Higher bilirubin on admission predicts better outcome in refractory cardiac arrest: A Prague OHCA trial analysis focused on the antioxidant effect of bilirubin

Background

Although bilirubin is a proven antioxidant substance and a protective factor against the development of various diseases, in emergency medicine, its increased concentration is considered solely a marker of organ damage and negative prognosis. However, clinical data on the role of bilirubin in cardiac arrest (CA) and reperfusion injury, are sparse. The presented study investigates the protective effects of increased serum bilirubin concentrations and genetic determinants (UGT1A1 promoter variations) on the outcomes of patients with refractory out-of-hospital CA (r-OHCA) in a randomized population.

Methods

Between March 1, 2013, and October 25, 2020, 256 randomized Prague OHCA patients with r-OHCA were evaluated for inclusion and categorized as having increased (>10 µmol/l) or low/normal serum bilirubin concentrations on hospital arrival and present or absent genetic variations for mild hyperbilirubinemia. The primary outcome was survival with a good neurological outcome (defined as cerebral performance category 1–2) 180 days after randomization.

Results

Finally, 164 patients were included in the bilirubin concentration analysis. Favorable neurological survival after 180 days occurred in 50 of 99 patients (50.5 %) in the group with higher initial serum bilirubin concentrations and 18 of 65 patients (27.7 %) in the low-bilirubin group (absolute difference 22.8 [8.1–37.5]; P = 0.006). The effect persisted also in multivariable analysis (OR for favorable outcome = 3.02 [95 % CI = 1.16–7.84]; P = 0.023). Genetic predisposition for mild hyperbilirubinemia was not associated with any patient outcomes.

Conclusions

A higher initial serum bilirubin concentration predicts better outcomes in patients with refractory OHCA regardless of the treatment used. UGT1A1 gene promotor variations are not associated with refractory OHCA patient outcomes.