THEOPHYLLINE TOXICITY IN CHILDREN - A RETROSPECTIVE REVIEW

Theophylline has been a mainstay of asthma therapy despite its narrow therapeutic index, which makes toxicity a common problem. To study tox icity in children, we reviewed hospital laboratory records (1980 to 19 88) and identified cases (n = 163) with theophylline concentrations of >133 mumol/L (24 mug/ml). We reviewed these cases for symptoms of the ophylline intoxication; we were interested in associating symptoms wit h serum drug concentrations and in understanding how intoxication occu rred. The median patient age was 3.0 years; 40/163 were younger than o ne year. Males were 90/163 patients (55%). Patients were classified by pattern of ingestion: 20 patients had acute ingestions; 17 patients h ad an acute ingestion while on chronic medication; and 126 patients be came toxic on chronic therapy. Symptoms were absent in 44/150 patients (29%) with theophylline concentrations of 139 to 278 mumol/L (25-50 m ug/ml); concentrations of >278 mumol/L (50 mug/ml) were always associa ted with symptoms. The most common clinical symptoms were tachycardia (47%) and vomiting (52%); both occurred more frequently with higher th eophylline concentrations (P < 0.002 and P < 0.01). Nine patients had seizures, including five who were previously neurologically normal. Se izures developed with a theophylline concentration of <278 mumol/L (50 mug/ml) in four of these five patients. There was no association betw een seizures and patient age or between seizures and a particular patt ern of theophylline use. In 105/126 cases of intoxication associated w ith chronic use, the cause of the intoxication could not be determined . Appropriate management of theophylline toxicity can occur only if to xicity is recognized. This study demonstrates that clinical evidence o f toxicity from theophylline in children is quite variable and cannot be used to screen for those who should have their serum levels measure d. All children who are taking theophylline should have their serum le vels monitored when they seek acute medical care.