Cardiac Surgery, Cardiopulmonary Bypass
Conditions
Brief summary
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.
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.
Interventions
DRUGPlacebo
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.
DRUGNorepinephrine
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.
OTHERIncrease infusion rate
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
OTHERDecrease infusion rate
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
Sponsors
Imam Abdulrahman Bin Faisal University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
The placebo and the norepinephrine solutions look identical and their infusions will be continued until 60 min after skin closure. The test solution will be prepared by one anesthesiologist before the induction of anesthesia.
Intervention model description
A single center, interventional, parallel, double-blind (patient - and outcome-assessor), prospective, trial in patients scheduled for elective cardiac procedures using CPB. The RCT will be conducted according to Good Clinical Practice (GCP) Guidelines and comply with the principles of the Declaration of Helsinki. The RCT will be registered in a public registry, and the study protocol with its statistical analysis plan will be published before enrolment of the first patient.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* American Society of Anesthesiologists (ASA) physical status between ІІІ and ІV * Scheduled for any type of elective cardiac surgery using CPB * General anesthesia provided in an endotracheally intubated patient.
Exclusion criteria
* Decline consent to participate. * Emergency surgery. * Ejection fraction (EF%) less than 35%. * Scheduled for re-do surgery. * Scheduled for emergency surgery. * Preoperative ventilator or circulatory support. * Body mass index (BMI) greater than 40 Kg/m2. * History of alcohol abuse. * History of drug abuse. * Pregnancy. * Consent for another interventional study during anaesthesia * No written informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in lactic acid level | For 24 hours after surgery from the start of surgery | perioperative changes in lactic acid level measured from arterial or venous blood |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Need for rescue doses of atropine | For the time of surgery | Use of rescue doses of atropine |
| Need for rescue doses of glycopyrrolate. | For the time of surgery | Use of rescue doses of glycopyrrolate |
| Intraoperative hypoxemia | For the time of surgery | Decrease of peripheral oxygen saturation less than 92% |
| Mean Arterial Pressure (MAP) | For 24 hours after surgery from the start of surgery | invasive arterial blood pressure measurement |
| Cardiac Index (CI) | For 24 hours after surgery from the start of surgery | measured as l/min/m2 |
| Systemic Vascular Resistance index (SVRI) | For 24 hours after surgery from the start of surgery | measured as dynes.sec.m2/cm5 |
| Stroke volume variation (SVV) | For 24 hours after surgery from the start of surgery | measured as ml/min/m2 |
| Need for rescue doses of phenylephrine | For the time of surgery | Use of rescue doses of phenylephrine |
| Need for rescue doses of norepinephrine | For the time of surgery | Use of rescue doses of norepinephrine |
| Need for rescue doses of ephedrine | For the time of surgery | Use of rescue doses of ephedrine |
| Need for rescue doses of nitroglycerine | For the time of surgery | Use of rescue doses of nitroglycerine |
| Need for rescue doses of labetalol | For the time of surgery | Use of rescue doses of labetalol |
| Need for rescue doses of esmolol | For the time of surgery | Use of rescue doses of esmolol |
| Intraoperative hypotension | For the time of surgery | Number of drops in systolic arterial pressure \< 90 mmHg for 3 minutes or longer for any reasons |
| Intraoperative bradycardia | For the time of surgery | Number of drops in heart rate lower than 40 beats.min-1 or 10% of baseline value for more than three minutes for any reasons. |
| Intraoperative myocardial ischemic episodes | For the time of surgery | Remarkable ischemic changes included those patients with ≥ 1- mv ST-segment depression or ≥ 2-mv ST-segment elevation lasting more than 1 minute |
| Number of patients who required pacemaker insertion | For the time of surgery | Need for pacemaker insertion following termination of cardiopulmonary bypass. |
| Number of patients who required direct current shocks | For the time of surgery | Need for direct current shock following termination of cardiopulmonary bypass.. |
| Number of patients who need for epinephrine | For the time of surgery | Need for epinephrine following termination of cardiopulmonary bypass. |
| Number of patients who need for norepinephrine | For the time of surgery | Need for norepinephrine following termination of cardiopulmonary bypass. |
| Number of patients who need for dobutamine | For the time of surgery | Need for dobutamine following termination of cardiopulmonary bypass. |
| Number of patients who need for milrinone | For the time of surgery | Need for milrinone following termination of cardiopulmonary bypass. |
| Number of patients who need for for Intra-Aortic Balloon Pump | For the time of surgery | Need for intra-aortic balloon counter pulsation pump following termination of cardiopulmonary bypass. |
| Intraoperative need for blood transfusion | For the time of surgery | The amount of transfused units of blood and blood products |
| Intraoperative fluid intake | For the time of surgery | The amount of infused crystalloids and colloids |
| ICU Stay | For 30 days after surgery | Length of ICU stay |
| Hospital Stay | For 30 days after surgery | Length of hospital stay |
| Mortality at 30 days | For 30 days after surgery | Alive or dead on postoperative day 30 |
| Mortality at 90 days | For 90 days after surgery | Alive or dead on postoperative day 90 |
| Postoperative need for reintubation | For 30 days after surgery | Postoperative need for reintubation during the first 30 days following surgery |
| Postoperative bleeding | For 30 days after surgery | Postoperative bleeding during the first 30 days following surgery |
| Postoperative cardiogenic shock | For 30 days after surgery | Postoperative cariogenic shock for the first 30 days following surgery |
| Postoperative acute kidney injury | For 30 days after surgery | Postoperative acute kidney injury for the first 30 days following surgery |
| Postoperative splanchnic ischemia | For 30 days after surgery | Postoperative mesenteric or splanchnic ischemia for the first 30 days following surgery |
| Postoperative myocardial ischemia | For 30 days after surgery | Postoperative acute coronary syndrome for the first 30 days following surgery |
| Postoperative wound infection | For 30 days after surgery | Postoperative wound infection for the first 30 days following surgery |
| Postoperative pneumonia | For 30 days after surgery | Postoperative pneumonia for the first 30 days following surgery |
| Intraoperative hypercapnia | For the time of surgery | Increase in end tidal carbon dioxide more than 45 mm Hg |
| Postoperative hypoxemia | For 30 days after surgery | Postoperative decrease in peripheral oxygen saturation less than 90 for the first 30 days following surgery |
| Postoperative stroke | For 30 days after surgery | Postoperative stroke for the first 30 days following surgery |
| Postoperative sternotomy | For 30 days after surgery | Postoperatively during hospital stay |
| Postoperative sternal dehiscence | For 30 days after surgery | Postoperatively during hospital stay |
| Postoperative mediastinitis | For 30 days after surgery | Postoperative mediastinitis for the first 30 days following surgery |
Countries
Saudi Arabia
Outcome results
None listed