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 sought to study the effect of Ketoconazole on post-burn cortisol levels and hyper-catabolic response.

Methods: Forty-nine severely burned pediatric patients with burns >30% total body surface area (TBSA) were enrolled into the study and were block randomized 2:1 to receive standard care (controls, n=32) or standard care plus ketoconazole (n=17). Patients were similar in age, and TBSA. Demographics, clinical data, serum hormones, serum cytokine expression profile, organ function, hypermetabolism, muscle protein synthesis, incidence of wound infection sepsis, and body composition were obtained throughout acute hospital course. Statistical analysis was performed using Student’s t-test or ANOVA where applicable.

Results: There were no significant differences in demographics between treatment groups. Ketoconazole effectively blocked cortisol production indicated by normalization of the 8-fold elevation of urine cortisol levels (p<0.05). 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. Both groups were markedly hypermetabolic and catabolic throughout acute hospital stay.

Conclusion: Normalization of hypercortisolemia with ketoconazole therapy had no effect on whole body catabolism, or the post-burn inflammatory or hypermetabolic response. The data suggests that hypercortisolemia does not play a central role in the post-burn hypermetabolic, catabolic response.