Norcal: Norepinephrine Infusion During Cardiopulmonary Bypass
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo Infusion of normal Saline 0.9%will be started following arterial cannulation before initiation of cardiopulmonary bypass and continued until aortic declamping time. |
Drug: Placebo
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.
Other: Increase 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
Other: Decrease 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
|
| Active Comparator: Norepinephrine Infusion of norepinephrine (40 µg/ml) will be started following arterial cannulation before initiation of cardiopulmonary bypass and continued until aortic declamping time. |
Drug: Norepinephrine
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.
Other: Increase 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
Other: Decrease 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
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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
- 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%
- Intraoperative hypercapnia [For the time of surgery]
Increase in end tidal carbon dioxide more than 45 mm Hg
- 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
- Postoperative mediastinitis [For 30 days after surgery]
Postoperative mediastinitis for the first 30 days following surgery
- 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
Eligibility Criteria
Criteria
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.
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Preoperative ventilator or circulatory support.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Dammam University | Khobar | Eastern | Saudi Arabia | 31952 |
| 2 | Imam Abdulrahamn Bin Faisal University (Former, Dammam University) | Dammam | Esatern | Saudi Arabia | 31952 |
Sponsors and Collaborators
- Imam Abdulrahman Bin Faisal University
Investigators
- Study Chair: Mohamed R El Tahan, MD, College of Medicine, Imam Abdulrahman Bin Faisal University
Study Documents (Full-Text)
None provided.More Information
Publications
- Chan JL, Kobashigawa JA, Aintablian TL, Li Y, Perry PA, Patel JK, Kittleson MM, Czer LS, Zarrini P, Velleca A, Rush J, Arabia FA, Trento A, Esmailian F. Vasoplegia after heart transplantation: outcomes at 1 year. Interact Cardiovasc Thorac Surg. 2017 Aug 1;25(2):212-217. doi: 10.1093/icvts/ivx081.
- Cotter EK, Kidd B, Flynn BC. Elevation of Intraoperative Lactate Levels During Cardiac Surgery: Is There Power in This Prognostication? J Cardiothorac Vasc Anesth. 2020 Apr;34(4):885-887. doi: 10.1053/j.jvca.2019.11.049. Epub 2019 Dec 9.
- Fischer GW, Levin MA. Vasoplegia during cardiac surgery: current concepts and management. Semin Thorac Cardiovasc Surg. 2010 Summer;22(2):140-4. doi: 10.1053/j.semtcvs.2010.09.007. Review.
- Ortoleva J, Shapeton A, Vanneman M, Dalia AA. Vasoplegia During Cardiopulmonary Bypass: Current Literature and Rescue Therapy Options. J Cardiothorac Vasc Anesth. 2020 Oct;34(10):2766-2775. doi: 10.1053/j.jvca.2019.12.013. Epub 2019 Dec 14. Review.
- Shaefi S, Mittel A, Klick J, Evans A, Ivascu NS, Gutsche J, Augoustides JGT. Vasoplegia After Cardiovascular Procedures-Pathophysiology and Targeted Therapy. J Cardiothorac Vasc Anesth. 2018 Apr;32(2):1013-1022. doi: 10.1053/j.jvca.2017.10.032. Epub 2017 Oct 27. Review.
- Sun LY, Chung AM, Farkouh ME, van Diepen S, Weinberger J, Bourke M, Ruel M. Defining an Intraoperative Hypotension Threshold in Association with Stroke in Cardiac Surgery. Anesthesiology. 2018 Sep;129(3):440-447. doi: 10.1097/ALN.0000000000002298. Erratum in: Anesthesiology. 2019 Feb;130(2):360.
- Truby LK, Takeda K, Farr M, Beck J, Yuzefpolskaya M, Colombo PC, Topkara VK, Mancini D, Naka Y, Takayama H. Incidence and Impact of On-Cardiopulmonary Bypass Vasoplegia During Heart Transplantation. ASAIO J. 2018 Jan/Feb;64(1):43-51. doi: 10.1097/MAT.0000000000000623.
- Tsiouris A, Wilson L, Haddadin AS, Yun JJ, Mangi AA. Risk assessment and outcomes of vasoplegia after cardiac surgery. Gen Thorac Cardiovasc Surg. 2017 Oct;65(10):557-565. doi: 10.1007/s11748-017-0789-6. Epub 2017 Jun 13.
- Norcal-03-2020