Clinical trial NCT03723993: Remote Ischemic Preconditioning During Cardiopulmonary Bypass
Official title: Effect of Remote Ischemic Preconditioning on Serum Lactate Levels As Well As Cardiac and Renal Functions During and After Open Heart Surgeries
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Lactic Acidosis
Keywords: Ischemic preconditioning
Lactate level
Cardiopulmonary bypass
Lead sponsor: Fayoum University
Sponsor class: OTHER
First posted: 2018-10-30
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Serum lactate level
timeFrame: 1 minute at the end of operation
Secondary outcomes:
measure: Serum lactate level
timeFrame: 3 minutes after induction of anesthesia
measure: Serum lactate level
timeFrame: 30 minutes, after cardiopulmonary bypass
measure: Serum lactate level
timeFrame: 1 minute before cardiopulmonary bypass
measure: Serum lactate level
timeFrame: 24 hours postoperatively.
measure: Serum lactate level
timeFrame: 48 hours postoperatively.
measure: Serum lactate level
timeFrame: 72 hours postoperatively.
measure: Heart rate
timeFrame: 2 minutes before induction of general anesthesia
measure: Heart rate
timeFrame: 3 minutes after induction of general anesthesia
measure: Heart rate
timeFrame: Every 30 minutes for 6 hours during surgery except at cardiopulmonary bypass as there is cardioplegia
measure: Systolic blood pressure
timeFrame: 2 minutes before induction of general anesthesia
measure: Systolic blood pressure
timeFrame: 3 minutes after induction
measure: Systolic blood pressure
timeFrame: Every 30 minutes for 6 hours during surgery except at cardiopulmonary bypass as there is cardioplegia and no pulsatile blood pressure
measure: Diastolic blood pressure
timeFrame: 2 minutes before induction of general anesthesia
measure: Diastolic blood pressure
timeFrame: 3 minutes after induction
measure: Diastolic blood pressure
timeFrame: Every 30 minutes for 6 hours during surgery except at cardiopulmonary bypass as there is cardioplegia and no pulsatile blood pressure
measure: Left ventricular fractional shortening (LVFS)
timeFrame: 12 hours before the operation
measure: Left ventricular fractional shortening (LVFS)
timeFrame: 2 hours after the operation
measure: Left ventricular fractional shortening (LVFS)
timeFrame: 4 hours after the operation
measure: Left ventricular fractional shortening (LVFS)
timeFrame: 12 hours after the operation
measure: Left ventricular fractional shortening (LVFS)
timeFrame: 24 hours after the operation
measure: Left ventricular fractional shortening (LVFS)
timeFrame: 48 hours after the operation
measure: Left ventricular fractional shortening (LVFS)
timeFrame: 72 hours after the operation
measure: Left ventricular ejection fraction (LVEF)
timeFrame: 12 hours before the operation
measure: Left ventricular ejection fraction (LVEF)
timeFrame: 2 hours after the operation
measure: Left ventricular ejection fraction (LVEF)
timeFrame: 4 hours after the operation
measure: Left ventricular ejection fraction (LVEF)
timeFrame: 12 hours after the operation
measure: Left ventricular ejection fraction (LVEF)
timeFrame: 24 hours after the operation
measure: Left ventricular ejection fraction (LVEF)
timeFrame: 48 hours after the operation
measure: Central venous pressure
timeFrame: Baseline 2 minutes after insertion of central venous catheter
measure: Central venous pressure
timeFrame: 2 minutes before cardiopulmonary bypass
measure: Central venous pressure
timeFrame: 2 minutes after cardiopulmonary bypass
measure: Central venous pressure
timeFrame: 1 minute after the end of operation
measure: Serum urea level
timeFrame: 5 minutes before beginning of operation
measure: Serum urea level
timeFrame: 5 minutes after ICU admission
measure: Serum creatinine level
timeFrame: 5 minutes before beginning of operation
measure: Serum creatinine level
timeFrame: 24 hours postoperatively
measure: Serum creatinine level
timeFrame: 48 hours postoperatively
measure: Serum creatinine level
timeFrame: 72 hours postoperatively
measure: Acute kidney injury (AKI) score
timeFrame: 24 hours postoperatively
measure: Acute kidney injury (AKI) score
timeFrame: 48 hours postoperatively
measure: Acute kidney injury (AKI) score
timeFrame: 72 hours postoperatively
measure: Serum sodium level
timeFrame: 5 minutes after ICU admission.
measure: Serum sodium level
timeFrame: 5 minutes before beginning of operation
measure: Serum potassium level
timeFrame: 5 minutes before beginning of operation
measure: Serum potassium level
timeFrame: 5 minutes after ICU admission
measure: Arterial oxygen pressure
timeFrame: 5 minutes before operation
measure: Arterial oxygen pressure
timeFrame: 2 minutes before cardiopulmonary bypass
measure: Arterial oxygen pressure
timeFrame: 2 minutes after cardiopulmonary bypass
measure: Arterial oxygen pressure
timeFrame: 1 minute after end of operation
measure: Arterial oxygen pressure
timeFrame: Every 6 hours for 24 hours in the ICU
measure: Arterial carbon dioxide pressure
timeFrame: 5 minutes before operation
measure: Arterial carbon dioxide pressure
timeFrame: 2 minutes before cardiopulmonary bypass
measure: Arterial carbon dioxide pressure
timeFrame: 2 minutes after cardiopulmonary bypass
measure: Arterial carbon dioxide pressure
timeFrame: 1 minute after end of operation
measure: Arterial carbon dioxide pressure
timeFrame: Every 6 hours for 24 hours in the ICU
measure: Power of hydrogen (pH)
timeFrame: 5 minutes before operation
measure: Power of hydrogen (pH)
timeFrame: 2 minutes before cardiopulmonary bypass
measure: Power of hydrogen (pH)
timeFrame: 2 minutes after cardiopulmonary bypass
measure: Power of hydrogen (pH)
timeFrame: 1 minute after end of operation
measure: Power of hydrogen (pH)
timeFrame: Every 6 hours for 24 hours in the ICU
measure: Standard bicarbonate level
timeFrame: 5 minutes before operation
measure: Standard bicarbonate level
timeFrame: 2 minutes before cardiopulmonary bypass
measure: Standard bicarbonate level
timeFrame: 2 minutes after cardiopulmonary bypass
measure: Standard bicarbonate level
timeFrame: 1 minute after end of operation
measure: Standard bicarbonate level
timeFrame: Every 6 hours for 24 hours in the ICU
Other outcomes:
measure: Age
timeFrame: 1 hour before operation once the patient is recruited
Locations:
city: Fayoum
country: Egypt
facility: Mohamed Hamed
Study officials:
affiliation: Faculty of medicine, Fayoum University
name: Mohamed A Hamed, MD
role: PRINCIPAL_INVESTIGATOR
References:
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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.
citation: 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.
citation: 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.