Evaluation of the Early Use of Norepinephrine in Major Abdominal Surgery on Postoperative Organ Dysfunction

NCT ID: NCT05276596

Last Updated: 2025-12-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 500 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-17
• Study Completion Date: 2025-11-29

Brief Summary

Hemodynamic instability is frequent during surgery and intraoperative hypotension is associated with excess morbidity and excess mortality in high-risk patients. In major abdominal surgery the incidence of intraoperative hypotension remains high.

For the past few years, some teams have proposed evaluating norepinephrine as a first-line drug in the presence of hypotension or even before hypotension occurs Thus in obstetrics, the preventive use of norepinephrine for cesareans performed under spinal anesthesia was associated with a reduction in the incidence of hypotension per operative without deleterious effect for the newborn or parturient. In the absence of any observed complications, several teams began to use noradrenaline prophylactically in other surgery. However, no study has demonstrated its benefit, particularly the term of surgical complication in abdominal surgery. The objective of this work is to assess the preventive use of norepinephrine in major abdominal surgery on the occurrence of intraoperative hypotension, postoperative organ dysfunction and postoperative medical and surgical complications.

Conditions

Norepinephrine; Hypotension; Anesthesiology; Major Abdominal Surgery

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Control group

The first anesthetic post-induction hypotension will be managed by intravenous injection of ephedrine (dilution: 3 mg / ml) at a dose of 6 mg (i.e. 2 ml). Any subsequent hypotension will be treated with ephedrine until injection of a total dose of 30 mg. Thereafter, if a new arterial hypotension occurs, we will pass to the administration of noradrenaline in intravenous injection using an electric syringe pump, at the dilution of 0.016 mg / ml, posology adapted to the objectives. blood pressure.

Group Type: ACTIVE_COMPARATOR

Ephedrine

Intervention Type: DRUG

The control group will be taken care of according to the protocols in force. The first anesthetic post-induction hypotension will be managed by intravenous injection of ephedrine (dilution: 3 mg / ml) at a dose of 6 mg (i.e. 2 ml). Any subsequent hypotension will be treated with ephedrine until injection of a total dose of 30 mg. Thereafter, if a new arterial hypotension occurs, we will pass to the administration of noradrenaline in intravenous injection using an electric syringe pump, at the dilution of 0.016 mg / ml, posology adapted to the objectives. blood pressure.

Test group

Immediately use of norepinephrine by intravenous injection using an electric syringe pump, at a dilution of 0.016 mg / ml, at the time of anesthetic induction and without waiting the 1st possible arterial hypotension. Noradrenaline will be started at a dose of 0.48 mg / h and then adapted according to the blood pressure objectives.

Group Type: EXPERIMENTAL

Norepinephrine

Intervention Type: DRUG

Immediately use of norepinephrine by intravenous injection using an electric syringe pump, at a dilution of 0.016 mg / ml, at the time of anesthetic induction and without waiting the 1st possible arterial hypotension. Noradrenaline will be started at a dose of 0.48 mg / h and then adapted according to the blood pressure objectives.

Interventions

Ephedrine

The control group will be taken care of according to the protocols in force. The first anesthetic post-induction hypotension will be managed by intravenous injection of ephedrine (dilution: 3 mg / ml) at a dose of 6 mg (i.e. 2 ml). Any subsequent hypotension will be treated with ephedrine until injection of a total dose of 30 mg. Thereafter, if a new arterial hypotension occurs, we will pass to the administration of noradrenaline in intravenous injection using an electric syringe pump, at the dilution of 0.016 mg / ml, posology adapted to the objectives. blood pressure.

Intervention Type: DRUG

Norepinephrine

Immediately use of norepinephrine by intravenous injection using an electric syringe pump, at a dilution of 0.016 mg / ml, at the time of anesthetic induction and without waiting the 1st possible arterial hypotension. Noradrenaline will be started at a dose of 0.48 mg / h and then adapted according to the blood pressure objectives.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients scheduled for major abdominal surgery (defined as surgery with a risk of cardiovascular complications of >1% and/or lasting more than 2 hours) with general anaesthesia.
• American Society of Anesthesiologists physical status (ASA-PS) score of ≥2.
• Age of ≥50 years and weighing more than 50 kg
• Written informed consent.

Exclusion Criteria

• Emergency surgery.
• Untreated or uncontrolled hypertension (systolic blood pressure of >150 mm Hg), despite medication.
• Any acute cardiovascular event, including acute or decompensated heart failure or acute coronary syndrome.
• Patients with chronic kidney disease with a glomerular filtration rate of <30 ml.min-1/1.73 m2 or requiring renal replacement therapy for end-stage renal disease.
• Patients with severe hepatic failure (ASAT/ALAT of >2N, elevated bilirubin level, PT of <50%).
• Preoperative sepsis, septic shock.
• Preoperative norepinephrine infusion.
• Patients eligible for a surgical procedure under locoregional anaesthesia.
• Pregnancy.
• Known allergy to study treatment.
• Patients unable to give informed consent for any reason.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire, Amiens

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

CHU Amiens

Amiens, , France

Countries

France

References

Trocheris-Fumery O, Scetbon C, Flet T, Meynier J, Sellier M, Rumbach M, Badaoui R, Villeret L, Tarpin P, Abou-Arab O, Bar S, Dupont H. Evaluation of the early use of norepinephrine in major abdominal surgery on medical and surgical postoperative complications: study protocol for a randomised controlled trial (EPON STUDY). BMJ Open. 2024 Apr 29;14(4):e083606. doi: 10.1136/bmjopen-2023-083606.

Reference Type: DERIVED

PMID: 38684243 (View on PubMed)

Other Identifiers

PI2021_843_0060

Identifier Type: -

Identifier Source: org_study_id