Mapping the Steroid Response to Major Trauma from Injury to Recovery: A Prospective Cohort Study

Abstract

Background: Survival rates after severe injury are improving, but complication rates and outcomes are variable. This study addressed the lack of data on adrenal and gonadal steroid response during recovery from major trauma in relation to clinical outcomes, exploring potential targets for future intervention. Methods: We undertook a prospective, observational cohort study at a major UK trauma centre and a military rehabilitation unit, studying patients within 24 hours of major trauma (estimated New Injury Severity Score (NISS) >15) and at regular intervals for six months. We recorded clinical outcomes (ventilator days, length of hospital stay, organ dysfunction, sepsis), measured adrenal and gonadal steroids by tandem mass spectrometry, and assessed muscle loss by ultrasound and nitrogen excretion. Findings: We screened 996 multiply injured adults, approached 106, and recruited 95 eligible patients; 87 survived. We analysed all male survivors <50 years not treated with steroids (N=60; median age 27 [interquartile range 24-31] years; median NISS 34 [29-44]). Urinary nitrogen excretion and muscle loss peaked one and six weeks post-injury, respectively. While glucocorticoid secretion remained within the reference range, serum testosterone, DHEA and DHEAS decreased sharply immediately after injury and took two, four, and more than six months, respectively, to recover; all three correlated with the sequential organ failure assessment (SOFA) score and probability of sepsis. Interpretation: The acute catabolic response to severe injury is accompanied by profound and sustained adrenal and gonadal androgen suppression. The impact of androgen supplementation on health outcomes after major trauma should be systematically explored. Funding: The Steroids and Immunity from injury through to Rehabilitation (SIR) Study was part of the Surgeon General’s Casualty Nutrition Study (SGCNS), supported by University Hospitals Birmingham NHS Foundation Trust (UHB) and the University of Birmingham. Additional funding was provided by the Drummond Trust Foundation. Declaration of Interest: There is no conflict of interests for any of the authors. JML and WA are supported by the National Institute for Health Research (NIHR) through the NIHR Birmingham Biomedical Research Centre. Ethical Approval: The protocol was approved by the NRES Committee South West – Frenchay 11/SW/0177 and MOD REC 116/Gen/10.