Effect of Remote Ischemic Preconditioning on the Incidence of Acute Kidney Injury in Patients Undergoing Coronary Artery Bypass Graft Surgery

Effect of Remote Ischemic Preconditioning on the Incidence of Acute Kidney Injury in Patients Undergoing Coronary Artery Bypass Graft Surgery

Effect of Remote Ischemic Preconditioning on the Incidence of Acute Kidney Injury in Patients Undergoing Coronary Artery Bypass Graft Surgery: A Randomized Controlled Trial

Background: Acute kidney injury (AKI) following coronary artery bypass graft (CABG) surgery is a major complication occurring in 1% to 53% of patients (depending on how it is defined) with the pooled rate of 18.2% and unfortunately 2.1% of them require renal replacement therapy. Cardiopulmonary bypass (CPB)-associated AKI increases mortality 2-4 fold regardless of AKI definition. It is also associated with increased risk of postoperative stroke, acute myocardial infarction, cardiac tamponade, heart failure, and lengthened intensive care unit and hospital stays. Even minor elevations of postoperative serum creatinine (SCr) have been associated with a significant increase in 30-day mortality, from a 3-fold increase risk for a small elevation of up to 0.5 mg/dL from baseline to an 18-fold increase risk of death with a SCr rise greater than 0.5 mg/dL. The pathogenesis of CPB-associated AKI is complicated and includes hemodynamic, inflammatory and other mechanisms that interact at a cellular level. To date, despite several clinical trials of pharmacologic interventions, none of them have demonstrated conclusively efficacy in the prevention of AKI after cardiac surgery. Remote ischemic preconditioning (RIPC) is a phenomenon in which brief ischemia of one organ or tissue, provokes a protective effect that can reduce the mass of infarction caused by vessel occlusion and reperfusion. In CABG surgery, cardiomyocyte injury caused by myocardial protection failure is predominantly responsible for adverse outcomes. RIPC was shown to reduce troponin release 24 h postoperatively in children undergoing corrective surgery for congenital heart disease. Other studies demonstrated that RIPC using brief ischemia and reperfusion of the upper limb reduces myocardial injury in adult patients undergoing CABG surgery. Due to the similarities between the mechanisms of ischemia-reperfusion injury produced by RIPC and those proposed for AKI after CPB, we decided to test the hypothesis that RIPC prevents AKI in patients undergoing CABG surgery. Methods: 180 patients who fulfill all inclusion and exclusion criteria will be divided into case and control groups (90 patients in the case and 90 patients in the control group). Patients in the treatment group will receive three sequential sphygmomanometer cuff inflations on their right upper arm after induction of anesthesia in the operating room. The cuff will be inflated by the OR nurse up to 200 mmHg for five minutes each occasion, with five minutes deflation in between inflations. Following this pre-conditioning phase, surgery will be started. The entire pre-conditioning phase will last 30 minutes. Patients in the control group will have the sphygmomanometer cuff placed on their right upper arm, but the cuff will not be inflated. Similar to patients in the treatment group, patients in the control group will undergo the same 30 minute delay before starting surgery. Complete blood count (CBC), SCr, liver function test (LFT), will be checked before surgery. After surgery, SCr will be checked daily. If AKI occurs, it will be managed and dialysis will be done if the patient requires it. All patients will undergo electrocardiogram and LFT after CABG surgery during hospital course.

remote ischemic preconditioning; transient limb ischemia; acute kidney injury; coronary artery bypass graft surgery

Patients in the remote ischemic preconditioning (RIPC) group will receive three sequential sphygmomanometer cuff inflations on their right upper arm after induction of anesthesia in the operating room. The cuff will be inflated by the OR nurse up to 200 mmHg for five minutes each occasion, with five minutes deflation in between inflations. Following this pre-conditioning phase, surgery will be started. The entire pre-conditioning phase will last 30 minutes.

Patients in the sham-RIPC group will have the sphygmomanometer cuff placed on their right upper arm, but the cuff will not be inflated. Similar to patients in the RIPC group, patients in the sham-RIPC group will undergo the same 30 minute delay before starting surgery.

Remote ischemic preconditioning (RIPC) is a phenomenon in which brief ischemia of one organ or tissue, provokes a protective effect that can reduce the mass of infarction caused by vessel occlusion and reperfusion.

By measuring serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), and albumin

Defined as a new ischemic or hemorrhagic cerebrovascular accident with neurological deficit lasting >24 h

Inclusion Criteria: Candidate cardiac surgical patients Elective or urgent on pump coronary artery bypass grafting (CABG) Age 18 to 85 years Signed informed consent Exclusion Criteria: End-stage renal disease (receiving hemodialysis or glomerular filtration rate <15 ml/min/1.73m2) Peripheral vascular disease Severe hepatic disease Planned off-pump surgery Pregnancy

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