Lin Lu-Lu, Gu Hui-Yun, Luo Jie, Wang Long, Zhang Chao, Niu Yu-Ming, Zuo Hong-Xia
Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
Department of Pathophysiology, School of Basic Medical Sciences of Wuhan University, Wuhan, China.
Front Pharmacol. 2019 Sep 24;10:1101. doi: 10.3389/fphar.2019.01101. eCollection 2019.
With new randomised pieces of evidence and the latest clinical practice guideline from the emerging in 2018, an updated analysis of best available evidence on the controversial effects of corticosteroids in sepsis is warranted. To comprehensively evaluate whether corticosteroids are beneficial in reducing mortality and what cumulative dosage, daily dosage, and duration of corticosteroid treatment would enable adult patients with sepsis to reach the critical point of benefits. Ovid MEDLINE, Ovid EMbase, Cochrane Library, and LILACS database were searched until March 22, 2019. Thirty RCTs with 8,836 participants were identified. Long course low-dose corticosteroid therapy could improve 28-day mortality (RR = 0.90, 95% CI = 0.84-0.97; high quality), intensive care unit mortality (RR = 0.87; 95% CI = 0.79-0.95; moderate quality), and in-hospital mortality (RR = 0.88, 95% CI = 0.79-0.997; high quality). However, we found no benefits for 90-day, 180-day, and 1-year mortality. Subgroup results of long course corticosteroid treatment in a population with septic shock and vasopressor-dependent septic shock, corticosteroid regimen with hydrocortisone plus fludrocortisone, corticosteroid dosing strategies including bolus dosing and infusion dosing, the strategies of abrupt discontinuation, timing of randomisation ≤24 h, impact factor of ≥10, and sample size ≥500 were associated with a marginally reduction in 28-day mortality. This meta-analysis found that the long course low-dose and not short course high-dose corticosteroid treatment could marginally improve short-term 28-day mortality with high quality, especially septic shock and vasopressor-dependent septic shock, and it is recommended that long course (about 7 days) low-dose (about 200-300mg per day) hydrocortisone (or equivalent) with cumulative dose (at least about 1,000mg) may be a viable management option for overall patients with sepsis, and it can be also adapted to patient with septic shock alone. Early hydrocortisone plus fludrocortisone administration, continuous infusion or bolus dosing, is also particularly important for the prognosis. Abrupt discontinuation of corticosteroids, as opposed to the conventional tapered discontinuation, may be considered as a desirable option in 28-day mortality. The safety profile of long course low-dose corticosteroid treatment, including adverse hyperglycaemia and hypernatraemia events, remains a concern, although these events could be easily treated. PROSPERO, identifier CRD 42018092849.
随着2018年新出现的随机证据和最新临床实践指南，有必要对皮质类固醇在脓毒症中存在争议的作用的现有最佳证据进行更新分析。以全面评估皮质类固醇在降低死亡率方面是否有益，以及何种累积剂量、每日剂量和皮质类固醇治疗持续时间能使成年脓毒症患者达到获益的临界点。检索了Ovid MEDLINE、Ovid EMbase、Cochrane图书馆和LILACS数据库，直至2019年3月22日。共纳入30项随机对照试验，涉及8836名参与者。长疗程低剂量皮质类固醇治疗可改善28天死亡率（风险比=0.90，95%置信区间=0.84 - 0.97；高质量）、重症监护病房死亡率（风险比=0.87；95%置信区间=0.79 - 0.95；中等质量）和住院死亡率（风险比=0.88，95%置信区间=0.79 - 0.997；高质量）。然而，我们未发现其对90天、180天和1年死亡率有获益。在感染性休克和血管升压药依赖的感染性休克人群中长疗程皮质类固醇治疗的亚组结果、氢化可的松加氟氢可的松的皮质类固醇方案、包括大剂量给药和输注给药的皮质类固醇给药策略、突然停药策略、随机分组时间≤24小时、影响因子≥10以及样本量≥500与28天死亡率的轻微降低相关。这项荟萃分析发现，长疗程低剂量而非短疗程高剂量皮质类固醇治疗可在高质量的情况下轻微改善短期28天死亡率，尤其是感染性休克和血管升压药依赖的感染性休克，建议长疗程（约7天）低剂量（约每日200 - 300毫克）氢化可的松（或等效药物）且累积剂量（至少约1000毫克）可能是脓毒症总体患者的一种可行治疗选择，也可适用于单独的感染性休克患者。早期给予氢化可的松加氟氢可的松、持续输注或大剂量给药对预后也尤为重要。与传统的逐渐减量停药相反，突然停用皮质类固醇在28天死亡率方面可能被视为一个理想的选择。长疗程低剂量皮质类固醇治疗的安全性，包括不良高血糖和高钠血症事件，仍然是一个问题，尽管这些事件易于治疗。国际前瞻性系统评价注册库，标识符CRD 42018092849。
