Norepinephrine versus phenylephrine for treating hypotension during general anaesthesia in adult patients undergoing major noncardiac surgery: a multicentre, open-label, cluster-randomised, crossover, feasibility, and pilot trial

Matthieu Legrand; Rishi Kothari; Nicholas Fong; Nandini Palaniappa; David Boldt; Lee-Lynn Chen; Philip Kurien; Eilon Gabel; Jillene Sturgess-DaPrato; Michael O Harhay; Romain Pirracchio; Michael P Bokoch; VEGA-1 trial investigators

doi:10.1016/j.bja.2023.02.004

Norepinephrine versus phenylephrine for treating hypotension during general anaesthesia in adult patients undergoing major noncardiac surgery: a multicentre, open-label, cluster-randomised, crossover, feasibility, and pilot trial

Br J Anaesth. 2023 May;130(5):519-527. doi: 10.1016/j.bja.2023.02.004. Epub 2023 Mar 14.

Affiliations

¹ Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA, USA; INI-CRCT Network, Nancy, France. Electronic address: Matthieu.Legrand@ucsf.edu.
² Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA, USA; Department of Anesthesiology and Perioperative Medicine, Thomas Jefferson University, Philadelphia, PA, USA.
³ Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA, USA; School of Medicine, University of California, San Francisco, CA, USA.
⁴ Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA, USA.
⁵ Department of Anesthesia and Perioperative Care, University of California, Los Angeles, USA.
⁶ Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

PMID: 36925330
DOI: 10.1016/j.bja.2023.02.004

Abstract

Background: Intraoperative hypotension is associated with postoperative complications. The use of vasopressors is often required to correct hypotension but the best vasopressor is unknown.

Methods: A multicentre, cluster-randomised, crossover, feasibility and pilot trial was conducted across five hospitals in California. Phenylephrine (PE) vs norepinephrine (NE) infusion as the first-line vasopressor in patients under general anaesthesia alternated monthly at each hospital for 6 months. The primary endpoint was first-line vasopressor administration compliance of 80% or higher. Secondary endpoints were acute kidney injury (AKI), 30-day mortality, myocardial injury after noncardiac surgery (MINS), hospital length of stay, and rehospitalisation within 30 days.

Results: A total of 3626 patients were enrolled over 6 months; 1809 patients were randomised in the NE group, 1817 in the PE group. Overall, 88.2% received the assigned first-line vasopressor. No drug infiltrations requiring treatment were reported in either group. Patients were median 63 yr old, 50% female, and 58% white. Randomisation in the NE group vs PE group did not reduce readmission within 30 days (adjusted odds ratio=0.92; 95% confidence interval, 0.6-1.39), 30-day mortality (1.01; 0.48-2.09), AKI (1.1; 0.92-1.31), or MINS (1.63; 0.84-3.16).

Conclusions: A large and diverse population undergoing major surgery under general anaesthesia was successfully enrolled and randomised to receive NE or PE infusion. This pilot and feasibility trial was not powered for adverse postoperative outcomes and a follow-up multicentre effectiveness trial is planned.

Clinical trial registration: NCT04789330 (ClinicalTrials.gov).

Keywords: acute kidney injury; cluster-randomised crossover trial; intraoperative hypotension; noncardiac surgery; norepinephrine; phenylephrine; postoperative outcomes; vasopressor.

Publication types

Randomized Controlled Trial
Multicenter Study

MeSH terms

Acute Kidney Injury*
Adult
Anesthesia, General / adverse effects
Feasibility Studies
Female
Humans
Hypotension* / drug therapy
Hypotension* / etiology
Male
Norepinephrine / therapeutic use
Phenylephrine
Pilot Projects
Treatment Outcome
Vasoconstrictor Agents / therapeutic use

Substances

Phenylephrine
Norepinephrine
Vasoconstrictor Agents

Associated data

ClinicalTrials.gov/NCT04789330