Is ketamine infusion effective and safe as an adjuvant of sedation in the PICU? Results from the Ketamine Infusion Sedation Study (KISS).

Abstract

We aimed to evaluate the efficacy and safety of ketamine in ensuring comfort and sparing conventional drugs when used as an adjuvant for analgesia and sedation in the Pediatric Intensive Care Unit (PICU) as a continuous infusion (≥12h). Observational prospective study. Tertiary-care-center PICU. All consecutive patients <18 years who received ketamine for ≥12 h between January 2019 and July 2021. ketamine infusion for ≥12 h. Seventy-seven patients (median age 16months, Interquartile Range (IQR) 7-43) were enrolled. Twenty-six percent of patients (n=20) were paralyzed, while 74% (n=57) were not. The median infusion duration was 90h (IQR 39-193), with doses between 15 (IQR 15-20) and 30 μg/kg/min (IQR 20-50). At 24 h of ketamine infusion, values of COMFORT-B-Scale (CBS) were significantly lower compared with values pre-ketamine (p < 0.001). Simultaneously, doses/kg/h of opioids and benzodiazepines significantly decreased at 24 h (p < 0.001 and p=0.002, respectively), while doses/kg/h of propofol (p=0.500) and dexmedetomidine (p=0.072) did not significantly change. Seventy-four percent of non-paralyzed patients (42/57) had a decrease in CBS ≥2 points with no increase of concomitant analgosedation drugs. Among paralyzed patients (n=20), 13 (65%) had no increase of concomitant analgosedation within 24 h after ketamine initiation. Overall, 55/77 (71%) of patients responded to ketamine. The mean and maximum ketamine infusion dosages were significantly higher in the non-responders (p=0.021 and 0.028, respectively). Eleven patients had adverse events potentially related to ketamine (hypersalivation, systemic hypertension, dystonia/dyskinesia, tachycardia, and agitation) and six patients required intervention (dose reduction, suspension, or pharmacologic therapy). None of the patients developed delirium during ketamine infusion. Ketamine used as a continuous infusion in the PICU might represent a valid strategy to ensure comfort and spare opioids and benzodiazepines in difficult-to-sedate PICU patients. Adverse events are minor and easily reversible. Future study will be needed to investigate long-term outcomes.