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

Abstract

Study Objective 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 (≥12 h). Design Observational prospective study. Setting Tertiary‐care‐center PICU. Patients All consecutive patients <18 years who received ketamine for ≥12 h between January 2019 and July 2021. Interventions ketamine infusion for ≥12 h. Measurements and Main Results Seventy‐seven patients (median age 16 months, 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 90 h (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. Conclusions 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.

Ketamine Clinical Use on the Pediatric Critically Ill Infant: A Global Bibliometric and Critical Review of Literature

“…Adverse reactions also varied across the studies, of which dissociative effects, agitation, and cognitive changes compose the main effects described [11,21,22,31,60]. Long-lasting neurobehavioral impairments caused by ketamine have also been reported [11,23]. Regarding comorbidities, respiratory system diseases were the most frequent in these studies [8,11,27,29,40,43,65].…”

“…The period of administration also varied between articles, ranging from acute administrations, such as in invasive procedures [33,38], to long-term dosages, such as in cases of patients on mechanical ventilation [11,21,24]. The principal psychotropic drugs associated with ketamine consisted of opioids and benzodiazepines, especially midazolam [11,20,23,24,29,37,40,41,47,63,64,67,68,70,72]. Adverse reactions also varied across the studies, of which dissociative effects, agitation, and cognitive changes compose the main effects described [11,21,22,31,60].…”

The Evolution of Ketamine in Severe Pediatric Traumatic Brain Injury, From Contraband to Promising Neuroprotectant?*

“…Ketamine merits further testing in larger studies both in the setting of raised ICP refractory to tier 1 therapy and/or as part of the baseline sedative-analgesia regimen in pediatric severe TBI. This is also true given the limited efficacy of fentanyl and/or midazolam to reduce ICP and improve CPP in prior reports (14,15), the known associations between benzodiazepine use and delirium in pediatric critical care (16), and recent reports suggesting possibly less delirium with ketamine use as an adjunct for analgesia and sedation in the PICU (17,18). Future prospective studies should seek to examine the effect of ketamine within the multimodal treatment of severe TBI patients.…”