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Abrupt withdrawal from intrathecal baclofen: recognition and management of a potentially life-threatening syndrome.

AbstractOBJECTIVE:
To suggest guidelines for the prevention, recognition, and management of a life-threatening syndrome (high fever, altered mental status, profound muscular rigidity that sometimes progressed to fatal rhabdomyolysis) in patients who experience the abrupt withdrawal of intrathecal baclofen (ITB) therapy.
DESIGN:
Retrospective literature and safety-file review.
SETTING:
Expert panel drawn from physiatry, neurology, and neurosurgery.
PARTICIPANTS:
Experienced users of ITB therapy in the pediatric and adult populations in the United States.
INTERVENTIONS:
Not applicable.
MAIN OUTCOME MEASURES:
We reviewed literature reports, MedWatch reports to the US Food and Drug Administration, and our own experiences. We critically analyzed patient management and drug therapy in the context of the pharmacology of baclofen and other antispastic agents.
RESULTS:
An abrupt reduction in gamma-aminobutyric acid(B) (GABA) agonist activity in the central nervous system can cause the ITB withdrawal syndrome, which is clinically and pathophysiologically distinct from autonomic dysreflexia, malignant hyperthermia, and neuroleptic-malignant syndrome. ITB withdrawal evolves over 1 to 3 days, but may become fulminant if not recognized and treated early. The syndrome can be interrupted by the restoration of ITB therapy. However, supportive measures and high-dose benzodiazepine infusion may be life saving in the interval before ITB therapy is resumed. Dantrolene infusion may relieve muscle rigidity but does not reverse the other manifestations of GABAergic agonist withdrawal.
CONCLUSIONS:
Most episodes of severe ITB withdrawal were preventable. Patients at risk can be identified and educated prospectively and given medication for emergency use. Treatment with GABAergic agonist drugs may prevent potentially fatal sequelae.
AuthorsRobert J Coffey, Terence S Edgar, Gerard E Francisco, Virginia Graziani, Jay M Meythaler, Patrick M Ridgely, Saud A Sadiq, Michael S Turner
JournalArchives of physical medicine and rehabilitation (Arch Phys Med Rehabil) Vol. 83 Issue 6 Pg. 735-41 (Jun 2002) ISSN: 0003-9993 [Print] United States
PMID12048649 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
CopyrightCopyright 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation
Chemical References
  • Anti-Anxiety Agents
  • GABA Agonists
  • Benzodiazepines
  • Baclofen
Topics
  • Anti-Anxiety Agents (therapeutic use)
  • Autonomic Dysreflexia (diagnosis)
  • Baclofen (adverse effects)
  • Benzodiazepines
  • Diagnosis, Differential
  • GABA Agonists (adverse effects)
  • Humans
  • Infusion Pumps, Implantable
  • Malignant Hyperthermia (diagnosis)
  • Neuroleptic Malignant Syndrome (diagnosis)
  • Retrospective Studies
  • Risk Factors
  • Substance Withdrawal Syndrome (diagnosis, drug therapy, etiology, prevention & control)

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