Critical illness-related corticosteroid insufficiency after acute brain hemorrhage surgery: a prospective cohort study with a randomized trial of hydrocortisone : HYdrocortisone theraPy in nEurocRitical illness; HYPER study

Abstract

Background Critical illness-related corticosteroid insufficiency (CIRCI) is a potentially underrecognized complication in postoperative patients with acute brain hemorrhage. Its incidence, associated risk factors, and the therapeutic role of corticosteroids in this population remain unclear. Method This multicenter study combined a prospective observational cohort with a single-blinded randomized controlled trial. Adult patients aged 18-80 years who underwent neurological surgery for acute brain hemorrhage within 48 h of admission at tertiary care hospitals were eligible for inclusion. Acute brain hemorrhage was confirmed by computed tomography or magnetic resonance imaging and included both traumatic (e.g., epidural or subdural hematoma) and non-traumatic etiologies (e.g., aneurysmal subarachnoid hemorrhage). Among 497 screened patients, 255 eligible postoperative patients underwent adrenal function testing using a high-dose corticotropin stimulation test (HDST) on postoperative day (POD) 2 or 3. Patients diagnosed with CIRCI (n = 64, 25.1%) were randomized in a 1:1 ratio to receive intravenous hydrocortisone or placebo. The primary outcome was neurological improvement at 30 days assessed using the modified Rankin Scale (mRS). Results CIRCI was diagnosed in 25.1% of patients. Independent predictors of CIRCI included traumatic subdural hematoma, epidural hematoma, mechanical ventilation, and fresh frozen plasma transfusion. While hydrocortisone did not significantly improve the primary outcome of 30-day neurological function, it significantly reduced mechanical ventilation duration (median [IQR], 5 [3-7] vs. 10 [6-16] days; p = 0.032) and ICU length of stay (5 [2-13] vs. 13 [3-18] days; p = 0.038). No increase in serious adverse events was observed. Conclusion CIRCI is common in postoperative patients with acute brain hemorrhage and is associated with specific clinical risk factors. Although targeted hydrocortisone therapy did not significantly improve functional outcomes at 30 days, it yielded significant improvements in short-term ICU parameters. These findings warrant further adequately powered studies to evaluate the role of corticosteroid therapy in patients with acute brain hemorrhage diagnosed with CIRCI. Clinical trial registration This study was registered with the Clinical Research Information Service (CRIS), a primary registry of the WHO International Clinical Trials Registry Platform, under the identifier KCT0004425. The trial was prospectively registered on 5 November 2019.