Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India.
School of Pharmacy and Medical Sciences, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.
Int J Clin Pract. 2021 Nov;75(11):e14645. doi: 10.1111/ijcp.14645. Epub 2021 Aug 4.
Evidence-based recommendations on the efficacy and safety of corticosteroids in acute respiratory distress syndrome (ARDS) remain a therapeutic challenge. Findings from several systematic reviews and meta-analyses are inconsistent. We aimed to assess the published meta-analyses through a systematic review approach and provide further insight into the current uncertainty and also to perform an updated meta-analysis from all the available primary studies.
We followed the Preferred Reporting Items for Systematic Review (PRISMA) guidelines to establish the patients, intervention, control and outcome (PICO) for reviewing published meta-analyses. Data sources such as PubMed/MEDLINE, SCOPUS, Cochrane and Google Scholar from inception to February 2021 were accessed. Prevention of ARDS, mortality, ventilator-free days, ICU stay and safety in terms of occurrence of adverse effects were the patient-related outcomes. The review also assessed meta-analysis design-related outcomes which includes the quality of meta-analysis, factors contributing to the risk of bias, extent and sources of heterogeneity, publication bias and robustness of findings. AMSTAR-2 checklist assessed the quality of published meta-analyses.
A total of 18 meta-analyses were reviewed comprising a total of 38 primary studies and 3760 patients. Fourteen studies were in ARDS, three in community-acquired pneumonia and one in critical care. The overall quality of meta-analyses was observed to be critically low to high. A non-significant risk of publication bias and non-significant level of heterogeneity was observed in the reviewed meta-analysis. Corticosteroid was significantly effective in preventing ARDS among CAP patients. The effect of corticosteroids on mortality was observed to be still inconsistent, whereas significant improvement was observed with ICU and ventilator outcomes compared with the control group. Our meta-analysis observed a significant reduction of mortality in RCTs (RR: 0.78; 95% CI: 0.61 to 0.99) and the duration of mechanical ventilation (MD: -4.75; 95% CI: -7.63 to -1.88); and a significant increase in ventilator-free days (MD: 6.03; 95% CI: 3.59 to 8.47) and ICU-free days (MD: 8.04; 95% CI: 2.70 to 13.38) in ARDS patients treated with corticosteroids compared with the control group.
The quality of included studies ranged from critically low to high demonstrating inconsistency in risk of bias. While older studies found no significant effect, recent meta-analyses of RCTs found a significant mortality reduction in the corticosteroid group with considerable levels of heterogeneity. The updated meta-analysis by our team found a significant reduction in mortality in the pooled estimation of RCTs but not in cohort studies. Corticosteroid therapy was effective in terms of ICU and ventilator outcomes with minimal safety concerns. Future meta-analyses should be well executed with specific research questions and well performed with minimal risk of bias to produce good quality evidence.
关于皮质类固醇在急性呼吸窘迫综合征(ARDS)中的疗效和安全性的循证建议仍然是一个治疗挑战。一些系统评价和荟萃分析的结果并不一致。我们旨在通过系统评价方法评估已发表的荟萃分析,并进一步了解当前的不确定性,并对所有可用的原始研究进行更新的荟萃分析。
我们遵循系统评价(PRISMA)的首选报告项目(PRISMA)指南,为审查已发表的荟萃分析建立患者、干预、对照和结局(PICO)。从成立到 2021 年 2 月,我们访问了 PubMed/MEDLINE、SCOPUS、Cochrane 和 Google Scholar 等数据源。预防 ARDS、死亡率、无呼吸机天数、入住 ICU 天数和安全性方面的不良反应发生率是患者相关的结局。该综述还评估了荟萃分析设计相关的结局,包括荟萃分析的质量、导致偏倚风险的因素、异质性的程度和来源、发表偏倚以及结果的稳健性。AMSTAR-2 清单评估了已发表的荟萃分析的质量。
共审查了 18 项荟萃分析,共纳入 38 项原始研究和 3760 名患者。14 项研究为 ARDS,3 项为社区获得性肺炎,1 项为重症监护。总体而言,荟萃分析的质量被观察为从严重到高。在综述的荟萃分析中观察到无显著发表偏倚风险和无显著异质性水平。皮质类固醇在 CAP 患者中预防 ARDS 是有效的。皮质类固醇对死亡率的影响仍然不一致,而与对照组相比,在 ICU 和呼吸机结局方面观察到显著改善。我们的荟萃分析观察到 RCT 中死亡率显著降低(RR:0.78;95%CI:0.61 至 0.99)和机械通气时间(MD:-4.75;95%CI:-7.63 至-1.88);以及 ARDS 患者接受皮质类固醇治疗后呼吸机无天数(MD:6.03;95%CI:3.59 至 8.47)和 ICU 无天数(MD:8.04;95%CI:2.70 至 13.38)显著增加。
纳入研究的质量从严重到高不等,表明偏倚风险不一致。虽然早期研究没有发现显著效果,但最近的皮质类固醇 RCT 荟萃分析发现,皮质类固醇组的死亡率显著降低,异质性水平相当高。我们团队的更新荟萃分析发现,在 RCT 的汇总估计中死亡率显著降低,但在队列研究中没有。皮质类固醇治疗在 ICU 和呼吸机结局方面有效,安全性问题最小。未来的荟萃分析应该有明确的研究问题,并且要经过精心设计,最大限度地降低偏倚风险,以产生高质量的证据。