Direct Hyperbilirubinemia Associated With Increased Mortality Rate in Children on ECMO

Abnormal high bilirubin test result with blood sample tube
Researchers investigated the risk factors for children to develop hyperbilirubinemia as a result of receiving extracorporeal membrane oxygenation and the association with mortality.

Direct hyperbilirubinemia (DHB) in children receiving extracorporeal membrane oxygenation (ECMO) support is associated with a higher mortality rate compared with children who did not develop DHB on ECMO, according to a study in the Journal of Pediatric Gastroenterology and Nutrition.

The single-center, retrospective study used electronic health records (EHR) from the Mayo Clinic from January 2010 to January 2020 to evaluate the frequency and risk factors for developing DHB on ECMO and its effect on mortality.

All children aged younger than 8 years who required ECMO support during their hospitalization were identified. They were then stratified into 2 groups: those who developed DHB after beginning ECMO (DHB group) and those who did not (control group). DHB was defined as direct bilirubin (DB) value greater than 1.0 mg/dL.

A total of 106 children (median age, 0.2 [IQR, 0-2.3] years; 51% boys) were included. Among the cohort, 36 children (34%) developed DHB on ECMO, with the peak DB 0.6 (0.4-1.8) mg/dL occurring on ECMO day 3 (2-6). The median peak total bilirubin was 3.5 (2-7.1) mg/dL.

DHB group patients were intubated and required ECMO support for a longer period vs the non-DHB group (P =.008 and P <.001, respectively). Disease acuity, according to vasoactive-ionotropic score (VIS), was higher in the DHB group and was statistically significant on ECMO days 2 and 7 (P =.046, .01, respectively). The cholestasis and control groups had comparable Acute Physiology and Chronic Health Evaluation II scores (P =.779).

The overall mortality rate among study participants was 43% (46/106). The DHB group had a higher mortality rate (72%) vs the control group (29%; P <.001). DHB independent of VIS was associated with a higher mortality rate.

Study limitations included the retrospective design and limited long-term follow-up data. In addition, participants had various ages and indications for ECMO. Furthermore, when using maximum pressor needs, the VIS over-represented the average clinical acuity for the day.

“Our study supports the use of DHB as a prognostic marker for children on ECMO support,” the researchers concluded. “Our findings are consistent with multiple adult studies reporting a role for elevated bilirubin in predicting outcomes on and after veno-arterial ECMO support. In this cohort, DHB was associated with a higher mortality rate, independent of disease acuity.”


Alexander E, O’Sullivan D, Aganga D, Hassan S, Ibrahim SH, Absah I. Clinical implications for children developing direct hyperbilirubinemia on extracorporeal membrane oxygenation. J Pediatr Gastroenterol Nutr. 2022;74(3):333-337. doi 10.1097/MPG.0000000000003364