To the Editor:--Lack of familiarity with a new drug may increase the likelihood of errors in dosing. An instance of this occurred in our operating theater.
A 7-month-old, 7-kg infant received 6 mg cisatracurium intravenously after induction of anesthesia with nitrous oxide and halothane. There was no change in heart rate, noninvasive blood pressure obtained with the cuff on the upper arm, or skin color, but when the surgery was concluded, neuromuscular block persisted to the extent that no posttetanic count could be elicited. The infant received midazolam and mechanical ventilation in the recovery room. One hundred minutes after the dose of 0.86 mg/kg cisatracurium, a very slight response of the adductor pollicis to stimulation of the ulnar nerve with 2 Hz, a train-of-four (TOF) every 60 s was documented by the Datex neuromuscular transmission monitor electromyogram in the uncalibrated mode. One hundred and ten minutes after the bolus of cisatracurium, four responses to the TOF were recorded. At this time, the patient's diaphragm, fingers, and toes were moving spontaneously. Propofol was administered by infusion to produce immobility. During the following 15 min, the TOF ratio increased to > 0.9. Propofol was discontinued, and 0.1 mg atropine followed by 5.0 mg edrophonium was administered to reverse any residual blockade. The trachea of the infant was extubated without complication several minutes later. This conservative approach was taken to be certain that the infant would not be clinically weak after extubation.
Because cisatracurium is one of the ten isomers that compose atracurium, it may be that the relatively minor age-related differences in potency that have been documented for atracurium [1,2]could also be documented for cisatracurium. The potency of atracurium in infants during halothane anesthesia is greater by 50% than in children. [2]The ED95 of cisatracurium in children is 0.041 mg/kg during halothane anesthesia. [3]Assuming that age-related differences in the potency of atracurium and cisatracurium are similar, the ED95 of cisatracurium in the infant population could be close to 0.027 mg/kg. Given these assumptions, this patient received more than 30 times an ED95 dose of cisatracurium. With regard to neuromuscular blocking potency, this dose of cisatracurium is equivalent to more than 4.5 mg/kg atracurium, 0.75 mg/kg vecuronium, 2.5 mg/kg mivacurium, or 15 mg/kg succinylcholine in an infant during halothane anesthesia. The effects of such a relatively large dose of neuromuscular blocker have not been documented previously.
No data exist regarding the expected duration or the pharmacokinetics of cisatracurium in infants. The elimination half-life of cisatracurium in adults is similar after doses of two and four times the ED95. [4]If the kinetics of cisatracurium are not dependent on dose, and the infant received approximately 32, or 2 [5]times an ED95 dose, then five elimination half-lives of 20 min should pass from administration of the overdose to the beginning of spontaneous recovery. This explanation is an extrapolation beyond the region of published data regarding cisatracurium, but it is consistent with the events in this patient.
Observation of more patients is necessary to appropriately compare variability in recovery from cisatracurium with variability in recovery from other drugs. However, we find it noteworthy that spontaneous recovery from one response to a train-of-four stimuli at the ulnar nerve to a train-of-four ratio of 1.0 occurred in this infant within an interval of 45 min. Similar recovery rates were observed after doses of one and two times the ED95 in children. [3]The recovery index, the time from 25% to 75% recovery of the amplitude of the response of the adductor pollicis to stimulation of ulnar nerve, was an average of 11 min (SEM = 0.6 min) in these children. [3]This suggests that the recovery index was between 10 and 15 min in our infant during spontaneous recovery from cisatracurium overdose. It has not always been the case that spontaneous recovery occurs at the same rate after administration of increasing doses of neuromuscular blocker. For example, the recovery index after administration of vecuronium increased significantly from an average of 7.9 min (SEM 0.6 min) to 22.6 min (SEM, 1.1 min) as the dose of vecuronium was increased from 0.1 to 0.4 mg/kg in children during balanced anesthesia. [5]
Barbara W. Brandom, M.D., Professor of Anesthesiology/Critical Care Medicine, Helen R. Westman, M.D., Associate Clinical Professor of Anesthesiology/Critical Care Medicine, University of Pittsburgh School of Medicine, Department of Anesthesiology, Children's Hospital of Pittsburgh, 3705 Fifth Avenue, Pittsburgh, Pennsylvania 15213-2583.
(Accepted for publication June 17, 1996.)
