The Effects of Low-Dose Morphine on Sleep and Breathlessness in COPD: A Randomized Trial.

IF 9.5 1区医学 Q1 CRITICAL CARE MEDICINE

Chest Pub Date : 2024-12-13 DOI:10.1016/j.chest.2024.11.040

Thomas James Altree, Alison Pinczel, Barbara Toson, Kelly Loffler, Anna Hudson, Jim Zeng, Simon Proctor, Ganesh Naik, Sutapa Mukherjee, Peter Catcheside, Andrew Somogyi, David Currow, Danny Eckert

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引用次数: 0

Abstract

Background: Low-dose morphine may be prescribed to reduce chronic breathlessness in COPD. Subjective findings suggest morphine may influence breathlessness through sleep-related mechanisms. However, concerns exist regarding opioid safety in COPD. The effects of morphine during sleep in COPD have not been objectively investigated. This study aimed to objectively determine the effects of low-dose morphine on sleep in COPD.

Research question: What are the effects of low-dose morphine on sleep efficiency and other sleep parameters in COPD?

Study design and methods: This was a randomized, double-blind, crossover trial of sustained-release morphine (20 mg/d for 3 days) (steady-state) vs placebo in 19 breathless people with COPD (n = 7 women). The primary outcome was sleep efficiency during in-laboratory overnight polysomnography. Secondary and exploratory outcome measures included sleep-disordered breathing (events/h), oxygenation, transcutaneous CO₂ levels, blood and physiology biomarkers, the relationship between sleep and breathlessness, external resistive load responses, and driving simulator performance. Physiology outcomes and pharmacokinetics were measured before and after each polysomnogram.

Results: Sleep efficiency was similar between placebo and morphine (66 ± 17% vs 67 ± 19%; P = .89). Morphine did not change the frequency of sleep-disordered breathing events but reduced breathing frequency. Morphine reduced mean and nadir overnight oxygen saturation by 2% (95% CI, -2.8% to -1.2%) and 5% (95% CI, -8% to -1%), respectively. Mean transcutaneous CO₂ was 3.3 mm Hg (95% CI, 1.6-5.1 mm Hg) higher during sleep with morphine vs placebo. Eight participants (42%) met American Academy of Sleep Medicine criteria for nocturnal hypoventilation with morphine vs four (21%) receiving placebo (P = .02). Morphine did not systematically reduce breathlessness or impair next-day driving simulator performance. Adverse events (most frequently nausea) were increased with morphine.

Interpretation: Steady-state, low-dose morphine does not change sleep efficiency, sleep-disordered breathing frequency, or next-day alertness but may cause hypoventilation during sleep, a potentially harmful effect.

Clinical trial registration: Australian New Zealand Clinical Trials Registry; No.: ACTRN12621000752864; URL: https://www.anzctr.org.au.

查看原文本刊更多论文

低剂量吗啡对COPD患者睡眠和呼吸困难的影响：一项随机试验。

背景：低剂量吗啡可用于减轻慢性阻塞性肺病（COPD）患者的长期憋气症状。最近的主观研究结果表明，吗啡可通过与睡眠相关的机制影响呼吸困难。然而，慢性阻塞性肺病患者对阿片类药物的安全性仍存在担忧。目前尚未对吗啡在慢性阻塞性肺病患者睡眠期间的影响进行客观调查。本研究旨在客观地确定低剂量吗啡对睡眠的影响：研究设计和方法：随机、双盲、交叉试验：在19名呼吸困难的慢性阻塞性肺病患者（女性，7人）中进行为期3天、每天20毫克的缓释吗啡（稳态）与安慰剂的对比试验。试验的主要结果是在实验室通宵多导睡眠图（PSG）检查中的睡眠效率。次要和探索性结果测量包括睡眠呼吸紊乱频率/小时、血氧饱和度、经皮二氧化碳（TcCO2）水平、血液和生理生物标志物、睡眠与憋气之间的关系、外部阻力负荷反应以及驾驶模拟器性能。每次 PSG 前后都对生理结果和药代动力学进行了测量：安慰剂和吗啡的睡眠效率相似（66±17% 对 67±19%，P=0.89）。吗啡没有改变睡眠呼吸障碍事件的频率，但降低了呼吸频率。吗啡使平均和最低夜间血氧饱和度分别降低了[95%CI] 2 [-2.8 至 -1.2] %和 5 [-8 至 -1] %。吗啡与安慰剂相比，睡眠时的平均 TcCO2 高出 3.3 [1.6 至 5.1] mmHg。使用吗啡时，有八名参与者（42%）符合美国睡眠医学会的夜间通气不足标准，而使用安慰剂时有四名参与者（21%）符合该标准，P=0.02。吗啡不会系统性地减轻窒息感，也不会影响第二天的模拟驾驶表现。使用吗啡会增加不良反应（最常见的是恶心）：解释：稳定状态下的小剂量吗啡不会改变睡眠效率、睡眠呼吸紊乱频率或第二天的警觉性，但可能会导致睡眠时通气不足，这是一种潜在的有害影响。

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

Chest 医学-呼吸系统

CiteScore

13.70

自引率

3.10%

发文量

3369

审稿时长

15 days

期刊介绍： At CHEST, our mission is to revolutionize patient care through the collaboration of multidisciplinary clinicians in the fields of pulmonary, critical care, and sleep medicine. We achieve this by publishing cutting-edge clinical research that addresses current challenges and brings forth future advancements. To enhance understanding in a rapidly evolving field, CHEST also features review articles, commentaries, and facilitates discussions on emerging controversies. We place great emphasis on scientific rigor, employing a rigorous peer review process, and ensuring all accepted content is published online within two weeks.