Selection of the initial methadone regimen for the management of iatrogenic opioid abstinence syndrome in critically ill children

Pharmacotherapy. 2012 Feb;32(2):148-57. doi: 10.1002/PHAR.1001. Epub 2012 Jan 24.


Iatrogenic opioid abstinence syndrome (IOAS) is a common complication in critically ill infants and children receiving prolonged exposure to continuous infusions of opioids. Although no guidelines are available regarding management of IOAS in children, several treatment options are available, including clonidine, morphine, and methadone. Methadone is commonly prescribed due to its long half-life and antagonism of the N-methyl-d-aspartate receptor. Different approaches, such as weight-based and formula-based methods, have been used to determine the initial methadone dosing regimen. Because of the vast differences in the recommended dosing regimen from these sources, we conducted a literature search to identify articles evaluating the initial methadone dosing regimen for prevention and/or treatment of IOAS in children. Specifically, we evaluated the reported frequency of withdrawal and oversedation after initiation of methadone treatment. Our literature search was limited to English-language articles in the MEDLINE (1950-March 2011), EMBASE (1988-March 2011), International Pharmaceutical Abstracts (1970-March 2011), and Cochrane Library (1996-March 2011) databases. Relevant abstracts and reference citations were also reviewed. A total of eight reports representing 183 patients were included in the analysis. There was wide discrepancy in the initial methadone dosing regimen. Approximately one-third of all patients experienced withdrawal after starting methadone, and there did not appear to be a difference between weight-based and formula-based regimens. Seven patients experienced oversedation; however, not all articles reported this complication. It appears that a standard approach to initial methadone dosing does not exist because withdrawal occurred despite the regimen started. Therefore, it seems best to begin with the lowest dose possible and titrate to the child's response to avoid complications such as oversedation. Routine monitoring should be performed in all patients to guide clinicians in the management of IOAS.

Publication types

  • Review

MeSH terms

  • Analgesics, Opioid / adverse effects*
  • Child
  • Clinical Trials as Topic
  • Critical Illness / epidemiology
  • Critical Illness / therapy*
  • Disease Management
  • Dose-Response Relationship, Drug
  • Humans
  • Iatrogenic Disease* / epidemiology
  • Methadone / administration & dosage*
  • Substance Withdrawal Syndrome / drug therapy*
  • Substance Withdrawal Syndrome / epidemiology
  • Substance Withdrawal Syndrome / pathology


  • Analgesics, Opioid
  • Methadone