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

ImportancePharmacogenomic (PGx) guidelines can improve medication efficacy and reduce toxicity, but their application in pediatric intensive care units (PICUs) remains largely unexplored. ObjectiveTo 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. DesignRetrospective cohort study integrating electronic medical record and exome sequencing data. SettingMorgan Stanley Childrens Hospital of NewYork-Presbyterian, a single center tertiary care childrens hospital. ParticipantsA 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). ExposureCritical illness requiring PICU admission. Main Outcomes and MeasuresFrequencies of administration of medications with established PGx guidelines in the PICU and the proportion of individuals with exome sequencing with identifiable PGx phenotypes. ResultsAmong 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 RelevanceMany 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. Key PointsO_ST_ABSQuestionC_ST_ABSDo critically ill children in a tertiary care hospital receive medications for which PGx guidelines exist, and does exome sequencing reliably identify relevant pharmacogenomic phenotype? FindingsAnalysis of electronic medical records from 4,939 critically ill children and exome sequencing of 192 patients demonstrated that many received medications that have established pharmacogenomic guidelines, and exome sequencing identified actionable pharmacogenomic variants with implications for treatment. MeaningMany critically ill children receive medications for which PGx guidelines exist but are not routinely applied. This represents a missed opportunity to apply precision medicine to improve the care of critically ill children.