Respiratory depressant and skeletal muscle relaxant effects of low-dose pancuronium bromide in spontaneously breathing, isoflurane-anesthetized dogs

Abstract

Objective: To assess and compare the respiratory depressant and skeletal muscle relaxant effects of two low doses of a nondepolarizing neuromuscular blocker, pancuronium bromide. To determine if a "low dose" of pancuronium bromide can produce selective skeletal muscle relaxation in extraocular muscles sufficient to perform intraocular surgery while sparing or minimizing depression of muscles of ventilation.

Study design: Blinded, randomized crossover, placebo controlled study.

Animals: Six healthy, adult mongrel dogs weighing 20.8 +/- 1.9 kg.

Methods: Spontaneously breathing, isoflurane-anesthetized dogs received 0.02 mg/kg pancuronium bromide, intravenously (i.v.), (high dose [HD]), 0.01 mg/kg pancuronium bromide, i.v., (low dose [LD]), or saline placebo i.v. in a blinded, randomized crossover study. Indices of patient ventilation including tidal volume (Vt), respiratory rate (RR), and minute ventilation (VE) were recorded throughout the study period. Serial arterial blood gas analyses were performed at timed intervals. Neuromuscular blockade of skeletal muscle was assessed at timed intervals with train-of-four stimulus/response ratios. Eye position scores, based on the degree of ocular rotation from a neutral gaze axis, were assigned by an ophthalmologist who was blinded to the treatment given.

Results: VT and VE in HD dogs decreased by 82% from baseline after administration of pancuronium bromide. Similarly, Vt and VE in LD dogs decreased 40% and 55%, respectively. Decreased ventilation in HD dogs corresponded with significant (P< .05) neuromuscular blockade, as indicated by train-of-four ratio less than 75% between 0 and 60 minutes. Eye position scores in HD and LD dogs were suitable for intraocular surgery between 0 and 60 minutes. Eye position scores in five of six control dogs were unsuitable for intraocular surgery at any time period.

Conclusions: LD dogs experienced only transient, mild to moderate respiratory depression compared with HD dogs, which experienced prolonged, moderate to severe respiratory depression. Both LD and HD dogs acquired and maintained eye position scores suitable for intraocular surgery between 0 to 60 minutes. A "low dose" of pancuronium bromide, which would provide adequate extraocular muscle relaxation while minimizing ventilatory depression, was not identified.

Clinical relevance: All patients receiving any dose of neuromuscular blocking agents should be closely monitored and receive ventilatory assistance as needed.