甲氧基氟醚与芬太尼和安慰剂对低血容量血症的血流动力学影响:在健康志愿者中进行的随机、双盲交叉研究

BJA open Pub Date : 2023-09-01 DOI:10.1016/j.bjao.2023.100204

Lars Øivind Høiseth , Lars Olav Fjose , Jonny Hisdal , Marlin Comelon , Leiv Arne Rosseland , Harald Lenz

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引用次数: 0

摘要

甲氧基氟醚被批准用于缓解有意识的成人创伤患者的中度至重度疼痛:它可以自我给药，非常适合在恶劣环境中使用。创伤患者可能会遭受损伤，导致隐性出血损害血流动力学稳定性，因此阐明甲氧基氟醚是否会对低血容量血症的血流动力学反应产生不利影响是很重要的。方法采用随机、双盲、安慰剂对照、三期交叉研究方法，对15例暴露于实验性低血容量下体负压模型的健康志愿者，分别吸入甲氧基氟醚3ml、芬太尼25 μg、安慰剂。主要终点是治疗对心输出量变化的影响，次要终点是卒中容量、平均动脉压和下体负压期间血流动力学失代偿时间的变化。结果治疗对下体负压期间心输出量、脑卒中量或平均动脉压的变化无统计学意义。与芬太尼相比，甲氧基氟醚的失代偿时间更长(风险比1.9;95%置信区间0.4-3.4;P=0.010)，而与安慰剂相比无显著差异(风险比- 1.3;95%置信区间为−2.8 ~ 0.23;P = 0.117)。结论本研究未表明甲氧基氟醚对低血容量清醒的成人有明显的不良血流动力学影响。临床试验注册:clinicaltrials .gov (NCT04641949)和EudraCT (2019-004144-29) https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-004144-29/NO。

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Haemodynamic effects of methoxyflurane versus fentanyl and placebo in hypovolaemia: a randomised, double-blind crossover study in healthy volunteers

Background

Methoxyflurane is approved for relief of moderate to severe pain in conscious adult trauma patients: it may be self-administrated and is well suited for use in austere environments. Trauma patients may sustain injuries causing occult haemorrhage compromising haemodynamic stability, and it is therefore important to elucidate whether methoxyflurane may adversely affect the haemodynamic response to hypovolaemia.

Methods

In this randomised, double-blinded, placebo-controlled, three-period crossover study, inhaled methoxyflurane 3 ml, i.v. fentanyl 25 μg, and placebo were administered to 15 healthy volunteers exposed to experimental hypovolaemia in the lower body negative pressure model. The primary endpoint was the effect of treatment on changes in cardiac output, while secondary endpoints were changes in stroke volume and mean arterial pressure and time to haemodynamic decompensation during lower body negative pressure.

Results

There were no statistically significant effects of treatment on the changes in cardiac output, stroke volume, or mean arterial pressure during lower body negative pressure. The time to decompensation was longer for methoxyflurane compared with fentanyl (hazard ratio 1.9; 95% confidence interval 0.4–3.4; P=0.010), whereas there was no significant difference to placebo (hazard ratio −1.3; 95% confidence interval −2.8 to 0.23; P=0.117).