Paracetamol therapy in a preterm newborn with patent ductus arteriosus

Year 2013, Volume: 48 Issue: 1, 82 - 84, 01.03.2013

Özmert Muhammet Ali Özdemir Kazım Küçüktaşçı Mustafa Doğan Özlem Şahin Hacer Ergin

Abstract

To the Editor Patent ductus arteriosus PDA is a problem which is especially frequently observed in very low birth weight preterm newborns Indomethacin and ibuprofen are used as medical therapies for closure of patent ductus arteriosus However these drugs may cause to some side effects Surgical closure is performed in newborns who have a contraindication for medical treatment or when medical treatment is unsuccessful However some complications may be observed during surgical closure or following surgical closure 1 2 In this letter a male preterm newborn whose PDA was not closed despite oral ibuprofen given for three times but was markedly reduced hemodynamically with paracetamol treatment before surgical closure and who did not need surgical intervention was presented The APGAR score at the first and fifth minutes of a male newborn who was born by cesarean section with a birth weight of 820 g at 24 weeks and 5 days 48 hours after administration of betamethasone because of preterm delivery and oligohydramniosis from the first pregnancy of a 26 year old mother were found to be 5 and 7 respectively Complete blood count of the patient who was followed up while receiving mechanical ventilation at the 6th hour after delivery was as follows: WBC: 74 600 micro;L hemoglobin 15 2 g dL platelets 417 000 micro;L peripheral smear: polymorphonuclear leukocytes 44 lymphocytes 18 bands 12 immature mature cell ratio 0 27 monocytes 10 promyelocytes 16 toxic granulation normoblasts 30 No blastic cell was observed With leukomoid reaction toxic granulation and an immature mature cell ratio of 0 27 early neonatal sepsis was considered and intravenous ampicillin and netylmycine were started at appropriate doses after obtaining regular cultures Respiratory distress syndrome was not considered radiologically and clinically Blood biochemical variables were evaluated to be normal In the follow up antibiotherapy was discontinued since the cultures remained negative and infection markers were found to be negative On the fourth day after delivery the patient had no murmur but Corrigan rsquo;s pulse was found in the femoral arteries and FiO2 was gt;40 Echocardiogram revealed a small secundum atrial septal defect The ductus was closed and follow up was recommended On the 8th day after delivery a 1 6 systolic murmur was heard on all cardiac areas The repeated ECHO revealed a 2 mm PDA and a left atrium LA aotric annulus Ao ratio of 1 5 Oral ibuprofen treatment was started On the second day of treatment ibuprofen was discontinued because of development of thrombocytopenia 28000 micro;L On the 11th day after delivery his murmur continued the platelet count was found to be 119000 micro;L and creatinine was found to be 0 8 mg dL The first oral ibuprofen treatment was administered at a dose of 10 5 5 mg kg day with 24 hour intervals The ECHO performed after the first treatment revealed a ductus diameter of 2 mm and a LA Ao ratio of 1 4 Two courses of oral ibuprofen treatment at the same dose were given to the patient who was found to have hemodynamically significant PDA Despite this treatment hemodynamically significant PDA persisted After obtaining written consent from the family oral paracetamol treatment 15 mg kg dose every 6 hours for 72 hours was given on the 20th day after delivery before surgical intervention Complete blood count peripheral smear and liver function tests were found to be normal before and after paracetamol treatment On ECHO performed after treatment it was observed that the ductus diameter was reduced to 1 mm and the LA7Ao ratio was reduced to 1 1 and follow up was recommended No murmur was heard in the patient on the 47th day after delivery On the 75th day the ductus was closed completely Table 1 In the follow up of the patient who had no intracranial bleeding severe bronchopulmonary dysplasia and grade 1 retinopathy of prematurity developed The patient was discharged on the 108th day after delivery without oxygen oxygen saturation gt;90 and was started to be followed up in the neonatology outpatient clinic Medical treatment is started in symptomatic PDA patients with hemodynamically significant ECHO findings LA Ao gt;1 4 ductus diameter gt;1 4 mm 1 Since indomehtacin may lead to complications including transient or persistent renal dysfunction necrotizing enterocolitis and decreased oxygen supply to the brain researchers have tended towards a safer pharmacological agent 3 4 It was shown that ibuprofen which is another cyclooxygenase inhibitor had fewer brain renal and mesenteric side effects increased the autoregulation of the brain blood flow and preserved neurologic functions following oxidative stress in animal experiments 5 6 7 In a study performed in our country it was reported that oral ibuprofen treatment was as efficient as intravenous indomethacin treatment and even more efficient than that in closure of PDA 8 In cases where medical treatment is contraindicated or unsuccessful surgical ligation is performed for closure of patent ductus arteriosus Complications including recurrent laryngeal nerve damage chylothorax pneumothorax left ventricular dysfunction and scoliosis may be observed in relation with surgical closure 1 Because of potential complications of medical and surgical closure treatments researchers have tended towards novel searches With this aim paracetamol which is a novel agent in PDA treatment has been started to be used 9 10 Paracetamol acts by inhibiting the peroxidase component of prostaglangin synthetase Hammerman et al 9 reported for the first time that the ductus closed or was reduced in all the patients in the first three days with oral paracetamol treatment given at a dose of 15mg kg dose every 6 hours in 5 patients whose PDA was not closed with two courses of ibuprofen treatment or who had contraindications for ibuporfen treatment and no side effects was observed The second study was conducted in our country and reported that success with a rate of 87 5 was obtained with paracetamol treatment given to 8 patients with the same justifications 10 Based on these two studies we administered paracetamol treatment for 72 hours at the same dose before surgical intervention to our patient whose PDA was not closed with three courses of oral ibuprofen treatment ECHO performed after treatment revealed that the ductus was hemodynamically regressed and reduced with a marked degree No side effect was found during treatment In the follow up patent dustus was reduced in size and was observed to be insignificant hemodynamically on follow up ECHOs performed It was found that the ductus was completely closed on the 75th day after delivery Based on this case presentation we think that the chance of paracetamol treatment before surgical intervention should be given to very low birth weight preterm newborns whose PDAs do not close with recurrent ibuprofen treatment Ad shy;dress for Cor shy;res shy;pon shy;den shy;ce: Kazım Küçüktaşçı MD Pamukkale University Medical Faculty Department of Pediatrics Division of Neanatology Denizli Turkey E mail: drkkucuktasci@gmail com Re shy;cei shy;ved: 08 07 2012 Ac shy;cep shy;ted: 09 17 2012 References 1 Hamrick SE Hansmann G Patent ductus arteriosus of the preterm infant Pediatrics 2010; 125 5 : 1020 1230 2 Chiruvolu A Jaleel MA Therapeutic management of patent ductus arteriosus Early Hum Dev 2009; 85 3 : 151 155 3 Betkerur MV Yeh TF Miller K Glasser RJ Pildes RS Indomethacin and its effect on renal function and urinary kallikrein excretion in premature infants with patent ductus arteriosus Pediatrics 1981; 68 1 : 99 102 4 Edwards AD Wyatt JS Richardson C Potter A Cope M Delpy DT Reynolds EO Effects of indomethacin on cerebral haemodynamics in very preterm infants Lancet 1990; 335 8704 : 1491 1495 5 Kushnir A Pinheiro JM Comparison of renal effects of ibuprofen versus indomethacin during treatment of patent ductus arteriosus in contiguous historical cohorts BMC Clin Pharmacol 2011; 11: 8 6 Patel J Roberts I Azzopardi D Hamilton P Edwards AD Randomized double blind controlled trial comparing the effects of ibuprofen with indomethacin on cerebral hemodynamics in preterm infants with patent ductus arteriosus Pediatr Res 2000; 47 1 : 36 42 7 Su PH Chen JY Su CM Huang TC Lee HS Comparison of ibuprofen and indomethacin therapy for patent ductus arteriosus in preterm infants Pediatr Intern 2003; 45 6 : 665 670 8 Tekşam Ö Yiğit Ş Karagöz T Korkmaz A Yurdakök M Tekinalp G Yenidoğan bebeklerde patent duktus arteriyozusun tedavisinde oral ibuprofen ve intravenöz indometazin: bir retrospektif çalışma Çocuk Sağlığı ve Hastalıkları Dergisi 2004; 47: 96 102 9 Hammerman C Bin Nun A Markovitch E Schimmel MS Kaplan M Fink D Ductal closure with paracetamol: a surprising new approach to patent ductus arteriosus treatment Pediatrics 2011; 128 6 : e1618 1621 10 Oncel MY Yurttutan S Degirmencioglu H Uras N Altug N Erdeve O Dilmen U Intravenous paracetamol treatment in the management of patent ductus arteriosus in extremely low birth weight infants Neonatology 2012; 103 3 : 165 168

Keywords

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Patent duktus arteriyozuslu erken doğan bir bebekte parasetamol tedavisi

Abstract

Patent duktus arteriyozus (PDA), özellikle aşırı düşük doğum ağırlıklı erken doğan yenidoğanlarda sık görülen bir sorundur. Patent duktus arteriyozus kapatılmasında tıbbi tedavi olarak indometazin ve ibuprofen kullanılmaktadır. Bununla birlikte bu ilaçlar bazı yan etkilere neden olabilmektedir. Cerrahi kapatma tıbbi tedavinin uygulanmasına bir engel olduğu veya başarısız olduğu yenidoğanlarda uygulanmaktadır. Ancak, cerrahi kapatma sırasında veya daha sonra bazı komplikasyonlar görülebilmektedir (1,2). Bu yazıda, ağızdan üç kez ibuprofen verilmesine rağmen PDA’sı kapanmayan ve cerrahi kapatma öncesi parasetamol tedavisi ile hemodinamik olarak duktusu belirgin küçülen ve cerrahi işlemden kurtulan bir erken doğmuş erkek bebek olgusu sunuldu.

Keywords

Patent duktus, arteriyozuslu, erken doğan

References

• Hamrick SE, Hansmann G. Patent ductus arteriosus of the preterm infant. Pediatrics 2010; 125(5): 1020-30.
• Chiruvolu A, Jaleel MA. Therapeutic management of patent ductus arteriosus. Early Hum Dev 2009; 85(3): 151-5.
• LA: Sol artriyum, Ao: Aort anulusu 83 Türk Ped Arfl 2013; 48: 82-4 Turk Arch Ped 2013; 48: 82-4 Özdemir ve ark.
• Patent duktus arteriyozuslu erken doğan bir bebek parasetamol tedavisi / Paracetamol therapy in a preterm newborn with patent ductus arteriosus