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

NCT ID: NCT05492968

Last Updated: 2022-10-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 225 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-01
• Study Completion Date: 2024-08-31

Brief Summary

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.

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.

Conditions

Cardiac Output, Low; Cardiac Output, High; Perfusion; Complications

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Epinephrin

Intervention Type: DRUG

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.

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.

Group Type: ACTIVE_COMPARATOR

Norepinephrine

Intervention Type: DRUG

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.

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.

Group Type: ACTIVE_COMPARATOR

Phenylephrine

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical University of Graz

OTHER

Sponsor Role: collaborator

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Christian Reiterer

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Medical University of Vienna

Vienna, , Austria

Site Status: RECRUITING

Countries

Austria

Central Contacts

Christian Reiterer, MD

Role: CONTACT

christian.reiterer@meduniwien.ac.at

0043 1 40400 ext. 20760

Alexander Taschner, MD

Role: CONTACT

alexander.taschner@meduniwien.ac.at

004340400 ext. 20760

Facility Contacts

Christian Reiterer, MD

Role: primary

christian.reiterer@meduniwien.ac.at

004340400 ext. 20760

Other Identifiers

RACE_01

Identifier Type: -

Identifier Source: org_study_id