DOSE-RESPONSE RELATIONSHIPS FOR NEOSTIGMINE ANTAGONISM OF ROCURONIUM-INDUCED NEUROMUSCULAR BLOCK IN CHILDREN AND ADULTS

Dose-response relationships for the antagonism of intermediate-acting neuromuscular blocking agents have not been evaluated previously in ch ildren. We have examined the dose-response relationships for neostigmi ne antagonism of 90% rocuronium-induced neuromuscular block in childre n and adults, during nitrous oxide-1 MAC of isoflurane anaesthesia. We studied 40 children, aged 2-10 yr, and 50 adults, aged 18-60 yr; all received a single bolus dose of rocuronium 0.6 mg kg(-1) and accelerom etry was used to monitor neuromuscular transmission. When the first tw itch of the train-of-four (TOF) response (T1) recovered to 10% of its control (T0), one of five doses of neostigmine 0, 5, 10, 20 or 50 mu g kg(-1) was given by random allocation to each of the study groups (n= 8 children and n=10 adults). Recovery of T1 and TOF ratio (T4/T1%) was recorded for 10 min after initial administration of neostigmine. Onse t time of rocuronium-induced block was faster in children than in adul ts (mean 64.6 (95% confidence intervals 57.7-71.5) s vs 83.7 (70.7-96. 6) s; P<0.05). The time to 10% recovery of T1/T0 was shorter in childr en than in adults (25.4 (22.9-27.9) min vs 38.8 (36.1-41.4) min; P<0.0 01). Spontaneous and antagonist-assisted recovery were more rapid in c hildren than in adults. Adequate recovery (T4/T1 of 80%) occurred in c hildren at 4, 5 and 8 min after neostigmine 50, 20 and 10 mu g kg(-1), respectively. Adequate recovery was not produced in adults by any dos e of neostigmine within 10 min. The effective doses of neostigmine req uired to achieve a TOF ratio of 80% (ED(80)) after 10 min in children and adults were, respectively, 7.10 (5.2-9.8) mu g kg(-1) and 56.56 (4 5.5-71.9) mu g kg(-1) (P<0.001). There was no advantage in administeri ng doses of neostigmine greater than 20 a mu g kg(-1) to antagonize 90 % rocuronium-induced neuromuscular block in children. In contrast, it appeared prudent to use neostigmine 50 mu g kg(-1) pr more for adequat e antagonism of a similar degree of block in adults.