Abstract
BackgroundThe gene ABCB1 encodes p-glycoprotein, a xenobiotic efflux pump capable of transporting certain opioids, including fentanyl. ABCB1 genotype has been previously associated with patient opioid requirements and may influence fentanyl dosing requirements in critically ill children.MethodsA diagnostically diverse cohort of 61 children who received a fentanyl infusion while admitted to the pediatric intensive care unit (PICU) were included in this study. We examined associations between fentanyl requirements, pain and sedation scores, serum fentanyl levels, and ABCB1 genotype.ResultsPatients with the AA allele at ABCB1 locus rs1045642 received less fentanyl compared with patients with the AG or GG allele. A multivariable model demonstrated that patients with the AA allele received 18.6 mcg/kg/day less fentanyl than patients with either the AG or GG allele (95% confidence interval -33.4 to -3.8 mcg/kg/day; P=0.014). Incorporating race in this model demonstrated a similar association, but did not reach the threshold for multiple testing.ConclusionABCB1 genotype rs1045642 AA is associated with fentanyl administration in this cohort of children admitted to the PICU, likely because of decreased expression and activity of p-glycoprotein. Prospective evaluation of the influence of ABCB1 in sedative-analgesia administration in critically ill children is warranted.