Theophylline toxicity in children: a retrospective review

• Published in: Pediatric emergency care Vol. 9; no. 3; p. 129
• Main Authors: Powell, E C, Reynolds, S L, Rubenstein, J S
• Format: Journal Article
• Language: English
• Published: United States 01-06-1993
• Subjects: Adolescent; Child; Child, Preschool; Female; Humans; Infant; Male; Retrospective Studies; Seizures - chemically induced; Tachycardia - chemically induced; Theophylline - adverse effects; Theophylline - blood; Vomiting - chemically induced
• ISSN: 0749-5161
• DOI: 10.1097/00006565-199306000-00002

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.