Is Indirect Hyperbilirubinemia a Useful Biomarker of Reduced Propofol Clearance in Neonates?

Abstract

Large interindividual variability in neonatal propofol clearance is documented which, in part, can be explained by postmenstrual age (PMA) and postnatal age (PNA). We aimed to document whether indirect bilirubin, instead of or in addition to PNA, could improve predictability of propofol clearance and serve as a useful biomarker of reduced propofol clearance in neonates. Indirect serum bilirubin was introduced as a dichotomous or continuous variable (both age-normalized) in a previously developed three-compartment pharmacokinetic model, based on 235 concentration-time points obtained in 25 neonates after single bolus administration of propofol. For pharmacokinetic analysis, nonlinear mixed effect modeling 6.2 was used. The covariates PMA and PNA explained 67% of the interindividual variability compared with 45% in the model with PMA and bilirubin. Age, reflected by PMA and PNA, is a more relevant clinical predictor of neonatal propofol clearance compared with PMA and raised indirect hyperbilirubinemia.