Department of Anaesthesiology and Pain Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea.
Department of Surgery, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea.
Sci Rep. 2019 Aug 2;9(1):11268. doi: 10.1038/s41598-019-47784-3.
Studies have reported that protracted dexamethasone treatment induces resistance to nondepolarizing neuromuscular blocking agents (NMBAs) and the association with nicotinic acetylcholine receptors in the diaphragm of rats. Here, we investigated the effect of protracted dexamethasone administration on the sensitivity to rocuronium and the recovery profile when reversed by sugammadex; additionally, we observed the recovery period of pharmacodynamic change after withdrawal. Sprague-Dawley rats received daily intraperitoneal injections of dexamethasone or saline for 14 days. On days 1, 3, and 7 after the last dexamethasone treatment (Dexa1, Dexa3, and Dexa7, respectively) or 1 day after saline (control group), the phrenic nerve-hemidiaphragm preparation was dissected for assay. The dose-response curve of rocuronium in Dexa1 was shifted to the right compared to controls, but curves in Dexa3 and Dexa7 were not significantly different. Groups were not significantly different in attaining the train-of-four ratio ≥ 0.9, but the recovery index in Dexa7 was shorter than that in control and Dexa1. Recovery profiles (period of sugammadex reversal) were not correlated with resistance properties but rather with total administered drugs (binding capacity of NMBAs and sugammadex). Protracted dexamethasone exposure induced resistance to rocuronium but seemed to have no effect on sugammadex reversal in the rat diaphragm.
研究报道，长期使用地塞米松会导致大鼠膈肌对非去极化神经肌肉阻滞剂（NMBAs）产生耐药性，并与烟碱型乙酰胆碱受体相关。在这里，我们研究了长期地塞米松给药对罗库溴铵敏感性的影响，以及用 sugammadex 逆转时的恢复情况；此外，我们还观察了停药后药效变化的恢复期。Sprague-Dawley 大鼠每天接受腹腔注射地塞米松或生理盐水 14 天。在最后一次地塞米松治疗（Dexa1、Dexa3 和 Dexa7）后第 1、3 和 7 天，或生理盐水（对照组）后第 1 天，分离膈神经-膈肌标本进行检测。与对照组相比，Dexa1 组的罗库溴铵剂量反应曲线向右移位，但 Dexa3 和 Dexa7 组的曲线无显著差异。各组达到四串比值≥0.9 的时间无显著差异，但 Dexa7 组的恢复指数短于对照组和 Dexa1 组。恢复曲线（sugammadex 逆转期）与耐药性无关，而与总给药药物有关（NMBAs 和 sugammadex 的结合能力）。长期地塞米松暴露会导致罗库溴铵耐药，但对大鼠膈肌中 sugammadex 的逆转似乎没有影响。
