Usefulness of plasma drug monitoring in severe baclofen poisoning

Cédric Cleophax, Antonio Goncalves, Céline Chasport, Eugénie de Beaugrenier, Laurence Labat, Xavier Declèves & Bruno Mégarbane – To link to this article: – 29/09/2015

To the Editor:
High-doses of baclofen, a β -( ρ -chlorophenyl)-derivative of γ -aminobutyric acid indicated to treat spasticity of spinal cord origin, are increasingly used to manage alcohol dependence despite the absence of high-level evidence. Baclofen poisoning may be responsible for encephalopathy, coma, respiratory depression, seizures, and hypothermia. 1 Regarding its pharmacokinetics,
baclofen is almost completely eliminated from the body by renal fi ltration and tubular secretion, whereas only a minor pathway involves liver metabolism. 2 Since baclofen is a small water-soluble molecule with limited volume of distribution ( ∼ 1 L/kg) and binding rate to plasma proteins ( ∼ 30%), hemodialysis may be useful for enhancing its elimination; 3 – 5 however, the definitive evidence of hemodialysis clinical usefulness is lacking.

A 29-year-old woman, suffering from neonatal spastic hemiplegia, was admitted to our intensive care unit (ICU), ∼ 16 hours after ingesting 3,500 mg baclofen, 150 mg desloratadine, and 84 mg esomeprazole. On admission, she was comatose (Glasgow Coma Score: 3) with pinpoint myosis but no other remarkable signs (blood pressure: 99/57 mmHg, heart rate: 67/min, respiratory rate: 18/min, and temperature: 36 ° C). She was intubated and mechanically ventilated. Electrocardiogram was normal; biochemical tests unremarkable and routine toxicological screening tests negative. Seizure activity was evidenced using continuous electroencephalogram monitoring and required multiple treatments including midazolam, phenytoin, phenobarbital, and thiopental. Hemodialysis (Fresenius 5008; Polysulfone membrane; blood fl ow: 250 mL/min; dialysate fl ow: 500 mL/min;
13 Fr-femoral catheter) was initiated with four 6-hour sessions guided by plasma baclofen concentrations, measured from 16 to
440 hours post-ingestion by liquid chromatography coupled to mass spectrometry in tandem developed with a Quantum Ultra
apparatus (Thermo Fisher Scientifi c) and electrospray source ionization in positive mode (limit of quantifi cation: 5 ng/mL).

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