Division of Nephrology, Department of Pediatrics, University of Alberta, 2B2-42 WC Mackenzie Health Sciences Centre, Edmonton, Alberta T6G 2R7, Canada.
Crit Care. 2009;13(5):R165. doi: 10.1186/cc8135. Epub 2009 Oct 20.
Induction of an inflammatory response is thought to have a significant role in the complications that follow cardiopulmonary bypass (CPB). The statin drugs are increasingly being recognized as having potent anti-inflammatory effects and hence have potential to influence an important mechanism of injury in CPB, although there is no current confirmation that this is indeed the case. Our objective was to systematically review if pre-operative prophylactic statin therapy, compared with placebo or standard of care, can decrease the inflammatory response in people undergoing heart surgery with CPB.
We performed a systematic and comprehensive literature search for all randomized controlled trials (RCTs) of open heart surgery with CPB in adults or children who received prophylactic statin treatment prior to CPB, with reported outcomes which included markers of inflammation. Two authors independently identified eligible studies, extracted data, and assessed study quality using standardized instruments. Weighted mean difference (WMD) was the primary summary statistic with data pooled using a random effects model. Descriptive analysis was used when data could not be pooled.
Eight RCTs were included in the review, with the number of trials for each inflammatory outcome being even more limited. Pooled data demonstrated benefit with the use of statin to attenuate the post-CPB increase in interleukins 6 and 8 (IL-6, IL-8), peak high sensitivity C-reactive protein (hsCRP), and tumor necrosis factor-alpha (TNF-alpha) post-CPB (WMD [95% confidence interval (CI)] -23.5 pg/ml [-36.6 to -10.5]; -23.4 pg/ml [-35.8 to -11.0]; -15.3 mg/L [CI -26.9 to -3.7]; -2.10 pg/ml [-3.83 to -0.37] respectively). Very limited RCT evidence suggests that prophylactic statin therapy may also decrease adhesion molecules following CPB including neutrophil CD11b and soluble P (sP)-selectin.
Although the RCT evidence may suggest a reduction in post-CPB inflammation by statin therapy, the evidence is not definitive due to significant limitations. Several of the trials were not methodologically rigorous and statin intervention was highly variable in this small number of studies. This systematic review demonstrates that there is a significant gap that exists in the current literature in regards to the potential anti-inflammatory effect of statin therapy prior to CPB.
人们认为，心肺转流术（CPB）后引发的炎症反应在其并发症中起着重要作用。他汀类药物的抗炎作用越来越受到重视，因此有可能影响 CPB 中的重要损伤机制，尽管目前尚无证据表明确实如此。我们的目的是系统地回顾术前预防性他汀类药物治疗与安慰剂或标准治疗相比，是否可以降低接受 CPB 心脏手术的患者的炎症反应。
我们对所有接受 CPB 心脏手术的成人或儿童的随机对照试验（RCT）进行了系统和全面的文献检索，这些 RCT 中患者在 CPB 前接受了预防性他汀类药物治疗，并报告了包括炎症标志物在内的治疗结果。两位作者独立确定了合格的研究，提取数据，并使用标准化工具评估了研究质量。主要汇总统计数据是加权均数差（WMD），并使用随机效应模型对数据进行汇总。当数据无法汇总时，使用描述性分析。
本综述共纳入了 8 项 RCT，每个炎症结果的试验数量更为有限。汇总数据表明，使用他汀类药物减轻 CPB 后白细胞介素 6（IL-6）和 8（IL-8）、峰值高敏 C 反应蛋白（hsCRP）和肿瘤坏死因子-α（TNF-α）的增加具有益处（WMD [95%置信区间（CI）] -23.5 pg/ml [-36.6 至 -10.5]；-23.4 pg/ml [-35.8 至 -11.0]；-15.3 mg/L [CI -26.9 至 -3.7]；-2.10 pg/ml [-3.83 至 -0.37]）。有限的 RCT 证据表明，预防性他汀类药物治疗也可能减少 CPB 后的粘附分子，包括中性粒细胞 CD11b 和可溶性 P（sP）-选择素。
尽管 RCT 证据表明他汀类药物治疗可降低 CPB 后的炎症反应，但由于存在严重局限性，证据并不明确。这些试验中有几个在方法学上不够严格，并且在为数不多的研究中他汀类药物的干预措施差异很大。本系统评价表明，CPB 前他汀类药物治疗的潜在抗炎作用在当前文献中存在显著差距。
