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 children. We have examined the dose-response relationships for neostigmine antagonism of 90% rocuronium-induced neuromuscular block in children 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 accelerometry was used to monitor neuromuscular transmission. When the first twitch 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 micrograms 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. Onset time of rocuronium-induced block was faster in children than in adults (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 children than in adults (25.4 (22.9-27.9) min vs 38.8 (36.1-41.4) min; P < 0.001). Spontaneous and antagonist-assisted recovery were more rapid in children than in adults. Adequate recovery (T4/T1 of 80%) occurred in children at 4, 5 and 8 min after neostigmine 50, 20 and 10 micrograms kg-1, respectively. Adequate recovery was not produced in adults by any dose of neostigmine within 10 min. The effective doses of neostigmine required to achieve a TOF ratio of 80% (ED80) after 10 min in children and adults were, respectively, 7.10 (5.2-9.8) micrograms kg-1 and 56.56 (45.5-71.9) micrograms kg-1 (P < 0.001). There was no advantage in administering doses of neostigmine greater than 20 micrograms kg-1 to antagonize 90% rocuronium-induced neuromuscular block in children. In contrast, it appeared prudent to use neostigmine 50 micrograms kg-1 or more for adequate antagonism of a similar degree of block in adults.
Abdulatif
M
M
Department of Anaesthesia, Cairo University, Egypt.
Mowafi
H
H
al-Ghamdi
A
A
el-Sanabary
M
M
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000732:Androstanols / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000769:Anesthesia, Inhalation; D002648:Child; D002675:Child, Preschool; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008875:Middle Aged; D009388:Neostigmine / Q000008:administration & dosage* / Q000494:pharmacology; D019148:Neuromuscular Blockade; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D003473:Neuromuscular Nondepolarizing Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000077123:Rocuronium; D009435:Synaptic Transmission / Q000187:drug effects
D000732:Androstanols; D002800:Cholinesterase Inhibitors; D003473:Neuromuscular Nondepolarizing Agents; D009388:Neostigmine; D000077123:Rocuronium