The effect of ketoconazole on post-burn inflammation, hypermetabolism and clinical outcomes

Marc G. Jeschke, Felicia N. Williams, Celeste Finnerty, Noe A. Rodriguez, Gabriela A. Kulp, Arny Ferrando, William Norbury, Oscar Suman, Robert Kraft, Ludwik Branski, Ahmed M. Al-mousawi, David Herndon

Research output: Contribution to journalArticle

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Abstract

Background: Hypercortisolemia has been suggested as a primary hormonal mediator of whole-body catabolism following severe burn injury. Ketoconazole, an anti-fungal agent, inhibits cortisol synthesis. We, therefore, studied the effect of ketoconazole on post-burn cortisol levels and the hyper-catabolic response in a prospective randomized trial (block randomization 2:1). Methodology/Principal Findings: Fifty-five severely burned pediatric patients with >30% total body surface area (TBSA) burns were enrolled in this trial. Patients were randomized to receive standard care plus either placebo (controls, n = 38) or ketoconazole (n = 23). Demographics, clinical data, serum hormone levels, serum cytokine expression profiles, organ function, hypermetabolism measures, muscle protein synthesis, incidence of wound infection sepsis, and body composition were obtained throughout the acute hospital course. Statistical analysis was performed using Fisher's exact test, Student's t-test, and parametric and non-parametric two-way repeated measures analysis of variance where applicable. Patients were similar in demographics, age, and TBSA burned. Ketoconazole effectively blocked cortisol production, as indicated by normalization of the 8-fold elevation in urine cortisol levels [F(1, 376) = 85.34, p<.001] with the initiation of treatment. However, there were no significant differences in the inflammatory response, acute-phase proteins, body composition, muscle protein breakdown or synthesis, or organ function between groups. Conclusions: Both groups were markedly hypermetabolic and catabolic throughout the acute hospital stay. Normalization of hypercortisolemia with ketoconazole therapy had no effect on whole-body catabolism or the post-burn inflammatory or hypermetabolic response, suggesting that hypercortisolemia does not play a central role in the post-burn hypermetabolic catabolic response. Trial Registration: ClinicalTrials.gov NCT00675714; and NCT00673309.

Original languageEnglish (US)
Article numbere35465
JournalPLoS One
Volume7
Issue number5
DOIs
StatePublished - May 11 2012

Fingerprint

ketoconazole
Ketoconazole
Burns
inflammation
cortisol
Hydrocortisone
Inflammation
Muscle Proteins
Body Surface Area
muscle protein
Body Composition
body composition
surface area
demographic statistics
Antifungal agents
burns (injuries)
Demography
sepsis (infection)
Pediatrics
antifungal agents

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Jeschke, M. G., Williams, F. N., Finnerty, C., Rodriguez, N. A., Kulp, G. A., Ferrando, A., ... Herndon, D. (2012). The effect of ketoconazole on post-burn inflammation, hypermetabolism and clinical outcomes. PLoS One, 7(5), [e35465]. https://doi.org/10.1371/journal.pone.0035465

The effect of ketoconazole on post-burn inflammation, hypermetabolism and clinical outcomes. / Jeschke, Marc G.; Williams, Felicia N.; Finnerty, Celeste; Rodriguez, Noe A.; Kulp, Gabriela A.; Ferrando, Arny; Norbury, William; Suman, Oscar; Kraft, Robert; Branski, Ludwik; Al-mousawi, Ahmed M.; Herndon, David.

In: PLoS One, Vol. 7, No. 5, e35465, 11.05.2012.

Research output: Contribution to journalArticle

Jeschke, MG, Williams, FN, Finnerty, C, Rodriguez, NA, Kulp, GA, Ferrando, A, Norbury, W, Suman, O, Kraft, R, Branski, L, Al-mousawi, AM & Herndon, D 2012, 'The effect of ketoconazole on post-burn inflammation, hypermetabolism and clinical outcomes', PLoS One, vol. 7, no. 5, e35465. https://doi.org/10.1371/journal.pone.0035465
Jeschke, Marc G. ; Williams, Felicia N. ; Finnerty, Celeste ; Rodriguez, Noe A. ; Kulp, Gabriela A. ; Ferrando, Arny ; Norbury, William ; Suman, Oscar ; Kraft, Robert ; Branski, Ludwik ; Al-mousawi, Ahmed M. ; Herndon, David. / The effect of ketoconazole on post-burn inflammation, hypermetabolism and clinical outcomes. In: PLoS One. 2012 ; Vol. 7, No. 5.
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