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

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 Prolonged Infusions in the Pediatric Intensive Care Unit: a Tertiary-Care Single-Center Analysis.

OBJECTIVE: Ketamine is commonly used as an anesthetic and analgesic agent for procedural sedation, but there is little evidence on its current use as a prolonged continuous infusion in the PICU. We sought to analyze the use of ketamine as a prolonged infusion in critically ill children, its indications, dosages, efficacy, and safety. METHODS: We retrospectively reviewed the clinical charts of patients receiving ketamine for ≥24 hours in the period 2017-2018 in our tertiary care center. Data on concomitant treatments pre and 24 hours post ketamine introduction and adverse events were also collected. RESULTS: Of the 60 patients included, 78% received ketamine as an adjuvant of analgosedation, 18% as an adjuvant of bronchospasm therapy, and 4% as an antiepileptic treatment. The median infusion duration was 103 hours (interquartile range [IQR], 58-159; range, 24-287), with median dosages between 15 (IQR, 10-20; range, 5-47) and 30 (IQR, 20-50; range, 10-100) mcg/kg/min. At 24 hours of ketamine infusion, dosages/kg/hr of opioids significantly decreased (p < 0.001), and 81% of patients had no increases in dosages of concomitant analgosedation. For 27% of patients with bronchospasm, the salbutamol infusions were lowered at 24 hours after ketamine introduction. Electroencephalograms of epileptic patients (n = 2) showed resolution of status epilepticus after ketamine administration. Adverse events most likely related to ketamine were hypertension (n = 1), hypersalivation (n = 1), and delirium (n = 1). CONCLUSIONS: Ketamine can be considered a worthy strategy for the analgosedation of difficult-to-sedate patients. Its use for prolonged sedation allows the sparing of opioids. Its efficacy in patients with bronchospasm or status epilepticus still needs to be investigated.

Predictors of mortality after admission to pediatric intensive care unit in oncohematologic patients without history of hematopoietic stem cell transplantation: A single-center experience.

BACKGROUND: Pediatric oncohematologic patients are a high-risk population for clinical deterioration that might require pediatric intensive care unit (PICU) admission. Several studies have described outcomes and mortality predictors for patients post hematopoietic stem cell transplantation (HSCT), but fewer data exist regarding the category of non-HSCT patients. PROCEDURE: All oncohematologic non-HSCT patients ≤18 years requiring PICU admission from 1998 to 2015 in our tertiary-care academic hospital were retrospectively evaluated by means of the pediatric hematology-oncology unit database and the Italian PICUs data network database. We assessed the relation between demographic and clinical characteristics and 90-day mortality after PICU admission. RESULTS: Of 3750 hospitalized oncohematologic patients, 3238 were non-HSCT and 63 (2%) of them were admitted to the PICU. Patients were mainly affected by hematological malignancies (70%) and mostly were in the induction-therapy phase. The main reasons for admission were respiratory failure (40%), sepsis (25%), and seizures (16%). The median PICU stay was 5 days (range 1-107). The mortality rate at PICU discharge was 30%, and at 90 days it was 35%. Fifty-five percent of deaths happened in the first 2 days of the PICU stay. Cardiac arrest (P = .007), presence of disseminated intravascular coagulation (DIC, P = .007), and acute kidney injury (AKI) at PICU admission (P < .001) and during PICU stay (P = .021) were significant predictors of mortality in the multivariate analysis. Respiratory failure and mechanical ventilation were not associated with mortality. CONCLUSIONS: A relatively small percentage of non-HSCT patients required PICU admission, but the mortality rate was still high. Hemodynamic instability, DIC, and AKI, but not respiratory failure, were significant predictors of mortality.