title: Abrupt withdrawal from intrathecal baclofen: recognition and management of a potentially life-threatening syndrome.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Retrospective literature and safety-file review.
  
  
  METHODS
  Expert panel drawn from physiatry, neurology, and neurosurgery.
  
  
  METHODS
  Experienced users of ITB therapy in the pediatric and adult populations in the United States.
  
  
  METHODS
  Not applicable.
  
  
  METHODS
  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.
authors.affiliation: Medtronic Inc, Minneapolis, MN 55432-5604, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Coffey
authors.forename: Terence S
authors.initials: TS
authors.lastname: Edgar
authors.forename: Gerard E
authors.initials: GE
authors.lastname: Francisco
authors.forename: Virginia
authors.initials: V
authors.lastname: Graziani
authors.forename: Jay M
authors.initials: JM
authors.lastname: Meythaler
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Ridgely
authors.forename: Saud A
authors.initials: SA
authors.lastname: Sadiq
authors.forename: Michael S
authors.initials: MS
authors.lastname: Turner
mesh_terms: D014151:Anti-Anxiety Agents / Q000627:therapeutic use; D020211:Autonomic Dysreflexia / Q000175:diagnosis; D001418:Baclofen / Q000009:adverse effects*; D001569:Benzodiazepines; D003937:Diagnosis, Differential; D018755:GABA Agonists / Q000009:adverse effects*; D006801:Humans; D015918:Infusion Pumps, Implantable; D008305:Malignant Hyperthermia / Q000175:diagnosis; D009459:Neuroleptic Malignant Syndrome / Q000175:diagnosis; D012189:Retrospective Studies; D012307:Risk Factors; D013375:Substance Withdrawal Syndrome / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology* / Q000517:prevention & control
chemical_list: D014151:Anti-Anxiety Agents; D018755:GABA Agonists; D001569:Benzodiazepines; D001418:Baclofen