Edwards J E, McQuay H J, Moore R A
Pain Research Unit, Nuffield Department of Anaesthetics, Churchill Hospital, Old Road, Oxford, UK, OX3 7LJ.
Cochrane Database Syst Rev. 2000;2000(4):CD002760. doi: 10.1002/14651858.CD002760.
Dihydrocodeine is a synthetic opioid analgesic developed in the early 1900s. Its structure and pharmacokinetics are similar to that of codeine and it is used for the treatment of postoperative pain or as an antitussive. It is becoming increasingly important to assess the relative efficacy and harm caused by different treatments. Relative efficacy can be determined when an analgesic is compared with control under similar clinical circumstances.
To quantitatively assess the analgesic efficacy and adverse effects of single-dose dihydrocodeine compared with placebo in randomised trials in moderate to severe postoperative pain.
Published reports were identified from a variety of electronic databases including Medline, Biological Abstracts, Embase, the Cochrane Library and the Oxford Pain Relief Database. Additional studies were identified from the reference lists of retrieved reports.
The following inclusion criteria were used: full journal publication, clinical trial, random allocation of patients to treatment groups, double blind design, adult patients, pain of moderate to severe intensity at baseline, postoperative administration of study drugs, treatment arms which included dihydrocodeine and placebo and either oral or injected (intramuscular or intravenous) administration of study drugs.
Data collection and analysis: Summed pain intensity and pain relief data over 4-6 hours were extracted and converted into dichotomous information to yield the number of patients obtaining at least 50% pain relief. This was used to calculate relative benefit and number-needed-to-treat for one patient to obtain at least 50% pain relief. Single-dose adverse effect data were collected and used to calculate relative risk and number-needed-to-harm.
Fifty-two reports were identified as possible randomised trials which assessed dihydrocodeine in postoperative pain. Four reports met the inclusion criteria; all assessed oral dihydrocodeine. Three reports (194 patients) compared dihydrocodeine with placebo and one (120 patients) compared dihydrocodeine (30 mg or 60 mg) with ibuprofen 400 mg. For a single dose of dihydrocodeine 30 mg in moderate to severe postoperative pain the NNT for at least 50% pain relief was 8.1 (95% confidence interval 4.1 to 540) when compared with placebo over a period of 4-6 hours. Pooled data showed significantly more patients to have reported adverse effects with dihydrocodeine 30 mg than with placebo. When compared to ibuprofen 400 mg both dihydrocodeine 30 mg and 60 mg were significantly inferior.
REVIEWER'S CONCLUSIONS: A single 30 mg dose of dihydrocodeine is not sufficient to provide adequate pain relief in postoperative pain. Statistical superiority of ibuprofen 400 mg over dihydrocodeine (30 mg or 60 mg) was shown.
二氢可待因是20世纪初研发的一种合成阿片类镇痛药。其结构和药代动力学与可待因相似,用于治疗术后疼痛或作为镇咳药。评估不同治疗方法的相对疗效和危害变得越来越重要。当在相似临床情况下将一种镇痛药与对照进行比较时,可以确定相对疗效。
在中度至重度术后疼痛的随机试验中,定量评估单剂量二氢可待因与安慰剂相比的镇痛效果和不良反应。
从包括Medline、生物学文摘、Embase、Cochrane图书馆和牛津疼痛缓解数据库在内的各种电子数据库中识别已发表的报告。从检索报告的参考文献列表中识别其他研究。
采用以下纳入标准:完整的期刊发表、临床试验、将患者随机分配至治疗组、双盲设计、成年患者、基线时为中度至重度疼痛、术后给予研究药物、治疗组包括二氢可待因和安慰剂以及口服或注射(肌肉注射或静脉注射)研究药物。
数据收集与分析:提取4至6小时内的疼痛强度总和及疼痛缓解数据,并将其转换为二分信息,以得出至少获得50%疼痛缓解的患者数量。这用于计算相对获益和一名患者获得至少50%疼痛缓解所需的治疗人数。收集单剂量不良反应数据并用于计算相对风险和伤害所需人数。
52篇报告被确定为可能评估二氢可待因在术后疼痛中的随机试验。4篇报告符合纳入标准;均评估口服二氢可待因。3篇报告(194例患者)将二氢可待因与安慰剂进行比较,1篇报告(120例患者)将二氢可待因(30毫克或60毫克)与400毫克布洛芬进行比较。对于中度至重度术后疼痛单剂量30毫克二氢可待因,与安慰剂相比,在4至6小时内至少获得50%疼痛缓解的所需治疗人数为8.1(95%置信区间4.1至540)。汇总数据显示,报告服用30毫克二氢可待因出现不良反应的患者明显多于服用安慰剂的患者。与400毫克布洛芬相比,30毫克和60毫克二氢可待因均明显较差。
单剂量30毫克二氢可待因不足以在术后疼痛中提供充分的疼痛缓解。显示400毫克布洛芬在统计学上优于二氢可待因(30毫克或60毫克)。