title: The use of methadone to facilitate opioid weaning in pediatric critical care patients: a systematic review of the literature and meta-analysis.
abstract: BACKGROUND
  Continuous opioid infusion therapy is commonly utilized in the pediatric intensive care setting to treat pain and facilitate tolerance of invasive therapies. Transitioning to methadone is one common strategy for weaning from continuous opioid infusions, but in practice this transition can be challenging, and many children still experience iatrogenic withdrawal.
  
  
  OBJECTIVE
  We reviewed the literature to evaluate the best available evidence to guide methadone therapy in this setting, and to summarize associated adverse events.
  
  
  METHODS
  We included all studies of methadone used to facilitate weaning from continuous opioid infusions in pediatric critical care patients, including medical, cardiac, and surgical patients, excluding case reports and studies treating neonatal abstinence syndrome, or acute or chronic pain. Medline, Embase, and CINAHL databases from inception to May 2015 were queried; references of included works and conference proceedings were also reviewed. Two authors independently extracted data from each study. Meta-analysis with fixed- and random-effects models was used to pool results of studies when applicable.
  
  
  RESULTS
  Twelve studies involving 459 patients met criteria for inclusion. A wide variety of methadone dosing and taper strategies were reported. Mean inpatient methadone taper times varied widely, from 4.3 to 26.2 days. Excessive sedation was the most frequently reported adverse event, occurring in up to 16% of patients. Withdrawal occurred in 27% of patients among studies reporting this outcome. In three of three studies in which a new methadone protocol was introduced, a decreased proportion of patients experienced withdrawal (standardized mean difference, SMD = -0.60, 95% CI = -0.998 to -0.195, P = 0.004).
  
  
  CONCLUSIONS
  We did not identify sufficient evidence to recommend any particular methadone weaning strategy, or to recommend methadone over other medications or prescribed infusion weaning, for successful weaning of continuous opioid infusions in the pediatric intensive care setting.
authors.affiliation: Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Leslie A
authors.identifier: http://orcid.org/0000-0002-4521-354X
authors.initials: LA
authors.lastname: Dervan
authors.affiliation: Department of Pediatrics, University of Kansas School of Medicine-Wichita, Wichita, KS, USA.
authors.forename: Beryl
authors.initials: B
authors.lastname: Yaghmai
authors.affiliation: Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA.|Center for Child Health, Behavior, and Development, Seattle Children's Research Institute, Seattle, WA, USA.
authors.forename: Robert Scott
authors.initials: RS
authors.lastname: Watson
authors.affiliation: Department of Biomedical Informatics and Medical Education, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Fredric M
authors.initials: FM
authors.lastname: Wolf
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use*; D002648:Child; D003422:Critical Care / Q000379:methods*; D006801:Humans; D008691:Methadone / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy*; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control*
chemical_list: D000701:Analgesics, Opioid; D008691:Methadone
keywords: methadone; opioid substitution treatment; pediatric; pediatric intensive care; substance withdrawal syndrome; systematic review