The Icahn School of Medicine at Mount Sinai NY, NY The Geriatric Surgical Patient: anesthetic technique, stress response, and postoperative cognition Stacie Deiner M.D. Assistant Professor of Anesthesiology, Geriatrics and Palliative Care, and Neurosurgery The Icahn School of Medicine at Mount Sinai NY, NY

GEMSSTAR Project Arose from my experience with the Dexlirium Project Found a low incidence of delirium in our population But many patients received Total IntraVenous Anesthesia (TIVA) NOT gas TIVA responsible for our findings? If so, what would be the mechanism?

TIVA Suppresses the stress response Increased stress response with worse cognitive outcomes in stressed geriatric rats (Chapman TR et al J Neurosci 2010) Caveats Delirium and Postoperative Cognitive Dysfunction (POCD) are not the same People are not animals Older patients are not the general population

Human Alzheimer and Inflammation Biomarkers after Anesthesia and Surgery. Tang, Junxia; Baranov, Dimitry; Hammond, Mary; Shaw, Leslie; Eckenhoff, Maryellen; Eckenhoff, Roderic Anesthesiology 2011. Some may speculate that the anesthetic drug itself is responsible for the stress or cytotoxicity underlying the biomarkers, but similar changes observed with different anesthetic approaches render this somewhat less likely. It is perhaps more likely to be caused by the surgery-induced inflammatory cascade, for which we provide ample biochemical evidence, as has been observed in brain tissue from wild-type mice undergoing hepatectomy. © 2011 American Society of Anesthesiologists, Inc. Published by American Society of Anesthesiologists, Inc. 2

Liu et al propofol v. sevoflurane v. epidural v. control 2 years after anesthesia, AD cases same between the groups. progressive MCI was greater in the sevoflurane group than in the control group. Inhaled Sevoflurane May Promote Progression of Amnestic Mild Cognitive Impairment: A Prospective, Randomized Parallel-Group Study. Liu Y, Pan N, Ma Y, Zhang S, Guo W, Li H, Zhou J, Liu G, Gao M. Am J Med Sci. 2013 Jan 2. Liu, Y et al Am J Med Sci 2013

Specific Aims Compare the stress response by measuring serum norepinephrine (NE) and cortisol in GS vs. TIVA groups Hypothesis: TIVA will be associated with a lesser stress response Determine the incidence of delirium and POCD in patients who receive GS vs. TIVA Hypothesis: TIVA will be associated with a lower incidence of delirium.

Study design Study design: Prospective cohort study (not randomized) Subjects: >68 years old for major elective noncardiac surgery. Identified by the computerized scheduling system at Mount Sinai Hospital Outcomes: Delirium, POCD, postoperative complications Measured at screen, 3 and 6 months. Predictors: Primary: anesthetics technique (GS vs. TIVA), Secondary: serum norepinephrine, cortisol

GEMSSTAR: Gas vs. TIVA Similarities: gender, diabetes, CVA, CAD, Renal disease Differences: Age 76.3 vs. 73.5 p=.021 ASA status: Gas group III> TIVA p=.021 Much higher peak norepinephrine (341 vs. 136 vs. pg/ml) p<.001 and cortisol (31.8 vs. 4.8 mcg/dl) p <.001 Pick out most important

Delirium Delirium in the recovery room 3.3% of Gas group 8.1% of TIVA group p=.622 Postoperative Delirium (days 1-3) 22.2% of Gas group 15% of TIVA group p= .556

Modeling causes of Delirium All variables with univariate association <.2 Baseline MMSE Recovery room delirium Diabetes ASA gender peak norepinephrine levels surgical duration Plus variables with clinical relevance: e.g.age

Model to Predict Delirium Including Diabetes, Serum Peak Norepinephrine, and Surgical Duration

The Plan Completed recruitment goal:76 patients Complete cognitive assessment at 3 and 6 months Analysis of blood samples for ApoE genotype Include Apo E genotype in the model Examine immediate stress response and long term cognition

Next research questions The role of DM in delirium Blood brain barrier dysfunction Interaction with stress response Microvascular disease The relationship between short term cognitive disturbance and long term cognitive outcomes Add frailty index, reference here

Thank you American Geriatrics Society NIA GEMSSTAR program Mt. Sinai Alzheimer’s Disease Research Center Columbia University Mailman School of Public Health MS/POR Scholars Program Mentor: Dr. Mary Sano Dr. Jeffrey Silverstein Mt. Sinai Research Coordinators Team

GEMSSTAR Program  Grants for Early Medical/Surgical Subspecialists’ Transition to Aging Research (R03)  Grants for Early Medical/Surgical Subspecialists’ Transition to Aging Research (R03) Supported by NIA Matched by American Geriatrics Society and Foundations for Anesthesia Education and Research Training award Pilot study Education Columbia Mailman School of Public Health Department of Biostatistics Master’s in Patient Oriented Research