Norepinephrine vs Phenylephrine During General Anesthesia
Condition: Anesthesia; Surgery; Hypotension
MeSH terms: Hypotension
Study type: Interventional
Phase: Phase 4

Summary: 
      50 million patients undergo surgery each year in the United States. Postoperative mortality
      is considered the third leading cause of death worldwide. Hypotension during surgery have
      been linked to increased postoperative morbidity and mortality. Episodes of hypotension
      during surgery are associated with an increased risk of acute kidney injury, stroke, cardiac
      events and death. Treating or preventing hypotension during general anesthesia and major
      surgery was found to improve outcomes. At this time, it is unclear what is the best
      vasopressor to maintain blood pressure during surgery under general anesthesia. With this
      pilot pragmatic trial, the investigators will explore the impact of norepinephrine (NE) or
      phenylephrine (PE) on post-operative events in patients undergoing major surgery with general
      anesthesia and needing vasopressors infusion to maintain their systemic arterial pressure.
    

Detailed description: 
      Postoperative mortality is considered the third leading cause of death worldwide. Hemodynamic
      instability and specifically hypotension during surgery have been linked to increased
      postoperative morbidity and mortality. Episodes of hypotension during surgery are associated
      with an increased risk of acute kidney injury, stroke, cardiac events and death. Treating or
      preventing hypotension during general anesthesia and major surgery was found to improve
      outcomes. At this time, it is unclear what is the best vasopressor to maintain blood pressure
      during surgery.

      Hypotension during anesthesia and surgery is commonly treated with vasopressors such as
      phenylephrine (PE), a synthetic pure vasoconstrictor, or norepinephrine (NE), which has both
      inotropic and vasoconstrictor activity. NE increases cardiac output and increases
      cardio-vascular coupling due to alpha-agonist effects compared to PE, a purely
      vasoconstrictive agent.

      The investigators hypothesize that norepinephrine will be superior to phenylephrine. The
      effect size is expected to be modest, therefore requiring a large sample size, and will vary
      between subgroups determined by patients' individual characteristics.

      This pilot trial (VEGA-1) will allow to 1) test the feasibility of the study using a
      cross-over cluster randomized controlled trial and 2) estimate the effect size of the use of
      NE or PE on post-operative outcome in the overall population but also investigate the
      Heterogeneity in Treatment Effect (HTE) of the drugs among subgroups or clusters of patients
      for designing a larger trial.

      Design: pragmatic, cluster-randomized, open-labeled, multiple-crossover trial across hospital
      from University of California, San Francisco (UCSF) and University of California, Los Angeles
      (UCLA). Centers will be assigned to use either PE or NE for the first-line intravenous
      infusion of vasopressor in the OR. Data will be collected in routine clinical care and
      automatically extracted from the electronic health record (EHR).

      Primary endpoint:

      - Separation between study groups in the first line vasopressor administration (% of cases
      with appropriate vasopressor with respect to group attribution).

      Secondary endpoints:

        -  Death within 30 days

        -  Acute kidney injury defined by the KDIGO definition

        -  Severe acute kidney injury (stage 2 or 3 of the KDIGO definition)

        -  Myocardial Injury following non-cardiac surgery (MINS)

        -  Adverse cardio-renal events

        -  Hospital length of stay

        -  Rehospitalization within 30 days
    

Intervention name(s): Norepinephrine; Phenylephrine
Intervention type(s): Drug; Drug
Intervention description(s): Norepinephrine administered during anesthesia; Phenylephrine administered during anesthesia
Intervention MeSH terms: Phenylephrine; Oxymetazoline; Norepinephrine
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: pragmatic, cluster-randomized, open-labeled, multiple-crossover trial
Masking: Single (Outcomes Assessor)
Primary purpose: Supportive Care
Keywords: vasopressor; outcome; AKI; cardiovascular; complications