Efficacy of corticosteroids in patients with acute respiratory distress syndrome: a meta-analysis

Acute respiratory distress syndrome (ARDS), are respiratory diseases with high morbidity and mortality. Clinical trials investigating the efficacy of corticosteroids in the treatment of ARDS often yield contradictory results. We hereby conducted a systematic review and meta-analysis to investigate the efficacy of corticosteroids in ARDS management. We conducted a search for randomized clinical trials (RCT) and observational studies that utilized corticosteroids for patients with ARDS in Web of Science, PubMed, and Embase. The primary outcome was mortality. Risk of bias was assessed using Cochrane or NOS scales. Statistical effect size was analyzed using the Mantel-Haenszel method. A total of 20 studies, comprising 11 observational studies and 9 RCTs, were eligible for analysis. In RCTs, corticosteroids were associated with a reduction of mortality in ARDS patients (relative risk [RR] = 0.80, 95%CI: 0.71-0.91, <i>p</i> = 0.001). Further subgroup analysis indicated that specific variables, such as low-dose (RR = 0.81; 95%CI: 0.67-0.98; <i>p</i> = 0.034), methylprednisolone (RR = 0.70; 95%CI: 0.49-0.98; <i>p</i> = 0.035), and dexamethasone (RR = 0.82; 95%CI: 0.69-0.98; <i>p</i> = 0.029) were associated with mortality among patients receiving corticosteroids. However, in observational studies, corticosteroids increased the risk of death (RR = 1.16, 95%CI: 1.04-1.29; <i>p</i> = 0.001). Subgroup analysis showed that the use of high-dose corticosteroids was associated with higher patient mortality (RR = 1.20; 95%CI: 1.04-1.38; <i>p</i> = 0.001). The efficacy of corticosteroids on the mortality of ARDS differed by the type and dosage of corticosteroids used, as well as the etiologies. Current data do not support routine use of corticosteroids in ARDS since protective effects were observed in RCTs but increased mortality was found in observational studies. More well designed and large clinical trials are needed to specify the favorable subgroups for corticosteroid therapy. Corticosteroid use may reduce the risk of death in patients with acute respiratory distress syndrome (ARDS) according to randomized controlled trials. Observational studies indicate that corticosteroid use may increase the risk of death in non-COVID-19 ARDS patients but not in COVID-19 ARDS patients. Both regular and low-dose corticosteroids show benefits in reducing mortality in RCTs, but observational studies associate these doses with increased mortality.

急性呼吸窘迫综合征（Acute respiratory distress syndrome, ARDS）是一类发病率与死亡率均较高的呼吸系统疾病。针对糖皮质激素治疗急性呼吸窘迫综合征的疗效开展的临床试验，常得出相互矛盾的研究结果。为此，本研究开展了一项系统评价与荟萃分析，以探究糖皮质激素在急性呼吸窘迫综合征临床管理中的应用疗效。本研究在Web of Science、PubMed及Embase数据库中，检索了针对急性呼吸窘迫综合征患者应用糖皮质激素的随机临床试验（randomized clinical trials, RCT）与观察性研究。本研究的主要结局指标为病死率；采用Cochrane偏倚风险工具或纽卡斯尔-渥太华量表（Newcastle-Ottawa Scale, NOS）评估研究偏倚风险；使用Mantel-Haenszel法分析统计效应量。最终共有20项研究符合分析纳入标准，其中包含11项观察性研究与9项随机临床试验。在随机临床试验中，糖皮质激素的使用与急性呼吸窘迫综合征患者的病死率降低显著相关（相对危险度[relative risk, RR] = 0.80，95%置信区间[confidence interval, CI]：0.71~0.91，P = 0.001）。进一步亚组分析显示，特定亚组人群可从糖皮质激素治疗中获益：如低剂量糖皮质激素（RR = 0.81；95%CI：0.67~0.98；P = 0.034）、甲泼尼龙（RR = 0.70；95%CI：0.49~0.98；P = 0.035）以及地塞米松（RR = 0.82；95%CI：0.69~0.98；P = 0.029）。但在观察性研究中，糖皮质激素的使用反而会升高患者的死亡风险（RR = 1.16；95%CI：1.04~1.29；P = 0.001）。亚组分析结果显示，大剂量糖皮质激素的使用与患者更高的病死率相关（RR = 1.20；95%CI：1.04~1.38；P = 0.001）。糖皮质激素对急性呼吸窘迫综合征患者病死率的影响，因所用糖皮质激素的种类、剂量以及病因不同而存在显著差异。现有研究证据并不支持在急性呼吸窘迫综合征患者中常规使用糖皮质激素：随机临床试验显示其具有保护作用，而观察性研究则发现其会升高患者的死亡风险。未来需开展更多设计严谨的大样本临床试验，以明确糖皮质激素治疗的获益亚组人群。随机临床试验结果显示，糖皮质激素的使用或许可降低急性呼吸窘迫综合征患者的死亡风险；而观察性研究则表明，糖皮质激素会升高非新型冠状病毒肺炎（non-coronavirus disease 2019, non-COVID-19）相关急性呼吸窘迫综合征患者的死亡风险，但对新型冠状病毒肺炎（coronavirus disease 2019, COVID-19）相关急性呼吸窘迫综合征患者无此不良影响。在随机临床试验中，常规剂量与低剂量糖皮质激素均能降低患者病死率，但观察性研究却显示此类剂量会升高患者的死亡风险。