Norepinephrine Infusion During Cardiopulmonary Bypass

NCT ID: NCT04312971

Last Updated: 2021-12-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-05-06

Study Completion Date

2021-09-20

Brief Summary

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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

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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.

Conditions

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Cardiac Surgery Cardiopulmonary Bypass

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Outcome Assessors
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.

Study Groups

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Placebo

Infusion of normal Saline 0.9%will be started following arterial cannulation before initiation of cardiopulmonary bypass and continued until aortic declamping time.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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.

Increase infusion rate

Intervention Type OTHER

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 rate

Intervention Type OTHER

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

Norepinephrine

Infusion of norepinephrine (40 µg/ml) will be started following arterial cannulation before initiation of cardiopulmonary bypass and continued until aortic declamping time.

Group Type ACTIVE_COMPARATOR

Norepinephrine

Intervention Type DRUG

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 rate

Intervention Type OTHER

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 rate

Intervention Type OTHER

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

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

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

Intervention Type 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

Intervention Type OTHER

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Imam Abdulrahman Bin Faisal University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mohamed R El Tahan, MD

Role: STUDY_CHAIR

College of Medicine, Imam Abdulrahman Bin Faisal University

Locations

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Dammam University

Khobar, Eastern Province, Saudi Arabia

Site Status

Imam Abdulrahamn Bin Faisal University (Former, Dammam University)

Dammam, Esatern, Saudi Arabia

Site Status

Countries

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Saudi Arabia

References

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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.

Reference Type BACKGROUND
PMID: 28612323 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21092891 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29223724 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28777136 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28459983 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29889106 (View on PubMed)

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. No abstract available.

Reference Type BACKGROUND
PMID: 31899137 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31917073 (View on PubMed)

Other Identifiers

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Norcal-03-2020

Identifier Type: -

Identifier Source: org_study_id