Abstract
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.
Highlights
Synthetic glucocorticoids are used to control inflammatory and autoimmune diseases, in the treatment of certain types of leukaemia, and for achieving immunosuppression after organ transplant
The first objective was to investigate the effect of protracted dexamethasone administration on the sensitivity to rocuronium-induced neuromuscular block and on the recovery profile when the blockade was reversed by sugammadex
We hypothesized that the recovery period would last 3–7 days, with the recovery period defined as adequate time to recover the normal pharmacodynamic effects of neuromuscular blocking agents (NMBAs) and sugammadex as comparable to a previous study[5]
Summary
Synthetic glucocorticoids are used to control inflammatory and autoimmune diseases, in the treatment of certain types of leukaemia, and for achieving immunosuppression after organ transplant. With regard to the neuromusculature, long-term treatment with glucocorticoids (including dexamethasone) has been reported to induce muscle atrophy, dysfunction[3,4,5] and resistance to nondepolarizing neuromuscular blocking agents (NMBAs)[6,7]. The effect of protracted exposure to dexamethasone on sugammadex reversal has not been investigated, and nor has the consequent recovery of the dexamethasone-induced neuromuscular pharmacodynamic change after discontinuation of dexamethasone treatment. This dearth of research directed the two objectives of the current study. We assessed the neuromuscular properties in association with the expression of α7-nAChRs
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