Clinical trial NCT05492968: The Effect of Epinephrine, Norepinephrine and Phenylephrine on Intraoperative Hemodynamic Performance
Official title: The Effect of Epinephrine, Norepinephrine and Phenylephrine on Intraoperative Hemodynamic Performance - a Prospective Double-blinded Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Cardiac Output, Low
Cardiac Output, High
Perfusion; Complications
Keywords: Norepinephrine
Epinephrine
Phenylephrine
Major abdominal surgery
Intraoperative Cardiac Output
Intraoperative Hemodynamic
Intraoperative Perfusion
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
Collaborators: name: Medical University of Graz
First posted: 2022-08-09
Enrollment: 225
Sex: ALL
Minimum age (years): 45
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Intraoperative cardiac output
timeFrame: Intraoperative
Secondary outcomes:
measure: Secondary Outcome 1: Intraoperative brain regional oxygen saturation
timeFrame: Intraoperative
measure: Secondary Outcome 2: Intraoperative tissue regional oxygen saturation
timeFrame: Intraoperative
Other outcomes:
measure: Tertiary Outcome 1: NT-proBNP
timeFrame: Within the first three postoperative days
measure: Tertiary Outcome 2: Troponin T
timeFrame: Within the first three postoperative days
measure: Tertiary Outcome 3: Copeptin
timeFrame: Within the first three postoperative days
measure: Exploratory Outcome 1:
timeFrame: Within the first three postoperative days
measure: Exploratory Outcome 2:
timeFrame: Through study completion, on average 7 days
measure: Exploratory Outcome 3:
timeFrame: During hospitalization, on average 7 days
measure: Exploratory Outcome 4:
timeFrame: During hospitalization, on average 7 days
measure: Exploratory Outcome 5:
timeFrame: During hospitalization, on average 7 days
measure: Exploratory Outcome 6:
timeFrame: During hospitalization, on average 7 days
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna
Study officials:
References: