Increased sensitivity to depolarization and nondepolarizing neuromuscular blocking agents in young rat hemidiaphragms.
BACKGROUND
Newborn neuromuscular junctions are more sensitive to d-tubocurarine than more mature preparations. It is unclear whether the same modifications occur with newer nondepolarizing agents and depolarizing agent succinylcholine. The purpose of this study was to determine the relative sensitivity of newborn neuromuscular junctions to succinylcholine and five nondepolarizing 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 from each group were exposed to one of six neuromuscular blocking agents (d-tubocurarine, cisatracurium, atracurium, vecuronium, rocuronium, and succinylcholine). Indirectly elicited twitch tension was measured during control conditions in the absence of blocking agent, followed by four concentrations of one of the six agents. Concentration-response curves were constructed and the EC50 (concentration required to produce 50% depression of twitch tension) 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 nondepolarizing agents, the potency ratio was in the 6-12 range. The EC50adult/EC50newborn were as follows, in decreasing potency order: d-tubocurarine, 1.68/0.23 microM; cisatracurium, 2.73/0.47 microM; vecuronium, 5.47/0.59 microM; rocuronium, 9.7/0.78 microM; and atracurium, 12.3/1.9 microM. Succinylcholine was three times as potent in newborn rats, with an EC50adult/EC50newborn of 21.3/7.3 microM. The ratio for succinylcholine was significantly less than for all nondepolarizing drugs (P < 0.02).


CONCLUSIONS
The newborn neuromuscular junction of the rat shows an increased sensitivity to all neuromuscular blocking agents tested, including succinylcholine. 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.
Fortier
L P
LP
Département d'anesthésiologie, Université de Montréal, Québec, Canada. hmranesth@odysee.net
Robitaille
R
R
Donati
F
F
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D003964:Diaphragm / Q000187:drug effects* / Q000254:growth & development*; D009119:Muscle Contraction / Q000187:drug effects; D024510:Muscle Development; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D009469:Neuromuscular Junction; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology*; D010791:Phrenic Nerve / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013390:Succinylcholine / Q000494:pharmacology; D014403:Tubocurarine / Q000494:pharmacology
D009467:Neuromuscular Depolarizing Agents; D003473:Neuromuscular Nondepolarizing Agents; D013390:Succinylcholine; D014403:Tubocurarine