CARDIAC RESPONSES TO IMIPRAMINE AND PANCURONIUM DURING ANESTHESIA WITH HALOTHANE OR ENFLURANE

The possibility that acute or chronic imipramine administration predisposes to development of cardiac arrhythmias from pancuronium during anesthesia with halothane or enflurane was explored. Acute administration of imipramine, 0.5, 1, 2 or 3 mg/kg, or pancuronium, 10, 40, or 80 .mu.g/kg, caused dose-dependent tachycardia in dogs anesthetized with halothane (n = 5) or enflurane (n = 5) except for the 3 mg/kg dose of imipramine, which decreased heart rate by 11 .+-. 1 beats/min (P < 0.01). Simultaneous administration of pancuronium and imipramine caused tachycardia in an additive manner in doses of pancuronium to 80 .mu.g/kg and imipramine to 2 mg/kg; at higher doses, the tachycardia became less than additive. Additional dogs (40) were given imipramine, 8 (n = 20) or 16 mg/day (n = 20), for 15 days and then anesthetized with either halothane or enflurane. Pancuronium, did not cause cardiac arrhythmias in the dogs anesthetized with enflurane. Pancuronium, 10 and 40 mg/kg, did not produce arrhythmias in the halothane-anesthetized dogs; the 80 .mu.g/kg dose produced premature ventricular contractions and ventricular tachycardia which rapidly progressed to ventricular fibrillation and cardiac arrest in 2 of 10 dogs given imipramine, 8 mg/kg per day, and in 4 of 10 dogs given imipramine, 16 mg/kg per day. Although only the dogs that had severe ventricular arrhythmias had significantly increased blood norepinephrine concentrations, the norepinephrine concentrations increased before the appearance of ventricular arrhythmias. Apparently severe ventricular arrhythmias may occur due to administration of pancuronium in dogs anesthetized with halothane and receiving imipramine chronically. Pancuronium apparently should be given with caution to a patient receiving chronic tricyclic antidepressant therapy who is anesthetized with halothane.