title: [Severe phenytoin intoxication in patients with hypoalbuminaemia].
abstract: Two patients, a 35-year-old woman and a 60-year-old man, developed severe neurological side effects during treatment with phenytoin: disorientation, myoclonia, hallucinations and drowsiness in the first patient and a comatose state in the second. The woman had spina bifida, a ventriculoperitoneal drain because of hydrocephalus, recurrent urinary-tract infection, and a history of status epilepticus. The man suffered from diabetic ketoacidosis complicated by epileptic convulsions. In both patients, the total phenytoin concentration in the blood was within the therapeutic range of 8-20 mg/l. However, both had low serum albumin concentrations, below 25 g/l. Low serum albumin levels are associated with increased concentrations of the free fraction of phenytoin. Toxic levels of free phenytoin were found: 4 and 8 mg/l, respectively, while the therapeutic range is 0.5-2 mg/l. The first patient recovered after treatment with phenytoin was stopped, after which she was placed on a lower dosage; the second patient died. When prescribing phenytoin to patients with hypoalbuminaemia, one should be aware of the risk of intoxication due to a high level of free phenytoin and consequently an increased risk of severe neurological side effects.
authors.affiliation: Academisch Medisch Centrum/Universiteit van Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam. e.m.kemper@amc.uva.nl
authors.forename: E M
authors.initials: EM
authors.lastname: Kemper
authors.forename: H J M
authors.initials: HJ
authors.lastname: van Kan
authors.forename: P
authors.initials: P
authors.lastname: Speelman
authors.forename: K
authors.initials: K
authors.lastname: de Gans
authors.forename: J H
authors.initials: JH
authors.lastname: Beijnen
authors.forename: J H M
authors.initials: JH
authors.lastname: Schellens
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D001798:Blood Proteins / Q000378:metabolism; D016903:Drug Monitoring; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D034141:Hypoalbuminemia / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D010672:Phenytoin / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D001798:Blood Proteins; D010672:Phenytoin