Letters to the Editor

Indian Pediatrics 2004; 41:1066-1068

Theophylline is an effective bronchodilator at therapeutic levels but administration of excessive amounts may produce serious toxicity including arrhythmias, seizures and death(1). We conducted a descriptive study during October-December 2002 on children presenting with acute respiratory infection (ARI) and CNS excitation symptoms to find out the cause for CNS excitation symptoms. The age, sex, clinical manifestations, concurrent medical illness and medications were recorded. Serum theophylline level samples were collected as soon as child arrived in emergency department in addition to serum electrolytes, serum calcium, CSF analysis and chest radiograph. Serum theophylline levels were determined by high-performance liquid chromatography (HPLC).

During the study period, a total of 10 children presented with acute respiratory infection and CNS excitation symptoms. 6 cases had evidence of acute theophylline over dosage. The clinical features of these children are given in Table I. The most common manifestations were irritability (100%), tremors (83.3%), seizures (66.6%), and vomiting (50%). Tachycardia and tachypnea were seen in all children. Hyperglycemia was seen in 2 (33%) children. All these 6 children had received theophylline preparations by local practitioners before admission. Out of the remaining 4 children, 2 had hypoxic seizures, one had acute CNS infection and one had probable inborn error of metabolism.

TABLE I

Clinical Profile and Investigations of Children with LRI and Theophylline Overdosage 

	Case 1	Case 2	Case 3	Case 4	Case 5	Case 6	%
Age	45 days	50 days	75 days	65 days	90 days	70 days
Sex	Male	Female	Male	Male	Male	Male	Male
Irritability	+	+	+	+	+	+	100
Tremors	+	+	-	+	+	+	83
Seizures	+	+	+	+	-	-	67
Vomiting	-	-	+	-	+	+	50
Hyperglycemia	+	-	-	-	-	+	33
S. theophylline
level (µg/mL)	16.2	17.7	18.9	26.8	21.6	24
S. Na, K, Ca	Normal	Normal	Normal	Normal	Normal	Normal
CSF analysis	Normal	Normal	Normal	Normal	Normal	Normal
Diagnosis	Bronchiolitis	Bronchiolitis	Pneumonia	Pneumonia	Pneumonia	Pneumonia
Outcome	Well	Well	Well	Well	Well	Well

The average pediatric serum half-life of theophylline is slightly less than the average adult serum half-life of four hours(2). The usual pediatric range is wide (2 to 12 hours)(3) and varies inversely with age, being quite prolonged in premature neonate. Correlations between serum theophylline levels and drug toxicity in children are scanty. Therapeutic range of serum theophylline levels were between 5-10 µg/mL in neonates and 10-15 µg/mL in infants. In 1993 Powel EC(4) had observed that seizures developed with a theophylline concentration of >50 µg/mL. In our study children had CNS signs even at serum theophylline concentration between 15-30 µg/mL. This may be due to the variation in time interval between theophylline administration and serum sampling of theophylline levels. In our study we could not assess the actual time interval between theophylline administration and serum. sampling for theophylline as all children were treated for ARI with theophylline preparations elsewhere before admission.

Douglas Baker had documented increased predisposition for theophylline toxicity in children with viral respiratory infection(5). 23% of their cases of theophylline toxicity occurred in children with respiratory infection receiving appropriate amount of theophylline. Most of our cases also had probable viral respiratory infection predisposing to theophylline toxicity.

Our observation highlights the possibility of theophylline over dosage in young infants treated for acute respiratory infection presenting with CNS excitation symptoms. Care should be taken to ensure appropriate dosage and frequency when administering theophylline preparations to young infants with respiratory infection.

T. Sathish Kumar,
Prabhakar D. Moses,*
Department of Child Health Unit III,
Christian Medical College,
Vellore 632 004, India.
*Corresponding author:
E-mail: [email protected]