Nitrite Infusion in High Risk Patients Undergoing Cardiopulmonary Bypass

Acute kidney injury is one of the most untoward consequences of cardiac-surgery with the use
of CPB. As such it is associated with a high mortality and morbidity and health care expense.
Unfortunately, currently, there is no effective preventive or treatment strategy for cardiac
surgery-associated (CSA) AKI other than renal replacement therapy.

It is postulated that a major mechanism of CSA-AKI is created by the ischemia reperfusion
injury (IRI) resulting from aortic cross clamping and unclamping. This creates a cascade of
events culminating in inflammation, microvascular dysfunction and tubular cell maladaptation
and eventually renal tissue damage. Current treatment modalities that target the
microcirculation such as blood pressure and cardiac output fails to prevent renal
abnormalities and as such may be deleterious to the renal tissue microcirculation. The PI
hypothesizes that a therapeutic strategy that limits IRI such as the administration of
inhaled nitric oxide (NO) or sodium nitrite (NaNO2) would ameliorate CSA-AKI by limiting
inflammatory injury to the kidney.

The anion nitrite (NO2-) releases NO in biological systems and has been demonstrated to
inhibit IR injury in the heart, liver and kidneys created by various pathologic states1-3 and
improve outcomes in patients with acute myocardial infarction, in patients with pulmonary
hypertension and is the putative active mediator of protection in liver-transplantation
patients receiving inhaled nitric oxide4.

The objective of this study is to determine whether the NO donor, nitrite will prevent I/R
injury in patients at high risk of development of CSA-AKI undergoing open-heart surgery with
cardiopulmonary bypass.

Inclusion Criteria:

- Patients CCFS score ≥ 6 (Table 1)

- Patients admitted to UAB cardiac intensive care unit (CICU) following elective cardiac
surgery with cardiopulmonary bypass under general endotracheal anesthesia

- 19 years old

- Estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73 m2

Exclusion Criteria:

- Prisoners directly admitted from a correctional facility.

- Children < 19 years or under 50 kg body weight if age is unknown.

- Patients enrolled in a concurrent ongoing interventional, randomized clinical trial.

- Patients with end stage renal disease or preexisting GFR <30 mL/min/1.73 m2 or need
for dialysis. 34

- Patients with end stage heart disease on the cardiac transplant list.

- Patients undergoing procedures without the use of CPB

- All transplant patients.

- Patients on ventricular assist devices.

- Patients undergoing emergency procedures.

- Patients with glucose 6-dehydrogenase deficiency

- Pregnancy