Neuromuscular, haemodynamic, and autonomic effects of a fast-onset, long-acting, nondepolarising, carborane neuromuscular blocking agent compared to rocuronium in rats.

Abstract

Background: We have previously introduced a long-acting, nondepolarising, neuromuscular blocking agent, pNMB (para-neuromuscular blocker). However, its neuromuscular, haemodynamic and autonomic effects as well as reversibility were not fully characterized.

Objective: We compared pNMB to rocuronium and tested the hypotheses that pNMB has a fast-onset, is long-acting, and its effects are reversed by sugammadex.

Design: Animal study.

Setting: Laboratory from January 2021 to February 2025.

Participants: Thirty-three adult male Sprague-Dawley rats.

Interventions: Rats were anesthetised and mechanically ventilated. Stimulating electrodes were attached to the sciatic and vagus nerves. Parasympathetic nerve activity was measured by vagal-induced bradycardia and sympathetic nerve activity by the nicotine pressor response.

Main outcome measures: Mechanomyography, mean arterial pressure (MAP) and heart rate (HR).

Results: Rocuronium and pNMB inhibited muscle twitch dose-dependently with effective dose (ED)50s (50% inhibition) of 0.28 (95% confidence interval (CI), 0.25 to 0.31) mg/kg, n = 6, and 1.05 (95% CI, 0.93 to 1.20) mg/kg, n = 6, respectively. Rocuronium and pNMB, at doses up to 3 mg/kg, had no effect on HR. Rocuronium 0.7 mg/kg and pNMB 6 mg/kg had no effect on MAP, mean ± SD, 153 ± 12 vs. 154 ± 14 mmHg, n = 4, P = 0.61, or decreased MAP 147 ± 9 vs. 72 ± 9 mmHg, n = 4, P < 0.01, respectively. Both rocuronium and pNMB were parasympatholytic with ED50s of 0.08 (95% CI, 0.06 to 0.09) mg/kg, n = 5, and 0.18 (95% CI, 0.14 to 0.22) mg/kg, n = 7, respectively. Rocuronium 0.7 mg/kg was not sympatholytic whereas pNMB 6 mg/kg was. Both rocuronium 0.7 mg/kg and pNMB 6 mg/kg decreased MAP in the presence of nicotine. Onset times of rocuronium 0.7 mg/kg and pNMB 6 mg/kg did not differ (P = 0.22). Rocuronium 0.7 mg/kg inhibited twitch for approximately 8 min, whereas pNMB 6 mg/kg inhibited twitch at a steady 80% for 60 min after administration. Sugammadex 10.9 mg/kg reversed the pNMB 3 mg/kg twitch blockade of 92.5% (95% CI, 85.9% to 99%), n = 6.

Conclusions: The nondepolarising NMBA, pNMB, had a fast-onset similar to rocuronium and was long-acting and reversible by sugammadex. Both rocuronium and pNMB had autonomic effects that were apparent at subparalytic doses and decreased blood pressure in the presence of nicotine. When administered alone, rocuronium did not decrease MAP whereas pNMB caused a marked hypotension. Neither NMBA affected HR. These findings are limited to rats, and generalisability to other animal species and humans is unknown.

Registration: University of Missouri IACUC (#9750, #40189), Columbia, Missouri, USA.