Cisatracurium-Induced Neuromuscular Blockade Is Affected by Chronic Phenytoin or Carbamazepine Treatment in Neurosurgical Patients

Abstract

The effect of chronic anticonvulsant therapy (CAT) on the maintenance and recovery profiles of cisatracurium-induced neuromuscular blockade has not been adequately studied. In this study, we compared the pharmacokinetics and pharmacodynamics of cisatracurium after a prolonged infusion in patients with or without CAT. Thirty patients undergoing intracranial surgery were enrolled in the study: 15 patients under CAT (carbamazepine and phenytoin, Group A) and 15 controls receiving no anticonvulsant therapy (Group C). Anesthesia was standardized and both groups received a bolus of cisatracurium followed by an infusion to maintain a 95% twitch depression. A steady-state was obtained and the infusion was kept constant for 2 additional hours. Neuromuscular blockade was then allowed to spontaneously recover. Blood samples were taken for measurement of cisatracurium plasma concentration during the steady-state period (Cp(ss)95) and at various times during recovery. Demographic and intraoperative data were similar. CAT resulted in faster 25% and 75% recovery of the first twitch. The rate of infusion of cisatracurium needed to maintain a 95% twitch depression at steady-state was 44% faster in Group A (P < 0.001). The clearance of cisatracurium was significantly faster in Group A when compared with Group C (7.12 +/- 1.87 versus 5.72 +/- 0.70 L . kg(-1) . min(-1), P = 0.01). The Cp(ss)95 was also significantly larger in Group A (191 +/- 45 versus 159 +/- 36 ng/mL, P = 0.04). In addition, patients receiving CAT had a 20% increase in the clearance of cisatracurium that, in turn, resulted in a faster recovery of neuromuscular blockade after an infusion of the drug. Also, patients under CAT had a 20% increase in their Cp(ss)95, indicating an increased resistance to the effect of cisatracurium.