低剂量氢化可的松用于感染性休克肝硬化患者：一项双盲随机安慰剂对照试验
Low-Dose Hydrocortisone in Cirrhotic Patients With Septic Shock: A Double-Blind Randomised Placebo-Controlled Trial.
作者信息
Meersseman Philippe, Hernández-Tejero María, Diaz Juan Manuel, Wauters Joost, Hermans Greet, Aziz Fátima, Ceunen Helga, Prado Veronica, Langouche Lies, Arteaga Mireya, Acevedo Juan, Lleixa Marc, Zapatero Juliana, Toapanta David, Arroyo Vicente, Wilmer Alexander, Fernandez Javier
机构信息
Medical Intensive Care Unit, Department of General Internal Medicine, University Hospital Leuven, Leuven, Belgium.
Liver ICU, Liver Unit, IDIBAPS and CIBERehd, Hospital Clinic, Barcelona, Spain.
出版信息
Liver Int. 2025 Sep;45(9):e70257. doi: 10.1111/liv.70257.
BACKGROUND AND AIMS
Steroid supplementation remains controversial in septic shock, partly due to the heterogeneity of the populations studied. Cirrhotic patients with sepsis frequently develop relative adrenal insufficiency, showing poor response to vasopressors and poor prognosis. Early administration of low-dose hydrocortisone might facilitate shock reversal and reduce mortality in this population.
METHODS
Double-blind, randomised, placebo-controlled multicentre trial, enrolling adult cirrhotic patients with septic shock. Patients were assigned to receive i.v. hydrocortisone (100 mg followed by a continuous infusion of 200 mg/24 h) or placebo, for at least 3 days, followed by a tapering period of 3-7 days, depending on the time of shock resolution. Primary endpoint was 28-day all-cause mortality.
RESULTS
After enrolment of 83 patients the trial was stopped early due to slow inclusions. Most patients required low-to-moderate doses of vasopressors. There was no difference in 28-day mortality (35% vs. 39.5%; p = 0.84) between hydrocortisone and placebo groups. Shock resolution (85% vs. 72.1%; p = 0.25) and days to shock resolution [3 days (2.2-4; IQR) vs. 4 (2-7.5; IQR)] were also similar between groups. More patients receiving placebo died of refractory shock (47.6% vs. 8.7%). No significant differences between treatment arms were observed in shock relapse, new shock episodes or bacterial or fungal superinfections during hospital stay. Hypo- and hyperglycaemias were more frequent in the hydrocortisone arm. Severity of ACLF at inclusion and inadequacy of empirical antibiotic therapy (HR = 6.40; 95% CI: 3.21-12.79) independently predicted 28-day mortality.
CONCLUSIONS
Supplemental hydrocortisone did not improve short-term survival in cirrhotic patients with septic shock requiring low-to-moderate doses of vasopressors.
TRIAL REGISTRATION
S-number University Hospitals Leuven, Belgium: S55168; EUDRACT: 2010-024273-38; Clinicaltrials.gov id: NCT02602210.
背景与目的
在感染性休克中，类固醇补充治疗仍存在争议，部分原因是所研究人群的异质性。肝硬化合并脓毒症的患者常出现相对肾上腺皮质功能不全，对血管升压药反应不佳且预后不良。早期给予低剂量氢化可的松可能有助于该人群休克逆转并降低死亡率。
方法
一项双盲、随机、安慰剂对照的多中心试验，纳入成年肝硬化合并感染性休克患者。患者被分配接受静脉注射氢化可的松（100mg，随后以200mg/24小时持续输注）或安慰剂，至少3天，然后根据休克缓解时间进行3 - 7天的减量期。主要终点是28天全因死亡率。
结果
在纳入83例患者后，由于入组缓慢，试验提前终止。大多数患者需要低至中等剂量的血管升压药。氢化可的松组和安慰剂组的28天死亡率无差异（35%对39.5%；p = 0.84）。休克缓解率（85%对72.1%；p = 0.25）以及休克缓解天数[3天（2.2 - 4；四分位间距）对4天（2 - 7.5；四分位间距）]在两组间也相似。更多接受安慰剂的患者死于难治性休克（47.6%对8.7%）。在住院期间，治疗组之间在休克复发、新的休克发作或细菌或真菌二重感染方面未观察到显著差异。氢化可的松组低血糖和高血糖更为常见。纳入时急性肝衰竭的严重程度和经验性抗生素治疗不足（HR = 6.40；95%置信区间：3.21 - 12.79）独立预测28天死亡率。
结论
对于需要低至中等剂量血管升压药的肝硬化合并感染性休克患者，补充氢化可的松并不能改善短期生存率。
试验注册
比利时鲁汶大学医院试验编号：S55168；欧盟临床试验注册号：2010 - 024273 - 38；美国国立医学图书馆临床试验标识符：NCT02602210。
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