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Baclofen


Overview

Baclofen is a gamma-aminobutyric acid (GABA) analogue. It is primarily used to treat muscle spasticity but more recently has found use in treating both alcohol and gamma-hydroxybutyrate (GHB) withdrawal.

In overdose it causes sedation, delirium, seizures and respiratory depression. Management is supportive with most patients recovering within 72 hours of ingestion.


Mechanism of Toxic Effects

Baclofen acts as an agonist at the GABAB receptor both at the level of the spinal cord and the brain. This reduces the release of excitatory neurotransmitters in the pre-synaptic neurons and stimulates inhibitory neuronal signals in the post-synaptic neurones.


Risk Assessment

Ingestion of over 200mg in a naïve patient can cause severe toxicity including coma, respiratory depression, seizures and prolonged delirium. Affects are dose dependant and with very large ingestions baclofen overdose can mimic brain death.


Kinetics in Overdose

Absorption

Baclofen has a bioavailability of 70-85% and is rapidly absorbed with peak levels approximately 2 hours post ingestion.

Distribution

It has a volume of distribution of 0.7 L/kg with protein binding of approximately 30% in therapeutic dosing.

Metabolism-Elimination

Baclofen is largely eliminated unchanged in the urine with only 15% undergoing hepatic metabolism to an inactive metabolite. The plasma half-life averages 2 to 4 hours.


Clinical Effects

The effects of baclofen in overdose mainly effect the central nervous system, with some effects also seen in the cardiovascular system.

CNS:

  • Sedation including coma.
  • Respiratory depression.
  • Myoclonus and seizures (seizures can occur early due to pre-synaptic GABA release or late if baclofen withdrawal develops).
  • Delirium – normally develops as coma resolves and can last 1-3 days.
  • Signs mimicking brain death: hypotonia, hyporeflexia, mydriasis, hypothermia, loss of brainstem reflexes. These normally last 24-48hrs.

CVS:

  • Bradycardia, tachycardia.
  • Hypertension, hypotension (infrequently).

Other:

  • Morbilliform rash (rare).

Investigations

  • 12-lead ECG
  • Renal function: If significant renal failure is present enhanced elimination with dialysis may be indicated.

Treatment

Supportive

Supportive care is the mainstay of baclofen overdose management. Particular attention should be paid to airway and breathing with the patient proceeding to intubation if they are unable to protect their airway or are not ventilating appropriately.

Baclofen induced seizures are generally short and self-limiting. However, if treatment is required for recurrent or persistent seizures then treatment with an intravenous benzodiazepine along standard lines is appropriate.

Baclofen withdrawal, which can result in a difficult to manage delirium, should be considered in patients on regular baclofen who miss several days of dosing (i.e. those intubated in ICU). Consider providing a dose of baclofen via the patients oral/nasogastric tube before extubation to help mitigate this risk. Benzodiazepines can also be used as an adjunct for its management.

Decontamination

Activated charcoal should be offered to alert and co-operative patients who present within 2 hours of an ingestion of 200mg of baclofen or greater.

If intubation is required, then activated charcoal can be offered anytime post ingestion via oral or nasogastric tube.

Enhanced Elimination

Baclofen is largely cleared unchanged in the urine. In patients with renal impairment toxicity may occur at therapeutic doses and be prolonged. In patients with renal failure, who develop coma following baclofen ingestion then dialysis is suggested to reduce the duration. As with most toxic ingestions, intermittent dialysis is the modality of choice.

Antidotes

There are no specific antidotes for the treatment of baclofen toxicity.


Observation and Disposition

Observe all patients for 6 hours post ingestion. If they have not shown any signs of toxicity, they are suitable for discharge.

In patients developing toxicity they should be observed until their symptoms have resolved and they are at their baseline level of functioning.


Further Reading

  1. Sullivan R, Hodgman M, Kao L and Tormoehlen L. “Baclofen overdose mimicking brain death.” Clin Tox 2012; 50: 141-4 PDF
  2. Leung N, Whyte I and Isbister G. “Baclofen overdose: defining the spectrum of toxicity.” Emergency Medicine Australasia 2006; 18:77-82 PDF
  3. Ross JC et al. “Acute intrathecal baclofen withdrawal: A Brief Review of Treatment Options.” Neurocrit Care 2011;14: 103-8 PDF
wikitox/baclofen.txt · Last modified: 2024/04/23 22:33 by kharris

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