Unsuspected rhabdomyolysis associated with phenytoin

A case of rhabdomyolysis, in which the etiology could be associated with phenytoin administration is presented and guidelines are described which may assist the early recognition, treatment and prevention of renal failure when such patients are treated in intensive care units. A 46-year-old white man experienced a generalized tonic-clonic seizure at home lasting approximately two minutes. The patient presented with similar crises when seen by the emergency services and had a neurological status of seven points on the Glasgow scale. He was intubated orotracheally and mechanically ventilated. Administration of a 1,250 mg loading dose of phenytoin in 250 ml 0.9% sodium chloride injection were administered intravenously according to guidelines approved by the hospital. These require administration of the loading dose over 30 - 60 minutes followed by phenytoin 150 mg/8 h i.v. administered as a drip diluted in 0.9% NaCl 50 ml over 30 - 60 minutes. Obtained plasma levels were within the therapeutic range but on Day 3 the level of creatine kinase (CK) increased. We initiated treatment to prevent renal failure but the level doubled daily reaching a peak of 54,000 U/I on the fifth day. It was suspected that the increase in CK was due to the treatment with phenytoin which was stopped and replaced by valproic acid 500 mg/8 h orally. The cumulative total dose of phenytoin was 3,050 mg. The subsequent serial determinations of CK showed a decrease beginning on the day phenytoin was stopped and levels falling to 14,229 U/l on the day the patient left the ICU. The patient had no recurrence of the convulsive episodes after the day of admission. In the neurology ward, the patient recovered satisfactorily and the CK value gradually returned to normal. The patient was asymptomatic when released on the ninth day.

The most likely cause of the rhabdomyolysis was phenytoin treatment because of the close temporal relationship between exposure to the drug and onset of symptoms and the rapid resolution of the symptoms and signs after phenytoin was discontinued. An objective causality assessment concluded that a possible adverse drug reaction had occurred.