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

26 Pages Posted: 11 Apr 2019

See all articles by Mark Anthony Foster

Mark Anthony Foster

Government of the United Kingdom - NIHR-Surgical Reconstruction and Microbiology Research Centre; Government of the United Kingdom - Royal Centre for Defence Medicine

Angela E. Taylor

University of Birmingham

Neil E. Hill

Imperial College London

Conor Bentley

Government of the United Kingdom - NIHR-Surgical Reconstruction and Microbiology Research Centre

Jon Bishop

Government of the United Kingdom - NIHR-Surgical Reconstruction and Microbiology Research Centre

Julian F. Bion

Government of the United Kingdom - Queen Elizabeth Hospital Birmingham

Joanne L. Fallowfield

Institute of Naval Medicine

David R. Woods

Government of the United Kingdom - Royal Centre for Defence Medicine

Irina Bancos

Mayo Clinic - Division of Endocrinology, Diabetes, Metabolism, and Nutrition

Mark Midwinter

University of Queensland, Faculty of Medicine, School Biomedical Science

Janet M. Lord

Government of the United Kingdom - NIHR-Surgical Reconstruction and Microbiology Research Centre

Wiebke Arlt

University of Birmingham

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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.

Keywords: major trauma; stress response; SIRS, catabolism; metabolism; critical illness; steroids; cortisol; DHEA; testosterone

Suggested Citation

Foster, Mark Anthony and Taylor, Angela E. and Hill, Neil E. and Bentley, Conor and Bishop, Jon and Bion, Julian F. and Fallowfield, Joanne L. and Woods, David R. and Bancos, Irina and Midwinter, Mark and Lord, Janet M. and Arlt, Wiebke, Mapping the Steroid Response to Major Trauma from Injury to Recovery: A Prospective Cohort Study (April 10, 2019). Available at SSRN: https://ssrn.com/abstract=3369777

Mark Anthony Foster (Contact Author)

Government of the United Kingdom - NIHR-Surgical Reconstruction and Microbiology Research Centre ( email )

Birmingham
United Kingdom

Government of the United Kingdom - Royal Centre for Defence Medicine ( email )

Birmingham
United Kingdom

Angela E. Taylor

University of Birmingham

Department of Civil Engineering
Edgbaston, VT Birmingham B15 2TT
United Kingdom

Neil E. Hill

Imperial College London

South Kensington Campus
Exhibition Road
London, Greater London SW7 2AZ
United Kingdom

Conor Bentley

Government of the United Kingdom - NIHR-Surgical Reconstruction and Microbiology Research Centre

Birmingham
United Kingdom

Jon Bishop

Government of the United Kingdom - NIHR-Surgical Reconstruction and Microbiology Research Centre

Birmingham
United Kingdom

Julian F. Bion

Government of the United Kingdom - Queen Elizabeth Hospital Birmingham

Mindelsohn Way
Birmingham, B15 2TH
United Kingdom

Joanne L. Fallowfield

Institute of Naval Medicine

Alverstoke
United Kingdom

David R. Woods

Government of the United Kingdom - Royal Centre for Defence Medicine

Birmingham
United Kingdom

Irina Bancos

Mayo Clinic - Division of Endocrinology, Diabetes, Metabolism, and Nutrition

200 First Street S.W
Rochester, MN 55905
United States

Mark Midwinter

University of Queensland, Faculty of Medicine, School Biomedical Science

QLD
Brisbane, Queensland 4072
Australia

Janet M. Lord

Government of the United Kingdom - NIHR-Surgical Reconstruction and Microbiology Research Centre

Birmingham
United Kingdom

Wiebke Arlt

University of Birmingham

Department of Civil Engineering
Edgbaston, VT Birmingham B15 2TT
United Kingdom

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