Neuromuscular blocking drugs and their antagonists are widely used in pediatric anesthesia. Because precise pharmacologic studies have not been performed in children, the clinician often must extrapolate from the data obtained in adults to determine the dose in children. However, children differ from adults in distribution volumes, metabolism and neuromuscular junction physiology and thus should respond differently to these drugs. Accordingly, we propose to determine the pharmacokinetics and pharmacodynamics of these drugs in neonates, infants and children with comparison to those obtained in adults. To date we have established dose response relationships, pharmacokinetic and/or pharmacodynamic studies of d-tubocurarine, vecuronium, a new neuromuscular blocking drug, and neostigmine. We will complete these studies and, in addition, will determine the dose-response relationships for neostigmine and the pharmacokinetics and dose-response relationships for edrophonium (an antagonist which appears to have advantages over neostigmine and pyridostigmine). We also will determine the effect of neuromuscular blocking drugs on oxygen consumption and evaluate whether """"""""respiratory-sparing"""""""" exists when neuromuscular blocking drugs are administered to infants. These studies should permit an improved understanding of the pharmacologic and physiologic effects of these drugs in children. In turn, neuromuscular relaxants and their antagonists may be used more appropriately in pediatric anesthesia.
