澳大利亚伍伦贡大学David C. Currow团队研究了常规低剂量缓释吗啡对慢性阻塞性肺病患者慢性呼吸障碍的影响。相关论文于2022年11月22日发表在《美国医学会杂志》上。

慢性呼吸困难在慢性阻塞性肺病（COPD）患者中很常见。常规、低剂量、缓释吗啡可能会缓解呼吸困难，但需要有关其疗效和剂量的证据。

为了探讨不同剂量缓释吗啡对COPD患者治疗1周后最严重呼吸困难的影响，研究组在澳大利亚的20个中心进行了一项多中心、双盲、安慰剂对照的随机临床试验，招募COPD患者和慢性呼吸困难患者（定义为改良医学研究委员会评分3至4）。患者于2016年9月1日至2019年11月20日期间入组，并随访至2019年12月26日。

在第1周，将受试者按1:1:1随机分组接受8mg/d或16mg/d口服缓释吗啡或安慰剂。在第2周和第3周开始时，将患者按1:1随机分组接受8mg/d的缓释吗啡，并将其添加到前一周的剂量或安慰剂中。

主要结局为8 mg/d和16 mg/d缓释吗啡组治疗第1周（第5至7天）后与安慰剂组相比，使用基线时的平均得分（从第-3至-1天开始），在数值评定量表（评分范围，0分[无]到10分[最差或最强烈]）上最差呼吸强度的变化。次要结局包括使用活动记录仪测量的从基线（第−1） 至第3周（从第19天到第21天）的平均步数变化。

160名随机受试者中，156名纳入初步分析（中位年龄为72岁；48%为女性），138名（88%）在第1周完成治疗（8 mg/d吗啡组48人，16 mg/d吗啡治疗组43人，安慰剂组47人）。8 mg/d吗啡组和安慰剂组或16mg/d吗啡组与安慰剂组之间在第1周时最严重呼吸困难的强度变化均没有显著差异。

在第3周，8mg/d吗啡组和安慰剂组的平均每日步数变化的次要结局平均差异为−1453，16mg/d吗啡组和安慰剂组之间平均差异为−1312，24mg/d吗啡组和安慰剂组之间平均差异为−692，32mg/d吗啡组与安慰剂组之间平均差异为−1924，组间均没有显著差异。

研究结果表明，在患有COPD和严重慢性呼吸困难的人群中，每日低剂量缓释吗啡并没有显著降低治疗1周后最严重呼吸困难的强度。这些发现并不支持使用这些剂量的缓释吗啡来缓解呼吸困难。

附：英文原文

Title: Effect of Regular, Low-Dose, Extended-release Morphine on Chronic Breathlessness in Chronic Obstructive Pulmonary Disease: The BEAMS Randomized Clinical Trial

Author: Magnus Ekstrm, Diana Ferreira, Sungwon Chang, Sandra Louw, Miriam J. Johnson, Danny J. Eckert, Belinda Fazekas, Katherine J. Clark, Meera R. Agar, David C. Currow, Australian National Palliative Care Clinical Studies Collaborative, Christine McDonald, John Miners, Carl Kirkpatrick, Andrew Somogyi, Linda Denehy, Nikki McCaffery, Lawrence Lam, Aine Greene, Brian Le, Katherine Clark, Kwun Fong, Meera Agar, Rohit Joshi, Sharon Kilbreath, Diana Ferreira, Angela Clow, Nina Smith, Richella Ryan, Sara Booth, Peter Martin, Suharsha Kanathigoda, Caitlin Sheehan, Jessica Lee, Peter Allcroft, Erica Cameron-Taylor, Philip Good, Louise Welch, Richard Chye, Jennifer Phillip, John Wheatley, Anu krishnan, Michael Epton, Rajesh Aggarwal, Philip McCloud, Jessie Chan, Douglas Bellamy, Frances Bellemore, Priyanka Bhatarai, Helen Biggins, Mary-Rose Birch, Lesley Burke, Tracey Burns, Naomi Byfieldt, Diana Charlesworth, Gillian Collins, Helen Cooper, Urska Cosic, Deborah Courtney, Georgie Cupples, Anna Dowd, Ruth Dunleavey, Terence Edgar, Amanda Fischer, Lisa Fuhrmeister, Jan Gesling, Rosetta Hart, Kim Hopkinson, Michelle Kaczurowski, Sally Kidd, Ngaire Kingi, Vera Margitanovic, Gillian McCarthy, Robin OReilly

Issue&Volume: 2022/11/22

Abstract:

Importance  Chronic breathlessness is common in people with chronic obstructive pulmonary disease (COPD). Regular, low-dose, extended-release morphine may relieve breathlessness, but evidence about its efficacy and dosing is needed.

Objective  To determine the effect of different doses of extended-release morphine on worst breathlessness in people with COPD after 1 week of treatment.

Design, Setting, and Participants  Multicenter, double-blind, placebo-controlled randomized clinical trial including people with COPD and chronic breathlessness (defined as a modified Medical Research Council score of 3 to 4) conducted at 20 centers in Australia. People were enrolled between September 1, 2016, and November 20, 2019, and followed up through December 26, 2019.

Interventions  People were randomized 1:1:1 to 8 mg/d or 16 mg/d of oral extended-release morphine or placebo during week 1. At the start of weeks 2 and 3, people were randomized 1:1 to 8 mg/d of extended-release morphine, which was added to the prior week’s dose, or placebo.

Main Outcomes and Measures  The primary outcome was change in the intensity of worst breathlessness on a numerical rating scale (score range, 0 [none] to 10 [being worst or most intense]) using the mean score at baseline (from days 3 to 1) to the mean score after week 1 of treatment (from days 5 to 7) in the 8 mg/d and 16 mg/d of extended-release morphine groups vs the placebo group. Secondary outcomes included change in daily step count measured using an actigraphy device from baseline (day 1) to the mean step count from week 3 (from days 19 to 21).

Results  Among the 160 people randomized, 156 were included in the primary analyses (median age, 72 years [IQR, 67 to 78 years]; 48% were women) and 138 (88%) completed treatment at week 1 (48 in the 8 mg/d of morphine group, 43 in the 16 mg/d of morphine group, and 47 in the placebo group). The change in the intensity of worst breathlessness at week 1 was not significantly different between the 8 mg/d of morphine group and the placebo group (mean difference, 0.3 [95% CI, 0.9 to 0.4]) or between the 16 mg/d of morphine group and the placebo group (mean difference, 0.3 [95%, CI, 1.0 to 0.4]). At week 3, the secondary outcome of change in mean daily step count was not significantly different between the 8 mg/d of morphine group and the placebo group (mean difference, 1453 [95% CI, 3310 to 405]), between the 16 mg/d of morphine group and the placebo group (mean difference, 1312 [95% CI, 3220 to 596]), between the 24 mg/d of morphine group and the placebo group (mean difference, 692 [95% CI, 2553 to 1170]), or between the 32 mg/d of morphine group and the placebo group (mean difference, 1924 [95% CI, 47699 to 921]).

Conclusions and Relevance  Among people with COPD and severe chronic breathlessness, daily low-dose, extended-release morphine did not significantly reduce the intensity of worst breathlessness after 1 week of treatment. These findings do not support the use of these doses of extended-release morphine to relieve breathlessness.

DOI: 10.1001/jama.2022.20206

Source: https://jamanetwork.com/journals/jama/article-abstract/2798741