Currow David C, Plummer John L, Cooney Neil J, Gorman David, Glare Paul A
Department of Palliative and Supportive Services , Flinders University, South Australia.
J Pain Symptom Manage. 2007 Jul;34(1):17-23. doi: 10.1016/j.jpainsymman.2006.10.011.
Diurnal variation in pain perception is recognized. The question of whether opioid prescribing should be adjusted to account for diurnal variation can be tested with the advent of once-daily sustained-release morphine. The study recruited 45 people with opioid-responsive pain on stable doses of analgesics and advanced cancer from five regional palliative care programs in Australia. Each participant took one placebo and a 24-hourly dose of sustained-release morphine daily, 12 hours apart-active dose in the morning for one week and in the evening for the other week. The order of the weeks was randomized in a double-blind manner. The primary outcome from the last two days (steady state) on both arms was averaged four-hourly pain scores while awake on a 100 mm visual analogue scale (VAS). Secondary outcomes included VAS and categorical scales for other pain parameters, quality of sleep, nausea, vomiting, constipation, confusion, and somnolence. Twenty-six of 42 participants completed the study and provided adequate power for analysis. Mean VAS was 16 mm for morning dosing and 14 mm for evening dosing (P=0.76, difference of adjusted means 2 mm, 95% confidence interval: -2, 6). No differences were found in pain control, pain during the day, pain disturbing sleep, or with breakthrough medication use. This study suggests that any difference between morning and evening dosing of once-daily sustained-release morphine in people with significant opioid-responsive pain and advanced cancer is small and unlikely to be clinically significant for most people.
疼痛感知的昼夜变化是公认的。随着每日一次缓释吗啡的出现，可以检验阿片类药物处方是否应根据昼夜变化进行调整。该研究从澳大利亚五个地区姑息治疗项目中招募了45名使用稳定剂量镇痛药且患有晚期癌症的阿片类药物反应性疼痛患者。每位参与者每天服用一片安慰剂和一剂24小时剂量的缓释吗啡，两者间隔12小时——一周在早上服用活性剂量，另一周在晚上服用。两周的顺序以双盲方式随机安排。双臂上最后两天（稳态）的主要结局是在100毫米视觉模拟量表（VAS）上清醒时每四小时的平均疼痛评分。次要结局包括用于其他疼痛参数、睡眠质量、恶心、呕吐、便秘、意识模糊和嗜睡的VAS和分类量表。42名参与者中有26名完成了研究并提供了足够的分析效力。早上给药时的平均VAS为16毫米，晚上给药时为14毫米（P = 0.76，调整后均值差异为2毫米，95%置信区间：-2, 6）。在疼痛控制、白天疼痛、干扰睡眠的疼痛或突破性药物使用方面未发现差异。这项研究表明，对于患有严重阿片类药物反应性疼痛和晚期癌症的患者，每日一次缓释吗啡早晚给药之间的任何差异都很小，对大多数人来说不太可能具有临床意义。
