The Effect of Epinephrine, Norepinephrine and Phenylephrine on Intraoperative Hemodynamic Performance (RACE)

The Effect of Epinephrine, Norepinephrine and Phenylephrine on Intraoperative Hemodynamic Performance - a Prospective Double-blinded Randomized Clinical Trial

The use of catecholamines for blood pressure and hemodynamic management is essential during undergoing surgery. The type of the catecholamine with the most clinical meaningful effect is still unknown. Therefore, the investigators evaluate the effect of intraoperative continuous infusion of epinephrine, norepinephrine and phenylephrine on intraoperative cardiac output. The investigators further evaluate the effect of epinephrine, norepinephrine and phenylephrine on regional brain and regional tissue oxygenation during surgery.

Study Overview

• Status: Recruiting
• Conditions: Perfusion; Complications; Cardiac Output, Low; Cardiac Output, High
• Intervention / Treatment: Drug: Epinephrin; Drug: Norepinephrine; Drug: Phenylephrine

Detailed Description

Background: The use of catecholamines for blood pressure and hemodynamic management is essential during undergoing surgery. The type of the catecholamine with the most clinical meaningful effect is still unknown. Therefore, the investigators evaluate the effect of intraoperative continuous infusion of epinephrine, norepinephrine and phenylephrine on intraoperative cardiac output. The investigators further evaluate the effect of epinephrine, norepinephrine and phenylephrine on regional brain and regional tissue oxygenation during surgery.

Methods: The study will include 225 patients ≥ 45 years of age undergoing moderate- to high-risk major open abdominal surgery lasting at least two hours in this prospective double-blinded randomized clinical trial. Patients will be randomly assigned to receive a continuous infusion of epinephrine, norepinephrine or phenylephrine for intraoperative blood pressure management. The primary outcome will be time weighted average (TWA) of cardiac output between continuous infusion of epinephrine, norepinephrine or phenylephrine. The secondary outcomes will be time weighted average of intraoperative brain regional oxygen saturation (brSO2) and tissue regional oxygen saturation (trSO2) between the groups.

Statistics: For the primary outcome, TWA of intraoperative cardiac output between the groups will be analyzed using an ANOVA. The primary outcome, TWA of intraoperative brSO2 and TWA of intraoperative trSO2 will be analysed using an ANOVA.

Level of originality: Data regarding the hemodynamic effects of commonly used intraoperative vasopressors on cardiac output are limited. In detail, effects of different types of catecholamines on hemodynamic parameters and subsequently tissue perfusion in the operative setting are lacking. This study will give further information of the different hemodynamic effects of the most used clinical used catecholamines which are used for intraoperative blood pressure management.

• Study Type: Interventional
• Enrollment (Anticipated): 225
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Christian Reiterer, MD; Phone Number: 20760 0043 1 40400; Email: christian.reiterer@meduniwien.ac.at
• Study Contact Backup: Name: Alexander Taschner, MD; Phone Number: 20760 004340400; Email: alexander.taschner@meduniwien.ac.at

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • Medical University of Vienna
    • Contact: Christian Reiterer, MD; Phone Number: 20760 004340400; Email: christian.reiterer@meduniwien.ac.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 43 years to 88 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ≥ 45 years old
• Scheduled for moderate- to high-risk major open abdominal surgery expected to last at least two hours
• ASA physical status ≥ 2

• At least one of the following risk factors:

  1. Age ≥75years
  2. History of peripheral arterial disease
  3. History of coronary artery disease
  4. History of stroke or transient ischemic attack/Stroke
  5. History of chronic kidney disease
  6. Diabetes requiring medical treatment
  7. Current smoking or history of 15 pack-years
  8. History of heart failure
  9. Preoperative high-sensitivity Troponin T ≥14ng.L-1
  10. Preoperative NT-proBNP ≥200 pg.mL-1

Exclusion Criteria:

1. Scheduled for pheochromocytoma surgery
2. Scheduled for liver and kidney transplantation
3. Requiring preoperative intravenous vasopressor medications
4. Contraindications to epinephrine, norepinephrine or phenylephrine per clinical judgement
5. Permanent atrial fibrillation
6. Preoperative heart rate >110 bpm

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Epinephrine Group; Patients in the epinephrine group will receive a continuous infusion containing epinephrine with a concentration of 0.02mg/ml for intraoperative blood pressure management. The infusion will be started with 0.15mL/kg/h and will be titrated to receive a mean arterial pressure of at least 75mmHg.	Drug: Epinephrin; Patients in the epinephrine group will receive a continuous infusion containing epinephrine with a concentration of 0.02mg/ml for intraoperative blood pressure management. The infusion will be started with 0.15mL/kg/h and will be titrated to receive a mean arterial pressure of at least 75mmHg.
Active Comparator: Norepinephrine Group; Patients in the norepinephrine group will receive a continuous infusion containing norepinephrine with a concentration of 0.02mg/ml for intraoperative blood pressure management. The infusion will be started with 0.15mL/kg/h and will be titrated to receive a mean arterial pressure of at least 75mmHg.	Drug: Norepinephrine; Patients in the norepinephrine group will receive a continuous infusion containing norepinephrine with a concentration of 0.02mg/ml for intraoperative blood pressure management. The infusion will be started with 0.15mL/kg/h and will be titrated to receive a mean arterial pressure of at least 75mmHg.
Active Comparator: Phenylephrine Group; Patients in the phenylephrine group will receive a continuous infusion containing phenylephrine with a concentration of 0.2mg/ml for intraoperative blood pressure management. The infusion will be started with 0.15mL/kg/h and will be titrated to receive a mean arterial pressure of at least 75mmHg.	Drug: Phenylephrine; Patients in the phenylephrine group will receive a continuous infusion containing phenylephrine with a concentration of 0.2mg/ml for intraoperative blood pressure management. The infusion will be started with 0.15mL/kg/h and will be titrated to receive a mean arterial pressure of at least 75mmHg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraoperative cardiac output	Time weighted average of intraoperative cardiac output	Intraoperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Outcome 1: Intraoperative brain regional oxygen saturation	Time weighted average of intraoperative brain regional oxygen saturation	Intraoperative
Secondary Outcome 2: Intraoperative tissue regional oxygen saturation	Time weighted average of intraoperative tissue regional oxygen saturation	Intraoperative

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tertiary Outcome 1: NT-proBNP	Maximum concentration of NT-proBNP in the first three postoperative days	Within the first three postoperative days
Tertiary Outcome 2: Troponin T	Maximum concentration of Troponin T in the first three postoperative days	Within the first three postoperative days
Tertiary Outcome 3: Copeptin	Maximum concentration of Copeptin in the first three postoperative days	Within the first three postoperative days
Exploratory Outcome 1:	Incidence of MINS	Within the first three postoperative days
Exploratory Outcome 2:	Incidence of atrial fibrillation	Through study completion, on average 7 days
Exploratory Outcome 3:	Incidence of acute kidney injury	During hospitalization, on average 7 days
Exploratory Outcome 4:	Incidence of myocardial infarction	During hospitalization, on average 7 days
Exploratory Outcome 5:	Incidence of stroke	During hospitalization, on average 7 days
Exploratory Outcome 6:	Incidence of wound related complications	During hospitalization, on average 7 days

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Collaborators: Medical University of Graz

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2022
• Primary Completion (Anticipated): August 1, 2024
• Study Completion (Anticipated): August 31, 2024

Study Registration Dates

• First Submitted: July 28, 2022
• First Submitted That Met QC Criteria: August 5, 2022
• First Posted (Actual): August 9, 2022

Study Record Updates

• Last Update Posted (Actual): October 19, 2022
• Last Update Submitted That Met QC Criteria: October 17, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Major abdominal surgery; Norepinephrine; Epinephrine; Phenylephrine; Intraoperative Cardiac Output; Intraoperative Hemodynamic; Intraoperative Perfusion
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Cardiac Output, Low; Cardiac Output, High; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-Agonists; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Nasal Decongestants; Adrenergic alpha-1 Receptor Agonists; Norepinephrine; Epinephrine; Phenylephrine; Oxymetazoline
• Other Study ID Numbers: RACE_01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No