Tolerance, withdrawal, and physical dependency after long-term sedation and analgesia of children in the pediatric intensive care unit

Crit Care Med. 2000 Jun;28(6):2122-32. doi: 10.1097/00003246-200006000-00079.


Objective: To describe the consequences of the prolonged administration of sedative and analgesic agents to the pediatric intensive care unit (PICU) patient. The problems to be investigated include tolerance, physical dependency, and withdrawal.

Data sources: A MEDLINE search was performed of literature published in the English language. Cross-reference searches were performed using the following terms: sedation, analgesia with PICU, children, physical dependency, withdrawal; tolerance with sedative, analgesics, benzodiazepines, opioids, inhalational anesthetic agents, nitrous oxide, ketamine, barbiturates, propofol, pentobarbital, phenobarbital.

Study selection: Studies dealing with the problems of tolerance, physical dependency, and withdrawal in children in the PICU population were selected.

Data extraction: All of the above-mentioned studies were reviewed in the current manuscript.

Data synthesis: A case by case review is presented, outlining the reported problems of tolerance, physical dependency, and withdrawal after the use of sedative/analgesic agents in the PICU population. This is followed up by a review of the literature discussing current treatment options for these problems.

Conclusions: Tolerance, physical dependency, and withdrawal can occur after the prolonged administration of any agent used for sedation and analgesia in the PICU population. Important components in the care of such patients include careful observation to identify the occurrence of withdrawal signs and symptoms. Treatment options after prolonged administration of sedative/analgesic agents include slowly tapering the intravenous administration of these agents or, depending on the drug, switching to subcutaneous or oral administration.

Publication types

  • Review

MeSH terms

  • Analgesics / adverse effects*
  • Child
  • Drug Tolerance
  • Humans
  • Hypnotics and Sedatives / adverse effects*
  • Intensive Care Units, Pediatric
  • Risk Factors
  • Substance Withdrawal Syndrome* / diagnosis
  • Substance Withdrawal Syndrome* / drug therapy
  • Substance Withdrawal Syndrome* / etiology
  • Time Factors


  • Analgesics
  • Hypnotics and Sedatives