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Letters to the Editor

Indian Pediatrics 2002; 39: 99-100  

Oral Ibuprofen for Closure of Hemodynamically Significant PDA in Premature Neonates

The most widely employed medical therapy for closure of hemodynamically significant PDA is Indomethacin followed by Mefenamic acid and Ibuprofen. Ibupropfen is a non steroidal anti-inflammatory drug devoid of serious side effects, which is easily available in suspension form. We present our experience with the use of oral Ibuprofen for closure of symptomatic PDA in 13 premature neonates.

We evaluated 13 premature neonates with detailed antenatal and postnatal records. They were assessed for gestational age based on Dubowitz physical and neurological criteria. Babies with congenital anomalies, complex heart disease, thrombocytopenia and DIC were excluded from the study.

Neonates were diagnosed to have symptomatic PDA based on the following criteria(2): (i) Systolic or continuous murmur (Grade II or more) in left infraclavicular region; (ii) Presence of at least three of the following; (a) basal tachycardia (>170/min), (b) bounding brachial and femoral arterial pulses; (c) Hyperdynamic left ventricular impulse; (d) Tachypnea (>70/min); (e) Other evidence of cardiac failure, e.g., tender palpable liver >3 cm below the costal margin and crepitations on chest auscultation; (iii) Cardiomegaly defined as cardiothoracic ratio >0.6; and (iv) Echocardiography. The babies were nursed under servo controlled radiant warmers and calculated intravenous fluids were given by Diginfusa.

All babies receiving Ibuprofen had a com-plete blood count, platelet count, prothrombin time, blood urea and urine examination done before and after therapy. Serum electrolytes and serum bilirubin were done if indicated. All neonates were observed closely for the presence of oliguria, bleeding diathesis and gastrointestinal signs. All babies underwent repeat echo-cardiography to confirm closure of PDA after one week.

Table I summarizes the outcome of these 13 neonates with symptomatic PDA who were treated with oral Ibuprofen (10 mg/kg - 1st dose, 5 mg/kg - 2 doses at 12 hourly intervals).

Eleven infants showed closure of patent ductus arteriosus on echocardiography after treatment. There were no significant side effects like oliguria or bleeding tendencies.

Ibuprofen like Indomethacin belongs to the group of NSAIDs and is a cyclo-oxygenase inhibitor preventing conversion of arachi-donic acid to PGE2 thus preventing patency of PDA.

Hemodynamically significant PDA may complicate the clinical outcome of preterm infants. Intravenous Indomethacin has been widely used for ductal closure in this situation but Indomethacin may affect renal, cerebral and gastrointestinal system leading to necro-tizing enterocolitis, gastrointestinal hemorr-hage or decrease in intra-cerebral oxygena-tion. In the last few years, much evidence has emerged regarding the safety and efficacy of Ibuprofen for the treatment of preterm PDA. Ibuprofen does not impair cerebral auto regulation and has much less adverse effects on renal and mesenteric circulation. A recent study conducted in a large number of preterm infants(4) suggests that Ibuprofen should be preferred as the first line of drug for closing PDA in preterm infants. Patients with oliguria, intraventri-cular hemorrhage, hyperbilirubinemia and thrombocytopenia were excluded in this trial; however, even in these situations Ibuprofen would not be safe.

In conclusion, in our limited experience we have found oral Ibuprofen to be a safe and effective drug for closure of hemo-dynami-cally significant PDA in preterm infants. Larger randomized controlled trials for comparison with other drugs like Indometha-cin and Mefenamic acid are warranted.

Table I__Summary of Outcome
Gestation (weeks) Diagnosis Weight (kg) Age at ibuprofen therapy (day) Outcome
32 AGA with HMD 1.49 5 Success
32 SGA/RDS with PDA 1.2 3 Success
28 AGA Apnea of prematurity 1.2 5 Success
30 AGA with Sepsis 1.3 3 Success
32 LGA with HIE 2.3 3 Success
32 AGA with RDS 1.5 3 Success
34 LGA with RDS 2.3 3 Success
32 AGA with Sepsis 1.3 5 Success
32 AGA with RDS 1.4 5 Success
28 AGA with HMD 1.1 3 Expired
28 AGA (ASD/VSD/PDA) 2.2 3 Failure
32 SGA with RDS/Sepsis 2 5 Success
35 AGA (Asphyxia) 1.4 3 Success

ASD - Atrial Septal defect; HMD - Hyaline membrane disease; AGA - Appropriate for gestational age; HIE - Hypoxic ischemic encephalopathy; LGA - Large for gestational age; PDA - Patent ductus arteriosus; RDS - Respiratory distress syndrome; SGA - Small for gestational age; VSD - Ventricular septal defect.


Pramila Hariprasad,
V. Sundarrajan,
G. Srimathy,
B. Suthagar,
B. Shyla
Correspondence to: Pramila Hariprasad,
G.K.N.M. Hospital,
P.B. No. 6327, Pappanaickenpalayam,
Coimbatore 641 037, Tamil Nadu, India.
E-mail: gknmh@vsnl.com



1. Pezzati M, Jangi V, Biagotti R, Bertinili, Ciancilli D, Rubal telli FT. Effects of Indomethacin and Ibuprofen on mesentric and renal blood flow in preterm infants with PDA. Pediatr 1999; 135: 733-738.

2. Shenoi A, Narang A, Bhakoo ON, Bidwai PS. Clinical profile and management of symptomatic patent ductus arteriosus in premature infants. Indian Pediatr 1991; 28: 125-130.

3. Gitenberger de Groot AC. Patent ductus arteriosus: Most probably a primary congential malformation. Br Heart J 1977; 6: 610-618.

4. Van Overmeire BV, Smets K, Lecoutere D, Vande Brock H, Weyler J, Degroote, et al. Comparison of Ibuprofen and Indomethacin for closure of patent ductus arteriosis. N Eng J Med 2000; 343: 674-681.


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