Baclofen toxicity

Baclofen in overdose produces a rapid onset of delirium, respiratory depression, coma and seizures. In large overdose the patient can appear brain dead and it has resulted in the pursuit of organ donation only for the patient to wake on the operating table. The mainstay of treatment is good supportive care.

Toxic Mechanism

Baclofen is a synthetic derivative of GABA. At a therapeutic dose it acts on spinal GABAb receptors but in overdose this selectivity is lost and the GABA receptors in the brain are targeted resulting in sedation and coma. Complicating this baclofen also mediates pre- and postsynaptic inhibition (therefore inhibiting the inhibitor) causing seizures in overdose. And like GABAa withdrawal the same situation can occur if a patient suddenly stops baclofen and withdrawal syndromes can manifest.

Toxicokinetics: 

• Rapidly and completely absorbed orally
• Peak serum concentration in 2 hours
• Penetrates the blood-brain-barrier
• Volume of distribution 0.7 L/kg
• 15% metabolised by the liver otherwise excreted unchanged in the urine
• Half life 3.5 hours

Resuscitation:

• Reduced GCS and respiratory depression: Early intubation and ventilation
• Seizures:
  • Can be managed with benzodiazepines (varying doses in the textbooks, easy method is 0.1mg/kg IV for lorazepam (max 4mg) / midazolam (max 10mg) / diazepam (max 10mg). Or…
  • Lorazepam 0.1mg/kg max 4mg
  • Diazepam 0.15mg/kg max 10mg
  • Midazolam 0.2mg/kg max 10mg
• Hypotension: Usually responds to fluid bolus and inotropes are rarely required.

Risk Assessment

• >200 mg in adults causes significant CNS depression, delirium, respiratory depression, coma and seizures.
• Intoxication will develop within 2 hours, delirium is most evident just prior to the onset of coma.
• The duration of coma can last 24 – 48 hours.
• In large overdoses patients can appear brain dead with fixed dilated pupils, hypotonia, areflexia (including absent brainstem reflexes)
• Cardiovascular symptoms include sinus bradycardia or tachycardia, hyper- or hypotension, 1st degree heart block and QT prolongation (rare).
• Children: one 25mg tablet can produce a coma in a 10 kg toddler.

Supportive Care

• If intubated see FASTHUGSINBED for further supportive care.
• Once the patient has recovered form the overdose it is important to re-institute the regular baclofen, otherwise a withdrawal state will occur mimicking ongoing toxicity (occurs 24 – 48 hours later with seizures, hallucinations, dyskinesia and visual disturbances)

Investigations

• Screening: 12 lead ECG, BSL, Paracetamol level

Decontamination:

• Activated charcoal 50 grams (1 g/kg in children) only once the airway has been secured.

Enhanced Elimination

• Not clinically useful

Antidotes

• None available

Disposition

• If asymptomatic at 4 hours the patient can be medically cleared (do not discharge overnight)
• Minor CNS depression requires a medical admission until symptoms resolve.
• Patients requiring intubation require ICU.

References and Additional Resources

Additional Resources:

• TPR – organ donation and baclofen case report.
• Tox conundrum 047 – Brain dead
• CCC – Sedative Toxidrome

References:

• Leung NY, Whyte IM, Isbister GK.  Baclofen overdose: Defining the spectrum of toxicity.  Emergency Medicine Australasia 2006;18:77-82.
• Murray L et al. Toxicology Handbook 3rd Edition. Elsevier Australia 2015. ISBN 9780729542241