Pharmacodynamics and pharmacokinetics of rocuronium in sevoflurane-anesthetized Thoroughbred horses.

Abstract

Objective: To investigate the pharmacodynamics and pharmacokinetics of rocuronium administered by bolus injection to sevoflurane-anesthetized horses.

Study design: Prospective, experimental, crossover study.

Animals: Five healthy adult Thoroughbred horses (body mass 368-470 kg, three females and two males).

Methods: Each horse was anesthetized twice with sevoflurane and assigned to be administered rocuronium bromide intravenously: 0.2 mg kg^-1 (R02) or 0.4 mg kg^-1 (R04). There was a minimum 2 week washout period between experiments. During anesthesia, the peroneal nerve was stimulated (train-of-four) and neuromuscular function was assessed with acceleromyography. Plasma rocuronium concentrations were measured using liquid chromatography-tandem mass spectrometry. Pharmacodynamic and pharmacokinetic data are presented as mean ± standard deviation and were statistically compared between R02 and R04 with a Student's paired t-test. Significance was set at p < 0.05.

Results: Complete neuromuscular blockade was observed in all horses. The duration of action was significantly shorter for R02 (42.5 ± 11.2 minutes) than for R04 (67.0 ± 17.8 minutes, p = 0.003). Plasma concentrations of rocuronium showed a biphasic elimination pattern. Systemic clearance was significantly higher for R04 (2.12 ± 1.15 mL minute^-1 kg^-1) than for R02 (1.07 ± 0.46 mL minute^-1 kg^-1, p = 0.034). Mean residence time was significantly shorter for R04 (109 ± 73.1 minutes) than for R02 (183 ± 64.6 minutes, p = 0.015).

Conclusions and clinical relevance: Rocuronium induced complete neuromuscular blockade with both R02 and R04, and exhibited a dose-dependent duration of action. Significantly higher systemic clearance and shorter mean residence time for the high dose (R04) were observed compared with the low dose (R02). The prolonged clearance of rocuronium in horses contributed to its extended duration of action in this species.