Norepinephrine Infusion During Cardiopulmonary Bypass

Imam Abdulrahman Bin Faisal University80 enrolled

Overview

The primary objective is to test the efficacy and safety of the accuracy of continuous intravenous infusion of norepinephrine during cardiopulmonary bypass (CPB) on the prevention of hyperlactatemia after cardiac surgery. "Efficacy" would be tested with measurement of the postoperative changes in lactic acid level over time from the baseline value before induction of general anesthesia. "safety" would be tested with observing the post-cardiotomy need for inotropic and vasopressor support, the incidence of postoperative acute kidney injury (AKI), changes in cardiac troponin level (CnTnI), and signs of ischemic splanchnic injury.

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.

Interventions

PlaceboDRUG

Patients undergoing different cardiac surgical procedures will receive a continuous intravenous infusion of Normal Saline 0.9% with a starting dose of 0.0025 ml/kg/min.

NorepinephrineDRUG

Patients undergoing different cardiac surgical procedures will receive a continuous intravenous infusion of norepinephrine (40 ug/ml) with a starting dose of 0.0025 ml/kg/min.

Increase infusion rateOTHER

Infusion rate will be increased as needed in order to maintain a MAP ≥65 mmHg during cardiopulmonary bypass period as per the discretion of the anesthesiologist using 0.00125 ml/kg/min increments

Decrease infusion rateOTHER

Infusion rate will be decreased as needed in order to maintain a MAP ≥65 mmHg during cardiopulmonary bypass period as per the discretion of the anesthesiologist using 0.00125 ml/kg/min decrements

Outcomes

Primary Outcomes

Changes in lactic acid level

perioperative changes in lactic acid level measured from arterial or venous blood

Time frame: For 24 hours after surgery from the start of surgery

Secondary Outcomes

Mean Arterial Pressure (MAP)

invasive arterial blood pressure measurement

Time frame: For 24 hours after surgery from the start of surgery

Cardiac Index (CI)

measured as l/min/m2

Time frame: For 24 hours after surgery from the start of surgery

Systemic Vascular Resistance index (SVRI)

measured as dynes.sec.m2/cm5

Time frame: For 24 hours after surgery from the start of surgery

Stroke volume variation (SVV)

measured as ml/min/m2

Time frame: For 24 hours after surgery from the start of surgery

Need for rescue doses of phenylephrine

Use of rescue doses of phenylephrine