Patient-Specific Factors Associated with Dexmedetomidine Dose Requirements in Critically Ill Children

Objective: To evaluate patient-specific factors associated with dexmedetomidine dose requirements during continuous infusion. Methods: A retrospective cross-sectional analysis of electronic health record-derived data spanning ten years for patients admitted with a primary respiratory diagnosis at a quaternary children’s hospital and who received a dexmedetomidine continuous infusion (N=346 patients) was conducted. Penalized regression was used to select demographic, clinical, and medication characteristics associated with median daily dexmedetomidine dose. Identified characteristics were included in multivariable linear regression models and sensitivity analyses. Results: Critically ill children had a median hourly dexmedetomidine dose of 0.5 mcg/kg/hr (range: 0.1 - 1.8), median daily dose of 6.8 mcg/kg/day (range: 0.9 - 38.4), and median infusion duration of 1.6 days (range: 0.25 - 5.0). Of 26 variables tested, 15 were selected in the final model with days of dexmedetomidine infusion (: 1.9; 95% CI: 1.6, 2.3), median daily morphine milligram equivalents dosing (mg/kg/day) (: 0.3; 95% CI: 0.1, 0.5), median daily ketamine dosing (mg/kg/day) (: 0.2; 95% CI: 0.1, 0.3), male sex (: -1.1; 95% CI: -2.0, -0.2), and non-Black reported race (: -1.2; 95% CI: -2.3, -0.08) significantly associated with median daily dexmedetomidine dose. Approximately 56% of dose variability was explained by the model. Conclusions: Readily obtainable information such as demographics, concomitant medications, and duration of infusion account for over half the variability in dexmedetomidine dosing. Identified factors, as well as additional environmental and genetic factors, warrant investigation in future studies to inform precision dosing strategies.