Delirium is a major challenge facing geriatric practice due to its prevalence, complex etiology, and potential severe impact on patients. Postoperative delirium is associated with longer hospital stays, poor functional outcomes, and higher healthcare costs. A milder form of acute cognitive change known as postoperative cognitive decline (POCD) is associated with long term declines in daily functioning. Despite the prevalence and clinical importance of postoperative delirium and POCD, a preventive therapy has not been identified. Patients'risk for the development of geriatric syndromes (such as delirium or POCD) is determined by predisposing baseline vulnerabilities and exposure to factors that precipitate poor patient outcomes (such as pain or new medications associated with surgery). In this proposal, we will use a strategy recognizing that baseline vulnerabilities increase geriatric patients risk for poor postoperative cognitive outcomes in conjunction with a disease-oriented focus to minimize the precipitating factors of postoperative delirium and POCD. This strategy is guided by our previous findings demonstrating that postoperative delirium is strongly related to the severity of pain, and probably to the central nervous system effects of opioid analgesics, the usual therapy for postoperative pain. In our framework, the presence of risks for delirium such as advanced age, cognitive impairment, depression, and preoperative medical burden make patients more vulnerable to experiencing adverse effects from the precipitating events of pain and postoperative opioids. The goal of this research is to determine whether an intervention aimed at reducing factors known to precipitate delirium and POCD leads to improvement in postoperative cognitive outcomes in the vulnerable geriatric patients. Based on our pilot study, we found a promising intervention involving the use of an adjunctive non-opioid therapy to reduce postoperative pain and the consumption of opioids, which ultimately resulted in a reduction of the incidence of postoperative delirium. We will conduct a double blind, placebo-controlled study using gabapentin, as an add-on agent in the treatment of postoperative pain in elderly patients undergoing non-cardiac surgery. Our proposed study will test the hypothesis that rates of delirium and POCD can be reduced in those who are vulnerable to experiencing these outcomes through intensive pain management after surgery. Our hypothesis if proven true will contribute not only to a better understanding of the precipitating factors of delirium and POCD and their interactions with baseline vulnerabilities, but will also provide new directions for management of the older surgical patients, hopefully leading to improved functional outcomes and quality of life. Our proposal meets with the major mission of the National Institute of Aging to reduce the burdens of illness and disability in the elderly.

Public Health Relevance

Our proposal aims to investigate the precipitating factors of delirium and POCD and their interactions with baseline vulnerabilities, in order to provide new directions for management of the older surgical patients. Our results will hopefully lead to improved functional outcomes and quality of life of these patients. Our proposal meets with the major mission of the National Institute of Aging to reduce the burden of illness and disability in the elderly.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
Project #
Application #
Study Section
Aging Systems and Geriatrics Study Section (ASG)
Program Officer
Wagster, Molly V
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Francisco
Schools of Medicine
San Francisco
United States
Zip Code
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
Hirsch, Jan; Vacas, Susana; Terrando, Niccolo et al. (2016) Perioperative cerebrospinal fluid and plasma inflammatory markers after orthopedic surgery. J Neuroinflammation 13:211
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
Hirsch, J; DePalma, G; Tsai, T T et al. (2015) Impact of intraoperative hypotension and blood pressure fluctuations on early postoperative delirium after non-cardiac surgery. Br J Anaesth 115:418-26
Wesselink, E M; Kappen, T H; van Klei, W A et al. (2015) Intraoperative hypotension and delirium after on-pump cardiac surgery. Br J Anaesth 115:427-33
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
Shim, Jewel; DePalma, Glen; Sands, Laura P et al. (2015) Prognostic Significance of Postoperative Subsyndromal Delirium. Psychosomatics 56:644-51
Long, Lawrence S; Wolpaw, Jed T; Leung, Jacqueline M (2015) Sensitivity and specificity of the animal fluency test for predicting postoperative delirium. Can J Anaesth 62:603-8
Leung, Jacqueline M; Sands, Laura P; Newman, Stacey et al. (2015) Preoperative Sleep Disruption and Postoperative Delirium. J Clin Sleep Med 11:907-13
Youngblom, Emily; DePalma, Glen; Sands, Laura et al. (2014) The temporal relationship between early postoperative delirium and postoperative cognitive dysfunction in older patients: a prospective cohort study. Can J Anaesth 61:1084-92

Showing the most recent 10 out of 22 publications