The Endocrine and Metabolic Response in Male Survivors of Major Trauma

Foster, M. A.; Taylor, A. E.; Hill, N. E.; Bentley, C.; Bishop, J.; Bion, J. F.; Fallowfield, J. L.; Woods, D. R.; Bancos, I.; Midwinter, M.; Lord, J.; Arlt, W.

doi:10.1101/577502

bioRxiv · 10.1101/577502

The Endocrine and Metabolic Response in Male Survivors of Major Trauma

Foster, M. A.·Taylor, A. E.·Hill, N. E.·Bentley, C.·Bishop, J.·Bion, J. F.·Fallowfield, J. L.·Woods, D. R.·Bancos, I.·Midwinter, M.·Lord, J.·Arlt, W.

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Abstract

ContextSurvival rates after severe injury are improving, but complication rates and outcomes are variable. ObjectiveThis cohort study addressed the lack of longitudinal data on the steroid response to major trauma and during recovery. DesignWe undertook a prospective, observational cohort study from time of injury to six months post-injury 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). Main outcome measuresWe measured adrenal and gonadal steroids in serum and 24-h urine by mass spectrometry, assessed muscle loss by ultrasound and nitrogen excretion, and recorded clinical outcomes (ventilator days, length of hospital stay, opioid use, incidence of organ dysfunction and sepsis); results were analysed by generalized mixed-effect linear models. FindingsWe screened 996 multiple 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 after one and six weeks, respectively. Serum testosterone, dehydroepiandrosterone and dehydroepiandrosterone sulfate decreased immediately after trauma and took two, four and more than six months, respectively, to recover; opioid treatment delayed dehydroepiandrosterone recovery in a dose-dependent fashion. Androgens and precursors correlated with SOFA score and probability of sepsis. ConclusionThe catabolic response to severe injury was accompanied by acute and sustained androgen suppression. Whether androgen supplementation improves health outcomes after major trauma requires further investigation. PrecisA cohort study in male survivors of major trauma revealed acute and sustained androgen suppression and protein catabolism including muscle loss. Serum androgens correlated with probability of sepsis.

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Foster, M. A., Taylor, A. E., Hill, N. E., Bentley, C., Bishop, J., Bion, J. F., Fallowfield, J. L., Woods, D. R., Bancos, I., Midwinter, M., Lord, J., Arlt, W.. 2019-03-14. The Endocrine and Metabolic Response in Male Survivors of Major Trauma. https://doi.org/10.1101/577502

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