Baclofen : Poisoning

• centrally acting skeletal muscle relaxant
• an agonist at gamma-aminobutyric acid B (GABAB) receptors.
• It is used primarily to treat severe muscle spasms, secondary to conditions such as multiple sclerosis and spinal cord injuries.
• The mechanism of action has not been fully established.
• proposed that baclofen inhibits the influx of calcium at the spinal cord preventing the transmission of excitatory synaptic reflexes.
• Baclofen is primarily renally excreted; therefore, patients with renal impairment are at risk for developing toxicity at therapeutic doses.
• Overdoses of baclofen may occur due pediatric ingestions, intentional ingestions by adults or due to complications and malfunctions with intrathecal pumps and spinal catheter systems.

Overdose Symptoms

• CNS depression, lethargy, somnolence, hallucinations, agitation, mydriasis, nausea and vomiting.
• Severe toxicity is associated with bradycardia, hypotension or hypertension, respiratory failure, hypothermia, seizures, coma and death.
• Rarely, status epilepticus, rhabdomyolysis, and conduction disturbances may occur.

Pharmacokinetics

• Urine toxicology screens do not routinely test for baclofen and serum concentrations are not readily available or useful.
• After a single therapeutic dose, baclofen is rapidly absorbed from the gastrointestinal tract. Blood levels peak within 2 hours.
• serum half-life is 2–6 hours, which can be significantly prolonged after an overdose.
• majority of this drug is excreted unchanged in the urine
• Clinical effects of baclofen overdose may last four to eight hours.
• While improvement in mental status was shown to parallel the fall in serum concentration in one study, Lipscomb et al., noted that serum elimination half-life may not reflect a slower elimination rate from the central nervous system.
• Delayed diffusion across the blood-brain barrier is thought to account for the lag of a few hours in clinical recovery observed in some people

Treatment

• Treatment of baclofen overdose consists of supportive care (e.g. IV fluids, endotracheal intubation, mechanical ventilation).
• Activated charcoal - may be warranted in acute ingestions.
• Benzodiazepines - may be required for agitation and/or seizures.
• Vasopressors - hypotensive patients may require it
• There are case reports of mild to moderate overdoses being treated with physostigmine with a slight benefit, but evidence to support its use is controversial.
• Hemodialysis increases the clearance of baclofen and shortens the duration of toxicity in patients with or without impaired renal function.
• Most ESRD patients experienced marked improvement in clinical toxicity following haemodialysis, compared with patients who did not receive haemodialysis

References

1. Marryland Poison Centre Weekly Update, Feb 2012.
2. Treatment of baclofen overdose by haemodialysis: a pharmacokinetic study. Nephrol Dial Transplant (2005) 20: 441–443
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3229794/
4. http://emj.bmj.com/content/22/9/673.full