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

Phase 4

Recruiting

• Conditions: Cardiac Output, Low; Cardiac Output, High; Perfusion; Complications
• Interventions: Drug: Epinephrin; Drug: Norepinephrine; Drug: Phenylephrine

• Registration Number: NCT05492968
• Lead Sponsor: Medical University of Vienna

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.

Study Timeline

• Study First Submitted: 2022-07-28
• Study First Submitted QC: 2022-08-05
• Study First Posted: 2022-08-09
• Study Start: 2022-09-01
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-17
• Last Update Posted: 2022-10-19
• Primary Completion: 2024-08-01
• Study Completion: 2024-08-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 225

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Epinephrine Group	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 Group	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 Group	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.

Primary Outcome Measures

Name	Time	Method
Intraoperative cardiac output	Intraoperative	Time weighted average of intraoperative cardiac output

Secondary Outcome Measures

Name	Time	Method
Secondary Outcome 2: Intraoperative tissue regional oxygen saturation	Intraoperative	Time weighted average of intraoperative tissue regional oxygen saturation
Secondary Outcome 1: Intraoperative brain regional oxygen saturation	Intraoperative	Time weighted average of intraoperative brain regional oxygen saturation

Trial Locations

Locations (1)

Medical University of Vienna; 🇦🇹 Vienna, Austria