Abstract
PurposeThis study aimed to evaluate predictive factors involved in efficacy and safety in Japanese infants who received theophylline therapy to prevent apnea of prematurity (AOP) after weaning from mechanical ventilation.MethodsWe retrospectively reviewed the medical records of infants who were administered intravenous aminophylline (theophylline ethylenediamine) for AOP at the neonatal intensive care unit, Kagoshima University Hospital, Japan, between January 2009 and June 2013.ResultsA total of 100 infants were evaluated as two separate groups in terms of efficacy and safety of theophylline. Sixty-seven (67.0%) infants had effective theophylline therapy. Multivariate logistic regression analysis showed that gestational age at birth was significant, with an odds ratio of 0.59 (p < 0.001). Receiver operating characteristic analysis showed that the cut-off value was 31.1 weeks old for predicting the efficacy of theophylline (specificity, 66.7%; sensitivity, 86.6%; p < 0.001; area under the curve, 0.750; 95% confidence interval, 0.45–0.74). Adverse reactions were identified in 21 (21.0%) infants. Multivariate logistic regression analysis showed that the number of days of theophylline administration from birth was associated with an increased risk of adverse reactions after theophylline administration (p = 0.01).ConclusionsPhysicians need to be aware of the possibility that theophylline fails to produce therapeutic effects for extubation in infants aged less than 31.1 weeks old, and adverse reactions can easily develop when theophylline is administered soon after birth.
Highlights
Apnea of prematurity (AOP) is defined as the cessation of breathing for greater than 20 seconds or cessation of breathing for less than 20 seconds accompanied by bradycardia or cyanosis [1, 2]
Receiver operating characteristic analysis showed that the cut-off value was 31.1 weeks old for predicting the efficacy of theophylline
Multivariate logistic regression analysis showed that the number of days of theophylline administration from birth was associated with an increased risk of adverse reactions after theophylline administration (p = 0.01)
Summary
Apnea of prematurity (AOP) is defined as the cessation of breathing for greater than 20 seconds or cessation of breathing for less than 20 seconds accompanied by bradycardia or cyanosis [1, 2]. The incidence of AOP is 25% in neonates who weigh more than 2500 g at birth, and it approaches 84% for those less than 1000 g at birth [3]. AOP can spontaneously occur and appears to be due to immaturity of the infant’s neurological and respiratory systems [3]. While appropriate respiratory support is essential in AOP, treatment of AOP is fairly limited and pharmacotherapy is important. First-line treatment for AOP consists of methylxanthines [4,5,6]. Theophylline, one of the methylxanthine drugs, is used for infants with AOP. Theophylline has a narrow therapeutic range [7], and it sometimes leads to adverse events and toxicity, such as vomiting, tachycardia, jitteriness, and irritability [8, 9]
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