Patent ductus arteriosus in preterm infants

Patent ductus arteriosus (PDA) is a major morbidity in preterm infants, especially in extremely premature infants less than 28 weeks. The clinical signs and symptoms of PDA in preterm infants are non specific and insensitive for making an early diagnosis of significant ductal shunting. Functional echocardiography is emerging as a new valuable bedside tool for early diagnosis of hemodynamically significant ductus, even though there are no universally accepted criteria for grading the hemodynamic significance. Echocardiography has also been used for early targeted treatment of ductus arteriosus, though the long term benefits of such strategy are debatable. The biomarkers like BNP and N-terminal pro-BNP are currently under research as diagnostic marker of PDA. The primary mode of treatment for PDA is pharmacological closure using cyclo-oxygenase inhibitors with closure rate of 70–80%. Oral ibuprofen is emerging as a better alternative especially in Indian scenario where parenteral preparations of indomethacin are unavailable and side effects are comparatively lesser. Though pharmacological closure of PDA is an established treatment modality, there is still lack of evidence for long term benefits of such therapy as well as there is some evidence for the possible adverse effects like increased ROP and BPD rates, especially if treated prophylactically. Hence, it is prudent to reserve treatment of PDA to infants with clinically significant ductus on the basis of gestation, birth weight, serial echocardiography and clinical status to individualize the decision to treat.     

Patent ductus arteriosus in preterm neonates

Failure of the ductus arteriosus to close within 48–96 hours of postnatal age results in a left to right shunt across the ductus and overloading of the pulmonary circulation. This is more likely to happen in premature neonates with respiratory distress syndrome. Deterioration in the respiratory status on day 3–4 in a ventilated neonate and unexplained metabolic acidosis may be the earliest indicators of a patent ductus arteriosus (PDA). Indomethacin is the main stay of medical management of PDA in preterm neonates. Guidelines for administration of indomethacin have been described in the protocol. Restricted fluid therapy may be beneficial in the prevention of PDA in preterm neonates. Presence of PDA in a term neonate should be investigated to rule out an underlying congenital heart disease.     

Patent ductus arteriosus in preterm neonates

Failure of the ductus arteriosus to close within 48–96 hours of postnatal age results in a left to right shunt across the ductus and overloading of the pulmonary circulation. This is more likely to happen in premature neonates with respiratory distress syndrome. Deterioration in the respiratory status on day 3–4 in a ventilated neonate and unexplained metabolic acidosis may be the earliest indicators of a patent ductus arteriosus (PDA). Indomethacin is the main stay of medical management of PDA in preterm neonates. Guidelines for administration of indomethacin have been described in the protocol. Restricted fluid therapy may be beneficial in the prevention of PDA in preterm neonates. Presence of PDA in a term neonate should be investigated to rule out an underlying congenital heart disease.     

Patent ductus arteriosus before and after surgery

Twenty five patients with patent ductus arteriosus, who had undergone surgical closure were studied retrospectively. Girls were more affected than boys; the sex ratio was 4:1. Associated cardiac lesions were diagnosed in 3 patients, two with ventricular septal defect and one with congenital mitral stenosis. Congestive heart failure was diagnosed in 5 patients before surgery. Typical continuous murmur was heard in most cases (76%), while in the rest only systolic murmur was detected. Electrocardiographic left atrial enlargement, left ventricular hypertrophy and right ventricular hypertrophy were found in 8%, 48% and 40%, respectively. Cardiomegaly with increased pulmonary vascular markings was found in 60% of cases, while ratio of left atrial to aortic root diameter greater than 1.2 was detected in 60% of patients. The PDA could be directly visualized by echocardiography in 15 cases. Cardiac catheterization was performed in 17 cases, 47% with hyperkinetic pulmonary hypertension, 41% with high pulmonary flow without pulmonary hypertension and 12% with mild increased pulmonary flow. The pulmonary-systemic flow ratio (Qp/Qs) was more correlated to pulmonary vascular markings rather than to cardio-thoracic ratio. Division of the ductus was the procedure of choice, but in 16% of cases ductal ligation was performed because of technical reasons. Postoperative catch-up in both weight and height was observed more clearly in children operated at earlier age. Ejection systolic murmur was still detected in 2 patients, in whom hyperkinetic pulmonary hypertension existed prior to surgery. No cardiomegaly was found in patients followed-up 1 year or more after surgery. The mortality was nil.     

Patent ductus arteriosus complicating the respiratory distress syndrome in preterm infants.

In 46 preterm infants with RDS the patency of the ductus arteriosus was established by single film aortography or by clinical diagnosis and confirmation at surgery. The estimated left-to-right shunt through the PDA by aortogram correlated well with the heart size and the clinical diagnosis of heart failure. In 14 infants massive cardiomegaly and heart failure with a PDA occurred before the appearance of a heart murmur. Twelve infants had severe RDS and 34 had mild or moderate RDS. Massive cardiomegaly occurred significantly earlier in infants with severe RDS. It is suggested that ductal ligation is indicated when an infant with massive cardiomegaly requires IPPV and whose aortagram shows that all of the contrast material is in the pulmonary arteries and none in the aortic arch. A heart murmur may or may not be present.     

Patent ductus arteriosus increases lung fluid filtration in preterm lambs.

Previous studies showed that increased pulmonary blood flow from a patent ductus arteriosus had little or no effect on the amount of fluid in the lungs of mechanically ventilated preterm lambs. The purpose of this study was to examine the effect of a patent ductus arteriosus on lung vascular permeability and to see whether increased pulmonary lymph flow might compensate for the increased rate of fluid filtration. Using a model that allows mechanical control of ductus patency, we studied the effects of increased pulmonary blood flow on lung vascular pressures in six mechanically ventilated premature lambs at 136 +/- 2 d gestation (mean +/- SD) (term = 145 d). We measured lung lymph flow and protein concentrations in lymph and plasma to assess pulmonary vascular fluid filtration and protein permeability. We studied each lamb during sequential steady state periods, first with the ductus open and then with it closed. When the ductus was open, pulmonary blood flow was twice what it was when the ductus was closed. Mean pulmonary artery pressure and left ventricular end-diastolic pressure were greater with the ductus open [40 +/- 5 torr (5.3 +/- 0.7 kPa) and 8 +/- 3 torr (1.1 +/- 0.4 kPa), respectively] than when it was closed [24 +/- 3 torr (3.2 +/- 0.4 kPa) and 4 +/- 2 torr (0.5 +/- 0.3 kPa), respectively]. When the ductus was open, lymph flow was 68% greater and lymph protein concentration was 17% lower than when the ductus was closed. Lymph protein clearance (lymph flow x lymph protein concentration/plasma protein concentration) was 39% greater when the ductus was open.(ABSTRACT TRUNCATED AT 250 WORDS)     

Patent ductus arteriosus and respiratory outcome in premature infants

A persistent ductus arteriosus is a common event in preterm infants. The systemic-to-pulmonary shunting that occurs as the pulmonary vascular resistance decreases after birth can have significant cardiovascular and respiratory consequences. Acute pulmonary effects include pulmonary edema and hemorrhage, worsened lung mechanics and deterioration in gas exchange with hypoxemia and hypercapnia. The increased pulmonary blood flow can also produce damage to the capillary endothelium and trigger an inflammatory cascade. This, plus the need for longer and more aggressive mechanical ventilation, can explain the association between patent ductus arteriosus and an increased risk for bronchopulmonary dysplasia in extremely premature infants.