Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
University of Warwick, Warwick, UK.
Cochrane Database Syst Rev. 2023 Oct 24;10(10):CD013584. doi: 10.1002/14651858.CD013584.pub2.
Organ injury is a common and severe complication of cardiac surgery that contributes to the majority of deaths. There are no effective treatment or prevention strategies. It has been suggested that innate immune system activation may have a causal role in organ injury. A wide range of organ protection interventions targeting the innate immune response have been evaluated in randomised controlled trials (RCTs) in adult cardiac surgery patients, with inconsistent results in terms of effectiveness.
The aim of the review was to summarise the results of RCTs of organ protection interventions targeting the innate immune response in adult cardiac surgery. The review considered whether the interventions had a treatment effect on inflammation, important clinical outcomes, or both.
CENTRAL, MEDLINE, Embase, conference proceedings and two trial registers were searched on October 2022 together with reference checking to identify additional studies.
RCTs comparing organ protection interventions targeting the innate immune response versus placebo or no treatment in adult patients undergoing cardiac surgery where the treatment effect on innate immune activation and on clinical outcomes of interest were reported.
Searches, study selection, quality assessment, and data extractions were performed independently by pairs of authors. The primary inflammation outcomes were peak IL-6 and IL-8 concentrations in blood post-surgery. The primary clinical outcome was in-hospital or 30-day mortality. Treatment effects were expressed as risk ratios (RR) and standardised mean difference (SMD) with 95% confidence intervals (CI). Meta-analyses were performed using random effects models, and heterogeneity was assessed using I.
A total of 40,255 participants from 328 RCTs were included in the synthesis. The effects of treatments on IL-6 (SMD -0.77, 95% CI -0.97 to -0.58, I = 92%) and IL-8 (SMD -0.92, 95% CI -1.20 to -0.65, I = 91%) were unclear due to heterogeneity. Heterogeneity for inflammation outcomes persisted across multiple sensitivity and moderator analyses. The pooled treatment effect for in-hospital or 30-day mortality was RR 0.78, 95% CI 0.68 to 0.91, I = 0%, suggesting a significant clinical benefit. There was little or no treatment effect on mortality when analyses were restricted to studies at low risk of bias. Post hoc analyses failed to demonstrate consistent treatment effects on inflammation and clinical outcomes. Levels of certainty for pooled treatment effects on the primary outcomes were very low.
AUTHORS' CONCLUSIONS: A systematic review of RCTs of organ protection interventions targeting innate immune system activation did not resolve uncertainty as to the effectiveness of these treatments, or the role of innate immunity in organ injury following cardiac surgery.
器官损伤是心脏手术中常见且严重的并发症，是大多数死亡的原因。目前尚无有效的治疗或预防策略。有研究表明，固有免疫系统的激活可能在器官损伤中起因果作用。已有大量针对固有免疫反应的器官保护干预措施的随机对照试验（RCT）在成人心脏手术患者中进行了评估，但在有效性方面的结果并不一致。
本综述旨在总结针对成人心脏手术中固有免疫反应的器官保护干预措施的 RCT 结果。该综述考虑了这些干预措施是否对炎症、重要临床结局或两者均有治疗作用。
于 2022 年 10 月，通过 CENTRAL、MEDLINE、Embase、会议论文集和两个试验登记处进行检索，并通过参考文献检查来确定其他研究。
比较针对固有免疫反应的器官保护干预措施与安慰剂或无治疗的 RCT，纳入在成人心脏手术患者中进行的 RCT，报告干预措施对固有免疫激活和感兴趣的临床结局的治疗效果。
由两名作者独立进行检索、研究选择、质量评估和数据提取。主要炎症结局为术后血液中 IL-6 和 IL-8 的峰值浓度。主要临床结局为院内或 30 天死亡率。治疗效果以风险比（RR）和标准化均数差（SMD）表示，置信区间（CI）为 95%。使用随机效应模型进行荟萃分析，并使用 I 评估异质性。
共有来自 328 项 RCT 的 40255 名参与者纳入本研究。由于存在异质性，治疗对 IL-6（SMD-0.77，95%CI-0.97 至-0.58，I=92%）和 IL-8（SMD-0.92，95%CI-1.20 至-0.65，I=91%）的影响并不明确。异质性在多项敏感性和调节因素分析中仍然存在。院内或 30 天死亡率的汇总治疗效果为 RR 0.78，95%CI 0.68 至 0.91，I=0%，表明具有显著的临床获益。当分析仅限于低偏倚风险的研究时，对死亡率的治疗效果较小或没有。事后分析未能证明炎症和临床结局的一致治疗效果。汇总治疗效果的确定性水平非常低。
对针对固有免疫系统激活的器官保护干预措施的 RCT 进行系统回顾，并未解决这些治疗方法有效性的不确定性，或固有免疫在心脏手术后器官损伤中的作用。
