Low-Dose Hydrocortisone in Cirrhotic Patients With Septic Shock: A Double-Blind Randomised Placebo-Controlled Trial

Abstract

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.

Keywords: ACLF; mortality; refractory shock; safety; shock reversal.

FIGURE 1

Flow chart of the study.

FIGURE 2

Cumulative incidence function of 28‐day mortality (panel A) and shock resolution (panel B) in patients receiving HCS (red line) or placebo (blue line).

FIGURE 3

Mean arterial pressure and norepinephrine requirements in patients receiving HCS (red line) or placebo (blue line) during the first 7 days of therapy.

FIGURE 4

Cumulative incidence function of new bacterial (panel A), new MDR bacterial (panel B), and new fungal infections (panel C) in patients receiving HCS (red line) or placebo (blue line).