Speed of reversal of vecuronium neuromuscular block with different doses of neostigmine in anesthetized dogs

Objectives

Neostigmine is routinely used to reverse non-depolarizing neuromuscular block. Given its indirect mechanism, a plateau may exist whereby increasing doses of neostigmine do not result in clinical benefit. This study was designed to measure the speed of reversal of vecuronium-induced neuromuscular block in isoflurane-anesthetized dogs after the administration of three doses of neostigmine as used in clinical practice.

Study design

Prospective, crossover, randomized study.

Animals

Seven adult, mixed-breed dogs with a mean ± standard deviation (SD) age of 2.0 ± 0.8 years and weight of 19.1 ± 9.1 kg.

Methods

Dogs were anesthetized on three occasions with isoflurane and administered vecuronium (0.1 mg kg^–1) intravenously (IV). The train-of-four (TOF) ratio was measured on the pelvic limb with acceleromyography. When the second twitch of the TOF had returned spontaneously, atropine (0.03 mg kg^–1) and neostigmine (0.02, 0.04 or 0.07 mg kg^–1) were administered IV. Time to reach a TOF ratio of ≥0.9 after neostigmine administration was recorded.

Results

Increasing the dose of neostigmine from 0.02 mg kg^–1 to 0.04 mg kg^–1 and 0.07 mg kg^–1 resulted in significant reductions in mean ± SD reversal times (10.5 ± 2.3, 7.4 ± 1.1 and 5.4 ± 0.5 minutes, respectively) (p < 0.0001) and smaller coefficients of variation (22%, 15% and 10%, respectively).

Conclusions and clinical relevance

Increasing the dose of neostigmine from 0.02 mg kg^–1 to 0.04 mg kg^–1 and 0.07 mg kg^–1 produced faster and less variable reversal of vecuronium-induced neuromuscular block in isoflurane-anesthetized dogs. No ceiling effect was observed at this dose range.