Increased sensitivity to depolarizing and nondepolarizing neuromuscular blocking agents in young rat hemidiaphragms

Background: Newborn neuromuscular junctions are more sensitive to d-tubocur arine than more mature preparations. It is unclear whether the same modific ations occur with newer nondepolarizing agents and depolarizing agent succi nylcholine. The purpose of this study was to determine the relative sensiti vity of newborn neuromuscular junctions to succinylcholine and five nondepo larizing agents. Methods: The phrenic nerve-hemidiaphragm. preparation from 60 rats was used , 30 aged 9-12 days (newborn) and 30 aged 27-33 days (adult). Five rats fro m each group were exposed to one of six neuromuscular blocking agents (d-tu bocurarine, cisatracurium, atracurium, vecuronium, rocuronium, and succinyl choline). Indirectly elicited twitch tension was measured during control co nditions in the absence of blocking agent, followed by four concentrations of one of the six agents. Concentration-response curves were constructed an d the EC50 (concentration required to produce 50% depression of twitch tens ion) was obtained. Potency ratios (EC50adult/EC50newborn) were derived for each agent. Results: Newborn preparations were significantly (P < 0.001) more sensitive than their adult counterparts for all six agents tested. For nondepolarizi ng agents, the potency ratio was in the 6-12 range. The EC50adult/EC50newbo rn were as follows, in decreasing potency order: d-tubocurarine, 1.68/0.23 muM; cisatracurium, 2.73/0.47 muM; vecuronium, 5.47/0.59 muM; rocuronium, 9 .7/0.78 muM; and atracurium, 12.3/1.9 muM. Succinylcholine was three times as potent in newborn rats, with an EC50adult/EC50newborn of 21.3/7.3 muM. T he ratio for succinylcholine was significantly less than for all nondepolar izing drugs (P < 0.02). Conclusion. The newborn neuromuscular junction of the rat shows an increase d sensitivity to all neuromuscular blocking agents tested, including succin ylcholine. However, the potency ratio was greater for nondepolarizing than depolarizing drugs. The optimal dose of these agents for certain situations such as cesarean section and anesthesia in neonates should be reassessed.