Effects of Ketamine Dosing on Delirium in Medical ICU Patients

Introduction: The 2018 PADIS guidelines recommend ketamine as an adjunct to reduce opioids but make no comment on its use for sedation. Ketamine has dissociative effects and literature on its effect on delirium is conflicting. The purpose of this study is to determine if high-dose ketamine increases incidence of delirium in intensive care unit (ICU) patients.


Methods: A retrospective cohort study of mechanically intubated ICU patients receiving continuous ketamine for sedation between January 1, 2013 and June 30, 2025 was conducted. Patients who received ketamine for < 24h or received continuous paralytic therapy were excluded. The primary outcome was a positive CAM-ICU score while receiving or up to 72h after ketamine. Secondary outcomes included cumulative analgesic, sedative, and antipsychotic requirements, hospital length of stay (LOS), ICU LOS, and mortality. Patients were grouped into low-dose ( < 1.2mg/kg/h) or high-dose (≥1.2mg/kg/h) based on the maximum rate.


Results: Of the 46 patients included, 27 received low-dose ketamine (median dose 0.6mg/kg/h) and 19 received high-dose (median dose 2.5mg/kg/h). The low-dose group had a lower cumulative (186mg [IQR: 814-6246] vs 8365mg [IQR:5029-13180], p< 0.01) and daily dose (711mg/day [IQR:429-1112] vs 2346 mg/day [IQR:1549-3335], p< 0.01); however, there was no difference in duration (197h [IQR:134-330] vs 50.1h [IQR:37-122], p=0.80 ).The high-dose arm had an increased incidence of substance use and/or psychiatric disorders. There was no difference in the primary outcome, incidence of positive CAM-ICU scores between the low and high-dose arms (29.6% vs 31.6%, p=0.89). There was no difference in the receipt of the following agents while on ketamine in the low and high-dose arms: propofol (41% vs 68%, p=0.09), midazolam (74% vs 90%, p=0.67), dexmedetomidine (37% vs 37%, p=0.67), and fentanyl (89% vs 100%, p=0.14). No differences were seen in hospital LOS, ICU LOS, or mortality.


Conclusions: Ketamine dosing did not have a significant effect on ICU delirium. There was no observed difference in sedative, analgesic, or antipsychotic use or patient outcomes between groups. Further research is needed to determine the effect of ketamine dosing on delirium.