[Severe phenytoin intoxication in patients with hypoalbuminaemia]

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.