Derry Sheena, Moore R Andrew, McQuay Henry J
Pain Research and Nuffield Department of Anaesthetics, University of Oxford, West Wing (Level 6), John Radcliffe Hospital, Oxford, Oxfordshire, UK, OX3 9DU.
Cochrane Database Syst Rev. 2010 Apr 14;2010(4):CD008099. doi: 10.1002/14651858.CD008099.pub2.
Codeine is an opioid metabolised to active analgesic compounds, including morphine. It is widely available by prescription, and combination drugs including low doses of codeine are commonly available without prescription.
To assess the efficacy, the time to onset of analgesia, the time to use of rescue medication and any associated adverse events of single dose oral codeine in acute postoperative pain.
We searched CENTRAL, MEDLINE, EMBASE and PubMed to November 2009.
Single oral dose, randomised, double-blind, placebo-controlled trials of codeine for relief of established moderate to severe postoperative pain in adults.
Studies were assessed for methodological quality and data independently extracted by two review authors. Summed total pain relief (TOTPAR) or pain intensity difference (SPID) over 4 to 6 hours were used to calculate the number of participants achieving at least 50% pain relief, which were used to calculate, with 95% confidence intervals, the relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over 4 to 6 hours. Numbers using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Data on adverse events and withdrawals were collected.
Thirty-five studies were included (1223 participants received codeine 60 mg, 27 codeine 90 mg, and 1252 placebo). Combining all types of surgery (33 studies, 2411 participants), codeine 60 mg had an NNT of at least 50% pain relief over 4 to 6 hours of 12 (8.4 to 18) compared with placebo. At least 50% pain relief was achieved by 26% on codeine 60 mg and 17% on placebo.Following dental surgery the NNT was 21 (12 to 96) (15 studies, 1146 participants), and following other types of surgery the NNT was 6.8 (4.6 to 13) (18 studies, 1265 participants). The NNT to prevent use of rescue medication within 4 to 6 hours was 11 (6.3 to 50) (11 studies, 765 participants, mostly non-dental); the mean time to its use was 2.7 hours with codeine and 2.0 hours with placebo. More participants experienced adverse events with codeine 60 mg than placebo; the difference was not significant and none were serious. Two adverse event withdrawals occurred with placebo.
AUTHORS' CONCLUSIONS: Single dose codeine 60 mg provides good analgesia to few individuals, and does not compare favourably with commonly used alternatives such as paracetamol, NSAIDs and their combinations with codeine, especially after dental surgery; the large difference between dental and other surgery was unexpected. Higher doses were not evaluated.
可待因是一种阿片类药物,可代谢为活性镇痛化合物,包括吗啡。它通过处方广泛可得,并且含低剂量可待因的复方药物通常无需处方即可获得。
评估单剂量口服可待因用于急性术后疼痛的疗效、镇痛起效时间、使用解救药物的时间以及任何相关不良事件。
我们检索了截至2009年11月的Cochrane系统评价数据库、医学期刊数据库、荷兰医学文摘数据库和美国国立医学图书馆医学期刊数据库。
关于可待因单剂量口服用于缓解成人已确诊的中度至重度术后疼痛的随机、双盲、安慰剂对照试验。
评估研究的方法学质量,由两位综述作者独立提取数据。使用4至6小时内的总疼痛缓解量(TOTPAR)或疼痛强度差值(SPID)来计算至少实现50%疼痛缓解的参与者数量,用于计算与安慰剂相比的相对获益以及让一名参与者在4至6小时内至少实现50%疼痛缓解所需治疗的人数(NNT)。寻求特定时间段内使用解救药物的人数以及使用解救药物的时间作为疗效的额外衡量指标。收集不良事件和退出研究的数据。
纳入35项研究(1223名参与者接受60毫克可待因,27名接受90毫克可待因,1252名接受安慰剂)。综合所有类型的手术(33项研究,2411名参与者),与安慰剂相比,60毫克可待因在4至6小时内实现至少50%疼痛缓解的NNT为12(8.4至18)。60毫克可待因组有26%的参与者、安慰剂组有17%的参与者至少实现了50%的疼痛缓解。牙科手术后NNT为21(12至96)(15项研究,1146名参与者),其他类型手术后NNT为6.8(4.6至13)(18项研究,1265名参与者)。在4至6小时内预防使用解救药物的NNT为11(6.3至50)(11项研究,765名参与者,大多为非牙科手术);使用可待因时使用解救药物的平均时间为2.7小时,使用安慰剂时为2.0小时。与安慰剂相比,更多使用60毫克可待因的参与者出现不良事件;差异不显著,且均不严重。安慰剂组有两例因不良事件退出研究。
单剂量60毫克可待因仅对少数个体提供良好镇痛效果,与对乙酰氨基酚、非甾体抗炎药及其与可待因的复方制剂等常用替代药物相比并无优势,尤其是在牙科手术后;牙科手术和其他手术之间的巨大差异出乎意料。未评估更高剂量。