Neal B, Rodgers A, Dunn L, Fransen M
Institute for International Health, University of Sydney, PO Box 1225, Crow's Nest, Sydney, New South Wales, Australia, 1585.
Cochrane Database Syst Rev. 2000(3):CD001160. doi: 10.1002/14651858.CD001160.
Heterotopic bone formation (HBF) in the soft tissues surrounding the hip joint is a frequent complication of hip surgery. Non-steroidal anti-inflammatory drugs (NSAIDs) administered in the immediate perioperative period reduce the risk of HBF. However, the magnitude of the effect on HBF, and the effects on other associated outcomes are uncertain.
To determine the effects of perioperative NSAID therapy versus control on the risk of HBF and other outcomes in patients undergoing hip arthroplasty.
Medline, Current Contents and Cochrane Controlled Trials Register, and reference lists of all relevant reports were searched. Principal investigators and the manufacturers of the study drugs of eligible trials were approached. The most recent search was conducted in July 1998.
All trials which enrolled patients scheduled to undergo hip arthroplasty with random or quasi-random allocation to perioperative NSAID or control and that recorded post-operative radiographically determined HBF. The primary outcome was post-operative radiographic HBF. Secondary outcomes were pain, disability, gastro-intestinal and other bleeding complications, and other causes of major morbidity or mortality.
Two reviewers independently assessed methodological quality and extracted data. All analyses were conducted on dichotomised outcomes.
Twelve randomised and two quasi-randomised trials involving a total of 4,377 patients were included. Overall, in 13 trials that examined the effects of medium to high doses of NSAIDs, there was a reduced risk of developing HBF after hip surgery (62% reduction, 95% confidence interval 56% to 67% reduction). In contrast, one large trial examining low-dose aspirin, demonstrated no effect on the risk of HBF (2% reduction, 95% confidence interval 15% reduction to 12% increase). There was strong evidence of differences in the size of the treatment effects observed between the trials examining medium to high doses of NSAIDs, but reasons were not clearly identified. There was a non-significant one third increased risk of gastro-intestinal side effects among patients assigned NSAIDs (29% increase, 95% confidence interval 5% reduction to 76% increase). Most of this increase was due to an increased risk of minor gastro-intestinal complications. Data on the late post-operative outcomes of pain, impaired physical function and range of joint movement were few and no formal overviews of the effects of NSAIDs on these outcomes were possible.
REVIEWER'S CONCLUSIONS: Perioperative NSAIDs appear to produce between a one half and two thirds reduction in the risk of HBF. With routine use, such agents may be able to prevent 15-20 cases of HBF (3-4 severe) among every 100 total hip replacements performed. However, while medium to high doses of perioperative NSAIDs clearly produce a substantial reduction in the incidence of radiographic HBF, there remains some uncertainty about short-term side effects of treatment and substantial uncertainty about effects on long-term clinical outcomes such as chronic pain and impaired physical function. The net effect of routine HBF prophylaxis with NSAIDs requires formal assessment in a randomised trial designed to determine the balance of benefits and risks for all outcomes.
髋关节周围软组织的异位骨化（HBF）是髋关节手术常见的并发症。围手术期即刻使用非甾体抗炎药（NSAIDs）可降低HBF的风险。然而，其对HBF的影响程度以及对其他相关结局的影响尚不确定。
确定围手术期NSAIDs治疗与对照相比，对接受髋关节置换术患者发生HBF及其他结局的风险的影响。
检索了医学索引数据库（Medline）、《现刊目次》、Cochrane对照试验注册库以及所有相关报告的参考文献列表。联系了符合条件试验的主要研究者和研究药物的制造商。最近一次检索于1998年7月进行。
所有纳入计划接受髋关节置换术患者的试验，采用随机或半随机分配至围手术期NSAIDs组或对照组，并记录术后经影像学确定的HBF情况。主要结局是术后影像学HBF。次要结局包括疼痛、残疾、胃肠道及其他出血并发症，以及其他主要发病或死亡原因。
两名评价者独立评估方法学质量并提取数据。所有分析均基于二分法结局进行。
纳入了12项随机试验和2项半随机试验，共4377例患者。总体而言，在13项研究中、高剂量NSAIDs效果的试验中，髋关节手术后发生HBF的风险降低（降低62%，95%可信区间为降低56%至67%）。相比之下，一项研究低剂量阿司匹林的大型试验显示对HBF风险无影响（降低2%，95%可信区间为降低15%至增加12%）。有强有力的证据表明，在研究中、高剂量NSAIDs的试验中观察到的治疗效果大小存在差异，但原因尚不清楚。使用NSAIDs的患者发生胃肠道副作用的风险有非显著性的三分之一增加（增加29%，95%可信区间为降低5%至增加76%）。这种增加主要是由于轻微胃肠道并发症风险增加。关于术后晚期疼痛、身体功能受损和关节活动范围的结局数据较少，无法对NSAIDs对这些结局的影响进行正式综述。
围手术期NSAIDs似乎可使HBF风险降低一半至三分之二。常规使用此类药物每100例全髋关节置换中可能预防15 - 20例HBF（3 - 4例严重HBF）。然而，虽然围手术期中、高剂量NSAIDs明显使影像学HBF的发生率大幅降低，但治疗的短期副作用仍存在一些不确定性，对慢性疼痛和身体功能受损等长期临床结局的影响也存在很大不确定性。NSAIDs常规预防HBF的净效应需要在一项旨在确定所有结局的利弊平衡的随机试验中进行正式评估。
