Mivacurium-induced neuromuscular block in adult patients suffering from Charcot-Marie-Tooth disease

PURPOSE: The response to non-depolarizing neuromuscular blocking drugs is variable in patients with Charcot-Marie-Tooth (CMT) disease. We speculated that CMT involvement of the monitored muscle may be partially responsible for this inconsistency. We therefore investigated the response to a standard dose of mivacurium simultaneously assessed at adductor pollicis (AP) and orbicularis oculi (OO) muscles in five patients with CMT. CLINICAL FEATURES: Over a period of one year, five adult patients with CMT scheduled for orthopedic surgery were studied. The right arm and the right supercilliary arch were prepared for acceleromyographic (AMG) neuromuscular monitoring. The AMG probes were attached at the distal interphalangeal joint of the right thumb and on the right upper eyelid to record the response of the AP and OO, respectively. The ulnar nerve and upper part of the facial nerve were stimulated supramaximally with repeated train-of-four stimuli (2 Hz, 0.2 msec) every 15 sec via applied surface electrodes. Following monitor calibration and induction of general anesthesia, mivacurium 0.2 mg x kg(- 1) iv was given, and the time course of relaxation and recovery were assessed. Times to spontaneous recovery of T1 to 25% were 15 +/- 3 vs 12 +/- 4 min in the AP and OO muscle groups respectively, whereas times to 90% recovery were 23 +/- 5 vs 29 +/- 10 min, respectively. CONCLUSION: The onset and recovery characteristics associated with mivacurium-induced neuromuscular block were similar at the AP and OO muscle groups. A near normal response to mivacurium was observed in this small series of patients with CMT disease.     

Mivacurium-induced neuromuscular blockade in patients with atypical plasma cholinesterase

The duration of action of mivacurium was evaluated during a modified neurolept anaesthesia in 17 patients heterozygous for the usual and the atypical plasma cholinesterase (pChe) gene (E^a₁E^a₁) and in five patients homozygous for the atypical gene (E^a₁E^a₁). The response to train-of-four nerve stimulation was recorded using a Myograph 2000. Five heterozygous patients were given a small dose of mivacurium 0.03 mg kg bw^-1 intravenously (Group 1). The mean (range) suppression of the first twitch in the train-of-four response (T₁) was 91% (69–100%). The time to 90% T₁ recovery was 23.9 min (14.0–31.3 min). Twelve other heterozygous patients (Group 2) received mivacurium 0.2 mg kg bw^-1 (2.5 * ED₉₅). In these patients the time to 100% T₁ suppression was 1.4 min (1.1–2.0 min). The time to reappearance of the T₁ response, to 90% T₁ recovery, and the recovery index (25.3 min (14.5–34.5), 45.5 min (30.9–59.2), and 9.8 min (6.8–19.6), respectively) were significantly longer than reported in phenotypically normal patients. Five patients homozygous for the atypical gene (Group 3) were given 0.03 mg kg bw^-1 mivacurium. The time to reappearance of T₁ response following this low dose of mivacurium ranged from 26–128 min. In all five patients the neuromuscular block was successfully antagonized with neostigmine preceded by atropine. In conclusion, mivacurium-induced neuromuscular blockade was moderately prolonged in patients heterozygous for the usual and the atypical gene for plasma cholinesterase. Patients homozygous for the atypical plasma cholinesterase gene appear to be markedly sensitive to mivacurium.     

Mivacurium-induced neuromuscular blockade during sevoflurane and halothane anaesthesia in children

The neuromuscular blocking effects of mivacurium during sevoflurane or halothane anaesthesia was studied in 38 paediatric patients aged 1–12 yr. All received premedication with midazolam, 0.5 mg · kg⁻¹ po and an inhalational induction with up to 3 MAC of either agent in 70% N₂O and O₂. The ulnar nerve was stimulated at the wrist by a train-of-four stimulus every ten seconds and the force of adduction of the thumb recorded with a Myotrace force transducer. Anaesthesia was maintained with a one MAC end-tidal equivalent of either volatile agent for five minutes before patients received mivacurium (0.2 mg · kg⁻¹) iv. The onset of maximal blockade occurred in 2.4 ± 1.26 (mean ± SD) min with halothane and 1.8 ± 0.54 min with sevoflurane (NS). Four patients failed to achieve 100% block (3 halothane, 1 sevoflurane). The times from injection to 5, 75, and 95% recovery during sevoflurane (9.8 ± 2.6, 19.5 ± 4.4, and 24.2 ± 4.8 min) were greater than during halothane anaesthesia (7.2 ± 2.2, 15.0 ± 4.0, 19.2 ± 4.9 min, respectively (P < 0.005). All patients demonstrated complete spontaneous recovery of neuromuscular function (T₁ > 95%, T₄/T₁ > 75%) during the surgery which lasted 24–63 min. All patients showed clinical signs of full recovery of neuromuscular blockade (i.e., headlift, gag, or cough). Pharmacological reversal was not required. It is concluded that following a single intubating dose of mivacurium, the time to maximum relaxation was not different during halothane and sevoflurane anaesthesia; recovery times to 5, 75 and 95% twitch height were longer during sevoflurane anaesthesia and neuromuscular reversal was not necessary. L’activité neurobloquante du mivacurium pendant l’anesthésie au sévoflurane ou à l’halothane fait l’objet de cette étude réalisée chez 38 enfants de 1 à 12 ans. Tous ont été prémédiqués au midazolam 0,5 mg · kg⁻¹ et l’anesthésie est induite avec un agent volatil jusqu’à MAC 3 de l’un des agents dans du N₂O à 70%. Le nerf cubital était stimulé au poignet au train de quatre aux dix seconds et la force de l’adduction du pouce mesurée avec un transducteur de force Myotrace. L’anesthésie était entretenue avec l’équivalent MAC I d’un des deux agents volatils pendant cinq minutes avant l’administration de mivacurium (0,2 mg · kg⁻¹). Le début du bloc maximum est survenu dans 2,4 ± 1,26 (moyenne ± SD) min avec l’halothane et 1,8 ± 0,54 min avec le sévoflurane (NS). Quatre patients n’ont pas été bloqués à 100% (trois avec l’halothane, un avec le sévoflurane). L’intervalle séparant l’injection à 5; 75, et 95% de la récupération pendant l’anesthésie au sévoflurane (9,8 ± 2,6, 19,5 ± 4,4 et 24,2 ± 4,8 min) a été plus long que pendant l’anesthésie à l’halothane (7,2 ± 2,2, 15,0 ± 4,0, 19,2 ± 4,9 min, respectivement (P < 0,005). An moniteur, chez tous les patients, la fonction neuromusculaire a récupéré spontanément (T₁ > 95%, T₄/T₁ > 75%) au cours de la chirurgie qui a duré de 24–63 min. Tous les patients montraient aussi les signes cliniques d’une récupération complète (par ex., levée de la tête, réflexe pharyngé ou toux). Aucun antagoniste pharmacologique n’a été requis. Il est conclu que le délai jusqu’à la relaxation maximum après une seule dose d’intubation de mivacurium ne diffère pas entre l’anesthésie à l’halothane et l’anesthésie au sévoflurane; les délais de retour à 5, 75 et 95% de la hauteur du twitch sont plus longs pendant l’anesthésie au sévoflurane et il n’est pas nécessaire d’antagoniser le bloc neuromusculaire.

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Supported in part by a grant from Abbott Laboratories, Chicago, Illinois.     

Extremely prolonged neuromuscular block after a single dose of rocuronium

Postoperative curarization in patients has been established. Nevertheless, extremely prolonged neuromuscular blockades are rare. We report the case of a prolonged neuromuscular blockade (lasting 10 hours) following a single dose of rocuronium, in an elderly patient with severe renal failure. We have studied the possible causes of prolonged curarization, and discussed the interest of the use of sugammadex in such cases.     

Genotyping the butyrylcholinesterase in patients with prolonged neuromuscular block after succinylcholine

BACKGROUND: Succinylcholine remains the standard neuromuscular blocking drug for tracheal intubation in emergency situations. The short duration of action is due to its rapid hydrolytic degradation by butyrylcholinesterase (plasmacholinesterase). Multiple variants of this enzyme are known (A, F, S, H, J, K variants) with different effects on enzyme activity. This study was undertaken to evaluate the use of molecular genetic methods in patients with clinically prolonged neuromuscular block. METHODS: Nine patients with a neuromuscular block of 14 min to 5 h were selected. All four exons of the butyrylcholinesterase were amplified by polymerase chain reaction and analyzed by automated sequencing. Molecular genetic results were compared with clinical relaxation time and with biochemical test results (total butyrylcholinesterase activity, dibucaine and fluoride inhibition). RESULTS: Seven of nine patients were mutation carriers. Five of these had more than one mutation. The A and K variants were the most frequent variations. Three of four patients who were homozygous for the A variant were also carriers of the K allele. The authors identified one novel mutation (G1294T) introducing a stop codon at amino acid position 432. The duration of neuromuscular block was substantially different between patients with identical butyrylcholinesterase genotypes. CONCLUSIONS: Variations in the genetic sequence of butyrylcholinesterase are frequent in patients with prolonged duration of action of succinylcholine. Direct sequencing of the whole butyrylcholinesterase gene is an appropriate method for genotyping and, accordingly, should be used in future clinical studies with drugs metabolized by this enzyme (e.g., succinylcholine, mivacurium).     

Reversal of neuromuscular block

The effect on heart rate of different rates of injection (10 seconds, 1, 3 and 5 minutes) of a fixed dose (neostigmine 2.5 mg and atropine 1.2 mg) and a weight-related dose (neostigmine 50 micrograms/kg and atropine 25 micrograms/kg) of neostigmine-atropine mixture given for the reversal of residual competitive neuromuscular block was studied in 196 healthy adult patients. In both series slow injection lessened and delayed the initial rise in heart rate. The subsequent fall in heart rate was less when the drugs were injected over 3 min compared with the 10 seconds and 1 minute injection groups but when given over 5 minutes there was a steady fall in heart rate, more so with the weight-related dose. It is recommended that a neostigmine and atropine mixture should be administered over 3 min.     

Monitoring of neuromuscular block

The first 150 words of the full text of this article appear below. Key points Postoperative residual curarization occurs evenafter administration of intermediate-acting non-depolarizingneuromuscular blocking drugs, for example, atracurium or vecuronium. Satisfactoryrecovery from neuromuscular block has not occured until thetrain-of-four ratio is >0.9. Quantitative methods of measuringevoked responses, for the example, acceleromyography or mechanomyography,are necessary to ensure adequate recovery from block. Onsetand recovery from neuromuscular block occurs at different ratesin different muscles. Anticholinesterases should not be usedto antagonize residual neuromuscular block unless full recoveryhas been demonstrated.   There is increasing evidence that residual neuromuscular blockis common, and also that it may adversely affect patient outcome.A study by Debaene and colleagues¹ found that 45% of patientshad residual curarization (train-of-four [TOF] ratio<0.9)in the postoperative recovery room after a single intubatingdose of the intermediate-acting drugs atracurium, vecuroniumor rocuronium. Another study found residual curarization (TOFratio<0.7) in 42% of patients in the . . . [Full Text of this Article]