Norepinephrine Infusion During Cardiopulmonary Bypass

NCT04312971 | Completed DMC

• 1 other identifier: Norcal-03-2020
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 2

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.

Conditions

Cardiac Surgery; Cardiopulmonary Bypass

Outcome Measures

Primary Outcomes (1)

• Changes in lactic acid level

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

  For 24 hours after surgery from the start of surgery

Secondary Outcomes (43)

• 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

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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; Other: Increase infusion rate; Other: Decrease infusion rate

Norepinephrine

ACTIVE COMPARATOR

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; Other: Increase infusion rate; Other: Decrease infusion rate

Interventions

Placebo 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.

Placebo

Norepinephrine 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.

Norepinephrine

Increase infusion rate 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

Norepinephrine; Placebo

Decrease infusion rate 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; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Imam Abdulrahman Bin Faisal University: lead

Study Sites (2)

Dammam University

Khobar, Eastern Province, 31952, Saudi Arabia

Location

Imam Abdulrahamn Bin Faisal University (Former, Dammam University)

Dammam, Esatern, 31952, Saudi Arabia

Location

Related Publications (8)

• 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.

  PMID: 28612323 BACKGROUND

• 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.

  PMID: 21092891 BACKGROUND

• 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.

  PMID: 29223724 BACKGROUND

• 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.

  PMID: 28777136 BACKGROUND

• 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.

  PMID: 28459983 BACKGROUND

• 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.

  PMID: 29889106 BACKGROUND

• 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.

  PMID: 31899137 BACKGROUND

• 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.

  PMID: 31917073 BACKGROUND

MeSH Terms

Interventions

Norepinephrine

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Mohamed R El Tahan, MD

  College of Medicine, Imam Abdulrahman Bin Faisal University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 15, 2020
• First Posted: March 18, 2020
• Study Start: May 6, 2020
• Primary Completion: April 10, 2021
• Study Completion: September 20, 2021
• Last Updated: December 10, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: After completion of the study
• Access Criteria: Permission for access to the database will be removed for all investigators, and the database will be archived.

Locations

SA (2)