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NEUROSURGICAL ANESTHESIA

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

Anouk Richard, MD, FRCPC^*, François Girard, MD, FRCPC^*, Dominique C. Girard, MD, FRCPC^*, Daniel Boudreault, MD, FRCPC^*, Philippe Chouinard, MD, FRCPC^*, Robert Moumdjian, MD, FRCS, Alain Bouthilier, MD, FRCS, Monique Ruel, RN, CCRP^*, Johanne Couture, RT, and France Varin, Bpharm, PhD

*Department of Anesthesiology and Neurosurgery Division, CHUM, Hôpital Notre-Dame; and Faculty of Pharmacy, Université de Montréal, Montréal, Canada

Address correspondence and reprint requests to François Girard, MD, FRCPC, Department of Anesthesiology, CHUM, Hôpital Notre-Dame, 1560 Sherbrooke East, Montreal, Canada, H2L 4M1. Address e-mail to francois.girard.chum{at}ssss.gouv.qc.ca.

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_ss95) 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_ss95 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_ss95, indicating an increased resistance to the effect of cisatracurium.

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999