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This retrospective study of 4,939 pediatric intensive care unit (PICU) patients found that 37.2% received at least one medication with established pharmacogenomic guidelines, yet these guidelines were not routinely applied in clinical practice. Among a subset of 192 patients who underwent exome sequencing, 62% had identifiable genetic variants affecting drug metabolism. The findings suggest that approximately 8.2% of PICU patients could benefit from pharmacogenomic-guided medication adjustments to improve treatment efficacy and reduce toxicity.
Why it matters
The study reveals a significant gap between available pharmacogenomic knowledge and its implementation in pediatric critical care, where medication precision is particularly important due to children's vulnerability and developmental differences in drug metabolism. Integrating genetic testing into PICU care could enable more personalized medication selection and dosing, potentially improving outcomes for thousands of critically ill children.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Importance Pharmacogenomic (PGx) guidelines can improve medication efficacy and reduce toxicity, but their application in pediatric intensive care units (PICUs) remains largely unexplored. Objective To determine the frequency of medications with established PGx guidelines administered in the PICU and assess the capacity of exome sequencing to capture PGx phenotypes for these medications. Design Retrospective cohort study integrating electronic medical record and exome sequencing data. Setting Morgan Stanley Children’s Hospital of NewYork-Presbyterian, a single center tertiary care children’s hospital. Participants A total of 4,939 children admitted to the PICU (2020 – 2024), and 192 children admitted to the PICU who underwent exome sequencing for research purposes (2015 – 2023). Exposure Critical illness requiring PICU admission. Main Outcomes and Measures Frequencies of administration of medications with established PGx guidelines in the PICU and the proportion of individuals with exome sequencing with identifiable PGx phenotypes. Results Among 4,939 PICU patients, 37.2% (n=1,837) received at least one medication with established PGx guidelines and 14.4% (n=712) received two or more such medications. Twenty PGx genes were implicated; CYP2C9 was most common (17.3%, n=853). An estimated 8.2% of patients received medications for which PGx-guided recommendations would have altered clinical management. Among 192 patients who underwent exome sequencing, at least one metabolizer phenotype was identified in 62% (n=119). Conclusions and Relevance Many critically ill children receive medications with established PGx guidelines. This study highlights an opportunity for more personalized medicine for critically ill children admitted to a tertiary care hospital and assesses the strengths and weaknesses of exome sequencing to uncover pertinent PGx phenotypes.