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Risk Factors Associated With Iatrogenic Opioid and Benzodiazepine Withdrawal in Critically Ill Pediatric Patients

A Systematic Review and Conceptual Model*

Best, Kaitlin M., RN1; Boullata, Joseph I., PharmD, RPh, BCNSP2; Curley, Martha A. Q., RN, PhD, FAAN3,4

Pediatric Critical Care Medicine: February 2015 - Volume 16 - Issue 2 - p 175–183
doi: 10.1097/PCC.0000000000000306
Review Article

Objectives: 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.

Data Sources: 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.

Study Selection: 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.

Data Extraction: 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.

Findings: 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.

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.

* See also p. 195.

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Supported, in part, by University of Pennsylvania Hillman Scholar’s Program in Nursing Innovation.

Dr. Best and her institution received grant support from the Hillman Foundation (As a Hillman Scholar in Nursing Innovation, Dr. Best receives tuition support and a stipend for her graduate nursing studies). The remaining authors have disclosed that they do not have any potential conflicts of interest.

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©2015The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies