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

IF 3.5 2区医学 Q1 PSYCHIATRY

Drug and alcohol dependence Pub Date : 2025-12-01 Epub Date: 2025-11-17 DOI:10.1016/j.drugalcdep.2025.112969

Nora Digranes , Emma Pettersson , Andreas Lervik , Inger Lise Bogen , Jannike Mørch Andersen , Janicke Nordgreen , Henning Andreas Haga

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Abstract

Background

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.

Material

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.

Results

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.

Conclusion

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.

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酮色林和纳洛酮逆转芬太尼诱导的喉痉挛：一项大鼠前瞻性随机盲法研究

芬太尼可以引起人类和大鼠的喉痉挛，如果不加以解决，这是一种致命的影响。目的是比较酮色林单独使用和纳洛酮联合使用对芬太尼引起的大鼠喉痉挛的缓解效果。材料雄性Sprague-Dawley大鼠（n = 75）在异氟醚麻醉下静脉置管，然后转入静脉注射α-氯氯糖（50-60 mg kg - 1）。每只大鼠静脉注射25µg kg - 1芬太尼或生理盐水（对照组），并进一步分配接受2mg kg - 1克坦色林和2mg kg - 1纳洛酮（芬太尼-酮色林-纳洛酮），生理盐水和2mg kg - 1纳洛酮（芬太尼-纳洛酮），2mg kg - 1克坦色林和生理盐水（芬太尼-酮色林），或两次注射生理盐水（芬太尼-生理盐水）。喉部的视频由口腔定位的内窥镜记录。由盲眼观察者回顾性测量声门直径。使用Wilcoxon秩和检验和bonferroni校正α值0.01分析治疗对注射拮抗剂或生理盐水后声门直径较基线变化的影响。结果芬太尼使声门开口降至中位- 100%。芬太尼-克坦瑟林-纳洛酮、芬太尼-纳洛酮、芬太尼-克坦瑟林和芬太尼-生理盐水的声门开口中位（IQR）变化分别为51%（10,96）、- 13%（- 40,10）、- 97%（-100,- 47）和- 100%（-100,- 72）。芬太尼-酮色林-纳洛酮与芬太尼-纳洛酮、芬太尼-酮色林和芬太尼-生理盐水差异有统计学意义（p < 0.001）。芬太尼-纳洛酮与芬太尼-生理盐水差异有统计学意义（p < 0.0001），芬太尼-酮色林与芬太尼-生理盐水差异无统计学意义。结论与基线相比，联合使用酮西林和纳洛酮可缓解芬太尼引起的喉痉挛，声门开口增强。研究结果表明阿片类药物和血清素能机制都可能参与芬太尼诱导的喉痉挛。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug and alcohol dependence 医学-精神病学

CiteScore

7.40

自引率

7.10%

发文量

409

审稿时长

41 days

期刊介绍： Drug and Alcohol Dependence is an international journal devoted to publishing original research, scholarly reviews, commentaries, and policy analyses in the area of drug, alcohol and tobacco use and dependence. Articles range from studies of the chemistry of substances of abuse, their actions at molecular and cellular sites, in vitro and in vivo investigations of their biochemical, pharmacological and behavioural actions, laboratory-based and clinical research in humans, substance abuse treatment and prevention research, and studies employing methods from epidemiology, sociology, and economics.