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Reversal of fentanyl-induced laryngospasm with ketanserin and naloxone: A prospective randomized blinded study in rats

Year: 2025

Type: article

Abstract: Fentanyl can induce laryngospasm in humans and rats, a lethal effect if unresolved. The aim was to compare the effect of ketanserin, alone and combined with naloxone, to resolve fentanyl-induced laryngospasm in a rat model. Male Sprague-Dawley rats (n=75) were instrumented with a venous catheter under isoflurane anesthesia before converting to IV α-chloralose (50-60 mg kg -1 ). Each rat was administered 25 µg kg -1 IV fentanyl or saline (Control) and further allocated to receive either 2 mg kg -1 ketanserin and 2 mg kg -1 naloxone (Fentanyl-Ketanserin-Naloxone), saline and 2 mg kg -1 naloxone (Fentanyl-Naloxone), 2 mg kg -1 ketanserin and saline (Fentanyl-Ketanserin), or two injections of saline (Fentanyl-Saline). Videos of the larynx were recorded by an endoscope positioned orally. The glottic diameter was measured retrospectively by a blinded observer. The effect of treatment on the change in glottic diameter from baseline after antagonist or saline injections was analyzed using a Wilcoxon Rank-Sum Test and a Bonferroni-corrected alpha of 0.01. Fentanyl reduced glottic opening to median -100%. Median (IQR) changes in glottic opening were 51% (10, 96), -13% (-40, 10), -97% (-100, -47) and -100% (-100, -72) for Fentanyl-Ketanserin-Naloxone, Fentanyl-Naloxone, Fentanyl-Ketanserin and Fentanyl-Saline respectively. Fentanyl-Ketanserin-Naloxone was significantly different from Fentanyl-Naloxone, Fentanyl-Ketanserin and Fentanyl-Saline (p<0.001). Fentanyl-Naloxone was significantly different from Fentanyl-Saline (p<0.0001), no significant difference was found between Fentanyl-Ketanserin and Fentanyl-Saline. Co-administration of ketanserin and naloxone resolved fentanyl-induced laryngospasm with an enhanced glottic opening compared to baseline. Findings suggest that both opioid and serotonergic mechanisms can be involved in fentanyl-induced laryngospasm. • Dual-treatment with ketanserin and naloxone resolves fentanyl-induced laryngospasm. • Fentanyl-induced laryngospasm might involve serotonergic mechanisms. • Ketanserin with naloxone provides an increased glottic opening compared to naloxone only. • Naloxone only resolved laryngospasm, but with individual variability.

Source: Drug and Alcohol Dependence

DOI: 10.1016/j.drugalcdep.2025.112969