Centre for Reviews and Dissemination, University of York, York, UK.
Health Technol Assess. 2010 Mar;14(17):1-153, iii-iv. doi: 10.3310/hta14170.
To determine which class of non-opioid analgesics - paracetamol (acetaminophen), NSAIDs or COX-2 inhibitors - is the most effective at reducing morphine consumption and associated adverse effects when used as part of multimodal analgesia following major surgery.
A systematic literature review was conducted using MEDLINE, EMBASE and CENTRAL databases, searched from January 2003 to February 2009 and updating an earlier review.
Randomised controlled trials comparing paracetamol, NSAIDs or COX-2 inhibitors to each other or placebo, in adults receiving patient-controlled analgesia (PCA) with morphine following major surgery, were included. The COX-2 inhibitors rofecoxib and valdecoxib were excluded. Only trials that reported 24-hour morphine consumption were included. Other outcomes of interest were morphine-related adverse effects and adverse effects related to the non-opioids. Adequacy of randomisation, concealment of allocation, double blinding, and the flow of patients within the trial was assessed. The main analysis was a mixed treatment comparison (MTC) evaluating the relative effects of the four treatment classes. Four main outcomes were prioritised: 24-hour morphine consumption, sedation, nausea and vomiting, and surgical bleeding. Studies reporting nausea alone were pooled with studies reporting postoperative nausea and vomiting (PONV). Comparisons were described as statistically significant (at 5% level) when the credibility interval (CrI) did not cross 1 for odds ratio (OR) and zero for mean difference (MD). Trials making direct comparisons between the active interventions were also pooled in a meta-analysis using a random effects model. Sensitivity analyses were performed to assess the effects of study quality, individual drugs, and baseline morphine consumption.
Sixty relevant studies were identified. When paracetamol, NSAIDs or COX-2 inhibitors were added to PCA morphine, there was a statistically significant reduction in morphine consumption: paracetamol (MD -6.34 mg; 95% CrI -9.02 to -3.65); NSAIDs (MD -10.18; 95% CrI -11.65 to -8.72); and COX-2 inhibitors (MD -10.92; 95% CrI -12.77 to -9.08). NSAIDs and COX-2 inhibitors were both significantly better than paracetamol, and there was no significant difference between NSAIDs and COX-2 inhibitors (MD -0.74; 95% CrI -3.03 to 1.56). There was a significant reduction in nausea and PONV with NSAIDs compared to placebo (OR 0.70; 95% CrI 0.53 to 0.88) but not for paracetamol or COX-2 inhibitors, nor for NSAIDs compared to paracetamol or COX-2 inhibitors.
24-hour morphine consumption decreased by 6.3 mg to 10.9 mg, compared to placebo, when paracetamol, NSAID or COX-2 inhibitors were added to PCA morphine following surgery. Differences in effect between the three drug classes were small and unlikely to be of clinical significance. There does not appear to be a strong case for recommending routine addition of any of the three non-opioids to PCA morphine in the 24 hours immediately after surgery, or for favouring one drug class above the others.
确定在术后立即使用的 24 小时内，哪类非阿片类镇痛药（扑热息痛、非甾体抗炎药或 COX-2 抑制剂）在作为多模式镇痛的一部分与吗啡联合使用时，减少吗啡消耗和相关不良反应的效果最佳。
系统检索了 2003 年 1 月至 2009 年 2 月的 MEDLINE、EMBASE 和 CENTRAL 数据库，并对早期的综述进行了更新。
纳入了比较扑热息痛、非甾体抗炎药或 COX-2 抑制剂与其他药物或安慰剂，在接受术后自控镇痛（PCA）的成年人中，在大手术后使用吗啡的随机对照试验。COX-2 抑制剂罗非昔布和伐地昔布被排除在外。只纳入了报告 24 小时吗啡消耗量的试验。其他感兴趣的结果是与吗啡相关的不良反应和与非阿片类药物相关的不良反应。评估了随机分组的充分性、分组隐藏、双盲、以及试验内患者的流程。主要分析是一种混合治疗比较（MTC），评估了四种治疗类别之间的相对效果。有四个主要结果被优先考虑：24 小时吗啡消耗量、镇静、恶心和呕吐以及手术出血。仅报告恶心的研究与报告术后恶心和呕吐（PONV）的研究合并。当可信度区间（CrI）没有跨越比值比（OR）的 1 和均数差（MD）的 0 时，将比较描述为具有统计学意义（在 5%水平）。也使用随机效应模型对直接比较活性干预措施的试验进行了汇总分析。进行了敏感性分析，以评估研究质量、个别药物和基线吗啡消耗的影响。
确定了 60 项相关研究。当扑热息痛、非甾体抗炎药或 COX-2 抑制剂与 PCA 吗啡联合使用时，吗啡消耗明显减少：扑热息痛（MD -6.34 mg；95%CrI -9.02 至 -3.65）；非甾体抗炎药（MD -10.18；95%CrI -11.65 至 -8.72）；COX-2 抑制剂（MD -10.92；95%CrI -12.77 至 -9.08）。非甾体抗炎药和 COX-2 抑制剂均明显优于扑热息痛，而非甾体抗炎药和 COX-2 抑制剂之间无显著差异（MD -0.74；95%CrI 3.03 至 1.56）。与安慰剂相比，非甾体抗炎药可显著减少恶心和 PONV（OR 0.70；95%CrI 0.53 至 0.88），但扑热息痛或 COX-2 抑制剂无此作用，也没有非甾体抗炎药与扑热息痛或 COX-2 抑制剂之间的差异。
与安慰剂相比，扑热息痛、非甾体抗炎药或 COX-2 抑制剂与 PCA 吗啡联合使用时，术后 24 小时吗啡消耗减少 6.3 mg 至 10.9 mg。三种药物类别的效果差异很小，不太可能具有临床意义。在术后立即使用的 24 小时内，似乎没有强有力的理由推荐常规添加任何三种非阿片类药物中的一种与 PCA 吗啡联合使用，也没有理由偏爱一种药物类别而不是其他药物类别。
