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Eight patients developed grand mal seizures during intravenous theophylline therapy. None had a history of neurologic disorder, and all were acutely ill with severe pulmonary or cardiovascular disease, or both. Serum theophylline concentrations obtained within 1 hour of the seizure ranged from 25 mug/ml to 70mug/ml, with a mean value (53 plus or minus 4.8 mug/ml) more than twice the upper limit of the recommended therapeutic concentration. This serum theophylline concentration was greater than the concentration found in a group of patients with less severe drug-related symptoms (35 plus or minus 1.8 mug/ml, P less than 0.01). A third group of patients without drug-related symptoms had a mean theophylline serum concentration of 19 plus or minus 2.0 mug/ml, which was less than that found in either group with toxicity symptoms (P less than 0.05). Factors predisposing to the high serum concentrations in the patients with seizures were both higher drug dosage, compared with the other groups (P less than 0.01), and hepatic dysfunction, which was more common in both groups with drug-related symptoms.

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