Caffeine Treatment for Prostaglandin E1-Induced Apnea Prevention in Congenital Heart Disease Neonates: A Randomized Clinical Trial.

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. 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. A total of 51 CHD neonates receiving PGE1 + caffeine ( = 25) and PGE1 ( = 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, =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 (=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, =0.04). 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. Iranian Registry of Clinical Trials: IRCT20220503054729N1.