Theophylline toxicity in children: a retrospective review

Abstract

Theophylline has been a mainstay of asthma therapy despite its narrow therapeutic index, which makes toxicity a common problem. To study toxicity in children, we reviewed hospital laboratory records (1980 to 1988) and identified cases (n = 163) with theophylline concentrations of > 133 mumol/L (24 micrograms/ml). We reviewed these cases for symptoms of theophylline intoxication; we were interested in associating symptoms with serum drug concentrations and in understanding how intoxication occurred. The median patient age was 3.0 years; 40/163 were younger than one year. Males were 90/163 patients (55%). Patients were classified by pattern of ingestion: 20 patients had acute ingestions; 17 patients had an acute ingestion while on chronic medication; and 126 patients became toxic on chronic therapy. Symptoms were absent in 44/150 patients (29%) with theophylline concentrations of 139 to 278 mumol/L (25-50 micrograms/ml); concentrations of > 278 mumol/L (50 micrograms/ml) were always associated with symptoms. The most common clinical symptoms were tachycardia (47%) and vomiting (52%); both occurred more frequently with higher theophylline concentrations (P < 0.002 and P < 0.01). Nine patients had seizures, including five who were previously neurologically normal. Seizures developed with a theophylline concentration of < 278 mumol/L (50 micrograms/ml) in four of these five patients. There was no association between seizures and patient age or between seizures and a particular pattern of theophylline use. In 105/126 cases of intoxication associated with chronic use, the cause of the intoxication could not be determined. Appropriate management of theophylline toxicity can occur only if toxicity is recognized.(ABSTRACT TRUNCATED AT 250 WORDS)