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Study Objective: To determine the neuromuscular blocking effect and recovery profile of cisatracurium besylate in children after administration of a bolus dose that was twice the estimated dose required to produce 95% of the maximum effect (2 x ED95; 0.08 mg/kg) followed by an infusion during halothane-nitrous oxide anesthesia., Study Design: Open-label study., Setting: Teaching hospital., Patients: 30 male and female (ASA physical status I and II) patients, 2 to 10 years of age, scheduled for elective surgery of low to moderate risk., Interventions: After induction of general anesthesia, patients received cisatracurium 0.08 mg/kg administered over 5 to 10 seconds. For surgical procedures requiring neuromuscular block for at least 60 minutes, a second bolus dose of cisatracurium 0.02 mg/kg was administered after the first response to a train-of-four stimuli (T1) recovered to 25% of baseline. When T1 was 5% of baseline after the second dose, a 3 microg/kg/min infusion of cisatracurium was initiated and titrated to maintain 89% to 99% block for the duration of the surgery. For procedures requiring neuromuscular block of less than 60 minutes, one or more maintenance doses of 0.02 mg/kg cisatracurium were administered when T1 was 25% of baseline after the preceding dose. In 10 patients, recovery was facilitated with edrophonium 1.0 mg/kg administered when T1 was 26% to 48% of the final baseline., Measurements and Main Results: Evoked muscular response at the adductor pollicis was measured by electromyography. With 0.08 mg/kg, onset time (mean +/- SEM) was 4.1 +/- 0.4 minutes, and clinically effective duration was 27.3 +/- 0.9 minutes. Mean 5% to 95% and 25% to 75% recovery indices were 28.4 +/- 2. 7 minutes and 11.2 +/- 0.8 minutes, respectively. The mean infusion rate necessary to maintain 89% to 99% T1 suppression for 17 to 145 minutes was 1.7 microg/kg/min. After termination of infusion, the mean 5% to 95% and 25% to 75% recovery indices were similar to those after a single bolus dose, and time to 95% recovery was 30.4 +/- 3.0 minutes. After administration of edrophonium, full recovery (T4:T1 > or = 70%) occurred in 1.5 +/- 0.4 minutes. No clinically significant changes in heart rate or blood pressure were noted during the first 5 minutes after administration of cisatracurium 0.08 mg/kg., Conclusions: Cisatracurium provided maximal neuromuscular block, cardiovascular stability, and predictable recovery at the doses tested. In view of this finding, cisatracurium should be a useful intermediate-duration neuromuscular blocking drug for children during general anesthesia.

Study Objective: To distinguish among potential predictors of early, easy intubation in children, including apnea, neuromuscular block at two sites, and time, after administration of 0.3 mg/kg of mivacurium., Design: Prospective, randomized study., Setting: Operating rooms of Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania., Patients: 60 ASA physical status I and II children aged 2 through 7 years, scheduled for elective surgical procedures requiring endotracheal intubation., Interventions and Measurements: After premedication with midazolam, general anesthesia was induced with halothane and nitrous oxide, and patients were randomly assigned to one of four groups. Mivacurium 0.3 mg/kg was given and tracheal intubation was begun 45 seconds after its injection, or when apnea, block of the orbicularis oculi, (OO) or block of the adductor pollicis (AP) was noted. Intubation conditions were evaluated by an experienced endoscopist., Main Results: The first clinical event after administration of mivacurium 0.3 mg/kg was apnea at 43 seconds (median) (average 48 seconds, SEM 2 seconds) after injection. The difference in the time at which neuromuscular block occurred at the AP (median 75 seconds) (average 77 seconds, SEM 2 seconds) and the OO (median 63 seconds) (average 68 seconds, SEM 4 seconds) was statistically, but not clinically, significantly different. All nine intubations that were begun at least 90 seconds after administration of mivacurium resulted in good or excellent intubation conditions, as did 30 of the 51 intubations started earlier., Conclusions: In children, there is no advantage to monitoring neuromuscular function at the OO rather than the AP. After administration of 0.3 mg/kg of mivacurium, a 90-second interval before the start of intubation was a better predictor of good intubation conditions during halothane anesthesia (1% inspired) than were changes in evoked neuromuscular function.

We have compared the effects of two different frequencies of train-of-four stimulation of the ulnar nerve (2-Hz stimulation once every 10 or 20 s) on onset time and potency of atracurium, vecuronium and mivacurium during balanced anaesthesia. The adductor pollicis EMG was recorded simultaneously in both hands of 24 children aged 2-12 yr. After administration of an ED50 dose of each blocker, onset times were mean 21 (SEM 10) s shorter (P < 0.05) and decreases in neuromuscular function were 22 (3)% greater (P < 0.001) in the hand which was stimulated once every 10 s. We conclude that it is not possible to compare potency estimates of neuromuscular blocking agents if different stimulation patterns have been used.

In 30 children under balanced anaesthesia, we have determined dose-response curves and maintenance requirement of three dose ratio combinations of atracurium and vecuronium (10:1, 4:1 or 1.6:1 on a microgram:microgram basis). Neuromuscular block was monitored by adductor pollicis EMG. An equipotent dose ratio (4:1) was most potent, with a mean (SEM) ED95 of atracurium 95 (6) micrograms kg-1 with vecuronium 24 (1) micrograms kg-1. The sum of these doses is only 58% of an ED95 value of one agent (P = 0.0001). The hourly requirement to maintain a 90-95% neuromuscular block was 2.0 (0.1) times an individual ED95 dose of any combination. Recovery index was 8.9 (0.5) min. These results indicate that a combination of atracurium and vecuronium is supra-additive compared with the effects of each drug alone. However, all combinations maintained an intermediate character of neuromuscular block. Combining atracurium with vecuronium may reduce drug requirement by 40%.

Study Objective: To determine the potentiation of the neuromuscular blockade induced by a titrated infusion of mivacurium in the presence of isoflurane versus a nitrous oxide (N2O)-opioid anesthesia., Design: An open-label, controlled study., Setting: The inpatient anesthesia service of two university medical centers., Patients: Thirty adults divided into two groups., Intervention: An intravenous infusion of mivacurium during anesthesia with N2O-opioid or N2O-isoflurane., Measurements and Main Results: A neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation at the ulnar nerve at 2 Hz for 2 seconds at 10-second intervals. The mivacurium infusion rate was significantly less in the presence of isoflurane [4.0 +/- 0.8 micrograms/kg/min (mean +/- SEM)] than during N2O-opioid anesthesia (6.4 +/- 0.6 micrograms/kg/min). The recovery rates did not differ between anesthetic groups. After the termination of the infusion, spontaneous recovery to T4/T1 of at least 0.75 occurred in an average of 17.9 +/- 1.5 minutes, with a mean recovery index (T25-75) of 6.0 +/- 0.7 minutes., Conclusion: Isoflurane anesthesia reduces the infusion rate of mivacurium required to produce about 95% depression of neuromuscular function.

The pharmacokinetics of atracurium were studied in infants and children anaesthetized with isoflurane and nitrous oxide in oxygen. There were no significant differences in volume of distribution (area) (139 v. 152 ml kg-1), clearance (5.1 v. 5.3 ml kg-1 min-1), T1/2 alpha (2.1 v. 2.0 min), or T1/2 beta (19.1 v. 20.3 min) between children with normal hepatic and renal function and those with moderately impaired hepatic function presenting for hepatic transplantation. There were significant differences in volume of distribution (area) (176 v. 139 ml kg-1) and in clearance of atracurium (9.1 v. 5.1 ml kg-1 min-1) between infants and children with normal excretory function. In infants the clearance of atracurium in ml m-2 min-1 (153 v. 133) tended to be greater and the T1/2 alpha and T1/2 beta tended to be shorter (1.0 v. 2.0 and 13.6 v. 19.1) than in children with normal excretory function; however, these trends did not reach statistical significance. Plasma laudanosine concentration was around 100 ng ml-1 greater in patients with liver disease than in normal children from 15-45 min following a bolus of atracurium 0.5 mg kg-1.

The potency of atracurium was determined in adolescents and children during nitrous oxide-halothane and nitrous oxide-thiopentone-fentanyl anaesthesia using single dose-response curves. Dose-response curves were parallel. The effective doses producing 95% twitch depression (ED95) (mg kg-1) during nitrous oxide-halothane were larger in younger children than in the adolescents. Halothane (0.8% end-tidal) did not significantly potentiate atracurium when compared with thiopentone-fentanyl. On a microgram m-2 basis there was no difference in the ED95 between patients of different age or those anaesthetized with different techniques. At approximately 95% twitch depression intubating conditions were excellent in all groups. Minimal cardiovascular effects were noted at several multiples of the ED95.

Mivacurium chloride is a new, short-acting nondepolarizing neuromuscular blocking agent presently undergoing clinical evaluation. The neuromuscular effects of mivacurium and suxamethonium given by bolus and infusion were compared in adult patients during nitrous oxide-oxygen-opioid anaesthesia. Neuromuscular block was monitored by recording the compound electromyogram of the adductor pollicis muscle resulting from supramaximal train-of-four stimuli applied to the ulnar nerve. Time to onset of complete block and recovery to T5 were significantly shorter for suxamethonium than for mivacurium (1.0 (0.1) v. 2.5 (0.3) min and 6.4 (0.7) v. 17.5 (1.8) min; mean (SEM]. Conditions for tracheal intubation were similar in the two groups although intubation was performed 0.75-1.3 min later following mivacurium. The infusion rate required to maintain neuromuscular block was 88.6 (10.4) micrograms kg-1 min-1 for suxamethonium and 7.8 (1.2) micrograms kg-1 min-1 for mivacurium. There was a significant negative correlation between recovery to T5 and infusion rate for mivacurium and for suxamethonium. It was equally easy to titrate the infusion rate to the desired degree of block in each group. The recovery index (T25-T75) after the infusion stopped was similar in patients who received mivacurium and those who received suxamethonium.