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)

Adult↗

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Accelerated recovery from doxacurium-induced neuromuscular blockade in patients receiving chronic anticonvulsant therapy.

STUDY OBJECTIVE: To determine whether a drug interaction exists between doxacurium and anticonvulsants. DESIGN: Open-label controlled study. SETTING: Inpatient neuroanesthesiology service at a university medical center. PATIENTS: Three groups of nine patients each, consisting of those chronically receiving carbamazepine, phenytoin, or no anticonvulsant therapy. INTERVENTION: Intravenous administration of doxacurium 60 micrograms/kg during anesthesia with nitrous oxide (N2O), fentanyl, and droperidol. MEASUREMENTS AND MAIN RESULTS: The adductor pollicis mechanical response to single 0.2-millisecond supramaximal pulses delivered to the ulnar nerve at 0.15 Hz was recorded. Patients receiving phenytoin or carbamazepine recovered neuromuscular function more quickly than did the control group. The times from doxacurium injection to 50% recovery of mechanomyographic response, for example, were as follows: control group, 161 +/- 55 minutes (mean +/- SD); phenytoin group, 76 +/- 31 minutes; and carbamazepine group, 66 +/- 27 minutes (p less than 0.05). The time for recovery from 75% to 25% blockade (recovery index) was decreased by 53% in the phenytoin group and by 67% in the carbamazepine group as compared with the control group (41.0 +/- 18.0 minutes and 28.6 +/- 8.6 minutes vs 86.4 +/- 45.2 minutes, respectively). CONCLUSION: Chronic treatment with anticonvulsants results in more rapid recovery from neuromuscular blockade produced by doxacurium.

Adult↗

PubMedDate not supplied

Effects of methylprednisolone on transplanted kidneys assessed by 131I-hippuran and 99mtechnetium-DTPA renograms.

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Aortography↗