AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• References

History of the Procedure

Galen initially described the ductus arteriosus in the early first century. Harvey undertook further physiologic study in fetal circulation. However, it was not until 1888 that Munro conducted the dissection and ligation of the ductus arteriosus in an infant cadaver, and it would be another 50 years before Robert E. Gross successfully ligated a patent ductus arteriosus (PDA) in a 7-year-old child. This was a landmark event in the history of surgery and heralded the true beginning of the field of congenital heart surgery.

Problem

PDA is a persistent communication between the descending thoracic aorta and the pulmonary artery that results from failure of normal physiological closure of the fetal ductus. In normal birth weight and full-term neonates, the ductus arteriosus (DA) closes within 3 days after birth. However, the DA is patent for more than 3 days after birth in 80% of preterm neonates weighing less than 750 g and its persistent patency is associated with increased morbidity and mortality. Furthermore, in the presence of a significant left-to-right ductal shunt in low birth weight (LBW) neonates, a decreased peripheral perfusion and oxygen delivery occurs.

Although frequently diagnosed in infants, the discovery of a PDA may be delayed until childhood or even adulthood. In isolated PDA, signs and symptoms are consistent with left-to-right shunting. The shunt volume is determined by the size of the open communication and the pulmonary vascular resistance. PDA may exist with other cardiac anomalies, which must be considered at the time of diagnosis. In many cases, the diagnosis and treatment of a PDA is critical for survival in neonates with severe obstructive lesions to either the right or left side of the heart.

Frequency

PDA occurs with an incidence of approximately 1 per 2000-2500 live births, comprising 5-10% of all congenital cardiac disease. Siblings have an increased incidence, suggesting a genetic component. Rubella, in the first trimester of the mother's pregnancy, has been associated with PDA and other congenital anomalies. For unknown reasons, PDA is more common in females by a ratio of 2:1. PDA is common in premature infants and may add significantly to morbidity and mortality.

Etiology

PDA is the result of failure of the fetal ductus arteriosus to constrict and close after birth.

Pathophysiology

In the fetal circulation, the ductus arteriosus is necessary to divert blood flow from the high-resistance pulmonary vascular bed, which receives only 5-8% of the right ventricular outflow, creating a right-to-left shunt. At birth, expansion of the neonatal lungs is associated with an immediate fall in pulmonary vascular resistance. Normal ductal constriction begins at this point and reaches completion in 8-10 hours. A second stage of closure related to fibrous proliferation of the intima is complete in 2-3 weeks. Patency after 3 months is considered abnormal, and treatment should be considered at this juncture, although urgency is seldom necessary.

The ductus is a muscular artery with a thick smooth muscle layer in its medial layer. It contracts and closes within a few days after birth. A balance of factors that cause relaxation and contraction determine the vascular tone of the ductus. Major factors causing relaxation are the high prostaglandin levels, hypoxemia, and nitric oxide production in the ductus. Factors resulting in contraction include decreased prostaglandin levels, increased oxygen partial pressure, increased endothelin-1, norepinephrine, acetylcholine, bradykinin, and decreased prostaglandin E receptors. Increased prostaglandin sensitivity, in conjunction with pulmonary immaturity leading to hypoxia, contributes to the increased frequency of PDA in premature neonates.

Failure of ductus arteriosus contraction in preterm neonates has been suggested to be due to poor prostaglandin metabolism because of immature lungs. Furthermore, high reactivity to prostaglandin and reduced calcium sensitivity to oxygen in vascular smooth muscle cells contribute to contraction of the ductus. The absence of DA contraction in full-term neonates might be due to failed prostaglandin metabolism most likely caused by hypoxemia, asphyxia, or increased pulmonary blood flow, renal failure, and respiratory disorders.

COX-2 (an isoform of COX-producing prostaglandins) induction and expression might also prevent ductal closure. The activation of G protein-coupled receptors EP4 by PGE2, the primary prostaglandin regulating ductal tone leads to ductal smooth muscle relaxation.

During late gestation, the decrease in prostaglandin levels results in constriction of the ductus arteriosus. Thus, the intimal cushions come into contact and occlude the ductus lumen.

A PDA is considered pathological when it persists beyond 3 months of age or is associated with symptoms. Spontaneous closure after 5 months is rare in the full-term infant. Left untreated, patients with a large PDA are at risk to develop Eisenmenger Syndrome, in which the pulmonary vascular resistance can exceed systemic vascular resistance, and the usual left-to-right shunting reverses to a right-to-left direction. At this stage, the pulmonary vascular disease is irreversible, closure of the PDA is contraindicated, and lung transplantation may be the only hope for long-term survival.

Clinical

Signs and symptoms of PDA are the result of left-to-right shunting and are proportional to the magnitude of the blood flow through the ductus.

History

Most patients with PDA present with a machinery murmur and are asymptomatic. Neonates and infants may present with signs of heart failure including tachypnea, diaphoresis, failure to thrive, inability to feed, and irritability. They may also have a history of frequent recurrent pulmonary infections. Adults whose PDA has gone undiagnosed may present with signs and symptoms of heart failure, atrial arrhythmia, or even differential cyanosis limited to the lower extremities, indicating shunting of unoxygenated blood from the pulmonary to systemic circulation.

Physical examination

Patients typically present in good health, with normal respirations and heart rate. If the ductus is moderate or large, widened pulse pressure and bounding peripheral pulses are frequently present, reflecting increased left ventricular stroke volume and diastolic runoff of blood into the initially lower-resistance pulmonary vascular bed. Prominent suprasternal and carotid pulsations may be noted secondary to increased left ventricular stroke volume.

The continuous murmur with a machinery quality is typically loudest at the left upper and midsternal border. In patients with severe heart failure and severe elevation of pulmonary vascular resistance, no audible murmur may be present. Patients with large PDA can develop Eisenmenger pathophysiology and present with cyanosis because of reversed shunting when pulmonary arterial pressures exceed systemic pressure as described earlier.

In neonates, a heart murmur is discovered within the first few days or weeks of life. The murmur is usually recognized as systolic rather than continuous in the first weeks of life and can mimic a benign systolic murmur.

Because of changes in the pulmonary vasculature, in adults, diastolic runoff decreases to the point that only a systolic component may exist.

Furthermore, distinguishing between clinically significant and nonsignificant PDA is important. A clinically significant PDA is characterized by respiratory problems with ventilation difficulties, coupled with pulmonary congestion with tachycardia, bounding pulses, and metabolic acidosis. The left-to-right shunt leads to an increased risk of complications that include intraventricular hemorrhage, narcotizing enterocolitis, chronic lung disease, and death.

INDICATIONS

Section 3 of 11  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• References

With rare exceptions, the presence of a patent ductus arteriosus (PDA) is an indication for surgical closure. In the infant, repair may be urgent for the symptomatic patient with evidence of cardiac or respiratory failure not adequately controlled with medications, or it may be delayed in the patient who is asymptomatic or well controlled on medical therapy.

Differential diagnoses

• Ventricular septal defect
• Aortopulmonary window (aortopulmonary fenestration)
• Venous hum
• Truncus arteriosus
• Absent pulmonary valve syndrome
• Ventricular septal defect with aortic regurgitation
• Ruptured sinus of Valsalva and fistula
• Systemic arteriovenous fistula
• Coronary artery fistula
• Pulmonary arteriovenous fistulae
• Bronchial pulmonary artery stenosis

RELEVANT ANATOMY

Section 4 of 11  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• References

The patent ductus arteriosus (PDA) connects the pulmonary artery to the descending thoracic aorta, usually 2-10 mm from the aortic origin of the left subclavian artery. It is commonly 5-10 mm long and tends to be shorter in the adult. The aortic orifice tends to be wider and narrows en route to the pulmonary opening.

In the presence of complex congenital heart defects, the usual anatomy of the ductus may not be present. Anatomic abnormalities can vary widely and are common in conjunction with complex aortic arch anomalies. Structures that have been mistaken for the PDA in surgical procedures include the aorta, the pulmonary artery, and the carotid artery. The left recurrent laryngeal nerve typically arises from the vagus nerve just anterior and caudal to the ductus and loops posteriorly around the ductus to ascend behind the aorta en route to the larynx. It is the most commonly injured anatomic structure in ductal ligation. Other less commonly injured structures include the phrenic nerve and the thoracic duct.

CONTRAINDICATIONS

Section 5 of 11  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• References

The primary contraindication to repair is severe pulmonary vascular disease. If transient intraoperative occlusion of the PDA does not decrease elevated pulmonary arterial pressures with a subsequent increase in aortic pressure, then the closure must be undertaken carefully and may be contraindicated. Closure of the ductus does not reverse preexisting pulmonary vascular disease.

A subset of associated cardiac anomalies—so-called ductal-dependent lesions—depend on flow through the PDA to maintain systemic blood flow. Premature closure of the ductus without concurrent repair of the following defects is contraindicated and may be fatal:

• Pulmonary artery hypoplasia
• Pulmonary atresia
• Tricuspid atresia
• Transposition of the great arteries
• Aortic valve atresia
• Mitral valve atresia with hypoplastic left ventricle
• Severe coarctation of the aorta

WORKUP

Section 6 of 11  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• References

Imaging Studies

• Radiographic findings
• • Large patent ductus arteriosus (PDA) - Marked cardiomegaly with predominant left atrial and left ventricular enlargement, marked enlargement of the main pulmonary artery, and accentuated peripheral pulmonary vascular markings; prominent ascending aorta; increased pulmonary venous markings, interstitial edema, and pulmonary edema when left ventricular failure intervenes; possible PDA calcification in adults
  • Moderate PDA - Moderate cardiomegaly with prominence of the left ventricle and signs of left atrial enlargement; prominent main pulmonary artery and increased pulmonary vascular markings in the peripheral lung fields; prominent ascending aorta; possible PDA calcification in adults
  • Small PDA - Usually normal; possible slight prominence of the main and peripheral pulmonary arteries
  • Studies have shown that chest radiographs have limited predictive value in determining which infants will benefit from ligation.
• Echocardiographic findings
• • The aortic end of the PDA is localized first and is then tracked back to the pulmonary artery. Precisely documenting the size, shape, and course of the ductus is difficult.
  • High velocity jets of turbulent flow in the pulmonary artery can be reliably detected by color flow Doppler imaging. This technique is sensitive in detecting even the small PDA.
  • Echocardiography provides important diagnostic information regarding associated congenital cardiovascular malformations.

Other Tests

• Electrocardiographic findings
• • Large PDA - Left ventricular hypertrophy and left atrial enlargement; with pulmonary hypertension, combined ventricular hypertrophy; when pulmonary vascular disease dominates, possible evidence of only right ventricular hypertrophy
  • Moderate PDA - Usually left ventricular hypertrophy
  • Small PDA - Usually normal

Diagnostic Procedures

• Cardiac catheterization and angiography
• • The diagnosis is almost always based on careful clinical evaluation, including physical examination showing the characteristic murmur, typical electrocardiographic abnormalities, radiographic changes, and echocardiographic/Doppler findings.
  • Color-flow Doppler mapping is more sensitive than cardiac catheterization in detecting a small PDA.
  • Cardiac catheterization may be required for confirmation of clinical diagnosis in children with pulmonary hypertension and/or associated congenital cardiovascular malformations; response to pulmonary vasodilators can be important in planning operative intervention.

TREATMENT

Section 7 of 11  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• References

Medical therapy

Infants with signs of failure may be treated initially with digoxin and diuretic therapy, but interruption of the ductus is required for definitive treatment.

• Indomethacin (Indocin): Indomethacin has proven efficacious resulting in twice the spontaneous closure rate. McCarthy et al demonstrated the successful effects of indomethacin therapy on patent ductus arteriosus (PDA) in 4 newborns with a birth weight of 1500-2075 g who were born at gestational age (GA) of 35 weeks or more (McCarthy, 1978). Watanabe et al evaluated indomethacin therapy in 13 infants with PDA complicated by congenital heart disease and reported closure in 4 of 7 infants with a birth weight of 2500 g or more (Watanabe, 2003). Indomethacin was shown to be successful in both cases; however, the ductus may reopen days or weeks later. Prophylactic indomethacin was also found to reduce the incidence of severe grades of intracranial hemorrhage. Side effects of indomethacin include cerebral vasoconstriction.
  
  Furthermore, these drugs cause adverse renal effects since renal perfusion and diuresis in early neonatal life are strongly influenced by the effects of prostaglandins on the afferent glomerular arterioles.
• Ibuprofen: Prophylactic ibuprofen is also widely used. When compared with indomethacin, ibuprofen is associated with a lower risk of oliguria in preterm infants. In addition, one study showed an increased risk of pulmonary hypertension in patients. The Cochrane evaluation on ibuprofen prophylaxis concluded that although prophylactic ibuprofen use reduces the incidence of PDA on day 3, potential adverse effects should be further addressed also looking at neurodevelopmental outcomes (Shah, 2003).
• Interventional radiology: Several techniques to occlude the PDA are available, although definitive closure rates do not approach those of surgery.
• Gianturco coils: Introduced in 1992, these coils are delivered to the PDA via venous or arterial systems. One to 5 coils are placed in the ductus. This method has been reported to be 75-100% effective but is limited to ductus that are only 4-5 mm in diameter. Fue et al showed that very high closure rates could be obtained in ducts less than 3 mm using coils, but that success significantly dropped when the ducts exceeded 3 mm.
• Amplatzer duct occluder: Larger ducts are closed using the amplatzer duct occluder. The major disadvantage of the design is that the aortic part of the device can protrude into the descending aorta and partly obstruct the lumen, especially in infants.
• Rashkind ductus occlusion device: This consists of a 2-umbrella system delivered to the ductus in either the transvenous pathway or transarterial pathway. This therapy has a reported occlusion rate of 83%. Although used internationally, it is not approved for use in the United States.
• Conservative treatment: Conservative standards include adaptation of ventilation by lowering inspiratory time and giving more positive end expiratory pressure (PEEP). Furthermore, fluid restriction that does not exceed 130 mL/kg/d beyond day 3 is also used. This procedure has found to have a high closure rate of PDA.

Surgical therapy

Surgery is the mainstay of treatment for PDA. If an infant has failed to thrive or has overt congestive heart failure, the ductus should be interrupted, regardless of age and size. If the patient is asymptomatic, elective ligation and division can be carried out at approximately age 4 years when the risks of intubation are decreased and the child is more capable of understanding the procedure and process. Some authorities recommend closure any time after age 12 months or when the patient becomes symptomatic.

The operative approach is performed using a left lateral posterior thoracotomy with the patient under general anesthesia. In small children, the incision can be limited to several centimeters. The thorax is entered through the third intercostal space in the infant and the fourth intercostal space after infancy. The PDA is identified, dissected, and doubly ligated. The earliest procedures involved double clamping of the ductus and oversewing each end. While this is still a definitive approach, it is not used nearly as frequently because division is not considered to be an essential part of the closure, and clamping can be risky when the ductal tissue is friable.

Alternatively, a modification of the technique to reduce the amount of dissection around the thin and friable ductus (and to reduce the risk of catastrophic bleeding) involves the application of metal surgical clips.

In surgical ligation, the tissue surrounding the ductus must be dissected so that a right angle clamp can be placed behind it to grasp the silk ligature. This can be hazardous and may result in the tearing of the friable ductus. Once the ductus is torn, the bleeding that ensues may be difficult to control and can be life threatening. The use of metal surgical clips requires minimal dissection and reduces the risk of this complication.

Alternatively, the surgical ligation is a longer operation than the clip application technique. The surgical ligation of the ductus necessitates longer retraction of the left lung, thus prolonging the difficulties of ventilation in an already-compromised neonate. An operative technique that requires shorter time is beneficial for sick neonates. Thus, the shorter time for the clip application procedure resulted from the need for less dissection and contributes to fewer perioperative complications.

A chest tube is usually placed intraoperatively and removed after 24 hours if no air leak ensues. The typical hospital stay is 3-4 days; however, newer studies report average stays of less than 2 days when using the muscle-sparing thoracotomy through an axillary approach or other less invasive incisions.

Preterm neonates

For neonates weighing 500-1200 g, the procedure is easily accomplished in the neonatal ICU under simulated operating room conditions. A 1.5-cm incision based posteriorly near the tip of the scapula is made with the child in the right lateral decubitus position. The lung is retracted medially, and the mediastinal pleura over the descending aorta and proximal subclavian artery is incised and retracted medially. This allows good visualization of the ductus and all important associated structures.

Vascular forceps may, on rare occasions, be used to occlude the structure thought to be the ductus if any doubt exists. At this juncture, the distal pulse oximeter and systemic pressure measurements can be used to confirm proper identification of the PDA. Again, this is rarely necessary. Two or more Hemoclips can then be used to close the duct. Dividing the duct in these critical neonates is usually not advisable. Operating in the neonatal ICU is important because these neonates are often in unstable, ventilator-dependent conditions that make transportation to the operating room more dangerous.

Overall benefits of early ligation or medical treatment in regard to decreased bronchopulmonary dysplasia, hospital costs, and mortality rates are unclear. The timing of duct closure is also somewhat controversial, but closure is often recommended when indomethacin therapy fails or is contraindicated in patients with subarachnoid hemorrhage or renal failure. While definitive data are not available, many aggressive neonatologists believe that early ligation of the ductus is an important adjunct in weaning these premature neonates from the ventilator.

Adults with calcified PDA

Cardiopulmonary bypass (CPB) is often necessary to safely close these communications because calcification may preclude ligation and the tissue may fracture, resulting in uncontrolled hemorrhage. A median sternotomy incision provides excellent exposure. The ductus can be patched through an incision in the pulmonary artery under low-flow conditions or after a balloon catheter is passed through the communication to prevent vigorous bleeding from the aorta during closure. An identical approach can be used for aneurysmal communications and may even require deep hypothermia with circulatory arrest to gain the necessary control and exposure.

Thoracoscopy - Minimally invasive surgery

Thoracoscopy provides an alternative to left posterior thoracotomy. It has been proven useful in both infants and adults. Whether thoracoscopy has benefits over muscle-sparing thoracotomy is debatable. It is not clear if thoracoscopy provides shorter hospital stays or decreases costs. Additionally, thoracoscopy is contraindicated for adults with calcified PDA. Its use in neonates is not widely advocated secondary to limited control and visualization, and it has no definite advantage since the open procedure uses such a small incision.

Intraoperative details

Infants

For PDA repair in the infant, either an operating room or a portable operating room in the neonatal ICU may suffice. The patient is prepared and draped in the right lateral decubitus position with the left arm extended above the head. Normothermia and proper attention to ventilation are imperative, especially in neonatal patients. The various incisions used are described above.

The left lung is retracted medially, taking care not to compromise ventilation or cardiac output any more than necessary. Meticulous dissection is performed as previously described, taking great care to identify the subclavian artery, descending aorta, distal arch, and ductus prior to performing any ligation, since catastrophic mistakes are easier to make than an inexperienced surgeon might imagine. The surgeon must make every effort to identify and preserve the left recurrent laryngeal nerve.

Once accurate identification of the patent ductus is made, it is isolated and ligated with either silk suture or stainless steel clips, depending on the size of the ductus. Several ties or clips are used since more than a single tie greatly reduces the chance of recanalization. Closing the mediastinal pleura is not necessary after most procedures. A chest tube may be placed at the end of the procedure; however, this step can often be safely omitted, depending on the surgeon's preference.

Adults

Many adolescent and adult patients can be approached via a standard left thoracotomy, much like younger patients. However, when the ductus is large, some risk may be present with simple ligation, including tearing and hemorrhage. In these cases, gentle double clamping with appropriate vascular clamps and division with oversewing using 4-0 Prolene suture is indicated. Because the PDA tends to be short and can be calcified at the aortic end, repair in adults may require a median sternotomy and CPB.

After preparation for CPB is complete, the aorta and pulmonary trunk are separated. Single venous cannulation is sufficient. After CPB is established and the heart is emptied, the patient is placed in the moderate Trendelenburg position, and the PDA is manually occluded by compressing the front wall of the left pulmonary artery against it. This maneuver prevents distension of the pulmonary vasculature and right ventricle.

The aorta is cross-clamped, and cardioplegia is infused to arrest the heart. Manual occlusion of the PDA is removed, and the pulmonary artery is opened opposite the PDA. Temporary low-flow perfusion is used while the blood from the duct is blocked with a balloon catheter or finger occlusion. Pledgeted 4-0 or 3-0 Prolene sutures are used to definitively close the ductus. In the rare cases in which the orifice is too large for this closure, a synthetic patch of Dacron or polytetrafluoroethylene can be sewn in. The pulmonary artery is closed with a running Prolene suture, and CPB is terminated in routine fashion after full rewarming. Mediastinal chest tubes are placed and may be routinely removed the morning following the operation.

Follow-up

Timely closure of a PDA is generally definitive treatment, and no special care or follow-up is necessary. While rare reports exist of recanalization and recurrence of a left-to-right shunt after PDA ligation, the risk is extremely low.

If a PDA has been closed by interventional radiologic techniques, obtaining follow-up echocardiograms until complete closure is confirmed is wise.

COMPLICATIONS

Section 8 of 11  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• References

Complications may include the following:

• Incomplete closure or recanalization
• Bleeding
• Pneumothorax
• Injured recurrent laryngeal nerve
• Chylothorax as a result of thoracic duct injury
• Rare ligation of nonductal tissue
• Residual shunting
• Vocal cord paralysis

OUTCOME AND PROGNOSIS

Section 9 of 11  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• References

The prognosis is generally considered excellent in patients in whom the patent ductus arteriosus (PDA) is the only problem. In premature infants who have other sequelae of prematurity, these sequelae tend to dictate prognosis of PDA.

Studies have shown that preterm babies with a gestational age of 30 weeks or younger had a 72% rate of spontaneous closure of PDA. In addition, 28% of children with PDA who were conservatively treated (with prophylactic ibuprofen) reported a 94% closure rate. This rate compared well with rates reported in literature following medical treatment (80-92%).

In the adult patient, prognosis is more dependent on the condition of the pulmonary vasculature and the status of the myocardium if congestive cardiomyopathy was present prior to ductal closure. Patients with minimal or reactive pulmonary hypertension and limited myocardial changes may have a normal life expectancy.

FUTURE AND CONTROVERSIES

Section 10 of 11  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• References

The future of patent ductus arteriosus (PDA) correction will be in the area of catheter closure as first described in 1971. Currently, the Rashkind device and the Gianturco coils are most promising. The efficacy of catheter closure does not equal that of surgical repair. With continued improvements, these less invasive and less costly techniques are likely to eventually replace surgical treatment in the typical patient. Thoracoscopy remains controversial, with several studies reporting very little benefit in hospital stay or cost compared with the muscle-sparing left lateral thoracotomy approach. Since both techniques are equally acceptable, the choice of surgical technique depends on the surgeon's preference.

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• References

• Allegaert K, Rayyan M, Anderson BJ. Impact of ibuprofen administration on renal drug clearance in the first weeks of life. Methods Find Exp Clin Pharmacol. Oct 2006;28(8):519-22.
• Edwards AD, Wyatt JS, Richardson C, et al. Effects of indomethacin on cerebral haemodynamics in very preterm infants. Lancet. Jun 23 1990;335(8704):1491-5.
• Galal O, Nehgme R, al-Fadley F. The role of surgical ligation of patent ductus arteriosus in the era of the Rashkind device. Ann Thorac Surg. Feb 1997;63(2):434-7. [Medline].
• Garson A. The Science and Practice of Pediatric Cardiology. 2nd ed. Lippincott Williams & Wilkins;1998:1181-1196; 2489-2508.
• Hines MH, Bensky AS, Hammon JW Jr, et al. Video-assisted thoracoscopic ligation of patent ductus arteriosus: safe and outpatient. Ann Thorac Surg. Sep 1998;66(3):853-8; discussion 858-9. [Medline].
• Kennedy AP Jr, Snyder CL, Ashcraft KW, et al. Comparison of muscle-sparing thoracotomy and thoracoscopic ligation for the treatment of patent ductus arteriosus. J Pediatr Surg. Feb 1998;33(2):259-61. [Medline].
• Kirklin JW, Barratt-Boyes B. Patent ductus arteriosus. In: Cardiac Surgery. 2nd ed. Churchill Livingstone;1993:841-856.
• Laborde F, Folliguet T, Batisse A, et al. Video-assisted thoracoscopic surgical interruption: the technique of choice for patent ductus arteriosus. Routine experience in 230 pediatric cases. J Thorac Cardiovasc Surg. Dec 1995;110(6):1681-4; discussion 1684-5. [Medline].
• Mandhan PL, Samarakkody U, Brown S, et al. Comparison of suture ligation and clip application for the treatment of patent ductus arteriosus in preterm neonates. J Thorac Cardiovasc Surg. Sep 2006;132(3):672-4.
• Masura J, Gavora P, Podnar T. Transcatheter occlusion of patent ductus arteriosus using a new angled Amplatzer duct occluder: initial clinical experience. Catheter Cardiovasc Interv. Feb 2003;58(2):261-7.
• Mavroudis C. Patent ductus arteriosus. In: Pediatric Cardiac Surgery. 2nd ed. Mosby-Year;1994:140-145.
• McCarthy JS, Zies LG, Gelband H. Age-dependent closure of the patent ductus arteriosus by indomethacin. Pediatrics. Nov 1978;62(5):706-12.
• Nichols DG. Patent ductus arteriosus. In: Critical Heart Disease in Infants and Children. Mosby-Year;1995:716-721.
• Novick WM, Watson DC Jr, Alpert BS. Patent ductus arteriosus ligation: are we doing better?. Ann Thorac Surg. Apr 1995;59(4):822-4. [Medline].
• Shah SS, Ohlsson A. Ibuprofen for the prevention of patent ductus arteriosus in preterm and/or low birth weight infants. Cochrane Database Syst Rev. 2006;CD004213. [Medline].
• Takami T, Yoda H, Kawakami T, et al. Usefulness of Indomethacin for Patent Ductus Arteriosus in Full-Term Infants. Pediatr Cardiol. Jan 2 2007.
• Vanhaesebrouck S, Zonnenberg I, Vandervoort P, et al. Conservative treatment for patent ductus arteriosus in the preterm. Arch Dis Child Fetal Neonatal Ed. Jan 9 2007.
• Watanabe K, Tomita H, Ono Y, et al. Intravenous indomethacin therapy in infants with a patent ductus arteriosus complicating other congenital heart defects. Circ J. Sep 2003;67(9):750-2.
• Weber HS, Cyran SE, Gleason MM. Transcatheter vascular occlusion of the small patent ductus arteriosus: an alternative method. Pediatr Cardiol. May-Jun 1996;17(3):181-3. [Medline].
• Wyllie J. Treatment of patent ductus arteriosus. Semin Neonatol. Dec 2003;8(6):425-32. [Medline].

Article Last Updated: Feb 17, 2007