European journal of anaesthesiology · 2025
Neuromuscular, haemodynamic, and autonomic effects of a fast-onset, long-acting, nondepolarising, carborane neuromuscular blocking agent compared to rocuronium in rats.
СтатьяСравнительное исследованиеНазвание и аннотация: Перевод в очереди
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Timko Noah J, Ghaly Tammer N, Goswami Lalit N, Ray Colleen L, Johnson Quinn L, Mraovic Boris, Vilceanu Daniel, Callahan Michael F, Kracke George R
Аннотация
BACKGROUND: We have previously introduced a long-acting, nondepolarising, neuromuscular blocking agent, p NMB ( para -neuromuscular blocker). However, its neuromuscular, haemodynamic and autonomic effects as well as reversibility were not fully characterized.
OBJECTIVE: We compared p NMB to rocuronium and tested the hypotheses that p NMB 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 p NMB 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 p NMB, at doses up to 3 mg/kg, had no effect on HR. Rocuronium 0.7 mg/kg and p NMB 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 p NMB 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 p NMB 6 mg/kg was. Both rocuronium 0.7 mg/kg and p NMB 6 mg/kg decreased MAP in the presence of nicotine. Onset times of rocuronium 0.7 mg/kg and p NMB 6 mg/kg did not differ ( P = 0.22). Rocuronium 0.7 mg/kg inhibited twitch for approximately 8 min, whereas p NMB 6 mg/kg inhibited twitch at a steady 80% for 60 min after administration. Sugammadex 10.9 mg/kg reversed the p NMB 3 mg/kg twitch blockade of 92.5% (95% CI, 85.9% to 99%), n = 6.
CONCLUSIONS: The nondepolarising NMBA, p NMB, had a fast-onset similar to rocuronium and was long-acting and reversible by sugammadex. Both rocuronium and p NMB 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 p NMB 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.
OBJECTIVE: We compared p NMB to rocuronium and tested the hypotheses that p NMB 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 p NMB 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 p NMB, at doses up to 3 mg/kg, had no effect on HR. Rocuronium 0.7 mg/kg and p NMB 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 p NMB 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 p NMB 6 mg/kg was. Both rocuronium 0.7 mg/kg and p NMB 6 mg/kg decreased MAP in the presence of nicotine. Onset times of rocuronium 0.7 mg/kg and p NMB 6 mg/kg did not differ ( P = 0.22). Rocuronium 0.7 mg/kg inhibited twitch for approximately 8 min, whereas p NMB 6 mg/kg inhibited twitch at a steady 80% for 60 min after administration. Sugammadex 10.9 mg/kg reversed the p NMB 3 mg/kg twitch blockade of 92.5% (95% CI, 85.9% to 99%), n = 6.
CONCLUSIONS: The nondepolarising NMBA, p NMB, had a fast-onset similar to rocuronium and was long-acting and reversible by sugammadex. Both rocuronium and p NMB 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 p NMB 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.