Remote Ischemic Preconditioning During Cardiopulmonary Bypass (RIPC)

Effect of Remote Ischemic Preconditioning on Serum Lactate Levels As Well As Cardiac and Renal Functions During and After Open Heart Surgeries

The objective of study is to detect effect of remote ischemic preconditioning on serum lactate levels during and after cardiac surgery with cardiopulmonary bypass in addition to its effect on cardiac and renal clinical outcomes.

Remote ischemic preconditioning (RIPC) is a phenomenon where transient non-injurious ischemia/ reperfusion episodes applied to an organ away from the heart can protect the myocardium from ischemia/reperfusion injury. RIPC has been found to be an attractive strategy to reduce myocardial injury and improve outcome in patients undergoing cardiac surgery. The exact mechanisms of this protection are not yet known, although stimulation of prosurvival intracellular kinase responses and inhibition of inflammatory pathways each play a role. RIPC can be performed by noninvasive inflation and deflation of a standard blood pressure cuff or pneumatic tourniquet on the upper or lower limbs to induce brief ischemia and reperfusion, which is the mechanism by which injury in patients undergoing open cardiac surgery occurs. ANESTHETIC TECHNIQUE All patients will be preoperatively examined and investigated by complete blood count, coagulation profile, renal and kidney functions and electrolytes. Electrocardiography, chest x ray and echocardiography will be routinely done. Coronary angiography and carotid arterial duplex will be requested in patients prepared for coronary artery bypass graft (CABG). Patient will be premedicated by intramuscular injection of 10mg morphine in the morning of the operation. Before induction of anesthesia, a five-lead electrocardiography system will be applied to monitor heart rate, rhythm, and ST segments (leads II and V5). A pulse oximeter probe will be attached, and a peripheral venous cannula will be placed. For measurement of arterial pressure and blood sampling, a 20 G cannula will be inserted into either right or left radial artery under local anesthesia. General anesthesia will be induced by fentanyl (3-5 μg/kg), propofol titrated according to response, followed by atracurium (0.5 mg/kg). Trachea will be intubated, patients will be mechanically ventilated with oxygen in air so as to achieve normocarbia. This will be confirmed by radial arterial blood gas analysis. An esophageal temperature probe and a Foley catheter will also be placed. For drug infusion, a triple-lumen central venous catheter will be inserted via the right internal jugular vein. Anesthesia will be maintained by inhaled isoflurane, with additional fentanyl injected prior to skin incision as well as sternotomy and atracurium infusion for continued muscle relaxation. During extracorporeal circulation, patients will receive propofol infusion in addition to atracurium infusion. Before initiation of cardiopulmonary bypass (CPB), the patients will receive intravenously tranexamic acid (2 g) and heparin (300-500 units/kg body weight) to achieve an activated clotting time > 400 s. CPB was instituted via an ascending aortic cannula and a two-stage right atrial cannula. Before, during, and after CPB (pump blood flow: 2.4 l/min/m2), mean arterial pressure was adjusted to exceed 60 mmHg. Cardiac arrest will be induced with cold antegrade crystalloid cardioplegia (St Thomas solution) or warm intermittent antegrade blood cardioplegia. Lactate-enriched Ringer's solution will be added to the CPB circuit to maintain reservoir volume when needed, and packed red blood cells will be added when hemoglobin concentration decrease to less than 7 g/dl. After rewarming the patient to 37°C and separation from CPB, reversal of heparin by protamine sulfate, and sternal closure, the patients will be transferred to the intensive care unit.

After patient being draped, applying cuff inflation will be done to the upper arm not having the arterial line inserted of about 200 mmHg or 15 mmHg above patient's systolic pressure 3 cycles 5 minutes each followed by 5 minutes of pressure relieve

Every 30 minutes for 6 hours during surgery except at cardiopulmonary bypass as there is cardioplegia

Every 30 minutes for 6 hours during surgery except at cardiopulmonary bypass as there is cardioplegia and no pulsatile blood pressure

Every 30 minutes for 6 hours during surgery except at cardiopulmonary bypass as there is cardioplegia and no pulsatile blood pressure

Grade 1: serum creatinine rise of 150%-200% of baseline and/or urine output <0.5 mL/kg/h for >6 contiguous hours. Grade 2: serum creatinine rise of 200%-300% of baseline and/or urine output <0.5 mL/kg/h for >12 contiguous hours. Grade 3: serum creatinine rise of >300% of baseline and/or urine output <0.3 mL/kg/h for >24 h or anuria for 12 h.

Grade 1: serum creatinine rise of 150%-200% of baseline and/or urine output <0.5 mL/kg/h for >6 contiguous hours. Grade 2: serum creatinine rise of 200%-300% of baseline and/or urine output <0.5 mL/kg/h for >12 contiguous hours. Grade 3: serum creatinine rise of >300% of baseline and/or urine output <0.3 mL/kg/h for >24 h or anuria for 12 h.

Grade 1: serum creatinine rise of 150%-200% of baseline and/or urine output <0.5 mL/kg/h for >6 contiguous hours. Grade 2: serum creatinine rise of 200%-300% of baseline and/or urine output <0.5 mL/kg/h for >12 contiguous hours. Grade 3: serum creatinine rise of >300% of baseline and/or urine output <0.3 mL/kg/h for >24 h or anuria for 12 h.

Inclusion Criteria: Patients 18 years of age or older Elective cardiovascular surgery requiring cardiopulmonary bypass either for CABG or valve replacement. Exclusion Criteria: Patients with emergency surgeries. Off pump heart surgery. Hepatic affection (INR>2). Renal affection (creatinine >1.6 mg/dl for men and >1.4 mg/dl for women). Peripheral vascular disease affecting upper limbs. Patients taking the antidiabetic sulphonylurea glyburide ( glibenclamide) or receiving nicorandil drug therapy will be excluded because these agents have been shown to abolish preconditioning. Patients being considered for radial artery conduit harvesting.

Saxena P, Newman MA, Shehatha JS, Redington AN, Konstantinov IE. Remote ischemic conditioning: evolution of the concept, mechanisms, and clinical application. J Card Surg. 2010 Jan-Feb;25(1):127-34. doi: 10.1111/j.1540-8191.2009.00820.x. Epub 2009 Jun 22.

Heusch G. Cardioprotection: chances and challenges of its translation to the clinic. Lancet. 2013 Jan 12;381(9861):166-75. doi: 10.1016/S0140-6736(12)60916-7. Epub 2012 Oct 22.

Thielmann M, Kottenberg E, Kleinbongard P, Wendt D, Gedik N, Pasa S, Price V, Tsagakis K, Neuhauser M, Peters J, Jakob H, Heusch G. Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised, double-blind, controlled trial. Lancet. 2013 Aug 17;382(9892):597-604. doi: 10.1016/S0140-6736(13)61450-6. Erratum In: Lancet. 2013 Sep 14;382(9896):940.

Badreldin AM, Doerr F, Elsobky S, Brehm BR, Abul-dahab M, Lehmann T, Bayer O, Wahlers T, Hekmat K. Mortality prediction after cardiac surgery: blood lactate is indispensible. Thorac Cardiovasc Surg. 2013 Dec;61(8):708-17. doi: 10.1055/s-0032-1324796. Epub 2013 Mar 11. Erratum In: Thorac Cardiovasc Surg. 2013 Jun;61(4):375. Elsobky, Sherif [removed]. Thorac Cardiovasc Surg. 2014 Apr; 62(3):273. Elsobky, Sherif [added].