Cisatracurium-induced neuromuscular blockade is affected by chronic phenytoin or carbamazepine treatment in neurosurgical patients.
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.
Richard
Anouk
A
*Department of Anesthesiology and †Neurosurgery Division, CHUM, Hôpital Notre-Dame; and ‡Faculty of Pharmacy, Université de Montréal, Montréal, Canada.
Girard
François
F
Girard
Dominique C
DC
Boudreault
Daniel
D
Chouinard
Philippe
P
Moumdjian
Robert
R
Bouthilier
Alain
A
Ruel
Monique
M
Couture
Johanne
J
Varin
France
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D000768:Anesthesia, General; D000927:Anticonvulsants / Q000494:pharmacology*; D001279:Atracurium / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002220:Carbamazepine / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D016343:Monitoring, Intraoperative; D009407:Nerve Block; D003473:Neuromuscular Nondepolarizing Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019635:Neurosurgical Procedures; D010672:Phenytoin / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects
D000927:Anticonvulsants; D003473:Neuromuscular Nondepolarizing Agents; D001279:Atracurium; D002220:Carbamazepine; D010672:Phenytoin