Efficacy and Safety of Dexmedetomidine for Prolonged Sedation in the PICU: A Prospective Multicenter Study (PROSDEX).

OBJECTIVES: We sought to evaluate dexmedetomidine efficacy in assuring comfort and sparing conventional drugs when used for prolonged sedation (≥24 hr) in critically ill patients, by using validated clinical scores while systematically collecting drug dosages. We also evaluated the safety profile of dexmedetomidine and the risk factors associated with adverse events. DESIGN: Observational prospective study. SETTING: Nine tertiary-care PICUs. PATIENTS: Patients less than 18 years who received dexmedetomidine for greater than or equal to 24 hours between January 2016 and December 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One-hundred sixty-three patients (median age, 13 mo; interquartile range, 4-71 mo) were enrolled. The main indication for dexmedetomidine use was as an adjuvant for drug-sparing (42%). Twenty-three patients (14%) received dexmedetomidine as monotherapy. Seven percent of patients received a loading dose. The median infusion duration was 108 hours (interquartile range, 60-168 hr), with dosages between 0.4 (interquartile range, 0.3-0.5) and 0.8 µg/kg/hr (interquartile range, 0.6-1.2 µg/kg/hr). At 24 hours of dexmedetomidine infusion, values of COMFORT-B Scale (n = 114), Withdrawal Assessment Tool-1 (n = 43) and Cornell Assessment of Pediatric Delirum (n = 6) were significantly decreased compared with values registered immediately pre dexmedetomidine (p < 0.001, p < 0.001, p = 0.027). Dosages/kg/hr of benzodiazepines, opioids, propofol, and ketamine were also significantly decreased (p < 0.001, p < 0.001, p = 0.001, p = 0.027). The infusion was weaned off in 85% of patients, over a median time of 36 hours (interquartile range, 12-48 hr), and abruptly discontinued in 15% of them. Thirty-seven percent of patients showed hemodynamic changes, and 9% displayed hemodynamic adverse events that required intervention (dose reduction in 79% of cases). A multivariate logistic regression model showed that a loading dose (odds ratio, 4.8; CI, 1.2-18.7) and dosages greater than 1.2 µg/kg/hr (odds ratio, 5.4; CI, 1.9-15.2) increased the odds of hemodynamic changes. CONCLUSIONS: Dexmedetomidine used for prolonged sedation assures comfort, spares use of other sedation drugs, and helps to attenuate withdrawal syndrome and delirium symptoms. Adverse events are mainly hemodynamic and are reversible following dose reduction. A loading dose and higher infusion dosages are independent risk factors for hemodynamic adverse events.

Prolonged sedation in critically ill children: is dexmedetomidine a safe option for younger age? An off-label experience.

BACKGROUND: Dexmedetomidine (DEX) is an alpha-2-adrenergic agonist, recently approved by Italian-Medicines-Agency for difficult sedation in pediatrics, but few data exist regarding prolonged infusions in critically-ill children, especially in younger ages. Aim of our study was to evaluate DEX use and safety for prolonged sedation in Pediatric Intensive Care Units (PICUs). METHODS: Patients receiving DEX for ≥24 hours were retrospectively evaluated to analyze DEX indications, dosages, use of analgesics or sedatives, adverse events (AEs), withdrawal syndrome or delirium. RESULTS: Forty-seven patients (median 0.7years) from nine PICUs were enrolled. Main indications were adjuvant for drugs sparing (59.6%) and for analgosedation weaning (36.2%). Median infusion duration was 82.0 hours (IQR 62.2-126.0), with dosages between 0.4 (IQR 0.2-0.5) and 0.8 mcg/kg/h (IQR 0.6-1.2). Fifty-nine-percent of patients received other sedatives, 83% other analgesics. Twenty-one-percent presented withdrawal syndrome, 4.2% delirium, none of them DEX-related. Forty-six-percent experienced a potentially-DEX-related AE. AEs were all hemodynamic, 14.9% requiring intervention but none DEX interruption. The median minimum and maximum dosages were significantly higher in patients with AEs (0.5 vs. 0.3,P=0.001; 1.0 vs. 0.7,P<0.001), without correlations with the infusion duration. AEs rate was higher in patients receiving benzodiazepines (P=0.020) or more than one analgesic (P=0.003) and in those presenting withdrawal syndrome (P<0.001). CONCLUSIONS: DEX was confirmed as useful and relatively safe drug for prolonged sedation in critically-ill children, particularly in younger ages. Main AEs were cardiovascular, reversible, related with higher doses, with the concomitant use of benzodiazepines or multiple sedation drugs and with the presence of withdrawal syndrome.