Noninvasive Measurements of Renal Perfusion During Cardiac Surgery

Acute kidney injury (AKI) is an unfortunately common complication of cardiac surgery that occurs in up to 40% of patients and results in increased mortality, prolonged ICU and hospital length of stay. AKI after cardiac surgery is not a benign complication, increasing mortality from 1% to 19% in those with AKI and to 63% mortality in those who required renal replacement therapy (RRT). In another study, patients with AKI with RRT after cardiac surgery had 39 times the mortality as patients without AKI (95% CI 32-48).[6] AKI has also been associated with increased morbidity and a larger number of patients requiring discharge to an extended care facility.

The pathophysiology of AKI after cardiac surgery is multifactorial. Patients undergoing cardiac surgery are likely more susceptible to AKI given their tendency to be older patients with multiple co-morbidities including pre-existing chronic kidney disease, cardiac dysfunction, diabetes mellitus, and advanced age. Cardiac surgery patients are also exposed to multiple nephrotoxic agents in the peri-operative period including radiocontrast dyes used for angiography, angiotensin converting enzyme inhibitors, and diuretics. Hemodynamically unstable patients may be subject to low cardiac output and low systemic blood pressure because of the pathological condition that brings them to the cardiac operating room in the first place. Low cardiac output and systemic blood pressure can result in reduced renal perfusion. Induction and the maintenance of anesthesia can result in myocardial depression and hemodynamic instability, reducing renal perfusion even further. In most cases, cardiac surgery is facilitated by cardiopulmonary bypass (CPB) which is the process of placing the patient on a heart and lung machine that pumps, oxygenates, and removes CO2 from the patient's blood for them while the heart is arrested. The CPB circuit itself is known to cause significant inflammation and hemodynamic changes that may cause renal injury particularly with prolonged CPB times. Vasopressor and inotropic agents such as vasopressin, norepinephrine, milrinone, and epinephrine are often used to maintain blood pressure and cardiac output. While some of these agents may increase systemic blood pressure by increasing the systemic vascular resistance, this may in fact result in a decrease in renal perfusion. The affect of these agents on the incidence of AKI is uncertain.

Traditionally, the diagnosis of AKI is based on either a sustained fall in urine output or a rise in serum creatinine. The 2012 Kidney Disease Improving Global Outcomes (KDIGO) classification defines AKI as an increase in serum creatinine by 0.3 mg/dl or more in 48 hours or a rise to at least 1.5 times baseline. Three stages of AKI are then defined based on increasing values of serum creatinine or duration of decreased urine output.

The major limitation of creatinine and urine output as a marker of kidney function is the time lag between injury and diagnosis. It often takes 24-36 hours after renal injury for serum creatinine levels to rise. Peri-operative urine output is affected by volume status, anesthetic drugs, and the use of diuretics and AKI is not diagnosed until oliguria has occurred for at least 6-12 hrs. This renders serum creatinine and urinary output measurements insensitive to acute changes in renal function and relatively useless in the acute diagnosis of AKI during and after cardiac surgery.

More recently, several early biomarkers have been developed to identify patients whom are at risk for developing AKI. Two of these biomarkers, TIMP-2 and IGFBP7, have been used for the early prediction of AKI in ICU and cardiac surgery patients. Nonetheless, "early detection" with these biomarkers is till limited to 3-4 hours (an in some studies 24 hours) after renal injury.