Baclofen toxicity

Background

• Baclofen is a synthetic derivative of GABA used to reduce spasticity in conditions such as multiple sclerosis and cerebral palsy, or to reduce muscular spasm in lower back pain.
  • May also be used for hiccups and alcohol use disorder
• At therapeutic doses, baclofen acts as a GABA-B receptor agonist in the spinal cord, causing inhibition of muscular tone.
• At higher doses, baclofen loses selectivity and can cause sedation.
• Primarily (80%) excreted by the kidneys
  • Dosage must be reduced in renal dysfunction and should be avoided with GFR < 30 mL/min/1.73 m².
  • Patients on chronic therapy may become toxic with new AKI.

Clinical Features

• Nausea and vomiting
• Depressed level of consciousness
• Delirium
• Seizures
  • Tonic-clonic
  • Non-convulsive status epilepticus
• Myoclonus
• Airway compromise and respiratory failure
• Hypothermia
• Hypotension
• Bradycardia and conduction abnormalities

Differential Diagnosis

Sedative/hypnotic toxicity

• Absinthe
• Barbiturates
• Benzodiazepines
  • Flunitrazepam (Rohypnol)
• Chloral hydrate
• Gamma hydroxybutyrate (GHB)
• Baclofen toxicity
• Opioids
  • Lomotil toxicity
  • Loperamide toxicity
• Toxic alcohols
  • Ethanol
  • Ethylene glycol
  • Isopropyl alcohol
  • Methanol
• Xylazine toxicity

Also consider co-ingestion with intentional overdose

• Acetaminophen toxicity
• Salicylate toxicity
• Ethanol toxicity

Evaluation

• Diagnosis of exclusion, based on history
  • Baclofen level can be measured but is not clinically useful
• In patients with intrathecal baclofen pump:
  • Obtain KUB to evaluate pump tubing integrity and placement
  • Consult the managing specialist to interrogate pump

Management

• Activated charcoal for recent ingestion
• Supportive care:
  • Respiratory support
  • IV fluids
  • Vasopressors for persistent hypotension
  • Benzodiazepines for seizures or severe myoclonus
    • CNS depressive effects of benzodiazepines will be increased
    • Use the lowest effective dose and be prepared for respiratory depression
• Hemodialysis for very severe toxicity
  • Probably not beneficial in patients with normal renal function
• For patients with intrathecal pump:
  • Consult managing specialist
  • Turn off pump
  • Can remove baclofen from pump reservoir and replace with normal saline
  • Consider large volume CSF removal via lumbar puncture to reduce level

References

• Jung, M. “Baclofen Overdoses”. Maryland Poison Center, University of Maryland School of Pharmacy. www.mdpoison.com Accessed April 29th, 2014.
• Nicola Y Leung, Ian M Whyte, Geoffrey K Isbister Baclofen overdose: defining the spectrum of toxicity. Emerg Med Australas: 2006, 18(1);77-82