Extended hypermetabolic response of the liver in severely burned pediatric patients

Hypothesis: The acute phase response is a cascade of events contributing to hypermetabolism and substrate catabolism. It was believed to persist for only a short time after injury. There is now evidence that systemic catabolism and hypermetabolism associated with thermal injury persevere for a long time. We hypothesize that the proinflammatory hepatic acute phase response perseveres for an extended time and enhances hypermetabolism longer than previously believed. Design: Prospective study. Setting: Intensive Care Burn Unit, Shriners Hospital for Children. Patients: Twenty-three children (aged 1-16 years) sustaining a severe thermal injury (≥40% total-body surface area) who remained in the intensive care unit longer than 30 days. Main Outcome Measures: Patient demographics, nutritional support, incidence of sepsis, inhalation injury, mortality, and levels of serum constitutive proteins, type I and type II acute phase proteins, free fatty acids, proinflammatory cytokines, insulin-like growth factor (IGF) I, IGF binding protein-1, IGF binding protein-3, and hepatocyte growth factor. Results: After thermal injury, constitutive hepatic protein levels decreased 2- to 3-fold 80 days after burn, whereas acute phase protein levels increased. Free fatty acid levels were increased 5 days after burn. Proinflammatory cytokine levels (interleukin [IL] 1, IL-6, IL-8, IL-10, and tumor necrosis factor) and IGF binding protein-1 levels were elevated for 40 days after burn, whereas serum IGF-I and IGF binding protein-3 levels were decreased. Hepatocyte growth factor levels were increased immediately after burn but rapidly returned to the normal range. Conclusions: Despite adequate nutritional support, a severe thermal injury induces the proinflammatory acute phase response for a prolonged period. Thus, the liver with the hepatic acute phase response plays a more important role during catabolism after burn than previously believed. Pharmacologic agents that improve hepatic function may be an effective approach to attenuate hypermetabolism after trauma.