Efficacy of α2-Agonists for Sedation in Pediatric Critical Care: A Systematic Review

Pediatr Crit Care Med. 2016 Feb;17(2):e66-75. doi: 10.1097/PCC.0000000000000599.


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.

Data sources: A systematic search was performed using the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, CINAHL, and LILACS.

Study selection: We included randomized controlled trials of children in PICU treated with clonidine or dexmedetomidine for the indication of sedation.

Data extraction: Two authors independently screened articles for inclusion.

Data synthesis: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adrenergic alpha-2 Receptor Agonists / therapeutic use*
  • Analgesics, Opioid / administration & dosage*
  • Child
  • Child, Preschool
  • Clonidine / therapeutic use
  • Conscious Sedation* / methods
  • Critical Care / methods
  • Dexmedetomidine / therapeutic use
  • Female
  • Humans
  • Hypnotics and Sedatives / therapeutic use*
  • Infant, Newborn
  • Intensive Care Units, Pediatric*
  • Male
  • Midazolam / therapeutic use
  • Treatment Outcome


  • Adrenergic alpha-2 Receptor Agonists
  • Analgesics, Opioid
  • Hypnotics and Sedatives
  • Dexmedetomidine
  • Clonidine
  • Midazolam