant differences between groups with respect to onset time (xenon 180 ± 64 vs propofol 195 ± 77 sec; P = 0.39), duration (xenon 16.18 ± 4.97 vs propofol 15.68 ± 6.17 min; P = 0.73), recovery index (xenon 5.63 ± 2.48 vs propofol 5.73 ± 2.12 min; P = 0.42) and clinical recovery (xenon 8.75 ± 2.57 vs propofol 9.28 ± 2.28 min; P = 0.22). Conclusion:We conclude that the neuromuscular blocking effects of mivacurium are similar when given during propofol vs xenon anesthesia. (xénon 180 ± 64 vs propofol 195 ± 77 s ; P = 0,39), à sa durée (xénon 16,18 ± 4,97 vs propofol 15,68 ± 6,17 min ; P = 0,73), à l'indice de récupération (xénon 5,63 ± 2,48 vs propofol 5,73 ± 2,12 min ; P = 0,42) et à la récupération clinique (xénon 8,75 ± 2,57 vs propofol 9,28 ± 2,28 min ; P = 0,22). Objectif : L'interaction entre le mivacurium et les anesthésiques Résultats : Il n'y a pas eu de différence intergroupe significative quant au délai d'installation du bloc Conclusion : Les effets neuromusculaires bloquants du mivacurium sont similaires pendant l'anesthésie au propofol ou au xénon.T HE combination of a short-acting opioid and neuromuscular blocking drug, such as remifentanil and mivacurium, allow rapid emergence and recovery from anesthesia. 1 On the other hand, it is well known that most inhaled anesthetics variably prolong and enhance the effects of nondepolarizing neuromuscular blocking drugs, compared to total iv anesthesia. 2-4 Xenon, a rediscovered inhaled anesthetic with an extremely low blood-gas solubility of 0.115 to 0.14 5 and a minimum alveolar concentration (MAC) of 63 to 71%, 6,7 has proven its clinical safety and efficacy in the past. 8 With its ecological and pharmacological qualities, xenon is an interesting alternative to other inhaled anesthetics. The combination of a short-acting opioid, a short duration

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Xenon does not modify mivacurium induced neuromuscular block

Kunitz

Baumert

Hecker

et al. 2005

“…7 For practical purposes, we investigated two periods of control stimulation: three minutes, which is the minimum period of control stimulation, 11 and ten minutes. Since there was no difference between the two periods, we do not believe that longer stabilization periods would yield any differences.…”

Section: Discussionmentioning

confidence: 99%

Duration of control stimulation does not affect onset and offset of neuromuscular blockade at the corrugator supercilii muscle measured with phonomyography or acceleromyography

Hemmerling

Donati

Babin

et al. 2002

P Pu ur rp po os se e: : Phonomyography (PMG) is a novel technique for measuring neuromuscular blockade (NMB). The effect of the duration of control stimulation on the onset and duration of blockade was investigated using PMG and acceleromyography (AMG).M Me et th ho od ds s: : After induction of anesthesia, a microphone was placed above the middle portion of the left eyebrow, and an acceleromyographic probe was placed above the middle portion of the right eyebrow. Twenty patients were randomized to receive bilateral, single-twitch, facial nerve stimulation (0.1 Hz, 20 mA) with three minutes (n = 10) or ten minutes (n = 10) of supramaximal stimulation before mivacurium 0.2 mg·kg -1 was administered. Onset, maximum effect, and offset of NMB were measured.

“…The end point of TOF ratio of 0.8 was chosen to represent adequate recovery according to recent guidelines compared with the previously used end point of 0.7. 8 The data of various time end points were subjected to analysis of variance, followed by post tests as indicated. The number of patients achieving reversal within the 15 min time period was subject to x 2 analysis.…”

mentioning

confidence: 99%

Neostigmine antagonism of rocuronium block during anesthesia with sevoflurance, isoflurane or propofol

Reid

Breslin

Mirakhur

et al. 2001

Purpose: To examine the influence of continuing administration of sevoflurane or isoflurane during reversal of rocuronium induced neuromuscular block with neostigmine.Methods: One hundred and twenty patients, divided into three equal groups, were randomly allocated to maintenance of anesthesia with sevoflurane, isoflurane or propofol. Neuromuscular block was induced with rocuronium and monitored using train-of-four (TOF) stimulation of the ulnar nerve and recording the force of contraction of the adductor pollicis muscle. Neostigmine was administered when the first response in TOF had recovered to 25%. At this time the volatile agent administration was stopped or propofol dosage reduced in half the patients in each group (n = 20 in each group). The times to attain TOF ratio of 0.8, and the number of patients attaining this end point within 15 min were recorded.Results: The times (mean ± SD) to recovery of the TOF ratio to 0.8 were 12.0 ± 5.5 and 6.8 ± 2.3 min in the sevoflurane continued and sevoflurane stopped groups, 9.0 ± 8.3 and 5.5 ± 3.0 min in the isoflurane continued and isoflurane stopped groups, and 5.2 ± 2.8 and 4.7 ±1.5 min in the propofol continued and propofol stopped groups (P < 0.5-01). Only 9 and 15 patients in the sevoflurane and isoflurane continued groups respectively had attained a TOF ratio of 0.8 within 15 min (P < 0.001 for sevoflurane).Conclusions: The continued administration of sevoflurane, and to a smaller extent isoflurane, results in delay in attaining adequate antagonism of rocuronium induced neuromuscular block. REVIOUS studies have shown that antagonism of block with relaxants such as vecuronium is impeded in the presence of potent volatile agents such as sevoflurane and isoflurane. [1][2][3] It has also been shown that sevoflurane anesthesia potentiates the effect of rocuronium compared with isoflurane and propofol anesthesia. 4 Although there are reports of antagonism of rocuronium block with neostigmine, these have generally examined the influence of the dosage or the timing of administration of the anticholinesterase. [5][6][7] The aim of the present study was to examine the effect of the sevoflurane on the antagonism of rocuronium by neostigmine, and compare it with the effects of isoflurane, and intravenous anesthesia.