Delirium is a major challenge facing anesthesiologists and surgeons due to its prevalence, complex etiology, and potential severe impact on patients. Postoperative delirium is associated with longer hospital stays, poor functional outcomes, higher healthcare costs, and increased mortality. A related phenomenon, postoperative cognitive decline (POCD) is also common and associated with worse functioning after hospital discharge. There is recent, but limited evidence to suggest that anesthetic depth is associated with poor postoperative cognitive outcomes. Specifically, several studies suggest that deeper level of anesthesia is associated with increased incidence of postoperative delirium and longer-term cognitive decline. In fact, some suggest that older patients undergoing surgery should routinely be monitored with an anesthetic depth monitor to allow the titration of anesthetics or sedation medications to lighter levels to promote better postoperative cognitive outcomes. However, such a practice has never been validated or proven to be feasible or safe. In this grant proposal, we will undertake a randomized control trial in a cohort of older patients undergoing major spine surgery to receive either a light vs. deep level of anesthesia as determined by a processed electroencephalogram. We will use a validated battery of tests to measure cognitive function before and after surgery. Postoperative delirium will be measured using the Confusion Assessment Method. In contrast to most previous studies that were cross-sectional, we will perform preoperative and serial follow-up assessments to measure the trajectory of cognitive function, and 6-week outcomes. In this study, our aims include determining the feasibility and safety of randomizing patients undergoing major spine surgery to receive deep vs. light anesthetic levels during surgery. Specifically we aim to determine whether two different anesthetic depths as measured by an anesthetic depth monitor can be practiced uniformly by a number of anesthesia providers across a large group of older surgical patients. Second, we will determine an effect size for designing a future larger trial to determine whether anesthetic depth contributes to an increased incidence of adverse postoperative cognitive outcomes as measured by delirium or cognitive decline. Third, we will determine whether preoperative level of cognitive impairment moderates the effect of deep vs. light levels of anesthesia on incident delirium or POCD. Our proposed exploratory clinical trial will be the first to randomize patients undergoing general anesthesia to receive either light vs. deep levels of anesthesia with simultaneous measurements of postoperative delirium and cognitive status. Our study will determine not only the feasibility of anesthetizing patients using two different levels of anesthetc depth, but also the safety of such an approach. In addition to measuring postoperative delirium and POCD, we will also be monitoring possible adverse consequences of light anesthesia. Our study results will provide critically important information to improve perioperative care to the older patients undergoing major surgery.

Public Health Relevance

Delirium is a major concern facing older surgical patients due to its potential severe impact on patients' long- term outcomes. Recent limited evidence suggests that anesthetic depth may influence postoperative cognitive outcomes. We propose an exploratory clinical trial to randomizing patients into receiving light vs. deep anesthesia to determine the feasibility and safety of such an approach, and to inform the effect size for a future larger trial.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Exploratory/Developmental Grants (R21)
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Surgery, Anesthesiology and Trauma Study Section (SAT)
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Wagster, Molly V
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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MacKenzie, Kristen K; Britt-Spells, Angelitta M; Sands, Laura P et al. (2018) Processed Electroencephalogram Monitoring and Postoperative Delirium: A Systematic Review and Meta-analysis. Anesthesiology 129:417-427
Muhlhofer, W G; Zak, R; Kamal, T et al. (2017) Burst-suppression ratio underestimates absolute duration of electroencephalogram suppression compared with visual analysis of intraoperative electroencephalogram. Br J Anaesth 118:755-761
Leung, Jacqueline M; Sands, Laura P; Chen, Ningning et al. (2017) Perioperative Gabapentin Does Not Reduce Postoperative Delirium in Older Surgical Patients: A Randomized Clinical Trial. Anesthesiology 127:633-644
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Vacas, Susana; McInrue, Erin; Gropper, Michael A et al. (2016) The Feasibility and Utility of Continuous Sleep Monitoring in Critically Ill Patients Using a Portable Electroencephalography Monitor. Anesth Analg 123:206-12
American Geriatrics Society Expert Panel on Postoperative Delirium in Older Adults (2015) American Geriatrics Society abstracted clinical practice guideline for postoperative delirium in older adults. J Am Geriatr Soc 63:142-50