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

John C Hayden¹, Cormac Breatnach, Dermot R Doherty

¹1School 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.

Pediatric Critical Care Medicine : a Journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

|December 26, 2015

Insights

Alpha-2 agonists like clonidine and dexmedetomidine may help reduce opioid use in pediatric intensive care units (PICUs). However, more research is needed to confirm their effectiveness in maintaining target sedation levels.

Area of Science:

Pediatric Critical Care Medicine
Pharmacology
Evidence-Based Medicine

Background:

Children in pediatric intensive care units (PICUs) often require analgesics and sedatives for comfort and cooperation.
Alpha-2 agonists, including clonidine and dexmedetomidine, are explored as adjunctive or alternative sedatives to traditional opioids and benzodiazepines.

Purpose of the Study:

To systematically review the effectiveness of alpha-2 agonists in maintaining target sedation scores in pediatric patients.
To assess the opioid-sparing potential of concurrent alpha-2 agonist use in PICU settings.

Main Methods:

A systematic search of multiple databases (Cochrane, PubMed, EMBASE, CINAHL, LILACS) was conducted.
Included were randomized controlled trials (RCTs) involving children in PICU treated with clonidine or dexmedetomidine for sedation.
Two authors independently screened articles, extracted data, and critically appraised six identified RCTs.

Main Results:

Six RCTs (three for clonidine, three for dexmedetomidine) were included; study heterogeneity precluded meta-analysis.
Clonidine showed decreased opioid use in neonates but not older children; inconsistent dosing was noted.
Dexmedetomidine demonstrated a potential opioid-sparing effect in two small trials.

Conclusions:

Reporting on maintaining target sedation scores with alpha-2 agonists was inadequate.
Clonidine was underpowered to demonstrate equivalence to midazolam.
Further high-quality studies, including dose-finding and sedation score-based outcome research, are necessary for both agents.

Read full analysis

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.

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.

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