BACKGROUND Low-dose morphine may be prescribed to reduce chronic breathlessness in chronic obstructive pulmonary disease (COPD). Recent 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. RESEARCH QUESTION What are the effects of low-dose morphine on sleep efficiency and other sleep parameters in COPD? STUDY DESIGN AND METHODS Randomized, double-blind, crossover trial of 20mg/day sustained-release morphine for three days (steady-state) versus placebo in nineteen breathless people with COPD (n=7 female). The primary outcome was sleep efficiency during in-laboratory overnight polysomnography (PSG). Secondary and exploratory outcome measures included sleep-disordered breathing frequency/hr, oxygenation, transcutaneous carbon dioxide (TcCO2) 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 PSG. RESULTS Sleep efficiency was similar between placebo and morphine (66±17 vs. 67±19%, p=0.89). Morphine did not change the frequency of sleep-disordered breathing events but reduced breathing frequency. Morphine reduced mean and nadir overnight oxygen saturation by [95%CI] 2 [-2.8 to -1.2] and 5 [-8 to -1]%, respectively. Mean TcCO2 was 3.3 [1.6 to 5.1]mmHg higher during sleep with morphine versus placebo. Eight participants (42%) met American Academy of Sleep Medicine criteria for nocturnal hypoventilation with morphine versus four (21%) on placebo, p=0.02. 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.

中文翻译：

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低剂量吗啡对 COPD 睡眠和呼吸困难的影响：一项随机试验。


背景 可以开具低剂量吗啡来减轻慢性阻塞性肺病 （COPD） 的慢性呼吸困难。最近的主观研究结果表明，吗啡可能通过与睡眠相关的机制影响呼吸困难。然而，对 COPD 中阿片类药物的安全性存在担忧。吗啡对 COPD 睡眠期间的影响尚未得到客观研究。本研究旨在客观确定低剂量吗啡对睡眠的影响。研究问题 低剂量吗啡对 COPD 患者的睡眠效率和其他睡眠参数有什么影响？研究设计和方法 在 19 名呼吸困难的 COPD 患者 （n=7 女性） 中，20 毫克/天缓释吗啡三天（稳态）与安慰剂的随机、双盲、交叉试验。主要结局是实验室内过夜多导睡眠图 （PSG） 期间的睡眠效率。次要和探索性结局指标包括睡眠呼吸障碍呼吸频率/小时、氧合、经皮二氧化碳 （TcCO2） 水平、血液和生理生物标志物、睡眠与呼吸困难之间的关系、外部阻力负荷反应和驾驶模拟器性能。在每次 PSG 之前和之后测量生理学结果和药代动力学。结果安慰剂和吗啡的睡眠效率相似 （66±17 vs. 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氧饱和度分别降低了 [95%CI] 2 [-2.8 至 -1.2] 和 5 [-8 至 -1]%。与安慰剂相比，吗啡组在睡眠期间的平均 TcCO2 高出 3.3 [1.6 至 5.1]mmHg。 8 名参与者 （42%） 符合美国睡眠医学会吗啡夜间通气不足的标准，而安慰剂组 4 名 （21%） 符合标准，p=0.02。吗啡并没有系统地减少呼吸困难或损害第二天驾驶模拟器的性能。吗啡增加了不良事件 （最常见的恶心）。解释 稳态、低剂量吗啡不会改变睡眠效率、睡眠呼吸障碍频率或第二天的警觉性，但可能导致睡眠期间通气不足，这是一种潜在的有害影响。