JAMA:脓毒性休克中氢化可的松与肾脏替代治疗风险因素的关系

Abstract

Importance: Sepsis-associated acute kidney injury (SA-AKI) is a common and clinically important condition in patients who are critically ill. Dysregulated inflammation may contribute to it. Intravenous hydrocortisone may decrease the risk of SA-AKI progression.重要性：脓毒症相关急性肾损伤（SA-AKI）是危重症患者中常见且具有临床重要性的病症。炎症调节失调可能促使其发生。静脉注射氢化可的松可能降低SA-AKI进展的风险。

Objective: To describe the associations of hydrocortisone use with the incidence and outcomes of requirement for kidney replacement therapy (KRT), as well as source of sepsis, mean arterial pressure (MAP), and MAP indexed to required vasopressor (norepinephrine equivalent [NEE]).目的：描述氢化可的松的使用与肾脏替代治疗（KRT）需求的发生率及结局之间的关联，以及脓毒症的来源、平均动脉压（MAP）、以及基于所需血管加压药（去甲肾上腺素当量[NEE]）调整的MAP。

Design, setting, and participants: This cohort study was conducted as a post hoc analysis of the Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock (ADRENAL) randomized clinical trial (RCT), a multicenter placebo-controlled RCT of hydrocortisone in patients with septic shock in 69 intensive care units in Australia, the United Kingdom, New Zealand, Saudi Arabia, and Denmark that recruited between 2013 and 2017. Participants were patients enrolled in the ADRENAL study with septic shock who did not require KRT in the 24 hours prior to randomization and who did not have a prior longstanding dialysis requirement. Data were analyzed between July and September 2024.设计、背景和参与者：这项队列研究是对 “重症脓毒性休克患者的辅助糖皮质激素治疗”（ADRENAL）随机临床试验（RCT）​ 的事后分析，该试验是一项多中心、安慰剂对照的RCT，在澳大利亚、英国、新西兰、沙特阿拉伯和丹麦的69个重症监护病房（ICU）中进行，招募时间为2013年至2017年。参与者为ADRENAL研究中纳入的脓毒性休克患者，这些患者在随机分组前24小时内未接受KRT，且既往无长期透析需求。数据分析时间为2024年7月至9月。

Exposures: Receipt of hydrocortisone (vs placebo), MAP at enrollment, vasopressor dose (NEE) and MAP:NEE ratio, source of sepsis, causative organism, bacteremia, and the use of nephrotoxic antimicrobials, vasopressin, or specific inotropes.暴露因素：接受氢化可的松（对比安慰剂）、入组时的MAP、血管加压药剂量（NEE）及MAP与NEE比值、脓毒症来源、致病微生物、菌血症，以及是否使用肾毒性抗菌药物、血管加压素或特定正性肌力药物。

Main outcomes and measures: Outcomes of interest were KRT requirement and liberation from KRT, measured as days alive and free of KRT.主要结局和测量指标：关注的结局是KRT需求及脱离KRT的情况，以“存活且无KRT的天数”进行衡量。

Results: A cohort of 3161 patients (median [IQR] age, 65 [53-74] years, 1921 [61%] male) was identified, including 1589 patients randomized to receive hydrocortisone and 1572 patients who received the placebo. Allocation to treatment with hydrocortisone was associated with a significantly reduced incidence of KRT requirement compared with placebo (329 patients [21%] vs 372 patients [24%]; odds ratio [OR], 0.84 [95% CI, 0.70 to 0.99]; P = .04). When controlled for factors associated with KRT requirement, randomization to hydrocortisone remained significantly associated with a reduced odds of new KRT requirement (OR, 0.79 [95% CI, 0.66 to 0.95]; P = .01). Among patients who started KRT following randomization, hydrocortisone was not associated with reduced days alive and free of KRT (mean difference, 1.28 [95% CI, -4.31 to 6.87] days; P = .65).结果：共纳入3161例患者（中位年龄[IQR] 65岁[53-74]，男性1921例[61%]），其中1589例被随机分配至氢化可的松组，1572例接受安慰剂。与安慰剂相比，分配至氢化可的松治疗组的患者新发KRT需求的发生率显著降低（329例[21%] vs 372例[24%]；比值比[OR] 0.84 [95% CI 0.70–0.99]；P = 0.04）。在校正与KRT需求相关的因素后，随机分配至氢化可的松组仍与较低的新发KRT需求几率显著相关（OR 0.79 [95% CI 0.66–0.95]；P = 0.01）。在随机分组后开始KRT的患者中，氢化可的松与“存活且无KRT的天数”减少无关（平均差异 1.28天 [95% CI -4.31–6.87]；P = 0.65）。

Conclusions and relevance: In this post hoc cohort study of patients with septic shock enrolled in a large RCT, intravenous hydrocortisone was associated with a reduced risk of new KRT requirement following randomization. 结论与意义：在这项针对大型RCT中脓毒性休克患者的事后队列研究中，静脉注射氢化可的松与随机分组后新发KRT需求的风险降低相关。