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

Cardiac Output, Low Clinical Trial

— RACE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05492968
• Other study ID #: RACE_01
• Status: Recruiting
• Phase: Phase 4
• Start date: September 1, 2022
• Est. completion date: August 31, 2024

Study information

• Verified date: October 2022
• Source: Medical University of Vienna
• Contact: Christian Reiterer, MD
• Phone: 0043 1 40400
• Email: christian.reiterer[@]meduniwien.ac.at
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 225
• Est. completion date: August 31, 2024
• Est. primary completion date: August 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
Austria	Medical University of Vienna	Vienna

Sponsors (2)

Lead Sponsor	Collaborator
Medical University of Vienna	Medical University of Graz

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Tertiary Outcome 1: NT-proBNP	Maximum concentration of NT-proBNP in the first three postoperative days	Within the first three postoperative days
Other	Tertiary Outcome 2: Troponin T	Maximum concentration of Troponin T in the first three postoperative days	Within the first three postoperative days
Other	Tertiary Outcome 3: Copeptin	Maximum concentration of Copeptin in the first three postoperative days	Within the first three postoperative days
Other	Exploratory Outcome 1:	Incidence of MINS	Within the first three postoperative days
Other	Exploratory Outcome 2:	Incidence of atrial fibrillation	Through study completion, on average 7 days
Other	Exploratory Outcome 3:	Incidence of acute kidney injury	During hospitalization, on average 7 days
Other	Exploratory Outcome 4:	Incidence of myocardial infarction	During hospitalization, on average 7 days
Other	Exploratory Outcome 5:	Incidence of stroke	During hospitalization, on average 7 days
Other	Exploratory Outcome 6:	Incidence of wound related complications	During hospitalization, on average 7 days
Primary	Intraoperative cardiac output	Time weighted average of intraoperative cardiac output	Intraoperative
Secondary	Secondary Outcome 1: Intraoperative brain regional oxygen saturation	Time weighted average of intraoperative brain regional oxygen saturation	Intraoperative
Secondary	Secondary Outcome 2: Intraoperative tissue regional oxygen saturation	Time weighted average of intraoperative tissue regional oxygen saturation	Intraoperative