Effects of Norepinephrine Infusion During Cardiopulmonary Bypass on Perioperative Changes in Lactic Acid Level: A Randomized Controlled Study

Brief Summary

Detailed Description

Rationale 1.1. Vasoplegia and cardiac surgery: Vasoplegia Syndrome (VS), prevailing in about 20% of cardiac surgical procedures (1), is defined as low mean arterial pressure (MAP) with normal or high cardiac indices and which is resistant to treatment with the commonly used vasopressors. (2,3) Vasoplegia might occur either during or after the cardiopulmonary bypass periods or during the postoperative period during the intensive care unit (ICU) stay. (3) Many factors have been found to be related to the increased Vasoplegia during the cardiopulmonary bypass period such as left ventricular ejection fraction more than 40%, male patients, elderly patients, higher body mass index, long cardiopulmonary bypass time, hypotension upon the start of cardiopulmonary bypass, perioperative use of angiotensin-converting enzyme inhibitors (ACE) and presence of infective endocarditis. (4,5) 1.2. Effects of Cardiopulmonary bypass (CPB) on Post cardiotomy Vasoplegia. Cardiopulmonary bypass itself may intensify the effects of vasoplegia due to hemodilution which decreases the blood viscosity, so, reducing the overall peripheral vascular resistance. Moreover, the interaction of blood with the tubing of the cardiopulmonary bypass machine results in the release of inflammatory mediators which play an important role in reducing the peripheral resistance and aggravating the hypotension. Although compensatory and auto-regulatory mechanisms play an important role in maintaining adequate tissue perfusion, hypotension during the cardiopulmonary bypass period may result in poor outcomes as postoperative stroke (4) especially if the mean arterial pressure is below 65 mmHg. (6) 1.3. Hyperlactatemia after cardiac surgery Lactate was used as a marker for adequate tissue perfusion since the mid-1800s. Although the literature has illustrated the undesirable effects of high lactate levels, however, the cause, the prevention as well as treatment measures of hyperlactatemia remain obscure. Additionally, lactic acidosis or hyperlactatemia might occur in cases of refractory vasoplegia. A rise in lactate levels is common during cardiac surgery and is well known for its deleterious and its association with poor patients' outcomes. (7) Owing to its detrimental effects, measures to reduce the effects and treat vasoplegia were used. Firstly, excluding any equipment or mechanical failure such as the arterial line monitor, adjusting the bypass flows for higher cardiac index (CI\>2.2), confirming the proper cannula position and ruling out any aortic dissection. Secondly, adjusting some physiological parameters is of great value as checking hematocrit level for excessive hemodilution, adjusting the anesthetics with severe vasodilatory properties, excluding the possibility of a drug reaction or anaphylaxis and temperature management during hypothermic bypass. Thirdly, the use of conventional vasopressor agents as phenylephrine, norepinephrine, and vasopressin. Finally, the use of some off-label agents as vitamin C, hydroxocobalamin, angiotensin 2, methylene blue and prostaglandin inhibitors. (8) 1.4. Why this clinical trial? The use of norepinephrine during CPB has its own potential benefits. It is not clear if the use of continuous norepinephrine infusion during CPB would be effective and safe in lessening the postoperative hyperlactatemia and development of vasoplegia after cardiac surgery. The here proposed randomized controlled clinical trial will test the use of continuous norepinephrine infusion during CPB with respect to the efficacy and safety to reduce the postoperative rise in blood lactate level.

Primary Outcomes

Secondary Outcomes

• Postoperative pneumonia(For 30 days after surgery)
• Postoperative hypoxemia(For 30 days after surgery)
• Postoperative sternotomy(For 30 days after surgery)
• Postoperative wound infection(For 30 days after surgery)
• Postoperative mediastinitis(For 30 days after surgery)
• Postoperative stroke(For 30 days after surgery)
• Need for rescue doses of esmolol(For the time of surgery)
• Need for rescue doses of atropine(For the time of surgery)
• Need for rescue doses of glycopyrrolate.(For the time of surgery)
• Intraoperative hypoxemia(For the time of surgery)
• Number of patients who required pacemaker insertion(For the time of surgery)
• Mean Arterial Pressure (MAP)(For 24 hours after surgery from the start of surgery)
• Cardiac Index (CI)(For 24 hours after surgery from the start of surgery)
• Systemic Vascular Resistance index (SVRI)(For 24 hours after surgery from the start of surgery)
• Stroke volume variation (SVV)(For 24 hours after surgery from the start of surgery)
• Need for rescue doses of phenylephrine(For the time of surgery)
• Need for rescue doses of norepinephrine(For the time of surgery)
• Need for rescue doses of ephedrine(For the time of surgery)
• Need for rescue doses of nitroglycerine(For the time of surgery)
• Need for rescue doses of labetalol(For the time of surgery)
• Mortality at 90 days(For 90 days after surgery)
• Postoperative need for reintubation(For 30 days after surgery)
• Postoperative bleeding(For 30 days after surgery)
• Postoperative cardiogenic shock(For 30 days after surgery)
• Postoperative acute kidney injury(For 30 days after surgery)
• Postoperative splanchnic ischemia(For 30 days after surgery)
• Postoperative myocardial ischemia(For 30 days after surgery)
• Postoperative sternal dehiscence(For 30 days after surgery)
• Intraoperative hypercapnia(For the time of surgery)
• Intraoperative hypotension(For the time of surgery)
• Intraoperative bradycardia(For the time of surgery)
• Intraoperative myocardial ischemic episodes(For the time of surgery)
• Number of patients who required direct current shocks(For the time of surgery)
• Hospital Stay(For 30 days after surgery)
• Mortality at 30 days(For 30 days after surgery)
• Number of patients who need for epinephrine(For the time of surgery)
• Number of patients who need for norepinephrine(For the time of surgery)
• Number of patients who need for dobutamine(For the time of surgery)
• Number of patients who need for milrinone(For the time of surgery)
• Number of patients who need for for Intra-Aortic Balloon Pump(For the time of surgery)
• Intraoperative need for blood transfusion(For the time of surgery)
• Intraoperative fluid intake(For the time of surgery)
• ICU Stay(For 30 days after surgery)