Impact of Prolonged Continuous Ketamine Infusions in Critically Ill Children: A Prospective Cohort Study

Background Ketamine has been considered as an adjunct for children who do not reach their predefined target sedation depth. However, there is limited evidence regarding the use of ketamine as a prolonged infusion (i.e., >24 hours) in the pediatric intensive care unit (PICU). Objective We sought to evaluate the safety and effectiveness of continuous ketamine infusion for >24 hours in mechanically ventilated children. Methods We conducted a prospective cohort study in a tertiary PICU from January 2020 to December 2022. The primary outcome was the incidence of adverse events (AEs) after ketamine initiation. The secondary outcome included assessing the median proportion of time the patient spent on the Richmond Agitation-Sedation Scale (RASS) goal after ketamine infusion. Patients were also divided into two groups based on the sedative regimen, ketamine-based or non-ketamine-based, to assess the incidence of delirium. Results A total of 269 patients were enrolled: 73 in the ketamine group and 196 in the non-ketamine group. The median infusion rate of ketamine was 1.4 mg/kg/h. Delirium occurred in 16 (22%) patients with ketamine and 15 (7.6%) patients without ketamine (p = 0.006). After adjusting for covariates, logistic regression showed that delirium was associated with comorbidities (odds ratio [OR] 4.2), neurodevelopmental delay (OR 0.23), fentanyl use (OR 7.35), and ketamine use (OR 4.17). Thirty-one (42%) of the patients experienced at least one AE following ketamine infusion. Other AEs likely related to ketamine were hypertension (n = 4), hypersecretion (n = 14), tachycardia (n = 6), and nystagmus (n = 2). There were no significant changes in hemodynamic variables 24 h after the initiation of ketamine. Regarding the secondary outcomes, patients were at their goal RASS level for a median of 76% (range 68-80.5%) of the time in the 24 hours before ketamine initiation, compared with 84% (range 74.5-90%) of the time during the 24 h after ketamine initiation (p < 0.001). The infusion rate of ketamine did not significantly affect concomitant analgesic and sedative infusions. The ketamine group experienced a longer duration of mechanical ventilation and a longer length of stay in the PICU and hospital than the non-ketamine group. Conclusion The use of ketamine infusion in PICU patients may be associated with an increased rate of adverse events, especially delirium. High-quality studies are needed before ketamine can be broadly recommended or adopted earlier in the sedation protocol.