Pancuronium-phenytoin interaction: a case of decreased duration of neuromuscular blockade.
A 33-year-old female presented for elective excision of a posterior fossa tumour following two generalized seizures six months earlier. The patient had been asymptomatic on phenytoin 300 mg/day. Two h pre-operatively, a 300-mg dose of phenytoin was administered, general anesthesia induced and pancuronium bromide given to achieve neuro-muscular paralysis. Respiration was supported and anesthesia maintained with isoflurane and nitrous oxide in oxygen. Thirty min into the operation a further 2-mg dose of pancuronium bromide was administered. One h later, the patient coughed. A peripheral nerve stimulator was applied to the right common peroneal nerve with surface electrodes. Over the next 75 min a total of 15 mg of pancuronium bromide was required. With each dose there was a complete loss of response to peripheral nerve stimulation, followed by a rapid return of full train-of-four response, accompanied by coughing and cerebral engorgement. At this point, metocurine iodide was administered with full sustained paralysis for 45 min. Blood samples collected during a second operation indicated the patient had an extremely short pancuronium elimination half-life and a small volume of distribution. Several explanations are offered including phenytoin induction of hepatic microsomal enzymes responsible for the biotransformation of pancuronium, alterations in tissue or protein binding and/or alterations in myoneuronal junctional response.
Liberman
B A
BA
Department of Anesthesia, Sunnybrook Medical Centre, University of Toronto, Canada.
Norman
P
P
Hardy
B G
BG
D000328:Adult; D001784:Blood Gas Analysis; D003975:Diazepam; D004347:Drug Interactions; D005260:Female; D006801:Humans; D009466:Neuromuscular Blocking Agents; D010197:Pancuronium / Q000494:pharmacology*; D010672:Phenytoin / Q000494:pharmacology*; D011229:Preanesthetic Medication; D013997:Time Factors
D009466:Neuromuscular Blocking Agents; D010672:Phenytoin; D010197:Pancuronium; D003975:Diazepam