Plasma Cortisol, Aldosterone, and Ascorbic Acid Concentrations in Patients with Septic Shock do not Predict Treatment Effect of Hydrocortisone on Mortality: A Nested Cohort Study.

Abstract

Whether biomarkers can identify subgroups of patients with septic shock with differential treatment responses to hydrocortisone is unknown. To determine if there is heterogeneity in effect for hydrocortisone on mortality, shock resolution and other clinical outcomes based on baseline cortisol, aldosterone and ascorbic acid concentrations. From May 2014 to April 2017, we obtained serum samples from 529 patients with septic shock from 22 intensive care units in Australia and New Zealand. There were no significant interactions between the association with 90-day mortality and treatment with either hydrocortisone or placebo for total cortisol (odds ratio 1.09, 95% confidence interval 1.02-1.16, vs odds ratio 1.07, 95% confidence interval 1.00-1.13, p=0.70), free cortisol (odds ratio 1.20, 95% confidence interval 1.04-1.38 vs odds ratio 1.16, 95% confidence interval 1.02-1.32, p=0.75), aldosterone (odds ratio 1.01, 95% confidence interval 0.97-1.05, vs odds ratio 1.01, 95% confidence interval 0.98-1.04, p=0.99), or ascorbic acid (odds ratio 1.11, 95% confidence interval 0.89-1.39 vs odds ratio 1.05, 95% confidence interval 0.91-1.22, p=0.70) respectively. Similar results were observed for the association with shock resolution. Elevated free cortisol was significantly associated with 90-day mortality (odds ratio 1.13, 95% confidence interval 1.00-1.27, p=0.04) but total cortisol, aldosterone and ascorbic acid were not. In patients with septic shock, there was no heterogeneity in effect of adjunctive hydrocortisone on mortality, shock resolution or other clinical outcomes based on cortisol, aldosterone and ascorbic acid concentrations. Plasma aldosterone and ascorbic acid concentrations are not associated with outcome.