Laudanosine (A Metabolite of Atracurium) Increases the Minimum Alveolar Concentration of Halothane in Rabbits

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Abstract
The authors hypothesized that laudanosine, a metabolite of atracurium and a central nervous system stimulant, might increase the minimum alveolar concentration (MAC) of halothane. An initial study in five rabbits anesthetized with halothane used two-compartment model to produce estimates of pharmacokinetic variables for laudanosine. These estimates were used to determine the rates of infusion that would produce steady state plasma concentrations of laudanosine of approximately 200, 400, and 800 ng .cntdot. ml-1. Subsequent infusion of laudanosine in eight rabbits produced mean (.+-. SD) steady state plasma concentrations of laudanosine of 234 .+-. 56, 457 .+-. 66, and 873 .+-. 105 ng .cntdot. ml-1. The control value for MAC of halothane was 1.08 .+-. 0.28%. At the lowest steady state plasma laudanosine concentration, MAC did not significantly differ from control (MAC = 1.15 .+-. 0.23%, P < 0.1). However, at 457 and 873 ng .cntdot. ml-1, laudanosine significantly increased the MAC of halothane by 23% and 30%, respectively. Infusion with saline in two additional rabbits did not affect MAC. Therefore, at the plasma concentrations of laudanosine found in human after administration of atracurium, laudanosine increased the MAC of halothane in rabbits.