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

NCT05276596 | Completed Phase 3

• 1 other identifier: PI2021_843_0060
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 1

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

Keywords

norepinephrine; ephedrine; Hypotension; anesthesiology; major abdominal surgery; Clavien Dindo score

Outcome Measures

Primary Outcomes (1)

• Variation of the of the Clavien Dindo surgical score between both groups

  The Clavien-Dindo Classification The therapy used to correct a specific complication is the basis of this classification in order to rank a complication in an objective and reproducible manner. It consists of 7 grades (I, II, IIIa, IIIb, IVa, IVb and V). The introduction of the subclasses a and b allows a contraction of the classification into 5 grades (I, II, III, IV and V) depending on the size of the population observed or the of the focus of a study. Complications that have the potential for long-lasting disability after patient's discharge (e.g.: paralysis of a voice cord after thyroid surgery) are highlighted in the present classification by a suffix ("d" for disability). This suffix indicates that a follow-up is required to comprehensively evaluate the outcome and related long-term quality of life

  one month

Secondary Outcomes (48)

• Variation of duration of hospital stay in days between both groups

  one month

• Length of intensive care unit stay

  1 month

• length of postoperative care unit stay

  1 month

• Postoperative renal function

  at 48 hours

• number of persistent circulatory shock

  at 48 hours

Study Arms (2)

Control group

ACTIVE COMPARATOR

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.

Drug: Ephedrine

Test group

EXPERIMENTAL

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.

Drug: Norepinephrine

Interventions

Ephedrine 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.

Control group

Norepinephrine 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.

Test group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centre Hospitalier Universitaire, Amiens: lead

Study Sites (1)

CHU Amiens

Amiens, 80480, France

Location

Related Publications (1)

• 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.

  PMID: 38684243 DERIVED

MeSH Terms

Conditions

Hypotension

Interventions

Ephedrine; Norepinephrine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Phenethylamines; Ethylamines; Ethanolamines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2022
• First Posted: March 11, 2022
• Study Start: November 17, 2021
• Primary Completion: December 17, 2024
• Study Completion: November 29, 2025
• Last Updated: December 3, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)