title: Risk factors associated with iatrogenic opioid and benzodiazepine withdrawal in critically ill pediatric patients: a systematic review and conceptual model.
abstract: OBJECTIVE
  Analgesia and sedation are common therapies in pediatric critical care, and rapid titration of these medications is associated with iatrogenic withdrawal syndrome. We performed a systematic review of the literature to identify all common and salient risk factors associated with iatrogenic withdrawal syndrome and build a conceptual model of iatrogenic withdrawal syndrome risk in critically ill pediatric patients.
  
  
  METHODS
  Multiple databases, including PubMed/Medline, EMBASE, CINAHL, and the Cochrane Central Registry of Clinical Trials, were searched using relevant terms from January 1, 1980, to August 1, 2014.
  
  
  METHODS
  Articles were included if they were published in English and discussed iatrogenic withdrawal syndrome following either opioid or benzodiazepine therapy in children in acute or intensive care settings. Articles were excluded if subjects were neonates born to opioid- or benzodiazepine-dependent mothers, children diagnosed as substance abusers, or subjects with cancer-related pain; if data about opioid or benzodiazepine treatment were not specified; or if primary data were not reported.
  
  
  METHODS
  In total, 1,395 articles were evaluated, 33 of which met the inclusion criteria. To facilitate analysis, all opioid and/or benzodiazepine doses were converted to morphine or midazolam equivalents, respectively. A table of evidence was developed for qualitative analysis of common themes, providing a framework for the construction of a conceptual model. The strongest risk factors associated with iatrogenic withdrawal syndrome include duration of therapy and cumulative dose. Additionally, evidence exists linking patient, process, and system factors in the development of iatrogenic withdrawal syndrome.
  
  
  RESULTS
  Most articles were prospective observational or interventional studies.
  
  
  CONCLUSIONS
  Given the state of existing evidence, well-designed prospective studies are required to better characterize iatrogenic withdrawal syndrome in critically ill pediatric patients. This review provides data to support the construction of a conceptual model of iatrogenic withdrawal syndrome risk that, if supported, could be useful in guiding future research.
authors.affiliation: 1School of Nursing, University of Pennsylvania, Philadelphia, PA. 2Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia, PA. 3Department of Family & Community Heath, School of Nursing, Philadelphia, PA.
authors.forename: Kaitlin M
authors.initials: KM
authors.lastname: Best
authors.forename: Joseph I
authors.initials: JI
authors.lastname: Boullata
authors.forename: Martha A Q
authors.initials: MA
authors.lastname: Curley
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects*; D001569:Benzodiazepines / Q000009:adverse effects*; D002648:Child; D003422:Critical Care; D016638:Critical Illness; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects*; D007049:Iatrogenic Disease; D008962:Models, Theoretical; D012307:Risk Factors; D013375:Substance Withdrawal Syndrome / Q000209:etiology*
chemical_list: D000701:Analgesics, Opioid; D006993:Hypnotics and Sedatives; D001569:Benzodiazepines