Effects of ketamine infusion rate and cumulative dosing on incidence of delirium in medical intensive care unit patients.

PURPOSE: Ketamine is increasingly used for analgosedation in mechanically ventilated intensive care unit (ICU) patients, but its association with delirium remains unclear. This study evaluated the relationship between maximum hourly ketamine rate and cumulative dose during hospitalization, with the incidence of delirium. METHODS: This multicenter retrospective cohort study included mechanically ventilated adult medical ICU patients who received ketamine infusions for sedation (January 2013-June 2025) at two tertiary centers. Data collected included demographics, sedation requirements, and daily Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). The primary outcome was delirium at any point during ICU stay. Primary and secondary exposure variables included maximum hourly ketamine rate and cumulative ketamine dose. A modified Poisson regression was used to evaluate associations between the exposure variables and incidence of delirium, adjusting for confounders. RESULTS: Of 837 screened patients, 114 met inclusion criteria and 42 (36.8%) developed delirium. Baseline characteristics were similar. Patients with delirium had longer duration of mechanical ventilation, (210.7 vs 140.9 hours, P <0.01), ICU length of stay (364.7 vs 268.6 hours, P =0.04), and higher morphine milligram equivalents (5,126.8 vs 2911.8, P = 0.04). No association was observed between delirium with maximum hourly ketamine rate (RR 1.15, P = 0.21) or cumulative dose (RR 1.0, p=0.97). Restricted cubic spline analysis showed a trend towards increased delirium risk with increasing maximum hourly ketamine rates (P = 0.06). CONCLUSION: Maximum hourly ketamine infusion rate and cumulative dose in mechanical ventilated patients in the medical ICU were not associated with ICU delirium.