Resistance to metocurine-induced neuromuscular blockade in patients receiving phenytoin.
Recent reports have described resistance to pancuronium-induced neuromuscular blockade in patients chronically receiving anticonvulsants. This study examines the pharmacokinetics and pharmacodynamics of metocurine (MTC) in 12 patients undergoing craniotomy--six on chronic phenytoin therapy and six comparable controls. Each patient received MTC 0.2 mg/kg during the induction of general anesthesia. Quantification of plasma MTC concentration was performed by radioimmunoassay, while the response to MTC was evaluated by evoked compound electromyography (ECEMG). Patients in the phenytoin group were resistant to this dosage of MTC, as demonstrated by their response (83 +/- 16% compared with 98 +/- 2% depression of ECEMG in control patients, P less than 0.05) and by recovery index, defined as the time required for recovery from 25 to 75% of the control ECEMG (53 +/- 22 min compared with 125 +/- 54 min in control patients, P less than 0.01). Similarly, the total duration of neuromuscular blockade, measured to recovery to 90% of control ECEMG, was significantly shorter in the phenytoin group (122 +/- 25 min compared with 269 +/- 64 min in the control group, P less than 0.01). Plasma concentration-time curves were fit to biexponential equations for both groups. These were used to generate two-compartment models. Neither the model parameters nor the plasma concentrations of MTC at any time in the study were significantly different for the two groups. The pharmacodynamic analysis, however, showed that patients on phenytoin require a higher plasma concentration of MTC (0.415 +/- 0.095 microgram/ml compared with 0.249 +/- 0.066 microgram/ml in control patients at 50% ECEMG, P less than 0.01) to effect a given level of neuromuscular blockade.(ABSTRACT TRUNCATED AT 250 WORDS)
Ornstein
E
E
Matteo
R S
RS
Young
W L
WL
Diaz
J
J
D000328:Adult; D004351:Drug Resistance; D004576:Electromyography / Q000379:methods; D005071:Evoked Potentials / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008875:Middle Aged; D008954:Models, Biological; D003473:Neuromuscular Nondepolarizing Agents / Q000037:antagonists & inhibitors* / Q000097:blood; D010672:Phenytoin / Q000494:pharmacology*; D014403:Tubocurarine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000097:blood
D003473:Neuromuscular Nondepolarizing Agents; D010672:Phenytoin; C032943:metocurine; D014403:Tubocurarine