title: Tolerance and withdrawal from prolonged opioid use in critically ill children.
abstract: OBJECTIVE
  After prolonged opioid exposure, children develop opioid-induced hyperalgesia, tolerance, and withdrawal. Strategies for prevention and management should be based on the mechanisms of opioid tolerance and withdrawal.
  
  
  METHODS
  Relevant manuscripts published in the English language were searched in Medline by using search terms "opioid," "opiate," "sedation," "analgesia," "child," "infant-newborn," "tolerance," "dependency," "withdrawal," "analgesic," "receptor," and "individual opioid drugs." Clinical and preclinical studies were reviewed for data synthesis.
  
  
  RESULTS
  Mechanisms of opioid-induced hyperalgesia and tolerance suggest important drug- and patient-related risk factors that lead to tolerance and withdrawal. Opioid tolerance occurs earlier in the younger age groups, develops commonly during critical illness, and results more frequently from prolonged intravenous infusions of short-acting opioids. Treatment options include slowly tapering opioid doses, switching to longer-acting opioids, or specifically treating the symptoms of opioid withdrawal. Novel therapies may also include blocking the mechanisms of opioid tolerance, which would enhance the safety and effectiveness of opioid analgesia.
  
  
  CONCLUSIONS
  Opioid tolerance and withdrawal occur frequently in critically ill children. Novel insights into opioid receptor physiology and cellular biochemical changes will inform scientific approaches for the use of opioid analgesia and the prevention of opioid tolerance and withdrawal.
authors.affiliation: Department of Pediatrics, Le Bonheur Children's Hospital and University of Tennessee Health Science Center, Memphis, Tennessee, USA. anandsunny@uams.edu
authors.forename: Kanwaljeet J S
authors.initials: KJ
authors.lastname: Anand
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Willson
authors.forename: John
authors.initials: J
authors.lastname: Berger
authors.forename: Rick
authors.initials: R
authors.lastname: Harrison
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Meert
authors.forename: Jerry
authors.initials: J
authors.lastname: Zimmerman
authors.forename: Joseph
authors.initials: J
authors.lastname: Carcillo
authors.forename: Christopher J L
authors.initials: CJ
authors.lastname: Newth
authors.forename: Parthak
authors.initials: P
authors.lastname: Prodhan
authors.forename: J Michael
authors.initials: JM
authors.lastname: Dean
authors.forename: Carol
authors.initials: C
authors.lastname: Nicholson
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects*; D001921:Brain / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D016638:Critical Illness; D004361:Drug Tolerance; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009474:Neurons / Q000187:drug effects; D009293:Opioid-Related Disorders / Q000517:prevention & control / Q000534:rehabilitation*; D010146:Pain / Q000188:drug therapy*; D011957:Receptors, Opioid / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000175:diagnosis* / Q000517:prevention & control; D013618:Tachyphylaxis
chemical_list: D000701:Analgesics, Opioid; D011957:Receptors, Opioid
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