TY - JOUR
T1 - Mapping the steroid response to major trauma from injury to recovery
T2 - a prospective cohort study
AU - Foster, Mark
AU - Taylor, Angela
AU - Bishop, Jon
AU - Gilligan, Lorna
AU - Bion, Julian
AU - Lord, Janet
AU - Arlt, Wiebke
PY - 2020/3
Y1 - 2020/3
N2 - 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 6 months postinjury 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-hour 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 analyzed by generalized mixed-effect linear models.FindingsWe screened 996 multiple injured adults, approached 106, and recruited 95 eligible patients; 87 survived. We analyzed 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 1 and 6 weeks, respectively. Serum testosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate decreased immediately after trauma and took 2, 4, and more than 6 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.
AB - 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 6 months postinjury 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-hour 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 analyzed by generalized mixed-effect linear models.FindingsWe screened 996 multiple injured adults, approached 106, and recruited 95 eligible patients; 87 survived. We analyzed 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 1 and 6 weeks, respectively. Serum testosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate decreased immediately after trauma and took 2, 4, and more than 6 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.
KW - DHEA
KW - Systemic Inflammatory Response Syndrome
KW - major trauma
KW - steroids
KW - stress response
KW - testosterone
UR - https://www.biorxiv.org/content/10.1101/577502v2
U2 - 10.1210/clinem/dgz302
DO - 10.1210/clinem/dgz302
M3 - Article
SN - 0021-972X
VL - 105
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 3
M1 - dgz302
ER -