Frequent Toxicity from IV Aminophylline Infusions in Critically Ill Patients

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Abstract
Use of recommended IV aminophylline dosage regimens in 48 older, acutely ill, hospitalized patients with chronic obstructive pulmonary disease (COPD) resulted in excessive plasma theophylline concentrations in 29 percent of these patients. A mean dose of 0.89 mg/kg/hr produced a plasma concentration which ranged from 7 to 52 mcg/ml with a mean of 21.9 mcg/ml. Plasma theophylline concentration was determined spectrophotometrically from plasma samples drawn at least 12 hours after a loading dose and initiation of a constant infusion. Severity of toxicity strongly correlated with the plasma theophylline concentration in 18 patients. Nausea and/or vomiting preceded life-threatening drug-induced arrhythmias and seizures less than half the time. Tachycardia was found to be the most consistent symptom associated with toxicity. These patients had lower plasma clearances than otherwise healthy younger adult asthmatics and healthy volunteers. Toxicity and identifiable risk factors for excessive plasma levels strongly correlated with reduced plasma clearance. Dosage modifications based upon plasma clearances from COPD patients without concurrent functional abnormalities and those with liver dysfunction and cardiac decompensation ranged from 0.7 to 0.12 mg/kg/hr. This study clearly demonstrates the poor correlation between dose and plasma concentration and the strong relationship between toxicity and plasma concentration. These results as well as those previously reported mandate that the relatively simple, rapid and inexpensive theophylline plasma measurement be used in all patients receiving IV aminophylline for longer than 24 hours in order to prevent toxicity.

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