Evaluating Mortality And Recovery Of Extreme Hyperbilirubinemia In Critically Ill Patients By Phasing The Peak Bilirubin Level: A Retrospective Cohort Study

Background Hyperbilirubinemia is a devastating complication in patients admitted to an intensive care unit (ICU). The sequential organ failure assessment (SOFA) score classifies hyperbilirubinemia without further detailed analyses for bilirubin increase above 12 mg/dL. We evaluated whether the level of bilirubin increase in patients with extreme hyperbilirubinemia (total bilirubin >= 12 mg/dL) affects and also helps estimate mortality or recovery. Methods A retrospective cohort analysis comprising 427 patients with extreme hyperbilirubinemia admitted to the ICU of Samsung Medical Center, Seoul, Korea between 2011 and 2015 was conducted. Extreme hyperbilirubinemia was classified into four grades: grade 1 (12-14.9 mg/dL), grade 2 (15-19.9 mg/dL), grade 3 (20-29.9 mg/dL), and grade 4 (>= 30 mg/dL). These grades were then assessed for their association with hospital mortality and recovery from hyperbilirubinemia to SOFA grade (point) 2 or below (total bilirubin < 6 mg/dL). The influences of various factors, some of which caused extreme hyperbilirubinemia, while others induced bilirubin recovery, were assessed. Results A total of 427 patients (mean age: 59.8 years, male: 67.0%) were evaluated, and the hospital mortality for these patients was very high (76.1%). Extreme hyperbilirubinemia was observed in 111 (grade 1, 26.0%), 99 (grade 2, 23.2%), 131 (grade3, 30.7%), and 86 (grade 4, 20.1%) patients with mortality rates of 62.2%, 71.7%, 81.7%, and 90.7%, respectively (p < 0.001). The peak bilirubin value correlated with the mortality (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.04-1.15, p < 0.001). Compared to those with grade 1 extreme hyperbilirubinemia, the mortality rate gradually increased as the grade increased (OR [95% CI]: 1.92 [0.70-5.28], 3.55 [1.33-9.48], and 12.47 [3.07-50.59] for grades 2, 3 and 4, respectively). The main causes of extreme hyperbilirubinemia were infection including sepsis and hypoxic hepatitis. The recovery from hyperbilirubinemia was observed in 110 (25.8%) patients. Mortality was lower for those who recovered from hyperbilirubinemia than for those who did not (29.1% vs. 92.4%, p < 0.001). The favorable factors of bilirubin recovery were albumin and ursodeoxycholic acid (UDCA). Conclusions This study determined that the level of extreme hyperbilirubinemia is an important prognostic factor in critically ill patients. We expect the results of this study to help predict the clinical course of and determine the optimal treatment for extreme hyperbilirubinemia.