Nitric Oxide Delivery via Oxygenator Protects Against Cardiopulmonary Bypass-Associated Acute Kidney Injury

Newswise — Acute kidney injury (AKI) represents a major morbidity following cardiac surgery; and, when moderate or severe, it is strongly associated with postoperative mortality. Approximately one-third of adults and up to half of all children who undergo cardiac surgery develop some degree of postoperative AKI. 

A primary contributor to post-operative AKI is the cardiopulmonary bypass (CPB) machine, which causes alterations in physiologic blood flow and leads to systemic oxidative stress, hemodilution, and hemolysis. Clinical trials have shown that exogenous nitric oxide (NO) infused through the CPB circuit during surgery provides cardioprotective benefits, shortens the length of stay in intensive care, and protects against postoperative AKI in adult patients. There are ongoing investigations in children. 

The physiologic mechanisms of action of NO in preventing CPB-associated AKI are not well understood, however, because histologic and pathophysiologic studies are lacking. Understanding how NO works for AKI prophylaxis and the physiologic effects of NO is important to inform clinical interventions. Animal studies can provide the benefits of such analyses, including physiologic standardization and histopathological analyses, which are less feasible in human clinical trials. 

Jason W.Greenberg, MD, and colleagues at Cincinnati Children's Hospital Medical Center, designed a large-animal (sheep) model of CPB-associated AKI to test the physiologic and histologic effects of NO for AKI prophylaxis. The use of an animal model also allowed for post-mortem histopathologic analyses of the kidneys that can’t be performed in humans. 

In the randomized-controlled trial, the experimental group (n=6) received NO via the oxygenator in the CPB circuit, whereas the control group (n=5) did not. The test initiated central CPB via right lateral thoracotomy, then reduced the flow rate by half for two hours to induce kidney injury, followed by an additional two hours of full flow. The four-hour CPB run closely approximated the bypass times required for many congenital cardiac surgical repairs; and the surgical CPB model reliably induced AKI at an incidence similar to that seen in children undergoing cardiac surgery. 

The animals were survived for 72 hours postoperatively. This duration resembles the “acute” postoperative ICU recovery period and allowed kidney injury to evolve/declare itself and for postoperative biomarkers to be trended. Upon histopathologic analysis, moderate/severe AKI occurred in 60% of the control animals (3/5) versus 0% in the NO animals (0/6).

In this survival ovine CPB model, NO administered via the CPB circuit demonstrated serologic and histopathologic evidence of protection from AKI. These results provide insight into one potential mechanism for CPB-associated AKI and support the continued study of the use of NO via the CPB circuit for preventing AKI. 

Dr. Greenberg comments, “We believe that this study has the potential to greatly impact clinical care and spur ongoing investigation into the use of NO for the prevention of CPB-associated AKI, particularly in the pediatric population.”

Dr. Greenberg will present the results of this study Monday, May 8, at the American Association for Thoracic Surgery (AATS) 103rd Annual Meeting in Los Angeles.

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ABOUT AATS

The American Association for Thoracic Surgery (AATS) is an international organization that encourages, promotes, and stimulates the scientific investigation of cardiothoracic surgery. Founded in 1917 by a respected group of the earliest pioneers in the field, its original mission was to “foster the evolution of an interest in surgery of the Thorax.” Today, the AATS is the premier association for cardiothoracic surgeons in the world and works to continually enhance the ability of cardiothoracic surgeons to provide the highest quality of patient care. Its more than 1,500 members have a proven record of distinction within the specialty and have made significant contributions to the care and treatment of cardiothoracic disease. Visit aats.org to learn more.