Corticotropin stimulated steroid profiles to predict shock development and mortality in sepsis: From the HYPRESS study

Abstract

Abstract Rationale: Steroid profiles combined with the corticotropin stimulation test can be used to obtain a more complete picture of adrenocortical function in critically ill patients. Objectives: Our objective was to investigate whether steroid profiles before and after corticotropin stimulation predict shock development and mortality in human sepsis. Methods: An exploratory data analysis of a double-blind, randomized trial in sepsis (HYPRESS [Hydrocortisone for the PRevention of Septic Shock]) was performed. The trial included adult patients with sepsis who were not in shock and were randomly assigned to placebo or hydrocortisone treatment (200 mg for 5 days). Corticotropin tests were performed in 206 patients before randomization and in 20 healthy subjects. Samples were analyzed using the multi-analyte stable isotope dilution method (LC-MS/MS) for steroid profiling. Steroid profiles of healthy subjects undergoing corticotropin tests served as controls to determine reference ranges. Measurements and Main Results: Corticotropin test samples from 180 patients and 20 volunteers were included. Compared to healthy subjects, patients with sepsis had elevated levels of 11-desoxycorticosterone and 11-desoxycortisol, consistent with activation of both glucocorticoid and mineralocorticoid pathways before stimulation. After stimulation with corticotropin, the cortisol response was subnormal in 12% and the corticosterone response in 50% of sepsis patients. A predominance of glucocorticoids over mineralocorticoids after corticotropin stimulation (cortisol-corticosterone ratio > 32.2) predicted the development of shock within 14 days and death within 90 days in the placebo group. Conclusions: In this exploratory data analysis, corticotropin stimulated cortisol-to-corticosterone ratio served as a criterion to predict shock development and mortality in sepsis. Clinical trial registered with www.clinicaltrials.gov Identifier: NCT00670254. Registered 1 May 2008.