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Impact of Prolonged Continuous Ketamine Infusions in Critically Ill Children: A Prospective Cohort Study
Paulo Sérgio Lucas da Silva1, Emerson Yukio Kubo2, Rafael da Motta Ramos Siqueira2
1Department of Pediatrics, Pediatric Intensive Care Unit, Hospital Estadual de Diadema, Rua José Bonifácio 1641, São Paulo, 09980-150, Brazil. psls.nat@terra.com.br.
Insights
Prolonged ketamine infusions (>24 hours) in pediatric intensive care units (PICU) were associated with increased adverse events, particularly delirium. Further research is needed before widespread adoption in pediatric sedation protocols.
Area of Science:
- Pediatric Critical Care Medicine
- Pharmacology
- Anesthesiology
Background:
- Limited evidence exists for prolonged ketamine infusions (>24 hours) in pediatric intensive care units (PICUs).
- Ketamine is considered as an adjunct for achieving target sedation depth in children.
Purpose of the Study:
- To evaluate the safety and effectiveness of continuous ketamine infusion for over 24 hours in mechanically ventilated children.
- To assess adverse events (AEs) and delirium incidence associated with prolonged ketamine use.
Main Methods:
- Prospective cohort study in a tertiary PICU (January 2020 - December 2022).
- Compared ketamine-based vs. non-ketamine-based sedative regimens.
- Primary outcome: incidence of AEs; Secondary outcomes: RASS goal achievement and delirium incidence.
Main Results:
- Delirium occurred in 22% of ketamine patients vs. 7.6% of non-ketamine patients (p=0.006).
- 42% of ketamine patients experienced AEs, including hypertension, hypersecretion, and tachycardia.
- Ketamine use was associated with increased odds of delirium (OR 4.17) after covariate adjustment.
- Patients on ketamine had longer mechanical ventilation duration and PICU/hospital stays.
Conclusions:
- Prolonged ketamine infusion in PICU patients may increase adverse events, especially delirium.
- High-quality studies are required to establish the safety and efficacy of early or broad ketamine adoption in pediatric sedation.
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.
