Discipline, Palliative and Supportive Services, Flinders University, Bedford Park, SA, Australia.
J Pain Symptom Manage. 2011 Sep;42(3):388-99. doi: 10.1016/j.jpainsymman.2010.11.021. Epub 2011 Mar 31.
Randomized controlled trials can answer questions of efficacy, but long-term pharmacovigilance studies generate complementary safety data.
Level I evidence supports short-term efficacy of opioids in reducing chronic refractory dyspnea. This study aimed to determine the minimum effective once-daily dose of sustained-release morphine, and whether net clinical benefits are sustained safely.
In a Phase II dose increment study, 10mg daily of sustained-release morphine was administered, and increased in nonresponders by 10mg daily each week to a maximum of 30 mg daily. The participant was withdrawn if there were unacceptable side effects or no response to maximum dose. If participants had a 10% improvement in dyspnea over their own baseline, they joined a long-term Phase IV effectiveness/safety study at that dose. Complying with Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines, response and side effects are described, with demographic and clinical characteristics of responders.
Eighty-three participants (53 males, mean age 75 years, 54% with chronic obstructive pulmonary disease) provided more than 30 patient-years of data. Fifty-two participants derived ≥ 10% benefit (on average 35% improvement over baseline), giving a response rate of 62% (number needed to treat of 1.6: number needed to harm 4.6); for 70%, this dose was 10mg/24h. Benefit was maintained at three months for 28 (33%) people. Ranking of breathlessness was reduced significantly (P<0.001), but constipation increased (P<0.001) despite laxatives. There were no episodes of respiratory depression or hospitalizations as a result of the sustained-release morphine. Overall, one in three people continued to derive benefit at three months.
Ten milligrams of sustained-release oral morphine once daily is safe and effective for most people who respond.
随机对照试验可以解答疗效问题，但长期药物警戒研究提供了补充安全性数据。
一级证据支持阿片类药物短期缓解慢性难治性呼吸困难的疗效。本研究旨在确定控释吗啡的最低有效日剂量，以及是否安全维持净临床获益。
在一项 2 期剂量递增研究中，给予 10mg 每日的控释吗啡，无应答者每周增加 10mg 每日，最大剂量至 30mg 每日。如果出现不可接受的副作用或最大剂量无反应，则退出研究。如果参与者呼吸困难较基线改善 10%，则在该剂量下加入长期 4 期有效性/安全性研究。根据加强观察性研究报告的流行病学（STROBE）指南，描述了应答和副作用，以及应答者的人口统计学和临床特征。
83 名参与者（53 名男性，平均年龄 75 岁，54%患有慢性阻塞性肺疾病）提供了超过 30 患者年的数据。52 名参与者获益≥10%（平均基线改善 35%），应答率为 62%（治疗人数比 1.6：需要损害的人数 4.6）；对于 70%的人，这个剂量是 10mg/24h。28 人（33%）在三个月时保持获益。呼吸困难的排序显著降低（P<0.001），但尽管使用了泻药，便秘仍增加（P<0.001）。没有因控释吗啡而出现呼吸抑制或住院的情况。总体而言，三分之一的人在三个月时仍继续获益。
大多数应答者每日口服 10mg 控释吗啡是安全有效的。
