Nitric Oxide Effect on Brain and Kidney in Pediatric Patients Undergoing Cardiopulmonary Bypass

Corrective cardiac surgery for congenital heart disease (CHD) requiring cardiopulmonary bypass (CPB) is associated with numerous postoperative complications including neural tissue damage resulting in long-term neurocognitive deficits as well as acute kidney injury impacting renal function. Non-cardiac organ complications result in an increased mortality and length of hospital stay. Nitric oxide (NO) has been shown to play a protective role in a systemic inflammatory response, with administration of NO reducing damage to the liver, lungs, kidney, and brain in experimental models. Recent studies have demonstrated that for pediatric CHD patients undergoing corrective surgery administration of NO to the bypass circuit resulted in myocardial protection, reduced incidence of low cardiac output syndrome, and improved post-operative ICU course. NO in adult populations undergoing CPB has also been demonstrated to decrease the incidence of acute kidney injury.

Though prior studies have shown wide ranging protective effects from NO during CPB, these have not been fully characterized for neural and renal tissue for the pediatric population. Due to NO's promise in protective effects for other end organ damage the investigators are interested in investigating its potential to mitigate damage to neural and renal tissue. The investigators hypothesize that NO administration during CPB will be associated with reduced acute neurologic insult, reduced acute kidney injury postoperatively, and increased ventilator-free days.

To test these hypotheses the investigators propose a study where one group receives the current standard of care at Vanderbilt (standard surgery and CPB) and the other group receives NO administration during CPB in addition to standard surgery and CPB. The investigators propose using validated biomarkers to determine the effect of NO on the brain and kidney. GFAP is a biomarker for acute neurologic injury and NGAL is a biomarker of acute kidney injury. The biomarkers will be analyzed from blood drawn prior to and during surgery from existing lines in place as part of the procedure and will not necessitate additional needle sticks. No devices will be evaluated in this study; the investigators will only be measuring the effect of NO on neurological, renal and other ICU outcomes.

• Daily prevalence of delirium as measured by preschool confusion assessment method for the ICU (psCAM-ICU) [Time frame: date of admission to date of discharge from ICU (approximately 14 days)]
• Length of ICU stay [Time frame: date of admission to date of discharge from ICU (approximately 14 days)]
• Duration of mechanical ventilation [Time frame: postoperative day 0 to hospital discharge (approximately 30 days)]
• Length of hospital stay [Time frame: date of admission to date of hospital discharge (approximately 30 days)]
• Mortality [Time frame: date of admission to date of hospital discharge and/or 90 days post operation (approximately 90 days)]
• Organ dysfunction as measured by the pediatric Sequential Organ Failure Assessment [Time frame: date of admission up to 14 days]
• Functional Status [Time frame: date of admission to date of hospital discharge (approximately 30 days)]