A breakthrough randomized controlled trial by Trocheris-Fumery et al. reveals that the early administration of norepinephrine during anesthesia induction significantly reduces postoperative complications in high-risk patients undergoing major abdominal surgery.

Background

Intraoperative hypotension, a common drop in blood pressure following the induction of anesthesia, has long been associated with adverse outcomes, including:

• Myocardial injury
• Acute kidney injury (AKI)
• Increased mortality risk
  

Despite this, standard vasopressor regimens vary, and evidence comparing strategies for preventing such hypotension is limited.

Study overview

A research team at Amiens Hospital University in France conducted the EPON trial (Early Use of Norepinephrine), a single-center, randomized controlled study, to evaluate whether prophylactic norepinephrine infusion could better prevent postinduction hypotension and its associated complications compared to standard treatment with reactive ephedrine boluses.

Key study details:

• Design: Prospective, randomized, open-label, single-center
  
• Patients: 500 adults aged >50 undergoing major abdominal surgery
  
• Groups:
  
  • Norepinephrine group: Prophylactic continuous infusion (0.48 mg/h)
    
  • Ephedrine group: Reactive boluses (3 mg each, max 30 mg)

How the intervention works

Core findings

Reduction in complications

• Primary endpoint: Medico-surgical complications within 30 days (Clavien–Dindo score ≥1)
  
  • Ephedrine group: 58%
    
  • Norepinephrine group: 44%
    
  • Relative risk (RR): 0.58 [0.40–0.83]; P = 0.004
    

Pulmonary benefits

• Postoperative pulmonary complications (PPCs) at 48 hours:
  
  • Ephedrine: 31%
    
  • Norepinephrine: 17%
    

Hemodynamic stability

• Hypotensive episodes occurred in:
  • 74% of ephedrine group
  • Only 15% of the norepinephrine group 
• Norepinephrine also resulted in:
  
  • Higher mean arterial pressure (MAP) post-induction
    
  • Lower intraoperative lactate levels (suggesting better organ perfusion)

How norepinephrine works

Norepinephrine is a potent α1- and β1-adrenergic agonist, leading to:

• Vasoconstriction (↑ blood pressure)
  
• Improved cardiac output
  
• Stable hemodynamics during anesthesia induction

Unlike ephedrine, it avoids tachyphylaxis (diminished effect with repeated use) and is increasingly considered for first-line vasopressor use in anesthesia.

Subgroup insights

Norepinephrine was especially effective in reducing complications among:

• ASA III patients 
• Men
• Patients without CKD 
• Patients undergoing digestive surgery 

Conclusion

Early, titrated norepinephrine infusion significantly reduces both hypotension and postoperative complications in high-risk patients undergoing major abdominal surgery. This proactive approach challenges conventional vasopressor strategies and may redefine intraoperative care in anesthesia.

Reference: Trocheris-Fumery O et al. Early Use of Norepinephrine in High-risk Patients Undergoing Major Abdominal Surgery: A Randomized Controlled Trial. Anesthesiology. 2025;143:1160-1170.

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