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ABCB1 genotype is associated with fentanyl requirements in critically ill children
Christopher M Horvat1, Alicia K Au1, Yvette P Conley2
1Department of Critical Care Medicine, Safar Center for Resuscitation Research and the Brain Care Institute at the Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Insights
The ABCB1 genotype rs1045642 AA variant is linked to reduced fentanyl requirements in critically ill children. This finding suggests genetic variations in ABCB1 influence opioid dosing in pediatric intensive care units.
Area of Science:
- Pharmacogenetics
- Critical Care Medicine
- Pediatric Anesthesiology
Background:
- The ABCB1 gene encodes p-glycoprotein, an efflux pump affecting opioid transport.
- ABCB1 genotype may influence fentanyl dosing in critically ill children.
Purpose of the Study:
- To investigate the association between ABCB1 genotype and fentanyl requirements in pediatric intensive care unit (PICU) patients.
- To examine the relationship between fentanyl dosing, pain/sedation scores, serum fentanyl levels, and ABCB1 genotype.
Main Methods:
- Studied a cohort of 61 children receiving fentanyl infusions in the PICU.
- Analyzed associations between fentanyl requirements, pain/sedation scores, serum fentanyl levels, and ABCB1 genotype (rs1045642).
Main Results:
- Patients with the ABCB1 rs1045642 AA allele required significantly less fentanyl (18.6 mcg/kg/day less) compared to AG or GG alleles.
- The AA allele was associated with lower fentanyl administration, potentially due to reduced p-glycoprotein activity.
Conclusions:
- ABCB1 genotype rs1045642 AA is associated with altered fentanyl administration in critically ill children.
- Further prospective studies are warranted to evaluate ABCB1's role in sedative-analgesia for critically ill pediatric patients.
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.