DOSE-RESPONSE CURVES FOR FOUR NEUROMUSCULAR BLOCKERS USING CONTINUOUS I.V. INFUSION

Cumulative dose-response curves were constructed in man for tubocurarine, pancuronium, gallamine and alcuronium from data obtained during barbiturate-narcotic-nitrous oxide anaesthesia. Fifty-six adult patients received one of these drugs, administered by constant-rate infusion, a technique enabling full characterization of the sigmoid curve for each patient. The individual curves were solved for several response levels and the results pooled to derive a composite dose-response curve for each drug. Using the mechanical twitch response, the ED50 for each neuromuscular blocking drug was: tubocurarine 0.236 mg kg"1, pancuronium 0.048 mg kg"1, gallamine l.Smgkg"1 and alcuronium 0.161 mg kg " '.The slopes of the composite curves for pancuronium and alcuronium were significantly steeper than those for tubocurarine and gallamine. In the alcuronium studies the simultaneous compound clcctromyogram was recorded, and usually this was more depressed than the mechanical twitch response, giving an ED50 of 0.135 rag kg"'. Many studies have examined the dose-response relationships of the non-depolarizing neuro-muscular blocking drugs during anaesthesia, most authors assessing the response in terms of the evoked single twitch response. However, many factors affect the dose-reponse curve, including the method by which the twitch is evoked. Rigorous techniques of motor nerve stimulation require a wave-form of short duration and correct polarity delivered at a truly supramaximal voltage. Further, for single events, the frequency of stimulation must allow sufficient time for each twitch response to recover from the effects of its predecessor. Slower stimulus frequencies produce dose—response curves which are to the right of those with more rapid rates (Savarese, Ali an