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

Abstract

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.

Current State of Analgesia and Sedation in the Pediatric Intensive Care Unit

“…Dexmedetomidine assured comfort, spared use of other sedatives, and attenuated withdrawal and delirium symptoms. The loading dose and infusion dosages of dexmedetomidine were independent risk factors for hemodynamic adverse events [ 168 ].…”

Pain and sedation management and monitoring in pediatric intensive care units across Europe: an ESPNIC survey

“…The recently published clinical practice guidelines for the management of Pain, Agitation, Neuromuscular Blockade, and Delirium in critically ill pediatric patients with consideration of the PICU Environment and Early Mobility (PANDEM) and the Recommendations for analgesia and sedation in critically ill children admitted to intensive care unit [ 8 , 19 ] both recommend the use of alpha 2 -agonists over benzodiazepines as a first-line sedative. It has been shown that alpha 2 -agonists is a safe and benzodiazepine sparing alternative for sedation in the pediatric population [ 20 – 22 ]. We could reveal that only as much as 11% of the responding PICUs in Europe would use dexmedetomidine as a first-choice sedative and only 7% opted for clonidine.…”

Dexmedetomidine for prevention of opioid/benzodiazepine withdrawal syndrome in pediatric intensive care unit: Interim analysis of a randomized controlled trial

“…Interestingly, this study also showed that the WAT-1 score significantly decreased at 24 h of DEX infusion by a median of 2 points (interquartile range (IQR), 1-4), and the prevalence of WS decreased from 19% to 2% after start of DEX infusion (p < 0.001). 23 These promising results certainly encouraged the design of this randomized clinical trial in the attempt to add further supporting evidence to the current knowledge for the use of DEX as an adjunctive treatment for WS. However, it may be appropriate to specify that the outcome measures of the PROSDEX study were evaluated at a single 24-hour timepoint, whereas in our F I G U R E 2 Study flow chart.…”

“…Overall, there were no AEs requiring intervention other than the DEX discontinuation, and this is consistent with what was described in previous studies. 23 However, less severe events, mostly bradycardia and/or hypotension, were recorded among patients in the DEX arm which led to DEX discontinuation and drop-out from the study. Thus, our study confirms that DEX infusion could be considered overall relatively safe; however, in some patients, there could be a particularly intense hemodynamic response, with the possible need to suspend the infusion.…”