Anesth Analg 2000;91:1392-1393
© 2000 International Anesthesia Research Society
PEDIATRIC ANESTHESIA
Prolonged Duration of Neuromuscular Block with Rapacuronium in the Presence of Sevoflurane
David Mills Cara, FRCA,
Pauline Armory, RGN, and
Ravi Prakash Mahajan, MD
University Department of Anaesthesia, Queen’s Medical Centre, Nottingham, United Kingdom
Address correspondence and reprint requests to Ravi Mahajan, MD, University Department of Anaesthesia, Queen’s Medical Centre, Nottingham NG7 2UH, United Kingdom. Address e-mail to ravi.mahajan{at}nottingham.ac.uk
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Abstract
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Implications: We report three cases of prolonged paralysis resulting from rapacuronium in the presence of sevoflurane.
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Introduction
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Prolongation of the actions of pancuronium, vecuronium, atracurium, mivacurium, and rocuronium by sevoflurane have been described (1–3). In view of the recent introduction of rapacuronium in the United States, we report cases of a trial comparing rapacuronium with succinylcholine in pediatric subjects anesthetized with sevoflurane in which neuromuscular blockade in the rapacuronium group was considerably more prolonged than expected. Because the surgery was brief and the protocol demanded spontaneous recovery of neuromuscular function, the trial was prematurely terminated.
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Case Reports
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After IRB approval and written, informed consent, we anticipated the recruitment of 40 pediatric subjects scheduled for adenotonsillectomy aged 2 to 12 yr and of ASA physical status I or II. They were allocated randomly to receive either succinylcholine 1 mg/kg or rapacuronium 2 mg/kg 5 min after an inhaled induction of anesthesia with sevoflurane (5%–8%) in oxygen. Anesthesia was maintained with sevoflurane (1.5%–4%) and nitrous oxide in 33% oxygen. After the induction of anesthesia, neuromuscular blockade was monitored at the adductor pollicis by using acceleromyography (TOF-Guard®) set to deliver a supramaximal train-of-four (TOF) stimuli every 15 s. The TOF-Guard Serial Card Reader was used to capture and record data. After ensuring a steady baseline, the neuromuscular blocking drug was given. Laryngoscopy was performed 60 s later and intubating conditions assessed as excellent, good, or poor according to criteria described by Viby-Mogensen et al. (4). Neuromuscular blockade was allowed to recover spontaneously and time to recovery of the first twitch (T1) to 5%, 25%, 75%, and 90% of the final baseline T1 twitch height was recorded. Reappearance of T3 and TOF ratios were also recorded.
Seven subjects were recruited before we stopped the trial. All were ASA physical status I. Four received succinylcholine and three received rapacuronium. The children’s ages were 8 (range 6–12) yr for rapacuronium and 7 (range 5–10) yr for succinylcholine and weights were 33.3 (range 20.9–52.7) kg and 27.0 (range 20–40) kg, respectively. Intubating conditions at 60 s were assessed as poor in one subject who received succinylcholine and excellent in the remaining six subjects. All subjects achieved 100% reduction in T1.
One rapacuronium subject was given neostigmine and glycopyrrolate 1 h after rapacuronium administration (when T1 was 70% and TOF ratio 0.71) and subsequent recovery data were therefore excluded. Certain recovery data were excluded for one other rapacuronium subject because of unintended movement of the monitored thumb 45 min after the rapacuronium dose. This precluded estimate of final (control) T1. Because the initial T1 had been stable for 7 min before the administration of rapacuronium, it was used as the control for calculation of recovery data in this patient only. The remaining recovery data are summarized in Table 1. Overall, all the variables indicated a considerably more prolonged recovery than expected; time to T1 25% recovery was well over 20 min in all three patients.
End-tidal sevoflurane concentrations ranged from 1.5% to 2.5% for maintenance of anesthesia. None of the subjects received, or were taking, drugs known to interfere with neuromuscular blockade. The temperature of the monitored hand was recorded and was warmer than 32°C in all subjects.
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Discussion
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Our results were unexpected and remarkably consistent among the three rapacuronium subjects. Although in one subject we calculated recovery data with reference to the initial T1 rather than the final T1, we had allowed 7 minutes for stabilization and, in our experience, the final T1 is always slightly higher than the initial T1, so the use of initial T1 as the control is likely to slightly underestimate the recovery times. Our use of acceleromyography may be criticized for greater baseline drift and relative underestimation of partial block compared with mechanomyography (5,6). However, the measurement of TOF ratio and reappearance of T3 are less likely to be affected by these errors.
The recovery times that we report are considerably prolonged compared with published literature (7–10). In subjects aged 6–12 years who received 2 mg/kg of rapacuronium under halothane anesthesia, Brandom et al. (7) reported mean recovery times to 25% T1 and to 70% TOF ratio of 14 minutes and 26 minutes respectively (assessed by electromyography). By using acceleromyography Motsch et al. (8) reported recovery of 70% TOF ratio at 18.3 minutes after rapacuronium 2 mg/kg in subjects aged 7–12 years in whom anesthesia was induced with thiopentone and maintained with opioid-nitrous oxide in oxygen. In similarly anesthetized older children Meakin et al. (9) reported recovery of T3 response at 8 minutes and 70% TOF ratio at 18 mins. The recovery times in our patients who received rapacuronium are approximately twice as long.
Recently Zhou et al. (10) reported prolonged recovery from rapacuronium block after the administration of edrophonium 1.0 mg/kg in 2 of 30 adults anesthetized with sevoflurane. However recovery data to 25% T1 (electromyography) were similar in subjects anesthetized with propofol infusion or sevoflurane.
Enhancement of neuromuscular blockade by anesthetics is well described but complicated. It is dependent both on the volatile anesthetic and the nondepolarizing muscle relaxant. Compared with halothane, enflurane prolongs the action of atracurium, pipecuronium, and pancuronium, but not vecuronium (11). Sevoflurane and isoflurane augment and prolong the neuromuscular blockade of vecuronium, pancuronium, and atracurium to a similar degree compared with opioid-nitrous oxide anesthesia (1). However, sevoflurane increases and prolongs the blockade of rocuronium more than isoflurane and propofol (3). Sevoflurane has similar effects on the action of mivacurium (2).
We suggest that the prolonged duration of action of rapacuronium is because of the presence of sevoflurane. If this observation is confirmed then there may be implications for the reversal of rapacuronium. Also, a smaller dose of rapacuronium may be more appropriate if sevoflurane is being used, and the use of neuromuscular monitoring should be considered mandatory.
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Acknowledgments
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Supported, in part, by Organon Teknika BV, the Netherlands.
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References
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Vanlinthout LEH, Booij LHDJ, Van Egmond J, et al. Effect of isoflurane and sevoflurane on the magnitude and time course of neuromuscular block produced by vecuronium, pancuronium and atracurium. Br J Anaesth 1996; 76: 389–95.[Abstract/Free Full Text]
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Viby-Mogensen J, Engbaek J, Eriksson LI, et al. Good clinical research practice in pharmacodynamic studies with neuromuscular blocking agents. Acta Anaesthesiol Scandanavia 1996; 40: 59–74.
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Accepted for publication August 21, 2000.
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Abstract
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