Razi Journal of Medical Sciences

en مقایسه تأثیر استامینوفن خوراکی و ایبوپروفن خوراکی در درمان نوزادان نارس مبتلا به PDA: (کارآزمایی بالینی) Comparison between the Efficacy of Oral Acetaminophen and Ibuprofen in the Treatment of Preterm Infants with PDA (A Clinical Trial) بیماری‌های اطفال Pediatric Disease پژوهشي Research <div style="text-align: justify;">زمینه و هدف: مجرای شریانی باز (PDA) یکی از شایع‌ترین نقص‌های مادرزادی قلب در نوزادان نارس است. یکی از راه های درمانی برای بسته شدن PDA استفاده از داروهایی همچون ایبوپروفن و استامینوفن است. این مطالعه به منظور مقایسه اثربخشی و عوارض استامینوفن و ایبوپروفن به صورت مصرف خوراکی در درمان PDA در نوزادان نارس طراحی شده است. روش کار: مطالعه حاضر کارآزمایی بالینی یک سو کور بر روی 60 نوزاد نارس که با تشخیص PDA در سال 1400 در بخش NICU بیمارستان اکبرآبادی بستری شدند، انجام گردید. نوزادان از لحاظ سن حاملگی، سن تقویمی و وزن تولد مشابه سازی شدند و به صورت راندوم و ساده در 2 گروه دریافت کننده ایبوپروفن خوراکی (30N=) و استامینوفن (30N=) تقسیم شدند و در نهایت میزان و مدت زمان بسته شدن PDA، و یافته های اکوکاردیوگرافی قبل و بعد از مداخله و عوارض جانبی احتمالی در نوزادان هر دو گروه مورد بررسی قرار گرفت. پس از جمع آوری اطلاعات، داده ها در SPSS مورد تجزیه و تحلیل آماری قرار گرفت.</div> <div style="text-align: justify;">یافته‌ها: میزان بسته شدن PDA در گروه دریافت کننده ایبوپروفن و استامینوفن به ترتیب برابر با 66/76% و 33/73% بود. (05/0 p>) در بیمارانی که ایبوپروفن و استامینوفن دریافت کرده بودند، به ترتیب علایم مبنی بر NEC (10% ،0 %) (01/0 p=)، هایپربیلیروبینمی (33/43 % ،66/26 %) (03/0 p=) و خونریزی گوارش (66/6% ، 0%) (04/0 p=) به طور معناداری شایع تر بود. همچنین به ترتیب 1 و 3 نفر از بیمارانی که تحت درمان با استامینوفن و ایبوپروفن قرار گرفته بودند، فوت شدند که این اختلاف از لحاظ آماری معنی دار نبود (24/0 p=).</div> <div style="text-align: justify;">نتیجه‌گیری: با وجود آن که میزان بسته شدن PDA با تجویز استامینوفن با ایبوپروفن خوراکی تفاوت معنی داری نداشت، بروز عوارض در استامینوفن کمتر از ایبوپروفن بود و این دارو می تواند جایگزین مناسبی برای استفاده در درمان نوزادان نارس دارای PDA باشد.</div> <div style="text-align: justify;">Background & Aims: Patent ductus arteriosus (PDA) is one of the most common congenital heart defects in premature infants. Despite the relatively high prevalence of PDA in preterm infants, there is still no clear treatment pattern for these patients. The main treatment options for PDA include surgical obstruction of the duct or the use of medications such as prostaglandin synthetase inhibitors. Previous studies have reported that surgery leads to complications, the most important of which include pneumothorax, chylothorax, infections, and ultimately increased mortality. Therefore, the option of surgical treatment for PDA is largely limited. Finding a suitable treatment option for uncomplicated recovery of PDA in premature infants is very valuable to increase the life of premature infants. Indomethacin was the first prostaglandin synthetase inhibitor to be used to treat PDA. However, due to its relatively common side effects, attempts were made to replace the drug, and the US Food and Drug Administration eventually authorized the intravenous administration of ibuprofen lysine (neoprofen) to premature infants with PDA. At present, according to the results of previous studies, ibuprofen is mainly used to close PDAs. Ibuprofen is as effective as indomethacin and has fewer renal side effects. Recent studies have shown that acetaminophen can also be used effectively to treat PDA in premature infants. However, the use of this drug (orally and parenteral) has not been widely studied in clinical trials. On the other hand, recent studies have examined the positive and uncomplicated effect of intravenous acetaminophen as well as ibuprofen on treat PDA. Therefore, conducting a study comparing the oral use of acetaminophen and ibuprofen in PDA closure in preterm infants is valuable and will greatly help in choosing the best treatment option in them. Therefore, in this study, the effect of oral acetaminophen and ibuprofen on premature infants with PDA was investigated. Methods: This interventional study was conducted from April to Nov 2020. A total of 60 preterm neonates with diagnosis of PDA admitted in NICU of Akbar Abadi Hospital Tehran were selected. Neonates were randomly assigned to two groups. In the first intervention group, oral Acetaminophen was prescribed every 6 hours at a dose of 15 mg/kg for 3 days. In the second intervention group, oral Ibuprofen was prescribed at a dose of 10 mg/kg for day one and 5 mg/kg for the next two consecutive days. Inclusion criteria included Parent's consent to participate in the study, Gestational age between 26 to 37 weeks, and Diagnosis of ductus arteriosus based on echocardiographic evidence at 24 to 72 hours after birth. Exclusion criteria included premature newborn with fever and seizure, life-threatening infections, clinical or radiographic evidence of necrotizing enterocolitis, evidence of bleeding, platelets less than 50,000 per ml, Liver failure, congenital brain-neurological disorders, metabolic and genetic syndromes, pulmonary hypoplasia syndrome, congenital heart anomalies or other fatal abnormalities. Finally, the extent and duration of PDA closure, and echocardiographic findings before and after the intervention and side effects in infants of both groups were evaluated. Data were entered in SPSS and analyzed. Results: The demographic characteristics in neonates showed that in terms of gender variability, the frequency  of boys and girls in the group of oral acetaminophen and ibuprofen were 16 (53.3%), 14 (46.7%) and 17 (56.7%) and 13(43.3%), respectively. The mean of gestational age was 33.15± 6 weeks. Total of 78.33% of patients underwent cesarean section. The mean birth weight of neonates at the time of diagnosis in the acetaminophen and ibuprofen groups was 2231.41± 690.25 and 1854± 453.47 gr, respectively.  About 26.66% of patients had Large PDA. The results of statistical analysis showed that the mean gestational age and weight in the two groups receiving Acetaminophen and Ibuprofen were not significantly different (P = 0.14), (P = 0.746). The LA / AO ratio in the acetaminophen and ibuprofen groups at the beginning of treatment was 0.42 ± 1.57 and 0.56 ± 1.74, respectively, which were not significantly different from each other. At the end of the treatment period, patients in both groups had a significant decrease in LA / AO ratio. After the intervention in the acetaminophen group was 0.36 ± 1.20 and compared to before the intervention was statistically significant (P = 0.013) and in the Ibuprofen group was 0.40 ± 1.38 .There was a statistically significant decrease compared to the results before the intervention (P = 0.017). However, the LA / AO ratio at the end of the treatment period did not differ significantly between the Acetaminophen and Ibuprofen groups (P = 0.412). PDA size in acetaminophen and ibuprofen groups at the beginning of treatment was 2.85(0.48) and 2.81(0.75), respectively, which was not significantly different from each other, but at the end of treatment patients in both groups was significantly reduced. There was a significant decrease in PDA size, this ratio was 1.72(0.92) in the acetaminophen group after the intervention and had a statistically significant decrease compared to the results before the intervention. (P = 0.001) In the ibuprofen group, it was equal to 1.74(1.02) which was significantly lower than before the intervention (P = 0.024). But PDA size at the end of treatment was not significantly different between acetaminophen and ibuprofen groups. After the first course of treatment in the ibuprofen and acetaminophen groups, 43.33% and 46.66% of PDA s were closed, respectively, which was not significantly different between the two groups (P = 09.79). After the second course of treatment, PDA closure was observed in 33.3% and 26.66% of ibuprofen and acetaminophen groups respectively, and there was no statistically significant difference between the two groups (P = 0.653). The most common clinical complications in patients receiving acetaminophen and ibuprofen were short-term hyperbilirubinemia (26.66% and 43.33%, respectively), which was significantly higher in the ibuprofen group (p = 0.03). Conclusion: Although the rate of PDA closure with oral acetaminophen compared to oral ibuprofen was not different, the incidence of side effects in acetaminophen group was lower than ibuprofen and this drug can be a suitable alternative for use in the treatment of preterm infants with PDA. </div> مجرای شریانی باز, استامینوفن, ایبوپروفن, درمان خوراکی, نوزاد نارس Patent Ductus Arteriosus, Acetaminophen, Ibuprofen, Oral medication, Preterm Infant 1 10 http://rjms.iums.ac.ir/browse.php?a_code=A-10-6806-1&slc_lang=en&sid=1 Semira Mehralizadeh سمیرا مهرعلیزاده 3900319475328460074641 3900319475328460074641 No Associate Professor, School of Medicine, Iran University of Medical Sciences, Aliasghar Children's Hospital, Tehran, Iran دانشیار، دانشکده پزشکی، دانشگاه علوم پزشکی ایران، بیمارستان کودکان علی اصغر، تهران، ایران Mandana Kashaki ماندانا کشاکی 3900319475328460074642 3900319475328460074642 No Associate Professor, School of Medicine, Iran University of Medical Sciences, Shahid Akbarabadi Hospital, Tehran, Iran دانشیار، دانشکده پزشکی، دانشگاه علوم پزشکی ایران، بیمارستان شهید اکبرآبادی، تهران، ایران Zahra Hadadi زهرا حدادی maede.haddadi@yahoo.com 3900319475328460074643 3900319475328460074643 Yes Pediatrician, School of Medicine, Iran University of Medical Sciences, Aliasghar Children's Hospital, Tehran, Iran متخصص کودکان، دانشکده پزشکی، دانشگاه علوم پزشکی ایران، بیمارستان کودکان علی اصغر، تهران، ایران Davood Amirkashani داود امیرکاشانی 3900319475328460074644 3900319475328460074644 No Associate Professor, School of Medicine, Aliasghr Children Hospital, Tehran, Iran استادیار، دانشکده پزشکی، بیمارستان کودکان علی اصغر، تهران، ایران