Continuing Education Activity

Medical knowledge and treatment advances have led to increased survival of extremely premature neonates. Prematurity increases the incidence of having a hemodynamically significant patent ductus arteriosus requiring pharmacologic, surgical, or device closure. These premature patients will often have to undergo a surgical procedure requiring anesthesia. It is essential for the anesthesia provider to have an understanding of the cardiac defect and the effects that ventilation, oxygenation, and anesthetics will have on pulmonary and systemic blood flow.

Objectives:

• Review the anatomy and function of the ductus arteriosus.
• Explain the effects of FiO2, PaCO2, and anesthetic agents on systemic and pulmonary blood flow with a patent ductus arteriosus.
• Outline clinical challenges when providing anesthesia to a preterm infant.
• Summarize some of the treatment options for a patent ductus arteriosus.

Introduction

The ductus arteriosus (DA) plays a crucial role in fetal circulation.[1] The ductus usually undergoes spontaneous "functional" closure from smooth muscle constriction within 18-24 hours after birth.[2] Anatomical closure of the ductal lumen will usually be complete by 2-3 weeks of age. The spontaneous closure of the ductus soon after birth can be interrupted or delayed, leading to a patent ductus arteriosus (PDA). Rarely, a PDA can even be discovered as a cardiac defect in adults.[3] A PDA is a fetal shunt that allows blood flow between the aorta and the pulmonary artery. Some factors that can lead to a PDA include hypoxemia, low Apgar scores, prenatal Rubella exposure, mechanical ventilation, and prematurity. Approximately 80% of neonates with a gestational age of 25 to 28 weeks will develop a PDA.[4] PDA is a commonly encountered cardiac defect for pediatric anesthesiologists. This defect accounts for 6-11% of all congenital cardiac lesions.[3] Preterm infants have a 20-60% incidence of PDA development versus 0.2% to 0.4% incidence of PDA with term birth.[3] Females are also found to have a PDA twice as often as males.[3]

In preterm infants, the PDA leads to systemic hypoperfusion and over-circulation of the pulmonary vasculature. [5] Also, PDA is associated with necrotizing enterocolitis (NEC), prolonged mechanical ventilation, bronchopulmonary dysplasia (BPD), intraventricular hemorrhage, and neurodevelopmental delays.[5][4] Treatment options include conservative therapy such as non-steroidal anti-inflammatory drugs (NSAIDs) and fluid restriction, or more invasive treatments such as surgical ligation or device closure in the cath lab.[5]

Infants with a ductal dependent congenital heart defect will need the ductus to remain open for survival before undergoing surgical correction of their cardiac lesions. An infusion of prostaglandin E1 is used to maintain ductal patency in these patients. These fragile infants will often require anesthesia for surgical procedures such as central line placement, exploratory laparotomy, congenital cardiac defect repair, PDA closure, and other neonatal emergencies. The anesthesiologist needs to understand the pathophysiology of this extracardiac left to right shunt and be able to manipulate ventilation, drugs, and perfusion to maintain a balance between systemic and pulmonary circulations.[6]

Function

In utero, the ductus arteriosus (DA) remains open because of exposure to prostaglandins produced by the placenta and the hypoxic fetal environment.[5] In the fetal circulation, oxygenated blood from the placenta enters the right atrium; most of this blood bypasses the lungs and is diverted to the left atrium via the foramen ovale.[1] The left heart pumps the oxygenated blood to the brain and periphery. The small amount of oxygenated blood that does enter the pulmonary artery is shunted to the aorta via the ductus arteriosus due to the high resistance to blood flow in the lungs.[7] 

After birth, the first breath of air expands the lungs with oxygenated air, which causes pulmonary vascular resistance to decrease dramatically. The systemic vascular resistance is also increased with umbilical cord clamping. As the pulmonary vascular resistance decreases, the blood flow in the DA changes from a right to left in utero shunt to bidirectional flow after birth. As the pulmonary blood flow increases, the DA will become a left to right shunt, and the left atrial pressures will rise enough to close the foramen ovale.[1]

The decrease in prostaglandin E and the increase in arterial oxygen tension will cause the DA smooth muscle to constrict within hours after birth. The presence of blood flow through the DA after the first 3 days of life is considered to be pathologic.[4] Even after this initial functional closure, stress, infection, inflammation, and prostaglandins can reopen the ductus, especially in preterm neonates.[5]

Prostaglandin E1 (PGE1) is life-saving for patients with ductal-dependent cardiac lesions. PGE1 is a naturally occurring prostaglandin. When given postnatally as a continuous infusion, the ductus arteriosus will remain open and dilated. The starting dose of prostaglandin is 0.025mcg/kg/minute up to 0.1 mcg/kg/minute. It is important that the anesthesia provider not interrupt this infusion while caring for these patients. Approximately 60-80% of PGE1 is metabolized during the first pass through the pulmonary system. This necessitates a continuous, uninterrupted infusion. If the infusion is stopped, the neonate will begin to deteriorate hemodynamically. Restarting the PGE1 will usually reopen the ductus within 30 to 120 minutes; instantaneous clinical response is completely dependent on the ductal flow for survival. The ductus is intentionally kept patent in lesions that have limited blood flow to the lungs or the body, or the pulmonary and systemic vessels are switched as in transposition of the great arteries.

Ductal dependent cardiac lesions that may be encountered providing anesthesia to neonates before corrective surgery:[8]

Issues of Concern

While providing anesthetic care for sick premature neonates, the location of the operation may not always be in the operating room. Occasionally, these infants are too sick to transport, and the operation needs to be done in the NICU. Typical bedside procedures requiring anesthesia services include exploratory laparotomy and PDA ligation. These patients often require unconventional ventilation or more precise ventilation than an anesthesia machine can provide.  While this is not optimal because the NICU patient rooms do not have the same infection standards and air exchange as the operating room, it may be the best option to avoid moving critically ill patients.[9] Transport of these patients can lead to hypothermia, disruption of infusions, loss of vascular access, accidental extubation, and disruption of ventilation, potentially leading to decompensation of the newborn.[10][9]

Pre-operatively, patients with a PDA may or may not be intubated, depending on the size of the patient and the size of the shunt. Infants with a significant flow through PDA experience pulmonary over-circulation, which can lead to systemic hypoperfusion (ductal steal), pulmonary edema, oliguria, and gut hypoperfusion leading to necrotizing enterocolitis (NEC).  A physical exam will reveal wide pulse pressures, coarse continuous machine murmur that gets louder during systole at the left sternal border and radiates to the back, and a hyperdynamic precordium.[4][2] An echocardiogram should be available for review pre-operatively. Review of ventilator settings, the fraction of inspired oxygen concentration (FiO2), infusions, and vascular access is also very important prior to providing an anesthetic. Remember, the goal is more than just survival; clinicians want to provide optimal care that is least likely to have any long-term effects.

Once the location of the operation has been determined, the anesthetic plan needs to be determined. The majority of these patients will have an IV in place pre-op, and some will also be intubated. High-dose fentanyl has been used since 1981 as the anesthetic of choice for sick neonates because it provides stable hemodynamics as well as adequate analgesia. Even today, fentanyl and a paralytic drug remain the anesthetic of choice for ductal ligation and other neonatal surgeries. A fentanyl dose of 25 mcg/kg can blunt stress response, but fentanyl doses as high as 100 mcg/kg have been used for neonatal surgery.[9] Stable, older patients can still have a slow inhalational induction with sevoflurane followed by vascular access, paralytic, and intubation. The anesthesia provider must pay close attention to changes in hemodynamics when using sevoflurane for induction and maintenance of anesthesia. The decrease in systemic vascular resistance can lead to a decrease in pulmonary flow and desaturation in a patient with a ductal dependant lesion. Also, increasing the inspired oxygen concentration will dilate the pulmonary vasculature and lead to systemic hypoperfusion. Care must be taken to maintain a balance between pulmonary and systemic blood flow, especially with a very large nonrestrictive PDA. The lowest FiO2 tolerated should be used in these patients. The techniques for managing a PDA are very similar to managing a ventricular septal defect.

Anesthesia for PDA ligation via thoracotomy without cardiopulmonary bypass in a neonate will require 2 intravenous lines, pre-ductal and postductal pulse oximetry, and NIBP (an arterial line is generally unnecessary). Cerebral oximetry monitoring is helpful as well as a blood pressure cuff on a lower extremity. The PDA can be as large as or larger than the aorta or pulmonary artery. A test clamp is usually performed to ensure the correct vessel will be ligated. A decrease in saturation or distal perfusion should be communicated immediately to the surgeon during test clamping. Once the ductus has been ligated, there should be an observable increase in diastolic blood pressure. The risk of subacute bacterial endocarditis (SBE) is very high in patients with a PDA. Antibiotics will be necessary before the start of surgery, following the American Heart Association guidelines. 

Transcatheter PDA device closure procedures in the cardiac cath lab have become very common. PDA device closures are becoming the preferred treatment in many patients as it is obviously less invasive than a thoracotomy. Some centers are even able to treat patients less than 1000g with a device closure.[10] Neonates who are bigger and stable enough to have a device closure are transported to the cath lab for general anesthesia. These infants may still be intubated but hemodynamically stable enough to tolerate the transport and conventional ventilation.

Clinical Significance

The advances in neonatal care have led to the increased survival of extremely premature neonates. However, these premature infants are at an increased risk for interruption of the natural closure of the ductus arteriosus after birth, causing the ductus to remain patent. Not all premature infants are cared for at a dedicated pediatric hospital; some remain in the NICU at community hospitals. It is important for all anesthesiologists, not just pediatric fellowship-trained, to be familiar with patients' physiology with a PDA and how to best manage them under anesthesia to ensure the best outcome.

Other Issues

Rarely, a PDA can be seen in an older child or adult. These patients may have a systolic murmur on the exam, cardiomegaly, and hyperdynamic precordium. Longstanding pulmonary over circulation can lead to congestive heart failure, calcifications, pulmonary hypertension, and infective endocarditis.[3] These complications will usually appear by the third decade of life. Endocarditis is the leading cause of death in adults with PDA.[3] Even very small, hemodynamically insignificant PDAs are closed in childhood to prevent endocarditis.

Enhancing Healthcare Team Outcomes

Managing these fragile patients requires coordination and communication among many subspecialists. Many of these neonates require transport for hundreds of miles to a pediatric hospital to close their cardiac defect. A coordinated effort between neonatologists, cardiologists, nursing, cardiothoracic surgeons, and anesthesiologists is essential to provide optimal care for these patients. An anesthesiologist needs to understand the patient's cardiac anatomy and review and communicate treatment goals pre-operative, intra-operative, and post-operative with all care team providers. It is essential that the anesthesiologist communicates clearly with the surgeon and understands the complications of PDA ligation, such as inadvertent ligation of the aorta or pulmonary artery. Knowledge and communication during test clamping can prevent devastating complications.