PDA- Diagnosis and Management

Facts Patent ductus arteriosus (PDA) is one of the most common problems for young-gestation and low-birth weight babies Incidence inversely proportional to gestational age (GA) and weight (wt) Can take several days (@ 72 hrs) to close as the pulmonary vascular resistance continues to fall

Facts Physiologic closure in term infants at 12-15 hrs of age, anatomic obliteration complete at several months of age Spontaneous closure in 90% of 30-37 wks, 50% for </= 30 wks, 55% </= 1750gms, only 20% </= 1000gms

What is a PDA? Stems from the aortic arch system which develops in the 5-6th weeks of gestation Six pairs of arches branch off the truncus arteriosus and connect to the dorsal aorta, eventually becoming arteries (R/L pulmonary arteries) Left sixth arch becomes the ductus arteriosus (DA) connecting the pulmonary artery to the descending aorta

FETAL CIRCULATION RED STARS REPRESENT FETAL CIRCULATORY SHUNTS FETAL CIRCULATION IS DESIGNED TO ENSURE DELIVERY OF BLOOD WITH THE HIGHEST O2 CONTENT TO THE BRAIN AND HEART AND TO SHUNT BLOOD AWAY FROM THE LUNGS FETAL BLOOD IS CARRIED VIA THE UMBILICAL VEIN TO THE LIVER WHERE 50 TO 60 PERCENT OF THE VOLUME SHUNTS THROUGH THE DUCTUS VENOSUS INTO THE IVC. BLOOD CIRCULATING TO THE LIVER EVENTUALLY RETURNS TO THE IVC AND CICULATES TO THE FETAL HEART BLOOD WITH THE HIGHEST O2 CONTENT GOES DIRECTLY TO THE RA WHERE 50 % IS SHUNTED ACROSS THE FO INTO THE LA, TO THE LV AND OUT INTO THE AORTA. ANATOMICAL FEATURES OF THE RA DECREASE THE AMOUNT OF MIXING BETWEEN OXYGENATED BLOOD FROM THE PLACENTA AND UNOXYGENATED BLOOD RETURNING FROM THE LOWER PORTION OF THE BODY THE REMAINDER OF OXYGENATED BLOOD MIXES WITH THE VENOUS RETURN IN THE RA, PASSES TO THE RV AND OUT INTO THE PA, WHERE 90% OF THIS FLOW IS SHUNTED ACROSS THE DUCTUS ARTERIOSUS INTO THE AORTA BLOOD FLOW FROM THE AORTA ENTERS THE ASCENDING AORTA PERFUSING THE CORONARY , CAROTID AND SUBCLAVIAN ARTERIES

What does it do? In utero, 90% of blood (R ventricular output) flows Right to Left: from pulmonary artery to descending aorta, across the PDA & away from fluid filled lungs secondary to high pulmonary vascular and low placental resistance only 10% of blood flows through the pulmonary vascular bed

What does it do? Blood is then oxygenated by the placenta and circulated to the fetus via the umbilical vein Patency is maintained by low O2 tension and production of prostaglandin E2, a vasodilator produced by DA

Closure of the ductus Clamping the cord ceases intrauterine circulation creating a rise in both the systemic blood pressure and vascular resistance Oxygen enters the lungs resulting in a fall in the pulmonary vascular resistance allowing blood to flow freely to the lungs and become more efficiently oxygenated (vs. placenta)

Ductal closure (cont.) Breathing causes the lungs to fill with air & fluid to be absorbed, also arterial oxygen tension rises Decreasing pulmonary pressure and increasing oxygenation (PaO2) from aortic blood flow reverses the direction of the fetal circulation, thus helping to close the PDA A (non-symptomatic) small L to R shunt may be present for the first few days of life until the normal decrease of in the high pulmonary vascular resistance occurs

CIRCULATORY ADAPTATION DUCTUS ARTERIOSUS CLOSED CIRCULATORY ADAPTATION FUNCTIONAL CLOSURE OF THE DUCTUS ARETERIOSUS OCCURS IN RESPONSE TO SEVERAL FACTORS: DIRECT SMOOTH MUSCLE CONTRACTION IN RESPONSE TO RISING LEVELS OF O2 DECREASED LEVELS OF DILATORY PROSTAGLANDINS DECREASED RECEPTOR SENSITIVITY TO PROSTAGLANDINS INTERACTION BETWEEN O2 AND DILATORY PROSTAGLANDINS IN THE HEALTHY TERM INFANT 20% OF DA CLOSE WITHIN THE FIRST 24HOURS OF LIFE WITH 100% CLOSED AT 96 HOURS OF LIFE. THIS IS A FUNCTIONAL CLOSURE AND MAY REVERSE UNDER CERTAIN CIRCUMSTANCES. ANATOMIC CLOSURE OF THE DUCTUS BY ATROPHY OF THE DUCTAL VESSEL MAY TAKE WEEKS TO MONTHS INCREASING SYSTEMIC VASCULAR RESISTANCE, WHICH CAUSES PRESSURE IN THE LEFT ATRIUM TO RISE RESULTS IN REVERAL OF BLOOD FLOW ACROSS THE FORAMEN OVALE FLOWING LEFT TO RIGHT THIS CHANGE IN PRESSURE AND FLOW LEADS TO FUNCTIONAL CLOSURE OF THE FO BY AN EXTENSION OF THE INTRAATRIAL SEPTUM, THE SEPTUM PRIMUM. ANATOMIC CLOSURE OCCURS AS A RESULT OF FIBRIN AND DEBRIS DEPOSITS AND MAY TAKE SEVERAL MONTHS TO COMPLETELY CLOSED

However……… O2 is the most potent stimulus to closing the PDA but it is more effective in term babies because premature infants lack ductal smooth muscle which prolongs patency patency or closure of the DA depends on the effectiveness of oxygen vs. prostaglandin, which varies at different GAs

And………… If breathing is not effective at birth or if baby develops respiratory distress or infection, patency is further prolonged due to surfactant administration (affects pulmonary vascular resistance which increases the L to R shunting of blood through the DA)

What happens if the PDA doesn’t close? The L to R shunt increases with ½ or more of the blood pumped into the aorta by the L ventricle flowing immediately through the PDA into the pulmonary artery, through the lungs, into the L atrium, into the L ventricle, & back out the aorta

What happens if the PDA doesn’t close? Continued ineffective shunting/backward flow of blood causes the diameter of the PDA to increase: leading to left ventricular hypertrophy (LVH), over perfusion to lungs (pulmonary hemorrhage and chronic lung disease),

What happens (cont) hypo perfusion to brain (intraventricular hemorrhage (IVH) and/or periventricular leukomalacia PVL), mesenteric (NEC), and renal systems (metabolic acidosis and oliguria), possibly even death

Risk Factors for PDA Prematurity Low birth wt RDS & surfactant therapy Excessive fluid administration within first few days of life Perinatal asphyxia Maternal Rubella infection

Signs and Symptoms of PDA When the pulmonary vascular resistance fails to decrease normally, symptoms of PDA occur secondary to the increasing L to R ductal shunting of blood away from the systemic circulation into the pulmonary vascular bed (thus, babies with pulmonary disease will not be symptomatic until disease improves---RDS) Absence/presence of continuous systolic and diastolic “machinery-like” murmur

Signs and Symptoms of PDA Hyperactive precordium Bounding peripheral pulses/palmar pulses Widened pulse pressures Tachycardia Tachypnea Increased ventilator needs or inability to wean

Diagnosis of PDA 2-D Echocardiogram with color Doppler- sensitive/specific Chest x-ray- diffuse, homogeneous increased lung density (opacity), increased heart size, increased prominence in pulmonary vasculature, & perihilar congestion

Management of PDA Fluid restriction Increased ventilatory support Blood transfusions Diuretics Indomethacin Ligation

Indomethacin Indocin, non-steroidal anti-inflammatory drug (NSAID), effective therapy for prophylactic/documented PDA and IVH prevention (accelerates maturation of germinal matrix microvasculature) Closes PDA by inhibiting the cyclooxegenase enzyme that catalyzes prostaglandin precursor formation from arachidonic acid, effective in @ 70% patients

Indomethacin Course = 3-4 doses of 0.1-0.25mg/kg every 12-24hrs over pump x 30” Eliminated by renal and biliary excretion, undergoes enterohepatic circulation Compatibility- Sterile H2O, D2.5W, D5W, NS, Insulin, Lasix, Nitroprusside, KCL, & HCO3 Incompatibility- D7.5W, D10W, AA, CaGluc, Dobutamine, Dopamine, Gentamicin, Tobramycin, Tolazoline, & Tagamet

Indomethacin Contraindications- proven/suspected untreated sepsis, bleeding (active IVH/GI), thrombocytopenia, coagulation defects, NEC, significant renal impairment, infants with congenital heart disease (PA, severe TOF or Coarctation of aorta

Side effects of Indomethacin Significant decrease in blood flow Cerebral – decreased velocity, oxygenation, & reactive postasphyxial hyperemia Mesenteric - GI distention, bleeding secondary to platelet dysfunction and inhibition of aggregation & spontaneous perforations Renal - oliguria, fluid retention, increased BUN & creatinine, reduced GFR and creatinine clearance, & electrolyte imbalances Other - tissue irritation at IV site

Indomethacin Monitoring- strict I & O, BUN, creatinine, electrolytes, CBC/platelets, abdomen, guaiac stools/aspirate, bleeding from old puncture sites, check Echo after each course of Indomethacin If Indomethacin therapy is ineffective, ligation is necessary

Ligation First line of defense for already compromised baby (pulmonary hemorrhage, NEC, or renal failure, ELBW), those who do not meet criteria for Indomethacin therapy (Contraindications, moderate-large PDA, minimal response to first course of Indomethacin), & those older than 10-12 days of age Chest x-ray after ligation to confirm location of clip and r/o pneumothorax/effusions

Alternative Therapy for PDA Ibuprofen- also NSAID, studied abroad with promising findings Same effectiveness as Indomethacin (@ 70%), much decreased side effects Can be given prophylactically, as well See Ibuprofen: Alternative treatment for Patent Ductus Arteriosus, March/April 2003 edition of Neonatal Network, published by me!

References Flores, M.; (2003).Ibuprofen: Alternative treatment for Patent Ductus Arteriosus, Neonatal Network Hamrick, S. & Hansmann, G. (2010). Patent Ductus Arteriosus of the Preterm Infant; Pediatrics 2010;125;1020-1030. Clyman RI, Chorne N. Patent ductus arteriosus: evidence for and against treatment. J Pediatr. 2007;150(3):216–219

References Noori S, McCoy M, Friedlich P, et al. Failure of ductus arteriosus closure is associated with increased mortality in preterm infants.  Pediatrics.2009;123(1). Available at: www.pediatrics.org/cgi/content/full/123/1/e138 Fowlie PW, Davis PG. Prophylactic intravenous indomethacin for preventing mortality and morbidity in preterm infants. Cochrane Database Syst Rev. 2002;(3).