Altree Thomas J, Toson Barbara, Loffler Kelly A, Ekström Magnus, Currow David C, Eckert Danny J
Flinders Health and Medical Research Institute-Adelaide Institute for Sleep Health, Flinders University, Bedford Park, South Australia, Australia.
Faculty of Medicine, Department of Clinical Sciences, Respiratory Medicine, Allergology and Palliative Medicine, Lund University, Lund, Sweden.
Am J Respir Crit Care Med. 2024 Nov 1;210(9):1113-1122. doi: 10.1164/rccm.202310-1780OC.
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. We sought to determine the effects of regular, low-dose, sustained-release morphine on sleep parameters in COPD. 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. 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], = 0.41; 16-mg group, -0.72 [-2.33, 0.9], = 0.38; ΔKSS vs. placebo, 8-mg group: 0.11 [-0.7, 0.9], = 0.78; 16-mg group, -0.41 [-1.31, 0.49], = 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. 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).
在慢性阻塞性肺疾病（COPD）中，经常会开具常规低剂量缓释吗啡来治疗持续性呼吸困难。然而，其对日间嗜睡、主观睡眠质量和日间功能的影响尚未得到严格研究。我们旨在确定常规低剂量缓释吗啡对COPD患者睡眠参数的影响。我们对一项随机试验中经过验证的睡眠问卷数据进行了预先设定的二次分析，该试验为期4周，每日服用低剂量缓释吗啡或安慰剂，起始剂量为8或16毫克/天，在2周内进行盲法滴定，最大剂量为32毫克/天。这些分析的主要结局是第1周时吗啡组与安慰剂组的爱泼沃斯嗜睡量表（ESS）和卡罗林斯卡嗜睡量表（KSS）得分。次要结局包括利兹睡眠评估问卷得分（第1周和第4周结束时）、第1周之后的KSS和ESS得分，以及呼吸困难、吗啡与问卷得分之间的关联。156人被随机分组。第1周时，吗啡组与安慰剂组的嗜睡得分无差异（与安慰剂相比，ESS的差值[95%置信区间]：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；与安慰剂相比，KSS的差值，8毫克组：0.11[-0.7, 0.9]，P = 0.78；16毫克组，-0.41[-1.31, 0.49]，P = 0.37）。这种中性效应在后续时间点持续存在。此外，在4周时报告使用吗啡后呼吸困难减轻的参与者，其利兹睡眠评估问卷领域得分（包括主观睡眠质量和日间功能）也有所改善。在COPD中，常规低剂量吗啡用于治疗呼吸困难时不会加重嗜睡。个体使用吗啡后呼吸困难的改善可能与睡眠改善有关。该临床试验已在www.clinicaltrials.gov注册（NCT02720822）。
