Norepinephrine vs Phenylephrine During General Anesthesia
- Conditions
- AnesthesiaSurgeryHypotension
- Interventions
- Registration Number
- NCT04789330
- Lead Sponsor
- University of California, San Francisco
- Brief 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 2000
- age 18 Years and older
- Surgery under general anesthesia and requiring infusion of vasopressors to maintain the mean arterial pressure.
- Surgery duration>2 hours
- Cardiac surgery
- Patients on ECMO
- Organ transplantation
- Outpatient (come-and-go surgery)
- Obstetric procedures
- Patient already receiving NE or PE before induction of anesthesia
- Patients transferred immediately (i.e. within 24 hours) after surgery to another hospital.
- Patients with severe trauma
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Norepinephrine Norepinephrine Norepinephrine continuous infusion as the first line vasopressor Phenylephrine Phenylephrine Phenylephrine continuous infusion as the first line vasopressor
- Primary Outcome Measures
Name Time Method Percent of total cases with assigned vasopressor given Anesthesia time, up to 24 hours First line vasopressor administration will be measured as a percent of total eligible cases with assigned vasopressor given during anesthesia time, up to 24 hours
- Secondary Outcome Measures
Name Time Method Acute kidney injury (AKI) 7 days AKI using the Kidney Disease: Improving Global Outcomes (KDIGO) definition based on serum creatinine
Severe acute kidney injury 7 days Stage 2 or 3 AKI using the KDIGO definition based on serum creatinine or need for Renal Replacement Therapy (RRT)
Myocardial Injury after non-cardiac surgery (MINS) 7 days Number of patients with post-operative myocardial injury defined as a troponin elevation
Death 30 days Number of participants dying within 30 days after surgery
Hospital length of stay In-hospital, up to 30 days Days between date of surgery and hospital discharge
Adverse Cardio-renal events 7 days Number of patients meeting a combined endpoint of AKI and/or MINS
Rehospitalization within 30 days 30 days Patients discharge and readmitted for more than 24 hours within 30 days after surgery
Trial Locations
- Locations (5)
UCSF Medical Center at Parnassus
🇺🇸San Francisco, California, United States
UCSF Medical Center at Mission Bay
🇺🇸San Francisco, California, United States
Ronald Reagan UCLA Medical Center
🇺🇸Los Angeles, California, United States
Zuckerberg San Francisco General Hospital
🇺🇸San Francisco, California, United States
UCSF Medical Center at Mount Zion
🇺🇸San Francisco, California, United States