More than 60,000 general anesthetics are performed daily in the U.S. — the majority of which require intravenous vasopressors to counteract general anesthesia-induced cardiovascular depression and hypotension. But while the choice between two drugs to treat intraoperative hypotension — norepinephrine and phenylephrine — is debated, few studies exist comparing them in the intraoperative setting.

A new University of Michigan study will assess current practice patterns and clinician attitudes in the use of norepinephrine and phenylephrine while laying the groundwork for a future clinical trial. Allison Janda, M.D., assistant professor, has received a National Institutes of Health K23 Mentored Patient-Oriented Research Career Development Award for the project from the National Heart, Lung, and Blood Institute.

“Over the past decade, the harmful effects of intraoperative hypotension — including myocardial injury, stroke, and acute kidney injury — have been repeatedly observed,” Janda said. “Given the common occurrence and serious consequences of intraoperative hypotension, there is an urgent need to determine the most appropriate choice for vasopressor therapy.”

Her research aims to:

• Assess variation in intraoperative vasopressor use through validated electronic health record data (EHR) provided through the Multicenter Perioperative Outcomes Group (MPOG); 
• Characterize anesthesiology clinician attitudes and opinions regarding intraoperative vasopressor selection using a multicenter mixed methods approach.; and
• Evaluate protocol adherence and feasibility of outcome ascertainment using pragmatic EHR data collection with a single-center pilot clinical trial. The pilot study would take place in eight operating rooms with similar surgical patients undergoing major surgery at Michigan Medicine with allocation of either phenylephrine or norepinephrine as the assigned first-line vasopressor over four, two-week crossover periods. 

The goal, Janda said, is to establish preliminary data and demonstrate feasibility for a large, multicenter, pragmatic trial. 

“There are widespread calls to increase the adoption of intraoperative norepinephrine as its effects confer a potential physiological advantage over phenylephrine in the treatment of general anesthesia-induced cardiovascular depression. Yet still, U.S. practice is dominated by phenylephrine use,” Janda said. 

“This line of investigation will test a promising candidate strategy for improving end-organ perfusion and mitigating end-organ injury.”

The K23 program provides support and protected time for early-career scientists to develop an intensive patient-oriented research experience. Through this study, Janda will gain experience in clinical informatics, mixed methods research techniques, and pragmatic clinical trial design and conduct. Her mentorship team includes:

Primary Mentors:

• Sachin Kheterpal, M.D., MBA, Kevin K Tremper Ph.D., M.D. Research Professor and professor of anesthesiology; executive director of outcomes research, Department of Anesthesiology; associate chair for strategy and technology, Medical School; associate dean for research information technology, Medical School; executive director, MPOG
• Daniel Clauw, M.D., professor of anesthesiology, internal medicine and psychiatry; executive director of pain & opioid research, Department of Anesthesiology; senior associate director, Michigan Institute for Clinical & Health Research (MICHR); director, Chronic Pain and Fatigue Research Center 

Co-mentors:

• Michael Fetters, M.D., MPH, M.A., professor of family medicine; director, Japanese Family Health Program, University of Michigan; co-founder and co-director, Mixed Methods Program (MMP), University of Michigan 
• Graciela Mentz, Ph.D., lead statistician, Department of Anesthesiology