The Effect of Phenytoin on the Magnitude and Duration of Neuromuscular Block Following Atracurium or Vecuronium

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Abstract
Patients chronically receiving anticonvulsants have been reported to be resistant to the long-acting competitive neuromuscular blockers. This study examines the effects of atracurium and vecuronium on 100 neurosurgical patients; 50 receiving chronic phenytoin therapy (group I) and 50 controls (group II). During O2/N2O/halothane anesthesia, five patients in each group were given a bolus of vecuronium 0.1 mg/kg, and a different five patients in each group were given atracurium 0.5 mg/kg, to produce neuromuscular blockade in excess of 95%. The time to maximum blockade and the recovery from atracurium was unaffected by phenytoin therapy. Recovery from vecuronium was enhanced in the phenytoin group, as demonstrated by the recovery index, defined as the time required for recovery from 25-75% of the control neuromuscular response (7.9 .+-. 2.2 min compared with 17.8 .+-. 5.1 min in controls, P < 0.005). Similarly, the total duration of neuromuscular blockade, defined as recovery to 90% of control response, was significantly shorter in the phenytoin group (31.9 .+-. 6.0 min compared with 69.7 .+-. 12.9 min in controls, P < 0.001). The remaining 40 patients from each group were given a preselected dose of either vecuronium (0.02-0.06 mg/kg) or atracurium (0.10-0.25 mg/kg) during anesthesia with O2/N2O/fentanyl, to generate dose-response curves for the relaxants. Using analysis of covariance, the slopes and elevations for atracurium were found to be essentially identical in the two groups; as were the calculated ED50 and ED95. Patients receiving chronic phenytoin therapy were resistant to vecuronium-induced neuromuscular blockade. With vecuronium, the dose-response curves for the two groups were parallel; the curve for phenytoin patients was shifted to the right. A larger dose of vecuronium is required in phenytoin-treated patients to provide a given level of neuromuscular blockade. For example, the ED50 was 0.042 mg/kg in the phenytoin group, compared to 0.028 mg/kg in the control group. This study demonstrates that, although vecuronium is affected by phenytoin in an interaction similar to that previously reported with the long-acting neuromuscular relaxants, atracurium is not similarly affected.

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