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Circadian Cortisol Rhythm after Burn Injury
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Introduction: The stress response to critical illness includes activation of the hypothalamic-pituitary-adrenal (HPA) axis, and increased release of cortisol and diminished or lost physiological diurnal variation. Details of this response were analyzed in consecutive burn patients.

Methods: Forty-nine patients, 15 women and 34 men, median age 41(range 19-60), median burn size 31 % (range 10-96)n and treated at Uppsala Burn Center were investigated during their first week after injury. Clinical parameters were registered daily, serum cortisol concentrations were analyzed four times daily for seven days, and the daily diurnal slope starting from the daily maximum was calculated. Relevant confounding variables were identified by means of a directed acyclic graph (DAG).

Results: The circadian zenith for free cortisol frequently occurred at noon rather that in early morning, it was not related to burn size, ventilator care, or surgery, but was weakly related to the SOFA score. Multilevel modeling revealed that burn size explained cortisol slope. After adjustments for covariates, including the SOFA score, the only significant covariate was the SOFA score itself. Ventilator care explained cortisol slope, but surgery the preceding day did not. Differences between large and small burns were only noticed for the free cortisol concentration at 6pm, suggesting that the flattening of the slope was primarily due to a slower decline in free cortisol from morning to evening.  When adjusting for all covariates, slope at 6pm was explained by burn size and P-CgA as well as SOFA score. Both burn size and SOFA score explained the daily coefficient of variability (CV) in free cortisol concentration. Similarly, burn size, P-CgA and SOFA explained AUC.

Conclusions: Free cortisol concentration was related to the size of burns, as was the circadian cortisol rhythm. This effect of burn size was related at least in part to its effect on organ function.

National Category
Medical and Health Sciences Surgery
Research subject
Plastic Surgery
URN: urn:nbn:se:uu:diva-198463OAI: oai:DiVA.org:uu-198463DiVA: diva2:618189
Available from: 2013-04-26 Created: 2013-04-15 Last updated: 2015-03-17
In thesis
1. Neuroendocrine Stress Response after Burn Trauma
Open this publication in new window or tab >>Neuroendocrine Stress Response after Burn Trauma
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Some aspects of the stress response during acute intensive care for severe burns are described and quantified by measuring hormonal and neuroendocrine patterns and relating these to organ function in the short term. This includes an assessment of whether there are markers for the severity of stress that are better than conventional descriptors of the severity of a burn in predicting failing organ function.

P-CgA after a major burn injury is an independent and better predictor of organ dysfunction assessed as SOFA score than the traditionally used TBSA% burned. The results also suggest that the extent of neuroendocrine activation is related to organ dysfunction, and this motivates a more extensive effort to evaluate P-CgA as a prognostic marker with respect to mortality and long-term outcome.

P-NT-proBNP exhibited a complex pattern with considerable inter-individual and day-to-day variations. Values of P-NT-proBNP were related to size of burn, water accumulation and systemic inflammatory response. A considerable covariation with trauma response and SOFA scores was observed in day by day analyses, but with weight change only on day 2.

Maximum P-NT-proBNP showed a stronger correlation with SOFA score on day 14, with mortality, and with LOS, than did age and TBSA% burned. High values were also independent predictors of all subsequent SOFA scores up to two weeks after injury.

P-NT-proBNP and NT-proANP reflect and predict organ function after burn injury similarly, notwithstanding a significantly larger intra-individual variability for P-NT-proBNP. P-NT-proBNP, but not NT-proANP, reflects the systemic inflammatory trauma response.

Free cortisol concentration was related to the size of burns, as was the circadian cortisol rhythm. This effect of burn size was, at least in part, related to its effect on organ function.

This thesis points to the fact that the stress response is richly interwoven, and cannot be adequately assessed by one biomarker only. All biomarkers studied here can be viewed as representing efferent limbs of the stress reaction, and they would need to be supplemented by biomarkers representing individual physiologic responses that follow the stress signaling.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 67 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 908
Burn, Injuries, Neuroendocrine, Intensive Care, Cortisol, Chromogranin A, Natriuretic peptides
National Category
Research subject
Plastic Surgery
urn:nbn:se:uu:diva-198466 (URN)978-91-554-8686-0 (ISBN)
Public defence
2013-06-14, Skoogsalen, Entrance 78-79, Akademiska Sjukhuset, Uppsala, 09:15 (Swedish)
Available from: 2013-05-24 Created: 2013-04-15 Last updated: 2013-08-30

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Lindahl, AndreasStridsberg, MatsGerdin, Bengt
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