PROLONGED PARALYSIS AFTER LONG-TERM, HIGH-DOSE INFUSION OF PANCURONIUM IN ANESTHETIZED CATS

We have studied the neuromuscular effects of a 48-h infusion of high-d ose pancuronium (400 mug kg-1 h-1) in four cats anaesthetized with pen tobarbitone, using contraction of tibialis anterior muscles after dire ct and indirect stimulation. After cessation of the pancuronium infusi on, prolonged paralysis existed. The first twitch in the train-of-four stimuli (TOF) reappeared 8-12 h after termination of the pancuronium infusion. Twenty-four hours after termination of the infusion, TOF rat ios were less than 0.08 and twitch contraction averaged 39 (SE 8) % of initial values. Twitch contraction after direct stimulation did not d iffer from initial values. Antagonism of paralysis was accomplished wi th neostigmine 60 mug kg-1 in two animals and neostigmine 90 mug kg-1 and 4-aminopyridine 500 mug kg-1 in the others. Steady-state plasma co ncentration of pancuronium (2000 ng ml-1) decreased rapidly after term ination of the infusion, but then stabilized at about 130 ng ml-1. The se results indicate that prolonged paralysis after long-term administr ation of high-dose pancuronium is caused primarily by failure of neuro muscular transmission, most likely caused by the persistent plasma con centrations of the drug in the pharmacologically active range.