Remote Ischemic Preconditioning During Cardiopulmonary Bypass

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Lactic Acidosis

Intervention / Treatment
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* Device: Inflated cuff
* Device: Non inflated cuff


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control group<br>control group will have non inflated cuff around the arm. | Device: Non inflated cuff<br>* non inflated cuff around the arm for the control group<br>|
| Active Comparator: RIPC group<br>Inflated cuff will be done systematically and regularly | Device: Inflated cuff<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum lactate level | mmol/l from arterial blood gas sample | 1 minute at the end of operation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum lactate level | mmol/l from arterial blood gas sample | 3 minutes after induction of anesthesia | 
| Serum lactate level | mmol/l from arterial blood gas sample | 30 minutes, after cardiopulmonary bypass | 
| Serum lactate level | mmol/l from arterial blood gas sample | 1 minute before cardiopulmonary bypass | 
| Serum lactate level | mmol/l from arterial blood gas sample | 24 hours postoperatively. | 
| Serum lactate level | mmol/l from arterial blood gas sample | 48 hours postoperatively. | 
| Serum lactate level | mmol/l from arterial blood gas sample | 72 hours postoperatively. | 
| Heart rate | beat per minute from electrocardiogram | 2 minutes before induction of general anesthesia | 
| Heart rate | beat per minute from electrocardiogram | 3 minutes after induction of general anesthesia | 
| Heart rate | beat per minute from electrocardiogram | Every 30 minutes for 6 hours during surgery except at cardiopulmonary bypass as there is cardioplegia | 
| Systolic blood pressure | Measured by mmHg from invasive arterial blood pressure | 2 minutes before induction of general anesthesia | 
| Systolic blood pressure | Measured by mmHg from invasive arterial blood pressure | 3 minutes after induction | 
| Systolic blood pressure | Measured by mmHg from invasive arterial blood pressure | Every 30 minutes for 6 hours during surgery except at cardiopulmonary bypass as there is cardioplegia and no pulsatile blood pressure | 
| Diastolic blood pressure | Measured by mmHg from invasive arterial blood pressure | 2 minutes before induction of general anesthesia | 
| Diastolic blood pressure | Measured by mmHg from invasive arterial blood pressure | 3 minutes after induction | 
| Diastolic blood pressure | Measured by mmHg from invasive arterial blood pressure | Every 30 minutes for 6 hours during surgery except at cardiopulmonary bypass as there is cardioplegia and no pulsatile blood pressure | 
| Left ventricular fractional shortening (LVFS) | measured in percentage derived from echocardiography | 12 hours before the operation | 
| Left ventricular fractional shortening (LVFS) | measured in percentage derived from echocardiography | 2 hours after the operation | 
| Left ventricular fractional shortening (LVFS) | measured in percentage derived from echocardiography | 4 hours after the operation | 
| Left ventricular fractional shortening (LVFS) | measured in percentage derived from echocardiography | 12 hours after the operation | 
| Left ventricular fractional shortening (LVFS) | measured in percentage derived from echocardiography | 24 hours after the operation | 
| Left ventricular fractional shortening (LVFS) | measured in percentage derived from echocardiography | 48 hours after the operation | 
| Left ventricular fractional shortening (LVFS) | measured in percentage derived from echocardiography | 72 hours after the operation | 
| Left ventricular ejection fraction (LVEF) | measured in percentage derived from echocardiography | 12 hours before the operation | 
| Left ventricular ejection fraction (LVEF) | measured in percentage derived from echocardiography | 2 hours after the operation | 
| Left ventricular ejection fraction (LVEF) | measured in percentage derived from echocardiography | 4 hours after the operation | 
| Left ventricular ejection fraction (LVEF) | measured in percentage derived from echocardiography | 12 hours after the operation | 
| Left ventricular ejection fraction (LVEF) | measured in percentage derived from echocardiography | 24 hours after the operation | 
| Left ventricular ejection fraction (LVEF) | measured in percentage derived from echocardiography | 48 hours after the operation | 
| Central venous pressure | from central venous catheter measured in cm H2O | Baseline 2 minutes after insertion of central venous catheter | 
| Central venous pressure | from central venous catheter measured in cm H2O | 2 minutes before cardiopulmonary bypass | 
| Central venous pressure | from central venous catheter measured in cm H2O | 2 minutes after cardiopulmonary bypass | 
| Central venous pressure | from central venous catheter measured in cm H2O | 1 minute after the end of operation | 
| Serum urea level | mmol/L | 5 minutes before beginning of operation | 
| Serum urea level | mmol/L | 5 minutes after ICU admission | 
| Serum creatinine level | mmol/L | 5 minutes before beginning of operation | 
| Serum creatinine level | mmol/L | 24 hours postoperatively | 
| Serum creatinine level | mmol/L | 48 hours postoperatively | 
| Serum creatinine level | mmol/L | 72 hours postoperatively | 
| Acute kidney injury (AKI) score | 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. | 24 hours postoperatively | 
| Acute kidney injury (AKI) score | 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. | 48 hours postoperatively | 
| Acute kidney injury (AKI) score | 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. | 72 hours postoperatively | 
| Serum sodium level | milliequivalent/L | 5 minutes after ICU admission. | 
| Serum sodium level | milliequivalent/L | 5 minutes before beginning of operation | 
| Serum potassium level | milliequivalent/L | 5 minutes before beginning of operation | 
| Serum potassium level | milliequivalent/L | 5 minutes after ICU admission | 
| Arterial oxygen pressure | From arterial blood gas sampling | 5 minutes before operation | 
| Arterial oxygen pressure | From arterial blood gas sampling | 2 minutes before cardiopulmonary bypass | 
| Arterial oxygen pressure | From arterial blood gas sampling | 2 minutes after cardiopulmonary bypass | 
| Arterial oxygen pressure | From arterial blood gas sampling | 1 minute after end of operation | 
| Arterial oxygen pressure | From arterial blood gas sampling | Every 6 hours for 24 hours in the ICU | 
| Arterial carbon dioxide pressure | From arterial blood gas sampling | 5 minutes before operation | 
| Arterial carbon dioxide pressure | From arterial blood gas sampling | 2 minutes before cardiopulmonary bypass | 
| Arterial carbon dioxide pressure | From arterial blood gas sampling | 2 minutes after cardiopulmonary bypass | 
| Arterial carbon dioxide pressure | From arterial blood gas sampling | 1 minute after end of operation | 
| Arterial carbon dioxide pressure | From arterial blood gas sampling | Every 6 hours for 24 hours in the ICU | 
| Power of hydrogen (pH) | From arterial blood gas sampling | 5 minutes before operation | 
| Power of hydrogen (pH) | From arterial blood gas sampling | 2 minutes before cardiopulmonary bypass | 
| Power of hydrogen (pH) | From arterial blood gas sampling | 2 minutes after cardiopulmonary bypass | 
| Power of hydrogen (pH) | From arterial blood gas sampling | 1 minute after end of operation | 
| Power of hydrogen (pH) | From arterial blood gas sampling | Every 6 hours for 24 hours in the ICU | 
| Standard bicarbonate level | From arterial blood gas sampling | 5 minutes before operation | 
| Standard bicarbonate level | From arterial blood gas sampling | 2 minutes before cardiopulmonary bypass | 
| Standard bicarbonate level | From arterial blood gas sampling | 2 minutes after cardiopulmonary bypass | 
| Standard bicarbonate level | From arterial blood gas sampling | 1 minute after end of operation | 
| Standard bicarbonate level | From arterial blood gas sampling | Every 6 hours for 24 hours in the ICU | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ischemic preconditioning, Lactate level, Cardiopulmonary bypass