In a controlled study, 150 Saudi preterm infants were treated with 1.5 mg/kg/day of theophylline for apnea of prematurity. In 96.8% of infants the apnea was either reduced by more than 50% or abolished completely. The effective therapeutic plasma level for these infants was 4.5 ±2.1 μg/mL. A loading dose was found to be unnecessary. Theophylline at these doses appears to be effective and safe treatment for apnea of prematurity in Saudi infants. KN Haque, M Al-Kharashi, C Waters, Theophylline Therapy for Apnea of Prematurity in Saudi Preterm Infants: Therapeutic Serum Level and Dosage. 1989; 9(2): 178-181 Theophylline, a methylxanthine derivative, is widely used in the treatment of apnea of prematurity.1,2 Although the pharmacokinetics of theophylline in preterm infants have been well studied, 3,4 the dose-response relationship has not been clearly established. Serum theophylline concentrations between 6 and 15 μg/mL have been suggested as optimal maintenance levels 1,5,6 for the treatment and prevention of apnea and bradycardia in preterm infants under 34 weeks of gestation. However, there is no general agreement, 7 and levels as far apart as 1.3 and 17.7 μg/ mL have been found to abolish apnea in preterm infants.
7This study on the use of theophylline in controlling apnea of prematurity set out to establish if a loading dose was necessary, and whether theophylline in a maintenance dose of 1.5 mg/kg/ day would be effective.
Patients and MethodsOne hundred fifty infants with a gestational age of less than 34 weeks (assessed by maternal dates and Ballard scoring system 8 ) were enrolled in the study. Apnea of prematurity was defined for this study as an absence of thoracic movement for more than 20 seconds or by a shorter arrest of respiration accompanied by bradycardia (heart rate less than 100 beats per minute) 9 or by cyanosis. Standard criteria were used to exclude other causes of apnea. Also excluded from the study were infants with obstructive apnea. Heart rate and chest wall movements were monitored by continuous recordings of an impedance pneumograph. Infants who had apnea due to sepsis, metabolic causes, necrotizing entercolitis, intracranial hemorrhage, or sedative ingestion, and those gestationally past 34 weeks were excluded from the study.Infants matched for gestational age, sex, and weight were randomly allocated into two groups. Group A received 5 mg/kg of aminophylline (1.25 mg aminophylline equals 1 mg of theophylline) intravenously as a loading dose. Group B did not receive such a loading dose. Both groups were given regular maintenance therapy of 1.5 mg/kg/day every 8 hours. The maintenance dose was administered intravenously if the infant was not being fed orally; otherwise an equivalent amount of theophylline was given orally. Therapy was started when spells of apnea were prolonged and repeated (i.e., more than 2 to 3 spells per hour) or when the infants required frequent bag and mask ventilation to recover from apnea. The infants acted as their own controls, as it would be unethical to wit...