COMPARATIVE STUDY OF THE EFFICACY OF ORAL AND CONTINUOUS VERSUS INTERMITTENT INFUSION OF PARACETAMOL ON CLOSURE OF PATENT DUCTUS ARTERIOSUS By

Background: Patent ductus arteriosus (PDA) is a persistent opening between pulmonary artery and aorta leading from the heart. Aim of study: The aim of this study was to know the most effective route of administration of paracetamol (oral & bolus or continuous infusion) in treatment of patent ductus arteriosus. Methods: A considerable number of patients (30) who were admitted in neonatal intensive care unit (NICU) of Pediatric Department at El-Minya health insurance Hospital, Al-Azhar University Assuit, from May 2022 to October 2022. Our studied newborn was classified into 3 groups according to route of administration of paracetamol. Each group included 10 newborns: group 1 (10 NB) received oral paracetamol, group 2 (10 NB) received bolus IV and group 3 (10 NB) received IV continuous infusion. All included neonates received the same dose 60mg/kg/day for 3 days for oral and IV bolus the dose was divided into 15 mg/kg every 6 h. Paracetamol was started at 4th to 7th day of birth. Results: There is statistically significant higher closure rate of PDA in infants received bolus IV and IV infusion paracetamol than those received oral paracetamol. Conclusion: Oral, bolus and continuous infusion administration of paracetamol were safe and effective in the treatment of patent ductus arteriosus. Both standard IV intermittent bolus paracetamol infusion and continuous IV paracetamol infusion were more effective in pharmacologic PDA closure compared with oral paracetamol infusion.


INTRODUCTION
Patent ductus arteriosus (PDA) is a persistent opening between the two major blood vessels leading from the heart.The opening (ductus arteriosus) is a normal part of a baby's circulatory system in the womb that usually closes shortly after birth.If

Sample size:
The sample size was done the Epi inf 7 programs for sample size calculation, setting.
The confidence level at 95% and margin of error at 10% based the work done by cakir et al., (2021), a total of 30 patients was estimated to be sufficient sample size.
Ethical Considerations: This study was carried out after being approved by the local Ethics Committee of the Faculty of medicine Al-Azhar University, Assuit, Egypt.Consent will be taken from the patients before including them in the study.Aim of the study and possible risks will be explained to patients.Privacy of collected data will be assured.

Inclusion criteria:
Preterm neonates with birth weight (BW) ≤ 1500 g and gestational age (GA) ≤ 30 weeks at birth Exclusion criteria: Neonates with major congenital and heart anomalies, infants who received paracetamol after having failed ibuprofen and infants treated with paracetamol for other indications besides PDA closure (e.g., pain management).

PATIENTS AND METHODS
This was a prospective comparative study, including.A considerable number of patients (30) who were admitted in neonatal intensive care unit (NICU) of Pediatric department at El-Minya health insurance Hospital, Al-Azhar University Assuit.During the period from May 2022 to October 2022.
Our studied newborn were classified into 3 groups according to route of administration of paracetamol.Each group included 10 newborns: • Group 1 (10 NB) received oral paracetamol, • Group 2 (10 NB) received bolus IV and • Group 3 (10 NB) received IV continuous infusion.
All included neonates received the same dose 60mg/kg/day for 3 days for oral and IV bolus, the dose was divided into 15 mg/kg every 6 h.Paracetamol was started at 4 th to 7 th day of birth The studied group was subjected to: -full history intake, -Complete general and local examination, also -Laboratory Investigation was done as: Complete blood count, kidney and liver function and electrolytes.
-CXR and Echo.also were done.Comparing groups was done using: Chi square-test (X²): for comparison of qualitative data.Student's "t"-test for comparison of quantitative data of 2 independent sample.ANOVA test for comparison of quantitative data of more than 2 independent sample.Study of the relationship between variables was done using correlation coefficient "Pearson correlation".

RESULTS
Our data will be demonstrated in the following tables: Comparison of PDA diameter before and after tttt, showed that there is statistically significant lower PDA diameter in infants after receiving oral paracetamol, bolus IV and IV infusion paracetamol than before receive paracetamol.

In agreement with our results
El-Khuffash et al., 2014 revealed that the short and long course of oral paracetamol, and intravenous administration of paracetamol resulted in significant improvement in PDA diameter.
Comparison of left atrium: aortic ratio before and after tttt, showed that there is statistically significant lower left atrium: aortic ratio in infants after receiving oral paracetamol, bolus IV and IV infusion paracetamol than before receive paracetamol.

Mehralizadeh et al., 2021
revealed that there was statistically significant improvement in left atrium:aortic ratio in both oral and IV Acetaminophen treatment.
In agreement with our results Vaidya et al., 2021 revealed that larger PDA was significantly associated with non-closure of PDA with acetaminophen in preterm infants.But in contrast to our results, they reported that left atrium:aortic ratio was no significantly associated with closure of PDA.
In the present study we found that PDA closure was higher in male and in normal vaginal delivery neonates.There is no statistically significant difference between infants closed and not closed PDA as regard the type of respiratory support, GA and birth weight.