Effects of Hyperglycemia During Cardiopulmonary Bypass on Renal Function

Significance:

Postoperative renal dysfunction is a common complication of cardiopulmonary bypass occurring
in nearly 8% of all patients undergoing myocardial revascularization. Both diabetes and
preoperative hyperglycemia are independent risk factors for postoperative renal dysfunction
after coronary artery bypass surgery.

The cause of renal injury is multifactoral and in most cases involves renal ischemia from
alteration of renal perfusion, resistance, metabolic byproducts (free-radical species),
inflammatory mediators and embolic processes.

In the setting of ischemia, specifically, neuronal, hyperglycemia has been shown to worsen
neurologic outcome and interfere with wound healing-possibly increasing the incidence of
wound infection.

Hyperglycemia is common during cardiopulmonary bypass in both diabetic and non-diabetic
patients as a result of altered glucose regulation during hypothermic conditions (body
temperature actively cooled to 28 degree centigrade) and, more importantly, from delivery of
cardioplegia to arrest the heart allowing for surgical repair in a non-beating heart. The
cardioplegia is rich in potassium, among other agents, believed to offer cardioprotection
during cardiopulmonary bypass and is prepared in Dextrose 5% and normal saline. On average,
each patient receives nearly 2 liters of this solution, amounting to 100 grams or more of
glucose. In this setting, hyperglycemia is also promoted from insulin suppression, stress
hormone induced gluconeogenesis and enhanced tubular resorption.

Only recently have perioperative clinicians become aware about potential ischemic effects of
hyperglycemia during bypass and the need to maintain 'tight' control of glucose to avoid
stroke. This practice, however, is inconsistent and mostly applied to diabetic patients.

We hypothesize that tubular injury may be exacerbated by hyperglycemia in non-diabetic
patients while undergoing hypothermic cardiopulmonary bypass and have undertaken this
prospective observational study to investigate the relationship between intraoperative
glucose and postoperative renal dysfunction.

Methodology:

We plan to study to 200 patients ≥ 50 years of age scheduled for procedures requiring
cardiopulmonary bypass whether for coronary revascularization or valvular surgery. After
informed consent is obtained each patient's preoperative lab values consisting of serum
glucose, urine glucose, creatinine and BUN will be noted. Each patient's pre-induction
hemodynamics will also be noted. During bypass, serum and urine glucose will be measured
every 20 minutes in addition to collecting information on temperature of cardioplegic
solution, lowest patient temperature, time of bypass, and use of diuretics, or vasoactive
drugs. Additional sampling of serum creatinine and glucose and vital signs will take place
upon arrival in the cardiac intensive care unit after surgery and throughout hospitalization
as is standard of care in cardiac surgery at this institution. No extra samples will be
taken but the standard measurements will be observed. The clinical outcome of interest is a
new onset of renal dysfunction defined as a post-operative serum creatinine change of 0.5
mg/dl or greater after surgery.

Inclusion Criteria:

1. Male and female patients ≥ 50 years of age

2. Patients undergoing on pump cardiopulmonary bypass for either myocardial
revascularization (coronary artery bypass graft) or valvular surgery (valve repair or
replacement)

Exclusion Criteria:

1. Patients with insulin dependent diabetes

2. Patients with preexisting renal dysfunction defined as Creatinine> 2 mg/dl

3. Patients in need of emergency cardiac procedures