NAMA NPM TUGAS

: SYAIFUL ANAM : 06700243 : dr. TRIJUNI A , Sp A

PATENT DUCTUS ARTERIOSUS (PDA) Patent ductus arteriosus (PDA), in which there is a persistent communication between the descending thoracic aorta and the pulmonary artery that results from failure of normal physiologic closure of the fetal ductus (see image below), is one of the more common congenital heart defects.

Schematic diagram of a left-to-right shunt of blood flow from the descending aorta via the patent ductus arteriosus (PDA) to the main pulmonary artery. The patient presentation of atent ductus arteriosus (PDA) varies widely. Although frequently diagnosed in infants, the discovery of this condition may be delayed until childhood or even adulthood. In isolated patent ductus arteriosus (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 (PVR). Patent ductus arteriosus (PDA) may also exist with other cardiac anomalies, which must be considered at the time of diagnosis. In many cases, the diagnosis and treatment of a patent ductus

arteriosus (PDA) is critical for survival in neonates with severe obstructive lesions to either the right or left side of the heart. Historical information 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-yearold child.[1] This was a landmark event in the history of surgery and heralded the true beginning of the field of congenital heart surgery. Catheter-based closure of the structure was first performed in 1971 ANTOMI During fetal life, the ductus arteriosus is a normal structure that allows most of the blood leaving the right ventricle to bypass the pulmonary circulation and pass into the descending aorta. Typically, only about 10% of the right ventricular output passes through the pulmonary vascular bed. The ductus arteriosus is a remnant of the distal sixth aortic arch and connects the pulmonary artery at the junction of the main pulmonary artery and the origin of the left pulmonary artery to the proximal descending aorta just after the origin of the left subclavian artery. It passes from the anterior aspect of the pulmonary artery to the posterior aspect of the aorta. Typically, the ductus has a conical shape with a large aortic end tapering into the small pulmonary connection. The ductus may take many shapes and forms, from short and tubular to long and tortuous. An anatomic marker of the ductus is the recurrent laryngeal nerve, which 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.

Most typically, the patent ductus arteriosus (PDA) is a left aortic remnant; however, it can be right-sided or on both the left side and right side. Although a left ductus arteriosus is a normal structure during normal fetal development, the presence of a right ductus arteriosus is usually associated with other congenital abnormalities of the cardiovascular system, most typically involving the aortic arch or conotruncal development. The Krichenko classification of PDA is based on angiography and includes type A (conical), type B (window), type C (tubular), type D (complex), and type E (elongated) PDA. 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 patent ductus arteriosus (PDA) in surgical procedures include the aorta, the pulmonary artery, and the carotid artery. PATHOFISIOLOGI The ductus arteriosus is normally patent during fetal life; it is an important structure in fetal development as it contributes to the flow of blood to the rest of the fetal organs and structure. From the 6th week of fetal life onwards, the ductus is responsible for most of the right ventricular outflow, and it contributes to 60% of the total cardiac output throughout the fetal life. Only about 5-10% of its outflow passes through the lungs. This patency is promoted by continual production of prostaglandin E2 (PGE2) by the ductus. Closure of the ductus before birth may lead to right heart failure. Prostaglandin antagonism, such as maternal use of nonsteroidal anti-inflammatory medications (NSAIDs), can cause fetal closure of the ductus arteriosus. Thus, a patent ductus arteriosus (PDA) produces a left-to-right shunt. In other words, it allows blood to go from the systemic circulation to the pulmonary circulation. Therefore, pulmonary blood flow is excessive (see the image below). Pulmonary engorgement results with decreased pulmonary compliance. The reaction of the pulmonary vasculature to the increased blood flow is unpredictable.

Schematic diagram of a left-to-right shunt of blood flow from the descending aorta via the patent ductus arteriosus (PDA) to the main pulmonary artery. The magnitude of the excess pulmonary blood flow depends on relatively few factors. The larger the internal diameter of the most narrow portion of the ductus arteriosus, the larger the left-toright shunt. If the ductus arteriosus is restrictive, then the length of the narrowed area also affects the magnitude of the shunt. A longer ductus is associated with a smaller shunt. Finally, the magnitude of the left-to-right shunt is partially controlled by the relationship of the pulmonary vascular resistance (PVR) to the systemic vascular resistance (SVR). If the SVR is high and/or the PVR is low, the flow through the ductus arteriosus is potentially large. Beginning at the ductus arteriosus, the course of blood flow (through systole and diastole) in a typical patent ductus arteriosus (PDA) with pulmonary overcirculation is as follows: patent ductus arteriosus (PDA), pulmonary arteries, pulmonary capillaries, pulmonary veins, left atrium, left ventricle, aorta, patent ductus arteriosus (PDA). Therefore, a large left-to-right shunt through a patent ductus arteriosus (PDA) results in left atrial and left ventricular enlargement. The pulmonary veins and the ascending aorta can also be dilated with a sufficiently large patent ductus arteriosus (PDA). In addition, if little or no restriction is present at the level of the patent ductus arteriosus (PDA), pulmonary hypertension results. Functional and anatomic closure In the fetus, the oxygen tension is relatively low, because the pulmonary system is nonfunctional. Coupled with high levels of circulating prostaglandins, this acts to keep the ductus open. The high levels of prostaglandins result from the little amount of pulmonary circulation and the high levels of production in the placenta.

At birth, the placenta is removed, eliminating a major source of prostaglandin production, and the lungs expand, activating the organ in which most prostaglandins are metabolized. In addition, with the onset of normal respiration, oxygen tension in the blood markedly increases. Pulmonary vascular resistance decreases with this activity. Normally, functional closure of the ductus arteriosus occurs by about 15 hours of life in healthy infants born at term. This occurs by abrupt contraction of the muscular wall of the ductus arteriosus, which is associated with increases in the partial pressure of oxygen (PO2) coincident with the first breath. A preferential shift of blood flow occurs; the blood moves away from the ductus and directly from the right ventricle into the lungs. Until functional closure is complete and PVR is lower than SVR, some residual left-to-right flow occurs from the aorta through the ductus and into the pulmonary arteries. This was first demonstrated by multiple experiments in the 1940s and has been subsequently confirmed. Although the neonatal ductus appears to be highly sensitive to changes in arterial oxygen tension, the actual reasons for closure or persistent patency are complex and involve manipulation by the autonomic nervous system, chemical mediators, and the ductal musculature. 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 PO2, increased endothelin-1, norepinephrine, acetylcholine, bradykinin, and decreased PGE receptors. Increased prostaglandin sensitivity, in conjunction with pulmonary immaturity leading to hypoxia, contributes to the increased frequency of patent ductus arteriosus (PDA) in premature neonates. Although functional closure usually occurs in the first few hours of life, true anatomic closure, in which the ductus loses the ability to reopen, may take several weeks. A second stage of closure related to fibrous proliferation of the intima is complete in 2-3 weeks. Cassels et al defined true persistence of the ductus arteriosus as a patent ductus arteriosus (PDA) present in infants older than 3 months.[2] Thus, patency after 3 months is considered abnormal, and treatment should be considered at this juncture, although urgency is seldom necessary. Some

canine breeds, such as certain strains of poodle, have a large prevalence of patent ductus arteriosus (PDA). Spontaneous closure after 5 months is rare in the full-term infant. Left untreated, patients with a large patent ductus arteriosus (PDA) are at risk to develop Eisenmenger Syndrome, in which the PVR can exceed SVR, and the usual left-to-right shunting reverses to a right-to-left direction. At this stage, the PVR is irreversible, closure of the patent ductus arteriosus (PDA) is contraindicated, and lung transplantation may be the only hope for long-term survival. Failure of ductus arteriosus to contract 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 ductus arteriosus 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. Cyclooxygenase (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. Volume-pressure relationships Further progression of disease is dependent on volume and pressure relationships, as follows:

Volume = pressure/resistance High volume yields increasing pulmonary artery pressures, eventually producing endothelial and muscular changes in the vessel wall

These changes may eventually lead to pulmonary vascular obstructive disease (PVOD), a condition of resistance to pulmonary blood flow that may be irreversible and will preclude definitive repair

HISTORY As discussed in Pathophysiology, the ductus arteriosus is always patent in the fetus if the cardiovascular system is otherwise normal. Normally, the ductus arteriosus closes functionally in the first 10-18 hours of life. Prematurity, perinatal distress, and hypoxia delay closure of the ductus arteriosus; however, most children who are found to have a ductus arteriosus have no history of precedent risk factors. Depending on the size of the patent ductus arteriosus (PDA), the gestational age of the neonate, and the pulmonary vascular resistance (PVR), a premature neonate may develop life-threatening pulmonary overcirculation in the first few days of life. Conversely, an adult with a small patent ductus arteriosus (PDA) may present with a newly discovered murmur well after adolescence. Symptoms Patients can present at any age. The typical child with a patent ductus arteriosus (PDA) is asymptomatic. At times, the patient may report decreased exercise tolerance or pulmonary congestion in conjunction with a murmur. Three-week to 6-week-old infants can present with tachypnea, diaphoresis, inability or difficulty with feeding, and weight loss or no weight gain. A ductus arteriosus with a moderate-to-large left-to-right shunt may be associated with a hoarse cry, cough, lower respiratory tract infections, atelectasis, or pneumonia. With large defects, the patient may have a history of feeding difficulties and poor growth during infancy, described as failure to thrive (FTT). However, frank symptoms of congestive heart failure (CHF) are rare. Adults whose patent ductus arteriosus (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 Diagnostic Considerations Distinguishing between clinically significant and nonsignificant patent ductus arteriosus (PDA) is important. A clinically significant patent ductus arteriosus (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. Note that congestive heart failure (CHF) may be mistaken as an upper respiratory infection (URI) in some cases. Other conditions that should be considered when evaluating a patient with suspected patent ductus arteriosus (PDA) include the following:

Absence pulmonary valve syndrome Acute anemia Aortic regurgitation Aortopulmonary window (aortopulmonary fenestration) Atrioventricular malformation Bacteremia and sepsis Bronchial pulmonary artery stenosis Cardiogenic shock Cervical venous hum (usually present on the right side of the neck and more prominent in the sitting position, varying with respiration)

Dilated cardiomyopathy Mitral regurgitation Ruptured sinus of Valsalva and fistula Peripheral pulmonary artery stenosis Persistent truncus arteriosus

Pulmonary arteriovenous fistula Systemic arteriovenous fistula (cerebrovascular or hepatic arteriovenous malformations) Total anomalous pulmonary venous return Venous hum Ventricular septal defect (VSD) with aortic regurgitation

Differential Diagnoses

Acute Pericarditis Aortopulmonary Septal Defect Coarctation of the Aorta Coronary Artery Fistula Pediatric Acute Respiratory Distress Syndrome Pediatric Sinus of Valsalva Aneurysm Pediatric Tachycardia Pediatric Tetralogy of Fallot With Absent Pulmonary Valve Pulmonic Valvular Stenosis Sickle Cell Anemia

Approach Considerations The diagnosis of patent ductus arteriosus (PDA) is almost always based on careful clinical evaluation, including physical examination showing the characteristic murmur, typical electrocardiographic (ECG) abnormalities, radiographic changes, and echocardiographic/Doppler findings. Echocardiography is the primary diagnostic study used to evaluate and diagnose patent ductus arteriosus (PDA). Chest radiography may provide some helpful information. Laboratory tests are generally not helpful in the workup of patent ductus arteriosus (PDA). Magnetic resonance angiography and cardiac computed tomography are alternative, more novel, diagnostic tools. CBC and metabolic panel

A complete blood cell (CBC) count with differential and a chemistry profile are obtained to determine the overall health of the child. However, findings are usually within reference ranges in patients with this condition. Polycythemia may be present if the child has other congenital heart defects. Pulse oximetry/ABG Pulse oximetry/arterial blood gas (ABG) analysis usually demonstrate normal saturation because of pulmonary overcirculation. A large ductus arteriosus could cause hypercarbia and hypoxemia from congestive heart failure (CHF) and air space disease (atelectasis or intra-alveolar fluid/pulmonary edema). In the event of pulmonary artery hypertension (PAH), right-to-left intracardiac shunting of blood, hypoxemia, cyanosis, and acidemia may be present Approach Considerations 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.

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.

Medication Summary Medication use in patent ductus arteriosus (PDA) is based upon the clinical status of the patient. In the presence of symptoms of pulmonary overcirculation or pulmonary hypertension related to a patent ductus arteriosus (PDA), closing the lesion is usually most prudent; therefore, anticongestive therapy is not discussed. Prostaglandins are utilized to maintain the patency of the ductus arteriosus until surgical ligation is performed. When surgical ligation is not indicated, prostaglandin inhibitors (eg, nonsteroid antiinflammatory drugs [NSAIDs]) are used to close the ductus arteriosus. Intravenous (IV) indomethacin or IV ibuprofen is used to treat patent ductus arteriosus (PDA) in the neonate and in premature infants. The dose used for ibuprofen is 10 mg/kg bolus followed by 5 mg/kg/d for 2 additional days. (IV ibuprofen became available in the United States on June 2009.) Ibuprofen was initially thought to have less adverse effects, such as a decreased incidence of oliguria, gastrointestinal (GI) toxicity, and cerebral hypoperfusion. The use of ibuprofen has been shown to increase the incidence of pulmonary hypertension and chronic lung disease. A Cochrane database review showed no statistically significant difference in closure between ibuprofen and indomethacin.[8] A decision to use one drug versus another should be based upon the infant's presentation and comorbidities. A similar Cochrane database article that looked at the initial treatment of symptomatic patent ductus arteriosus (PDA) in preterm infants showed no difference in risks or benefits of surgery versus the use of cyclooxygenase inhibitors.[26]

In a prospective, randomized, controlled trial, Attridge et al found that patients administered btype natriuretic peptide (BNP) received fewer primary indomethacin doses compared with those who were not guided by BNP concentrations.[6] Renal toxicity is associated with indomethacin, and dose reduction guided by BNP may reduce this risk

Sumber : http://emedicine.medscape.com/article/891096-medication