Cardiac Output and Onset Time of Different Muscle Relaxants

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In Response: We appreciate the interest of Simhi and Brandom in our study [1]. We agree with their view that the onset time of neuromuscular blockade depends on both circulatory and noncirculatory factors. This has been shown in a recent study in patients, which found a faster onset time of mivacurium in the orbicularis oculi than in the adductor pollicis, despite the fact that the blood flow at the last muscle (as measured by laser Doppler flowmetry) was several times higher than blood flow at the orbicularis oculi [2]. Regarding the findings of Audibert and Donati [3,4] showing that the onset of action of succinylcholine and rocuronium, but not of vecuronium and mivacurium, was modified by tourniquet inflation, an additional interpretation is through the participation of an artifact introduced by the experimental design itself. The tourniquet was inflated (and the blood flow to the arm stopped) at 20% of neuromuscular blockade with all relaxants, which means that in the case of fast-acting blockers, less time was allowed for the circulation to carry a given amount of drug to the arm before it was isolated, compared with slower-acting muscle relaxants. Thus, the earlier inflation of the tourniquet with rocuronium might have left a submaximal dose of drug, resulting in a slower onset of action. In the case of mivacurium and vecuronium, a relatively higher amount of drug had already reached the arm before the delayed inflation of the tourniquet, so that maximal neuromuscular blockade was still possible. This possibility is supported by the significantly shorter time from injection until tourniquet inflation with rocuronium (58 +/- 19 s) versus vecuronium (83 +/- 23 s) and mivacurium (82 +/- 15 s) [4] (P < 0.05 with one-way analysis of variance). With respect to a possible difference in the effects of circulatory factors, and indirectly of atropine and ephedrine, on the onset time of relaxants with fast and intermediate onset, a simple way to get a clue supporting or rejecting this hypothesis is by comparing the effects of these drugs on muscle relaxants with different onset times. Finally, the ultimate mechanism by which different drugs thought to increase cardiac output and muscle blood flow, such as atropine and ephedrine, can influence the onset time of muscle relaxants remains speculative until these hemodynamic variables are measured. Hernan R. Munoz, MD, MSc Alejandro G. Gonzalez, MD Jorge A. Dagnino, MD Department of Anesthesiology; Catholic University of Chile; School of Medicine; Marcoleta 367, Santiago, Chile