title: Efficacy of α2-Agonists for Sedation in Pediatric Critical Care: A Systematic Review.
abstract: OBJECTIVE
  Children in PICUs normally require analgesics and sedatives to maintain comfort, safety, and cooperation with interventions. α2-agonists (clonidine and dexmedetomidine) have been described as adjunctive (or alternative) sedative agents alongside opioids and benzodiazepines. This systematic review aimed to determine whether α2-agonists were effective in maintaining patients at a target sedation score over time compared with a comparator group. We also aimed to determine whether concurrent use of α2-agonists provided opioid-sparing effects.
  
  
  METHODS
  A systematic search was performed using the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, CINAHL, and LILACS.
  
  
  METHODS
  We included randomized controlled trials of children in PICU treated with clonidine or dexmedetomidine for the indication of sedation.
  
  
  METHODS
  Two authors independently screened articles for inclusion.
  
  
  RESULTS
  Six randomized controlled trials with sufficient data were identified and critically appraised. Three clonidine trials (two vs placebo and one vs midazolam) and three dexmedetomidine trials (two vs fentanyl, one vs midazolam) were included. Due to study heterogeneity it was not possible to pool studies. A narrative synthesis is provided.
  
  
  CONCLUSIONS
  Reporting of study results using the outcome "time maintained at target sedation score' for clonidine or dexmedetomidine was poor. Only one trial compared clonidine with midazolam using a sedation score outcome. This study was underpowered to demonstrate equivalence to midazolam as a sedative. The adjunctive use of clonidine demonstrated significant decreases in opioid use in neonates but not in older groups. Clonidine dose was inconsistent between studies. Dexmedetomidine demonstrated an opioid-sparing effect in two small trials. Further studies, including dose-finding studies and studies with sedation score-based outcomes, are needed.
authors.affiliation: 1School of Pharmacy, Royal College of Surgeons in Ireland, Dublin, Ireland. 2Paediatric Intensive Care Unit, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland. 3Paediatric Intensive Care Unit, Children's University Hospital, Temple Street, Dublin, Ireland.
authors.forename: John C
authors.initials: JC
authors.lastname: Hayden
authors.forename: Cormac
authors.initials: C
authors.lastname: Breatnach
authors.forename: Dermot R
authors.initials: DR
authors.lastname: Doherty
authors.forename: Martina
authors.initials: M
authors.lastname: Healy
authors.forename: Moninne M
authors.initials: MM
authors.lastname: Howlett
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Gallagher
authors.forename: Gráinne
authors.initials: G
authors.lastname: Cousins
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000627:therapeutic use*; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D003000:Clonidine / Q000627:therapeutic use; D016292:Procedural Sedation / Q000379:methods; D003422:Critical Care / Q000379:methods; D020927:Dexmedetomidine / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000627:therapeutic use*; D007231:Infant, Newborn; D015278:Intensive Care Units, Pediatric; D008297:Male; D008874:Midazolam / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000701:Analgesics, Opioid; D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine; D003000:Clonidine; D008874:Midazolam