Abstract
Background: Congenital heart diseases (CHDs) are structural abnormalities of the heart or great vessels. Prostaglandin E1 (PGE1) is used to maintain the ductus arteriosus open in neonates with ductal-dependent heart lesions but is associated with apnea. We aimed to investigate the effects of caffeine therapy on the occurrence of apnea in neonates with CHD. Methods: This single-blinded randomized clinical trial was performed on 51 CHD neonates who were treated with PGE1 or PGE1 + caffeine. PGE1 dose ranged from 0.01 to 0.1 mcg/kg/min, and caffeine was administered initially at 20 mg/kg, followed by a daily bolus dose of 10 mg/kg. Demographic and clinical data, prevalence of apnea, and PGE1 side effects were recorded and analyzed. Results: A total of 51 CHD neonates receiving PGE1 + caffeine (n = 25) and PGE1 (n = 26) were included. The median age of total neonates was 2 (1-7) days, and 57% were female. There was no statistically significant difference between the baseline characteristics of participants, but neonates in the caffeine group received a higher mean dose of PGE1 (0.03 ± 0.17 vs. 0.02 ± 0.02, p=0.049) over the course of the treatment. The prevalence of apnea was 20% in the PGE1 + caffeine group and 42% in the PGE1 group (p=0.086). In the Cox regression model, the age of neonates had a significant effect on time to apnea in patients receiving caffeine (HR = 0.87, p=0.04). Conclusion: Our findings fail to demonstrate that caffeine therapy reduces PGE1-induced apnea. A larger randomized controlled trial is required to confirm or refute the efficacy of caffeine in reducing the incidence of apnea associated with PGE1 infusion. Trial Registration: Iranian Registry of Clinical Trials: IRCT20220503054729N1.