A Randomized Controlled Trial Comparing Serum Theophylline Levels and Side Effects between Two Regimens of Aminophylline in Preterm Infants
Kanmalee Jenjarat MD1, Napol Chitsrisakda MD1, Nithipun Suksumek MD1, Sangkae Chamnanvanakij MD1
Affiliation : 1 Department of Pediatrics, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand
Background : Aminophylline is the medication use for treating apnea of prematurity and facilitating endotracheal extubation
in preterm infants. The regimen of aminophylline therapy varies among institutions. However, the data on its safety are limited.
Objective : To compare rate of achieving theophylline therapeutic level and side effects between two regimens of aminophylline
therapy in preterm infants.
Materials and Methods: Infants of gestational age less than 35 weeks and birthweight less than 2,000 grams who required
aminophylline treatment or prophylaxis for apnea of prematurity were randomly allocated to one of two groups. Group 1 received
an intravenous aminophylline loading dose at 5 mg/kg and then maintenance at 6 mg/kg/day. Group 2 received a loading dose at
8 mg/kg and maintenance at 4 mg/kg/day. Serum theophylline levels were measured at 2 to 3 hours after the loading dose and
before the sixth maintenance dose. Apnea episodes, heart rate, and urine volume were closely monitored.
Results : Twenty-two infants were enrolled to each group. No differences of gestational age, birthweight, and indication were found
among the two groups. At 2 to 3 hours after the loading dose, infants of group 2 had signi(cid:976)icantly higher rate of serum theophylline
levels within the therapeutic range than group 1 (59.1% vs. 4.5%). This difference was not observed before the sixth maintenance
dose. Frequency of apnea episodes was not different between the two groups. Only infants of group 2 had signi(cid:976)icant increases in
heart rate after the loading dose. Both groups had signi(cid:976)icant increased in urine output volume after the loading dose.
Conclusion : The high loading-low maintenance regimen of aminophylline had advantage in achieving the therapeutic level more
rapidly, whereas the low loading-high maintenance regimen had lower risk of tachycardia. Physicians should weigh between bene(cid:976)it
and risk before choosing a regimen of aminophylline for preterm infants.
Keywords : Aminophylline, Theophylline, Apnea of prematurity
