Patent Ductus Arteriosus (PDA) Treatment & Management

Spontaneous closure of the patent ductus arteriosus (PDA) is common. If significant respiratory distress or impaired systemic oxygen delivery is present, therapy is usually prudent. Intravenous (IV) indomethacin (or the newer preparation of IV ibuprofen) is frequently effective in closing a patent ductus arteriosus (PDA) if it is administered in the first 10-14 days of life. Other options are catheter closure (see Cardiac Catheterization) and surgical ligation, which entails a thoracotomy (see Surgical Ligation) (see the following image).

Diagram illustrating the patent ductus arteriosus.

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Medical management also consists of amelioration of congestive heart failure (CHF) symptoms. CHF is an indication for closure of the patent ductus arteriosus (PDA) in infancy. If medical therapy is ineffective, urgent intervention to close the structure should be undertaken.

All patent ductus arteriosus (PDA) should be closed because of the risk of bacterial endocarditis associated with the open structure. Over time, the increased pulmonary blood flow precipitates pulmonary vascular obstructive disease, which is ultimately fatal.

Identification of additional cardiac malformations, such as coarctation or interrupted aortic arch or pulmonary atresia, is the most important requirement before pharmacologic or surgical closure of the patent ductus arteriosus (PDA). When surgical ligation is not indicated, prostaglandin inhibitors (eg, nonsteroid antiinflammatory drugs [NSAIDs]) are used to close the ductus arteriosus.

A ductal dependent lesion requires the persistence of a patent ductus arteriosus (PDA) to ensure adequate pulmonary blood flow.

Prehospital and emergency department care

General measures in prehospital and emergency department (ED) care for a patient with suspected patent ductus arteriosus (PDA) consist of supplemental oxygen for any hypoxia, pulmonary support, and supportive care. Other measures include sodium and fluid restriction as well as correction of any anemia.

Transfer

Transfer to a tertiary care center is mandatory for a patient in extremis presenting in florid CHF once stabilized with diuretics and positive pressure ventilation, as indicated.

Consultations

Consultation with a pediatric cardiologist and pediatric cardiovascular surgeon may be indicated.

Because patients presenting with a patent ductus arteriosus (PDA) are usually asymptomatic, no acute management is needed. However, until the patency of the ductus is corrected, administer antibiotics in patients during instances of high exposure to bacteremia (eg, instrumentation, dental procedures), as recommended by the American Heart Association for the prevention of bacterial endocarditis. ^[4]

Conservative standards include adaptation of ventilation by lowering inspiratory time and giving more positive end expiratory pressure (PEEP). ^[5] Furthermore, fluid restriction that does not exceed 130 mL/kg/d beyond day 3 is also used. This has been found to have a high closure rate of patent ductus arteriosus (PDA).

In infants who present with congestive heart failure (CHF), the standard treatment of digoxin and diuretic therapy usually palliates the condition. These children can be treated until they are several years old and are good candidates for ductal closure. When medical treatment of congestive heart failure fails in infants, the patients are referred early for surgical closure of the structure.

Closure of the patent ductus arteriosus (PDA) is stimulated by administration of prostaglandin synthesis inhibitors, such as indomethacin or aspirin, which is effective in premature infants (see Pharmacologic Management and Medication). Indomethacin (0.1 mg/kg body weight) is administered orally at 8-hour intervals. This treatment is particularly valuable in premature infants presenting with respiratory distress syndrome complicated by left-to-right shunting through the ductus.

One study concluded that B-type natriuretic peptide can be used to guide treatment, reducing the number of primary indomethacin doses. ^[6]

Additionally, a study of 50 preterm infants born at less than 33 weeks’ gestation found that obtaining N-terminal-pro-brain natriuretic peptide (NT-proBNP) levels on day 2 of life may be an effective guide for early targeted indomethacin therapy for PDA in preterm infants. This method may reduce later onset of hemodynamic significant PDA and unnecessary exposures to indomethacin. ^[7]

The premature neonate with a significant patent ductus arteriosus (PDA) is usually treated with intravenous (IV) indomethacin or ibuprofen. ^[8] This has been quite successful in most patients. Whether results with IV indomethacin are superior to those with surgical closure of the patent ductus arteriosus (PDA), even in the premature neonate in whom the safety of the surgery is a concern, is unclear. ^[9]

IV indomethacin was the standard drug treatment. Then, IV ibuprofen was approved by the US Food and Drug Association (FDA). Although ibuprofen and indomethacin are equally effective, other differences are noted: Indomethacin appears to decrease the incidence of intraventricular hemorrhage, whereas ibuprofen has less renal toxicity.

Indomethacin (Indocin)

Indomethacin has proven efficacious, resulting in twice the spontaneous closure rate. ^[10] 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 a gestational age (GA) of 35 weeks or more. ^[11]

Watanabe et al evaluated indomethacin therapy in 13 infants with patent ductus arteriosus (PDA) complicated by congenital heart disease and reported closure in 4 of 7 infants with a birth weight of 2500 g or more. ^[12] 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. ^[12]

These drugs cause adverse renal effects, because renal perfusion and diuresis in early neonatal life are strongly influenced by the effects of prostaglandins on the afferent glomerular arterioles.

Ibuprofen (NeoProfen)

Prophylactic ibuprofen is also widely used. The dose used for ibuprofen is 10 mg/kg bolus followed by 5 mg/kg/d for 2 additional days.

When compared with indomethacin, ibuprofen is associated with a lower risk of oliguria in preterm infants. However, 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 patent ductus arteriosus (PDA) on day 3, potential adverse effects should be further addressed that also look at neurodevelopmental outcomes. ^[13]

Patent ductus arteriosus (PDA) closure is gestation dependent, with a cumulative closure rate of 65%. A similar proportion of infants had patent ductus arteriosus (PDA) closure following first and second courses of ibuprofen, regardless of gestation, suggesting that a second course of ibuprofen may be effective in closing a patent ductus arteriosus (PDA), obviating the need for surgery. ^[14]

Studies comparing indomethacin vs ibuprofen

A meta-analysis by Ohlssen et al found ibuprofen is as effective as indomethacin in closing a patent ductus arteriosus (PDA) and reduces the risk of necrotizing enterocolitis and transient renal insufficiency associated with indomethacin. ^[15]

A meta-analysis by Jones et al confirmed that both indomethacin and ibuprofen treatments promote patent ductus arteriosus (PDA) closure better than placebo. ^[16] Ibuprofen and indomethacin appear to be equally effective, with similar rates of complications after therapy except for the development of chronic lung disease (30% greater risk in ibuprofen treatment arm). However, the investigators did not discuss if chronic lung disease might have reflected selection bias or if the degree of chronic lung disease in these patients resulted in poorer long-term outcomes. ^[16]

Diuretic agents

Although diuretics and fluid restriction have been recommended for the treatment of symptomatic neonates, no rigorously collected data support this approach. In fact, a systematic review of furosemide use in preterm neonates with respiratory distress syndrome showed no long-term benefits and an increased risk of symptomatic patent ductus arteriosus (PDA). ^[17]

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

The use of the percutaneous route to close the patent ductus arteriosus (PDA) is becoming more common. Transcatheter occlusion is an effective alternative to surgical intervention and is becoming the treatment of choice for most cases of patent ductus arteriosus (PDA) in children and adults. ^{[18, 19, 20, 21, 22]}

Most patients with an isolated patent ductus arteriosus (PDA) can have successful treatment by catheterization after the first few months of life.

After the first birthday, the most common treatment for a patent ductus arteriosus (PDA) is occlusion at cardiac catheterization. In fact, as catheterization techniques advance, the ability to close defects in smaller infants has also been reported with high levels of success. Over the last 4 decades, many techniques and devices have been used for patent ductus arteriosus (PDA) occlusion, although definitive closure rates do not approach those of surgery. Contraindications to catheter-based closure involve the size of the patient.

Gianturco spring occluding coils

Introduced in 1992, Gianturco spring occluding coils have been the most common device used for patent ductus arteriosus (PDA) occlusion for many years. The coils are delivered to the patent ductus arteriosus (PDA) via venous or arterial systems: 1-5 coils are placed in the ductus. In experienced hands with proper patient selection, this has become a procedure associated with high success and low morbidity. This method has been reported to be 75-100% effective but is limited to ductus that are only 4-5 mm in diameter. Coil occlusion is best suited to close a patent ductus arteriosus (PDA) with a minimal internal diameter of less than 2.5 mm. 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

More recently, the Amplatzer device has expanded the ability to close patent ductus arteriosus (PDA) at cardiac catheterization. This device is more reliable and easier to implant in a large patent ductus arteriosus (PDA) than spring occluding coils. 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. However, the Amplatzer duct occluder II (ADO II), a nitinol flexible mesh with a symmetrical design to provide high conformability, has been approved in Europe for treatment of all types of patent ductus arteriosus (PDA). ^[23]

Rashkind ductus occlusion device

The Rashkind ductus occlusion device 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.

Postcatheterization risks

Typically, complete occlusion is achieved at catheterization. Occasionally, a tiny residual left-to-right shunt remains at the end of the procedure, which closes by thrombus formation over the following days or weeks. Left-to-right shunt rarely persists through a partially occluded patent ductus arteriosus (PDA). Usually, the magnitude of the shunt is significantly smaller than before occlusion. Due to concerns about the long-term risk of endocarditis, this residual defect should be closed. Often, this can be accomplished with a second catheter procedure. Rare reports describe association of a persistently patent ductus after occlusion attempts with hemolysis or endocarditis.

Procedural risks of patent ductus arteriosus (PDA) occlusion by catheter are few and largely influenced by the experience of the physician performing the procedure. These risks include embolization of the device being used to occlude the patent ductus arteriosus (PDA), blood vessel injury, access site bleeding, infection, and stroke, among others. In the case of device embolization, the device can usually be retrieved by transcatheter techniques, and a second device can be successfully placed in the patent ductus arteriosus (PDA).

Surgical ligation or surgical ligation and division remain the standard treatment of large patent ductus arteriosus (PDA) that require treatment in infancy (see the following image). This is a particularly successful, low-risk procedure in the hands of an experienced pediatric cardiovascular surgeon. This is true even in the smallest premature babies. (See also Patent Ductus Arteriosus Surgery.)

Diagram illustrating ligation of the patent ductus arteriosus.

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Ligation (with or without division of the patent ductus arteriosus [PDA]) without cardiopulmonary bypass can be performed through a left posterolateral thoracotomy. Video-assisted thoracoscopic surgery (VATS) ligation of patent ductus arteriosus (PDA) is less invasive than the posterolateral thoracotomy and has been shown to be safe and effective. ^[24]

Indications

With rare exceptions, the presence of a patent ductus arteriosus (PDA) is an indication for surgical closure. Clearly, attention must be paid to the existence of other congenital heart lesions that impair pulmonary blood flow. In these patients, all attempts should be made to preserve ductal flow until a more permanent palliative shunt can be constructed or definitive repair can be undertaken. Very small premature infants still require 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.

Postoperative results are best if the patent ductus arteriosus (PDA) is closed while the patient is younger than 3 years. ^[25] An increased incidence of elevated pulmonary vascular resistance (PVR) and pulmonary hypertension occurs if the lesion closed in those older than 3 years.

Thus, indications for surgical treatment include the following:

• Failure of indomethacin treatment

• Contraindications to medical therapy (eg, thrombocytopenia, renal insufficiency)

• Signs and symptoms of congestive heart failure (CHF)

• Patent ductus arteriosus (PDA) found in an older infant

• Infants found to have an asymptomatic patent ductus arteriosus (PDA) after the neonatal period should undergo surgical ligation preferably before the age of 1 year to prevent future complications of a patent ductus arteriosus (PDA)

• Ductal closure is indicated for cardiovascular compromise (ie, pulmonary complications) and for reduction of the risk of infective endocarditis (subacute bacterial endocarditis)

Contraindications

The primary contraindication to repair is severe pulmonary vascular disease. If transient intraoperative occlusion of the patent ductus arteriosus (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 patent ductus arteriosus (PDA) to maintain systemic blood flow. Premature closure of the ductus without concurrent repair of the following defects is contraindicated and may be fatal:

• Aortic valve atresia

• Mitral valve atresia with hypoplastic left ventricle

• Pulmonary artery hypoplasia

• Pulmonary atresia

• Severe coarctation of the aorta

• Tricuspid atresia

• Transposition of the great arteries

Other contraindications to surgical closure include concurrent uncontrolled sepsis and an inability of the patient to tolerate general anesthesia.

Medical vs surgical therapy

Although indomethacin therapy is preferred in most intensive care nurseries (NICUs) as the first-line approach to effect patent ductus arteriosus (PDA) closure, the benefits of this approach over surgical ligation are not obvious. In most studies that attempt to evaluate differences in the outcomes for indomethacin therapy and surgical closure, results are similar. A Cochrane review failed to demonstrate that the net harm-to-benefit ratio favored either surgical ligation or medical therapy. ^[8] Observational studies suggest that surgical ligation is associated with higher likelihood of chronic lung disease, retinopathy of prematurity, and neurosensory impairment. These data may be questionable, because surgical ligation is not available in every nursery, whereas medical therapy is widely available.

A meta-analysis by Weisz et al did suggest that compared with pharmacologic treatment, surgical ligation for patent ductus arteriosus in preterm infants is associated with a reduced mortality rate but also with an increased morbidity risk. Again, however, the results were uncertain. In the report, derived from 39 cohort studies and 1 randomized, controlled trial, the investigators found that in infants born at less than 32 weeks’ gestation, the mortality rate in those who underwent ligation for patent ductus arteriosus was about half that of infants who were treated with medication for the condition. ^{[26, 27]}

In contrast, the incidence of neurodevelopmental impairment (NDI), chronic lung disease, and severe retinopathy of prematurity was increased in infants who underwent ligation, with adjusted odds ratios of 1.54, 2.51, and 2.23, respectively. However, the investigators were unable to draw conclusions from the meta-analysis because almost none of the cohort studies took into account survival bias or considered important confounders, such as ventilator dependence, sepsis, or intraventricular hemorrhage, that may have been present prior to ligation. ^{[26, 27]}

Complications

Complications of surgical ligation are mostly related to the left lateral thoracotomy. Surgical morbidity and mortality rates are negligible, and early postoperative complications are associated with other complications of prematurity. However, possible injury to the aorta, pulmonary artery, ^[28] and other structures should be noted.

The results from a study of 125 premature infants found that while PDA ligation was well tolerated overall, a high risk of neurological disability or death from bronchopulmonary dysplasia at 1 year was noted. Increased mortality at 1 year was also associated with increasing preoperative fractional inspired oxygen (FiO₂) and lack of prior treatment with cyclooxygenase inhibitors. ^[29]

Typically, hospitalization following treatment for patent ductus arteriosus (PDA) is minimal. Patients who have catheter closure of patent ductus arteriosus (PDA) are usually sent home on the day of the procedure. Even patients who have standard surgery with a thoracotomy rarely are hospitalized for longer than 2 or 3 days.

The appropriate care and length of hospitalization of premature neonates with a patent ductus arteriosus (PDA) are primarily determined based on abnormalities of other organ systems. However, babies who have effective closure of patent ductus arteriosus (PDA) appear to have shorter hospital stays than babies whose patent ductus arteriosus (PDA) remains a problem.

Complications of untreated patent ductus arteriosus (PDA) include bacterial endocarditis, late congestive heart failure (CHF), and the development of pulmonary vascular obstructive disease. Patent ductus arteriosus (PDA) can complicate other circulatory or ventilatory abnormalities, such as the following:

• Aortic rupture

• Eisenmenger physiology

• Left heart failure

• Myocardial ischemia

• Necrotizing enterocolitis

• Pulmonary hypertension

• Right heart hypertrophy and failure

Prostaglandin E1 (PGE1) should be used to maintain patency of the ductus arteriosus once it is established that a ductal dependent lesion exists. However, PGE is a pulmonary vasodilator and could cause exacerbation of CHF by means of increasing pulmonary blood flow.

Parents of children with this lesion should be aware that patent ductus arteriosus (PDA) does not have any significant inheritance pattern.

Once the patent ductus arteriosus (PDA) is closed, no special limitations or care is necessary. No exercise restriction is required in the absence of pulmonary hypertension.

Most physicians recommend antibiotic prophylaxis at times of risk of bacteremia for 6-12 months following closure, whether by catheter or surgery. (Specific recommendations for prophylactic antibiotics can be found in any current infectious disease or antibiotic reference, or refer to the American Heart Association recommendations. ^[4] )

Although rare reports exist of recanalization and recurrence of a left-to-right shunt after patent ductus arteriosus (PDA) ligation, the risk is extremely low. If a patent ductus arteriosus (PDA) has been closed by interventional radiologic techniques, obtaining follow-up echocardiograms echocardiography 2-3 weeks after the procedure until complete closure is confirmed is wise.