Dexmedetomidine for Prolonged Sedation in the PICU: A Systematic Review and Meta-Analysis*

Abstract

Objectives: We aimed to systematically describe the use of dexmedetomidine as a treatment regimen for prolonged sedation in children and perform a meta-analysis of its safety profile. Data Sources: PubMed, EMBASE, Cochrane Library, Scopus, Web of Science, ClinicalTrials.gov, and CINAHL were searched from inception to November 30, 2018. Study Selection: We included studies involving hospitalized critically ill patients less than or equal to 18 years old receiving dexmedetomidine for prolonged infusion (≥ 24 hr). Data Extraction: Data extraction included study characteristics, patient demographics, modality of dexmedetomidine use, associated analgesia and sedation details, comfort and withdrawal evaluation scales, withdrawal symptoms, and side effects. Data Synthesis: Literature search identified 32 studies, including a total of 3,267 patients. Most of the studies were monocentric (91%) and retrospective (88%); one was a randomized trial. Minimum and maximum infusion dosages varied from 0.1–0.5 µg/kg/hr to 0.3–2.5 µg/kg/hr, respectively. The mean/median duration range was 25–540 hours. The use of a loading bolus was reported in eight studies (25%) (range, 0.5–1 µg/kg), the mode of weaning in 11 (34%), and the weaning time in six of 11 (55%; range, 9–96 hr). The pooled prevalence of bradycardia was 2.6% (n = 10 studies; 14/387 patients; 95% CI, 0.3–7.3; I 2 = 75%), the pooled prevalence incidence of bradycardia was 2.6% (n = 10 studies; 14/387 patients; 95% CI, 0.3–7.3; I 2 = 75%), the pooled incidence of hypotension was 6.1% (n = 8 studies; 19/304 patients; 95% CI, 0.8–15.9; I 2 = 84%). Three studies (9%) reported side effects’ onset time which in all cases was within 12 hours of the infusion starting. Conclusions: High-quality data on dexmedetomidine use for prolonged sedation and a consensus on correct dosing and weaning protocols in children are currently missing. Infusion of dexmedetomidine can be considered relatively safe in pediatrics even when longer than 24 hours.

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 in Children on Extracorporeal Membrane Oxygenation: Pharmacokinetic Data Exploration Using Previously Published Models

“…As expected, observed concentrations increased with dexmedetomidine infusion rates, as shown in Figure 1 . Considering that the maximum dosing rate in our study was 1.1 mcg/kg/h, our results suggest that the proposed threshold of concentration >700 pg/mL is attainable in children on ECMO while staying within the dosing range of 0.1 and 2.5 mcg/kg/h reported in critically ill children ( 35 ). However, the exact dexmedetomidine concentrations leading to adequate sedation in an acute care setting remain to be determined, especially in children on ECMO, considering the more invasive equipment and severity of the disease contributing to greater discomfort.…”

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

“…11,12 However, a systematic review including 32 studies using DEX infusion in the PICU showed that only five studies reported the use of DEX as an adjuvant for weaning, and only two described its use for treatment of WS. 22 In a recent prospective multicenter study (PROSDEX) including 163 pediatric patients, DEX was confirmed to be used both for prevention of WS (12% of patients) and as an adjuvant for its treatment (15%).…”