Faculty of Medicine and Health, School of Public Health.
Institute for Musculoskeletal Health, Sydney Local Health District, Sydney, NSW, Australia.
Clin J Pain. 2019 Oct;35(10):836-843. doi: 10.1097/AJP.0000000000000746.
To investigate the efficacy and safety of combination analgesic products containing low-dose codeine (up to 30 mg/dose) for pain.
Electronic databases were used to identify eligible placebo-controlled, randomized controlled trials (RCTs). Two authors extracted data and assessed the risk of bias. Data were pooled using a random-effects model with the strength of evidence assessed using Grading of Recommendations Assessment, Development and Evaluation. The primary outcome was immediate pain relief (3 hours post administration) on a 0 to 100 pain scale.
Ten RCTs were eligible. There is low-quality evidence (4 RCTs, n=211 participants) that a single dose of a combination analgesic product (with an nonsteroidal anti-inflammatory) containing low-dose codeine (15 to 30 mg) provides small pain relief for acute dental pain (mean difference [MD], -12.7; 95% confidence interval [CI], -18.5 to -6.9) and moderate-quality evidence (1 RCT, n=93) of small pain relief for post-episiotomy pain and orthopedic surgery pain (MD,, -10.0; 95% CI, -19.0 to -1.0 and MD, -11.0; 95% CI, -20.7 to -1.3), respectively. There is low-quality evidence (1 RCT, n=80) that a multiple-dose regimen provides small pain relief for acute pain following photorefractive keratectomy (MD, -16.0; 95% CI, -24.5 to -7.5) and moderate-quality evidence of moderate pain relief for certain chronic pain conditions: for hip osteoarthritis (MD, -19.0; 95% CI, -31.2 to -6.8) and for temporomandibular joint pain (MD, -26.0; 95% CI, -44.5 to -7.5). Two studies reported a higher incidence of drowsiness in the treatment group compared with the placebo group (relative risk, 8.50; 95% CI, 1.96, 36.8 and 19.3; 95% CI, 1.2-306.5, respectively).
There is low to moderate level evidence that combination analgesic products containing low-dose codeine provide small to moderate pain relief for acute and chronic pain conditions in the immediate short term with limited trial data on use beyond 24 hours. Further research examining regular use of these medicines is needed with more emphasis on measuring potential harmful effects.
研究含低剂量可待因（每次剂量不超过 30 毫克）的复方镇痛药治疗疼痛的疗效和安全性。
电子数据库用于确定合格的安慰剂对照、随机对照试验（RCT）。两位作者提取数据并评估偏倚风险。使用随机效应模型对数据进行汇总，并使用推荐评估、制定和评估（Grading of Recommendations Assessment, Development and Evaluation，GRADE）评估证据强度。主要结局是在 0 到 100 的疼痛量表上评估给药后 3 小时即刻止痛。
10 项 RCT 符合条件。有低质量证据（4 项 RCT，211 名参与者）表明，单次使用含有低剂量可待因（15 至 30 毫克）的复方镇痛药（与非甾体抗炎药合用）可轻度缓解急性牙痛（平均差异[MD]，-12.7；95%置信区间[CI]，-18.5 至-6.9）和中质量证据（1 项 RCT，93 名参与者）表明，术后切口痛和骨科手术后疼痛的疼痛缓解程度较小（MD，-10.0；95%CI，-19.0 至-1.0 和 MD，-11.0；95%CI，-20.7 至-1.3）。有低质量证据（1 项 RCT，80 名参与者）表明，多剂量方案可轻度缓解光折射性角膜切除术（PRK）后急性疼痛，中度质量证据表明某些慢性疼痛状况中度缓解疼痛：髋关节骨关节炎（MD，-19.0；95%CI，-31.2 至-6.8）和颞下颌关节疼痛（MD，-26.0；95%CI，-44.5 至-7.5）。两项研究报告称，治疗组与安慰剂组相比，嗜睡发生率更高（相对风险，8.50；95%CI，1.96，36.8 和 19.3；95%CI，1.2-306.5）。
有低到中等质量的证据表明，含低剂量可待因的复方镇痛药可在短期即刻缓解急性和慢性疼痛状况，但 24 小时后使用的试验数据有限，关于这些药物的常规使用还需要进一步研究，更应注重测量潜在的有害影响。
