Low-Dose Morphine Does Not Cause Sleepiness in Chronic Obstructive Pulmonary Disease: A Secondary Analysis of a Randomized Clinical Trial.

IF 19.3 1区医学 Q1 CRITICAL CARE MEDICINE American journal of respiratory and critical care medicine Pub Date : 2024-11-01 DOI:10.1164/rccm.202310-1780OC

Thomas J Altree, Barbara Toson, Kelly A Loffler, Magnus Ekström, David C Currow, Danny J Eckert

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Abstract

Rationale: Regular, low-dose, sustained-release morphine is frequently prescribed for persistent breathlessness in chronic obstructive pulmonary disease (COPD). However, effects on daytime sleepiness, perceived sleep quality, and daytime function have not been rigorously investigated. Objectives: We sought to determine the effects of regular, low-dose, sustained-release morphine on sleep parameters in COPD. Methods: We conducted prespecified secondary analyses of validated sleep questionnaire data from a randomized trial of daily, low-dose, sustained-release morphine versus placebo over 4 weeks commencing at 8 or 16 mg/d with blinded up-titration over 2 weeks to a maximum of 32 mg/d. Primary outcomes for these analyses were Week-1 Epworth Sleepiness Scale (ESS) and Karolinska Sleepiness Scale (KSS) scores on morphine versus placebo. Secondary outcomes included Leeds Sleep Evaluation Questionnaire scores (end of Weeks 1 and 4), KSS and ESS scores beyond Week 1, and associations between breathlessness, morphine, and questionnaire scores. Measurements and Main Results: One hundred fifty-six people were randomized. Week-1 sleepiness scores were not different on morphine versus placebo (ΔESS [95% confidence interval] versus placebo: 8-mg group, -0.59 [-1.99, 0.81], P = 0.41; 16-mg group, -0.72 [-2.33, 0.9], P = 0.38; ΔKSS vs. placebo, 8-mg group: 0.11 [-0.7, 0.9], P = 0.78; 16-mg group, -0.41 [-1.31, 0.49], P = 0.37). This neutral effect persisted at later time points. In addition, participants who reported reduced breathlessness with morphine at 4 weeks also showed improvement in LSEQ domain scores including perceived sleep quality and daytime function. Conclusions: Regular, low-dose morphine does not worsen sleepiness when used for breathlessness in COPD. Individual improvements in breathlessness with morphine may be related to improvements in sleep. Clinical trial registered with www.clinicaltrials.gov (NCT02720822).

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小剂量吗啡不会导致慢性阻塞性肺病患者嗜睡：一项随机试验的二次分析。

理由：常规、低剂量、缓释吗啡经常被用于治疗慢性阻塞性肺病（COPD）患者的持续性呼吸困难。然而，该药物对白天嗜睡、感知睡眠质量和日间功能的影响尚未得到严格研究：确定常规、低剂量、缓释吗啡对慢性阻塞性肺病患者睡眠参数的影响：方法：对一项随机试验中的有效睡眠问卷数据进行预先指定的二次分析，该试验采用每日低剂量缓释吗啡与安慰剂对比的方法，为期四周，吗啡剂量为 8 毫克或 16 毫克/天，并在两周内进行盲法加量，最大剂量为 32 毫克/天。这些分析的主要结果是吗啡与安慰剂的第一周埃普沃思嗜睡量表（ESS）和卡罗林斯卡嗜睡量表（KSS）反应。次要结果包括利兹睡眠评估问卷（LSEQ）得分（第1周和第4周结束时）、第1周以后的KSS和ESS以及窒息感、吗啡和问卷得分之间的关联：156人接受了随机治疗。吗啡与安慰剂的第一周嗜睡评分没有差异（∆ESS [95%CI] 与安慰剂：8 毫克组：-0.59 [-1.99, 0.81]，p=0.41；16 毫克组：-0.72 [-2.33, 0.9]，p=0.38；∆KSS 与安慰剂：8 毫克组：-0.11 [-0.7, 0.9]，p=0.38）：0.11 [-0.7, 0.9]，p=0.78；16 毫克组：-0.41 [-1.31, 0.49]，p=0.37）。这种中性效应在后来的时间点上持续存在。此外，服用吗啡4周后呼吸困难减轻的参与者在LSEQ领域的评分也有所改善，包括睡眠质量和日间功能：结论：常规、低剂量吗啡用于治疗慢性阻塞性肺病患者的呼吸困难时不会加重嗜睡。使用吗啡改善呼吸困难可能与睡眠改善有关。

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来源期刊

American journal of respiratory and critical care medicine 医学-呼吸系统

CiteScore

27.30

自引率

4.50%

发文量

1313

审稿时长

3-6 weeks

期刊介绍： The American Journal of Respiratory and Critical Care Medicine focuses on human biology and disease, as well as animal studies that contribute to the understanding of pathophysiology and treatment of diseases that affect the respiratory system and critically ill patients. Papers that are solely or predominantly based in cell and molecular biology are published in the companion journal, the American Journal of Respiratory Cell and Molecular Biology. The Journal also seeks to publish clinical trials and outstanding review articles on areas of interest in several forms. The State-of-the-Art review is a treatise usually covering a broad field that brings bench research to the bedside. Shorter reviews are published as Critical Care Perspectives or Pulmonary Perspectives. These are generally focused on a more limited area and advance a concerted opinion about care for a specific process. Concise Clinical Reviews provide an evidence-based synthesis of the literature pertaining to topics of fundamental importance to the practice of pulmonary, critical care, and sleep medicine. Images providing advances or unusual contributions to the field are published as Images in Pulmonary, Critical Care, Sleep Medicine and the Sciences. A recent trend and future direction of the Journal has been to include debates of a topical nature on issues of importance in pulmonary and critical care medicine and to the membership of the American Thoracic Society. Other recent changes have included encompassing works from the field of critical care medicine and the extension of the editorial governing of journal policy to colleagues outside of the United States of America. The focus and direction of the Journal is to establish an international forum for state-of-the-art respiratory and critical care medicine.