Optimizing anesthesia to prevent postoperative cognitive and functional decline in older adults

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ABSTRACT: Background: Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are the most common surgical complications in older adults and are associated with increased hospital length of stay, functional disability, mortality, and risk of Alzheimer’s. In the U.S., anesthesia is maintained with inhalational agents (GAS) in up to 90% of operations; however, maintenance with intravenous agents (IV) is an alternative technique with potential advantages. There is a significant gap in knowledge regarding whether IV vs. GAS can decrease the risk of deleterious postoperative outcomes in older surgical patients. This is a critical public health problem considering over half of older Americans will undergo surgery during their lives, and the surgical population is aging faster than the U.S. population. Considering both GAS and IV are readily available, effective, safe, and cost-effective, switching from one to the other would be a simple clinical practice change. Career Development Plan: The candidate is dedicated to an academic career in perioperative aging research and will focus on four objectives. (1) Training to become a clinical trialist and lead multidisciplinary teams conducting trials in older adults. Develop expertise in incorporating (2) geriatric medicine principles and (3) biomarker investigations into perioperative intervention trials in older adults. (4) Enhance leadership training to be an effective leader in geriatric anesthesiology research and effect change in clinical practice. Objectives will be met by formal coursework, meetings, seminars, mentoring, skills training, and experiential learning with a dedicated mentorship team in a supportive academic department and institution. Completion will enable the candidate to achieve the goal of becoming an independent physician-scientist and a leader in geriatric anesthesia research focused on preventing neurocognitive and functional decline in older surgical patients. Research Proposal: The specific aims are to determine the effects of IV vs. GAS on (1) incidence of POD and POCD in older adults; (2) incidence of postoperative functional decline and patient-reported outcomes (PROs) in older adults; and (3) levels of phosphorylated tau 181 (p-tau181) and other blood biomarkers in older adults. Hypotheses: There is a decreased incidence of POD, POCD, and functional decline following surgery and general anesthesia with IV vs. GAS. Next, compared to GAS, IV will improve PROs and decrease neuroinflammatory and Alzheimer’s blood-based biomarkers. Specifically, the postoperative increase in blood p-tau181 is greater in GAS than IV and is associated with POD and POCD. Approach: This single-center, 1:1 randomized, double-blind clinical trial will compare GAS vs. IV on POD, POCD, functional status, and PROs in men and women ≥ 75 years of age undergoing elective, inpatient, non-cardiac surgery. Results will provide evidence to aid the choice of general anesthetic (IV vs. GAS) to optimize outcomes in geriatric surgical patients. This aligns with the NIA’s strategic goal to develop effective interventions to maintain health, well-being, and function, and reduce the burden of age-related disorders and disabilities.