Comparison between the Effect of Oral Paracetamol versus Oral Ibuprofen in the treatment of Patent Ductus Arteriosus in Preterm and Low Birth Weight Infants

Abstract

PDA is an essential part of the fetal circulation. Functional closure occurs at 3 days postnatally and anatomical closure occurs at around 3 months. It usually remains patent in preterm infants and closure is then dependent upon certain factors. Failure of the ductus arteriosus to close within 48-96 hours of postnatal age results in left to right shunts across the ductus and overloading of the pulmonary circulation. This may lead to increased risk for intraventricular hemorrhage, necrotizing enterocolitis, deterioration of the respiratory status and failure to thrive. Paracetamol could offer several important therapeutic advantages over existing therapies: It has no peripheral vasoconstrictive effect, it can be given to infants with clinical contraindications for nonsteroidal anti-inflammatory drugs; and it seems to be effective after some ibuprofen treatment failure when the only other therapeutic option is surgery. The present study was designed to compare the safety and efficacy between oral ibuprofen and oral paracetamol in treatment of PDA in preterm and low birthweight infants. This randomized control trial was conducted on 30 preterm neonates delivered in Obstetrics and Gynecology Hospital, Ain- Shams University and admitted to NICU in the same hospital, over the period from June 2013 to January 2015. Neonates were diagnosed with PDA. Diagnosis of PDA was done clinically & confirmed by 2D, M-mode and color Doppler echocardiography. Neonates were randomly assigned into one of two groups either ibuprofen group (n=15) or paracetamol group (n=15). Regarding the demographic criteria of the two groups, our study had no significant differences; as both groups were mostly the same regarding sex, gestational age, birth weight, APGAR score in both 1st and 5th minutes, and mode of delivery. As regards the clinical criteria, no significant difference was found in the heart rate, systolic, diastolic or mean blood pressure neither before nor after ibuprofen/paracetamol treatment, also there was no significant difference as regards urinary output between both groups. There was no statistically significant difference between both groups as regards pre treatment values of Echocardiographic examination between both groups. The age at which oral paracetamol treatment was started was comparable with the age of start of oral ibuprofen. Concerning Echo measurements, ibuprofen group showed statistically significant decrease in duct size, LPA and RVSP, also significant difference was noted in the shunt direction after administration of 1st and 2nd course of ibuprofen. In the paracetamol group, there was significant decrease in Echo measurments regarding the size of the duct, end diastolic flow velocity in the left pulmonary artery and right ventricular systolic pressure after 1st and 2nd courses of paracetamol, compared to the pre-paracetamol measurements. Moreover, there was significant difference in the direction of the shunt. In our analysis, there was no statistically significant difference between paracetamol and ibuprofen groups as regards the primary outcome closure of PDA after 1st and 2nd course of treatment, and total ductal non-surgical closure. In view of our primary outcome; as regards ibuprofen group ductal closure was observed in 12 out of 15 (80%) premature infants given Ibuprofen 6 (40%) after the first course, 2 (13%) of them after the second course and 4 (26%) showed shunting after the second course but did not require respiratory support or further treatment of the ductus which closed spontaneously before discharge, one patient (6%) required surgical ligation.