Acute Lung Injury Induced by Cardiopulmonary Bypass

What is a congenital heart defect?

Congenital heart defects are problems with the heart’s structure that are present at birth and can change the normal flow of blood through the heart. These defects can range from simple, with no symptoms, to complex, with severe, life-threatening symptoms, and defects can involve the interior walls of the heart, the valves inside the heart, and/or the arteries and veins that carry blood to the heart or the body.1 Complex congenital heart defects require special medical care soon after birth, and these generally require congenital heart repair surgery.

Thanks to the diagnosis and treatment of complex heart defects, almost all children survive to adulthood and can live active, productive lives.

What are the types of congenital heart defects?

There are many types of congenital heart defects. Many defects are simple conditions which do not need treatment or are easily fixed, while some are more complex and require special medical care.1

Treatment is dependent on the age of diagnosis, the seriousness of symptoms, and other conditions. Sometimes surgery is needed. Examples of complex congenital heart defects which may require surgery include atrial septal defect, atrioventricular septal defect, ventricular septal defect, coarctation of the aorta, hypoplastic left heart syndrome, pulmonary atresia, tetralogy of fallot, total anomalous pulmonary venous return, tricuspid atresia, d-transposition of the great arteries, and truncus arteriosus.2

How common are congenital heart defects?

Congenital heart defects are the most common type of birth defect, as they affect 8 out of every 1,000 newborns. More than 35,000 babies in the United States are born with congenital heart defects every year. It is estimated that more than 1 million adults are living with congenital heart defects today.1

What causes congenital heart defects?

Although some congenital heart defects have been linked to genetic disorders, maternal conditions and environmental factors, the causes for the majority of congenital heart defects are unknown.3
What are current treatment options for congenital heart defects?

According to the American Heart Association, “Not all people with congenital heart defects require treatment. Some may only need to be observed and visit their cardiologist. In other cases, surgery or a cardiac catheterization may be needed to reduce the effects of and/or repair the defect. Even when a defect is treated as a child, further conditions may develop that would benefit from additional medical treatment”.4 For those undergoing congenital heart repair surgery, cardiopulmonary bypass is the technique most commonly used.

What is cardiopulmonary bypass?

During surgery, cardiopulmonary bypass is used to maintain the circulation of blood and the oxygen content of the body, by temporarily taking over the function of the heart and lungs. The cardiopulmonary bypass pump itself is also known as a heart–lung machine or “the pump”.5 The cardiopulmonary bypass pump is essential because it allows the surgical team to “pause” the heart to perform the surgery, since it would be difficult to operate on a beating heart.
What are the risks of cardiopulmonary bypass?

While cardiopulmonary bypass is both necessary and beneficial for surgery, it may have a wide range of negative effects on the patient’s body. Many organ systems are affected by cardiopulmonary bypass, but effects can mainly be noted in the heart, lungs, brain, and kidneys. The severity of effects depends on several factors, including the patients’ general condition prior to surgery, the amount of time a patient is on cardiopulmonary bypass and the difficulty of the procedure. After bypass surgery, the function of the heart and kidneys may be compromised. In addition, some patients experience subtle neurologic changes.6

Cardiopulmonary bypass can also have an effect on the circulating amounts of citrulline, a naturally occurring amino acid, necessary for maintaining levels of nitric oxide in the blood. Nitric oxide (NO) helps improve blood and oxygen flow by acting as a vasodilator (expanding blood vessels). In studies performed at Vanderbilt, researchers observed that children who developed complications, such as postoperative pulmonary dysfunction, following cardiopulmonary bypass had lower levels of citrulline, and thus nitric oxide, in their bodies than those who did not develop complications.1

What is cardiopulmonary bypass induced postoperative pulmonary dysfunction?

The cause of postoperative pulmonary dysfunction (PPD), a frequent and significant complication after cardiac surgery, is unclear but appears to be associated with a systemic inflammatory response.7 For most patients, some degree of postoperative pulmonary dysfunction is an inevitable consequence of cardiac surgery. Symptoms include difficulty breathing, shallow respiration, inability to cough properly and low levels of oxygen in the blood.8 It has been observed to be related to the lower levels of circulating citrulline, and thus nitric oxide availability, in the blood.1

What are current treatment options for cardiopulmonary bypass induced postoperative pulmonary dysfunction?

Currently, treatment is reactive, as it occurs post-surgery once the patient has already developed complications. Most interventions focus specifically on airway management to include various endotracheal suctioning, intubation, physiotherapy that includes deep breathing and coughing exercises, incentive spirometry, as well as the use of a plethora of maneuvers to achieve positive airway pressures and alveolar recruitment.8
Asklepion’s Research IV citrulline is not a treatment for lung damage once it occurs, but it is being studied to determine if it helps prevent or lessen the severity of problems resulting from acute lung injury in pediatric patients undergoing cardiopulmonary bypass for congenital heart defects.

Citrulline is a naturally occurring amino acid. Citrulline is a protein building block in the body that can convert into another substance, nitric oxide (NO), which controls blood pressure in the lungs, among other things. Increased blood pressure in the lungs can be an important surgical problem; it may also lead to problems following surgery, such as severe high blood pressure in the lungs (pulmonary hypertension), increased time spent on a breathing machine, and a longer stay in the intensive care unit (ICU).

Researchers at Vanderbilt University found that cardiopulmonary bypass significantly decreased availability of arginine, citrulline, and nitric oxide metabolites in the postoperative period. The decreased availability of nitric oxide precursors may contribute to the increased risk of postoperative pulmonary hypertension.9 Further research suggests that citrulline supplementation during surgery may increase plasma citrulline and arginine concentrations resulting in better post-surgery outcomes.10


1 “What Are Congenital Heart Defects?” National Heart Lung and Blood Institute. July 01, 2011. Accessed August 10, 2017. https://www.nhlbi.nih.gov/health/health-topics/topics/chd.
2 “Congenital Heart Defects (CHDs).” Centers for Disease Control and Prevention. December 22, 2015. Accessed August 10, 2017. https://www.cdc.gov/ncbddd/heartdefects/specificdefects.html.
3 Jenkins, Kathy J., Adolfo Correa, Jeffrey A. Feinstein, Lorenzo Botto, Amy E. Britt, Stephen R. Daniels, Marsha Elixson, Carole A. Warnes, and Catherine L. Webb. “Noninherited risk factors and congenital cardiovascular defects: current knowledge.” Circulation 115, no. 23 (2007): 2995-3014.
4 “Care and Treatment for Congenital Heart Defects.” Heart.org. October 26, 2105. Accessed August 10, 2017. http://www.heart.org/HEARTORG/Conditions/CongenitalHeartDefects/CareTreatmentforCongenitalHeartDefects/Care-and-Treatment-for-Congenital-Heart-Defects_UCM_002030_Article.jsp#.WYydHmcm5D8.
5 “What is Cardiopulmonary Bypass?” Perfusion.com. September 1, 2004. Accessed August 10, 2017. http://www.perfusion.com/cgi-bin/absolutenm/templates/articledisplay.asp?articleid=1549#.WYyWLmcm5D8.
6 Westaby, S. “Complement and the damaging effects of cardiopulmonary bypass.” Thorax 38, no. 5 (1983): 321.
7 Rafael Badenes, Angels Lozano, and F. Javier Belda, “Postoperative Pulmonary Dysfunction and Mechanical Ventilation in Cardiac Surgery,” Critical Care Research and Practice, vol. 2015, Article ID 420513, 8 pages, 2015. doi:10.1155/2015/420513
8 Wynne, Rochelle, and Mari Botti. “Postoperative pulmonary dysfunction in adults after cardiac surgery with cardiopulmonary bypass: clinical significance and implications for practice.” American journal of critical care 13, no. 5 (2004): 384-393.
9 Barr, Frederick E., Heidi Beverley, Kristin VanHook, Emma Cermak, Karla Christian, Davis Drinkwater, Karrie Dyer et al. “Effect of cardiopulmonary bypass on urea cycle intermediates and nitric oxide levels after congenital heart surgery.” The Journal of pediatrics 142, no. 1 (2003): 26-30.
10 Barr, Frederick E., Rommel G. Tirona, Mary B. Taylor, Geraldine Rice, Judith Arnold, Gary Cunningham, Heidi AB Smith et al. “Pharmacokinetics and safety of intravenously administered citrulline in children undergoing congenital heart surgery: potential therapy for postoperative pulmonary hypertension.” The Journal of thoracic and cardiovascular surgery 134, no. 2 (2007): 319-326.