Characterisation and Prognostic Implication of Cholestasis After Burn Injury

BACKGROUND: Cholestasis is a frequent phenomenon in patients with burn injury and linked with impaired outcomes. AIMS: To explore longitudinal trajectories of cholestasis and validate the proposed definition of burn-associated cholestasis (BAC). METHODS: 532 patients admitted to an intensive care unit (ICU) for burn injury over a 10-year timeframe were included in this single-center, retrospective cohort study. Burn severity, ICU treatment, and laboratory parameters were longitudinally collected from admission to discharge or death. RESULTS: Median total body surface area burned was 15% and 234 patients (44%) had severe burn (≥ 20%). 118 patients (22%) met the proposed criteria of BAC while 41%, 30%, and 68% developed elevated alkaline phosphatase, bilirubin, and gamma-glutamyl transferase, respectively. BAC was associated with burn severity, ketamine use, mechanical ventilation, and parenteral nutrition, and 85% of cases occurred in patients exposed to ketamine, mechanical ventilation, and parenteral nutrition. Hyperbilirubinemia (≥ 2× upper-limit-of-normal, i.e., BAC subtype B/C) was independently associated with mortality adjusting for burn severity, critical illness severity, and ICU-specific treatment. However, bilirubin alone provided better discrimination, especially regarding excess deaths after ≥ 7 days (Harrel's C: 0.80-0.83). Concordant increases in bilirubin and alkaline phosphatase/gamma-glutamyl transferase allow for early identification of an at-risk population. Developing hyperbilirubinemia until Day 14 identified a subgroup with severely impaired prognosis (survival at 90 days: 46% vs. 95%). CONCLUSIONS: Cholestasis is frequent following burn injury. Prognosis is determined by bilirubin dynamics independently of disease and burn severity. Hyperbilirubinemia is associated with excess mortality ≥ 7 days after surviving burn injury.