Remote Ischemic Preconditioning During Cardiopulmonary Bypass

Lactic Acidosis Clinical Trial

— RIPC  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03723993
• Other study ID #: R123
• Status: Withdrawn
• Phase: N/A
• Start date: January 15, 2018
• Est. completion date: December 15, 2018

Study information

• Verified date: February 2021
• Source: Fayoum University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 15, 2018
• Est. primary completion date: November 15, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acidosis
• Acidosis, Lactic
• Lactic Acidosis

Intervention

Device:
• Inflated cuff
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
• Non inflated cuff
non inflated cuff around the arm for the control group

Locations

Country	Name	City	State
Egypt	Mohamed Hamed	Fayoum

Sponsors (1)

Lead Sponsor	Collaborator
Fayoum University

Country where clinical trial is conducted

Egypt, 

References & Publications (4)

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]. — View Citation

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. Review. — View Citation

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. Review. — View Citation

Thielmann M, Kottenberg E, Kleinbongard P, Wendt D, Gedik N, Pasa S, Price V, Tsagakis K, Neuhäuser 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Age	in years	1 hour before operation once the patient is recruited
Primary	Serum lactate level	mmol/l from arterial blood gas sample	1 minute at the end of operation
Secondary	Serum lactate level	mmol/l from arterial blood gas sample	3 minutes after induction of anesthesia
Secondary	Serum lactate level	mmol/l from arterial blood gas sample	30 minutes, after cardiopulmonary bypass
Secondary	Serum lactate level	mmol/l from arterial blood gas sample	1 minute before cardiopulmonary bypass
Secondary	Serum lactate level	mmol/l from arterial blood gas sample	24 hours postoperatively.
Secondary	Serum lactate level	mmol/l from arterial blood gas sample	48 hours postoperatively.
Secondary	Serum lactate level	mmol/l from arterial blood gas sample	72 hours postoperatively.
Secondary	Heart rate	beat per minute from electrocardiogram	2 minutes before induction of general anesthesia
Secondary	Heart rate	beat per minute from electrocardiogram	3 minutes after induction of general anesthesia
Secondary	Heart rate	beat per minute from electrocardiogram	Every 30 minutes for 6 hours during surgery except at cardiopulmonary bypass as there is cardioplegia
Secondary	Systolic blood pressure	Measured by mmHg from invasive arterial blood pressure	2 minutes before induction of general anesthesia
Secondary	Systolic blood pressure	Measured by mmHg from invasive arterial blood pressure	3 minutes after induction
Secondary	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
Secondary	Diastolic blood pressure	Measured by mmHg from invasive arterial blood pressure	2 minutes before induction of general anesthesia
Secondary	Diastolic blood pressure	Measured by mmHg from invasive arterial blood pressure	3 minutes after induction
Secondary	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
Secondary	Left ventricular fractional shortening (LVFS)	measured in percentage derived from echocardiography	12 hours before the operation
Secondary	Left ventricular fractional shortening (LVFS)	measured in percentage derived from echocardiography	2 hours after the operation
Secondary	Left ventricular fractional shortening (LVFS)	measured in percentage derived from echocardiography	4 hours after the operation
Secondary	Left ventricular fractional shortening (LVFS)	measured in percentage derived from echocardiography	12 hours after the operation
Secondary	Left ventricular fractional shortening (LVFS)	measured in percentage derived from echocardiography	24 hours after the operation
Secondary	Left ventricular fractional shortening (LVFS)	measured in percentage derived from echocardiography	48 hours after the operation
Secondary	Left ventricular fractional shortening (LVFS)	measured in percentage derived from echocardiography	72 hours after the operation
Secondary	Left ventricular ejection fraction (LVEF)	measured in percentage derived from echocardiography	12 hours before the operation
Secondary	Left ventricular ejection fraction (LVEF)	measured in percentage derived from echocardiography	2 hours after the operation
Secondary	Left ventricular ejection fraction (LVEF)	measured in percentage derived from echocardiography	4 hours after the operation
Secondary	Left ventricular ejection fraction (LVEF)	measured in percentage derived from echocardiography	12 hours after the operation
Secondary	Left ventricular ejection fraction (LVEF)	measured in percentage derived from echocardiography	24 hours after the operation
Secondary	Left ventricular ejection fraction (LVEF)	measured in percentage derived from echocardiography	48 hours after the operation
Secondary	Central venous pressure	from central venous catheter measured in cm H2O	Baseline 2 minutes after insertion of central venous catheter
Secondary	Central venous pressure	from central venous catheter measured in cm H2O	2 minutes before cardiopulmonary bypass
Secondary	Central venous pressure	from central venous catheter measured in cm H2O	2 minutes after cardiopulmonary bypass
Secondary	Central venous pressure	from central venous catheter measured in cm H2O	1 minute after the end of operation
Secondary	Serum urea level	mmol/L	5 minutes before beginning of operation
Secondary	Serum urea level	mmol/L	5 minutes after ICU admission
Secondary	Serum creatinine level	mmol/L	5 minutes before beginning of operation
Secondary	Serum creatinine level	mmol/L	24 hours postoperatively
Secondary	Serum creatinine level	mmol/L	48 hours postoperatively
Secondary	Serum creatinine level	mmol/L	72 hours postoperatively
Secondary	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
Secondary	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
Secondary	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
Secondary	Serum sodium level	milliequivalent/L	5 minutes after ICU admission.
Secondary	Serum sodium level	milliequivalent/L	5 minutes before beginning of operation
Secondary	Serum potassium level	milliequivalent/L	5 minutes before beginning of operation
Secondary	Serum potassium level	milliequivalent/L	5 minutes after ICU admission
Secondary	Arterial oxygen pressure	From arterial blood gas sampling	5 minutes before operation
Secondary	Arterial oxygen pressure	From arterial blood gas sampling	2 minutes before cardiopulmonary bypass
Secondary	Arterial oxygen pressure	From arterial blood gas sampling	2 minutes after cardiopulmonary bypass
Secondary	Arterial oxygen pressure	From arterial blood gas sampling	1 minute after end of operation
Secondary	Arterial oxygen pressure	From arterial blood gas sampling	Every 6 hours for 24 hours in the ICU
Secondary	Arterial carbon dioxide pressure	From arterial blood gas sampling	5 minutes before operation
Secondary	Arterial carbon dioxide pressure	From arterial blood gas sampling	2 minutes before cardiopulmonary bypass
Secondary	Arterial carbon dioxide pressure	From arterial blood gas sampling	2 minutes after cardiopulmonary bypass
Secondary	Arterial carbon dioxide pressure	From arterial blood gas sampling	1 minute after end of operation
Secondary	Arterial carbon dioxide pressure	From arterial blood gas sampling	Every 6 hours for 24 hours in the ICU
Secondary	Power of hydrogen (pH)	From arterial blood gas sampling	5 minutes before operation
Secondary	Power of hydrogen (pH)	From arterial blood gas sampling	2 minutes before cardiopulmonary bypass
Secondary	Power of hydrogen (pH)	From arterial blood gas sampling	2 minutes after cardiopulmonary bypass
Secondary	Power of hydrogen (pH)	From arterial blood gas sampling	1 minute after end of operation
Secondary	Power of hydrogen (pH)	From arterial blood gas sampling	Every 6 hours for 24 hours in the ICU
Secondary	Standard bicarbonate level	From arterial blood gas sampling	5 minutes before operation
Secondary	Standard bicarbonate level	From arterial blood gas sampling	2 minutes before cardiopulmonary bypass
Secondary	Standard bicarbonate level	From arterial blood gas sampling	2 minutes after cardiopulmonary bypass
Secondary	Standard bicarbonate level	From arterial blood gas sampling	1 minute after end of operation
Secondary	Standard bicarbonate level	From arterial blood gas sampling	Every 6 hours for 24 hours in the ICU