Critically Ill Children Frequently Receive Medications with Established but Unused Pharmacogenomic Guidelines: Actionable Findings from an Integrated Electronic Medical Record and Exome Sequencing Study.

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; 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.