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Postoperative Cognitive Dysfunction: The Next Challenge in Geriatric Anesthesia

Postoperative Cognitive Dysfunction: The Next Challenge in Geriatric Anesthesia . Terri G. Monk, M.D. Professor Department of Anesthesiology University of Florida Gainesville, FL. Emery A. Rovenstine Memorial Lecture October 13, 2003. Geriatrics 1946 vol. 1, no. 1.

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Postoperative Cognitive Dysfunction: The Next Challenge in Geriatric Anesthesia

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  1. Postoperative Cognitive Dysfunction: The Next Challenge in Geriatric Anesthesia Terri G. Monk, M.D. Professor Department of Anesthesiology University of Florida Gainesville, FL Emery A. Rovenstine Memorial Lecture October 13, 2003

  2. Geriatrics 1946 vol. 1, no. 1. E.A. Rovenstine, M.D. New York City

  3. Table of Contents - Geriatrics 1946;1(1) • GERIATRIC ANESTHESIAE. A. Rovenstine, M.D. • SPECIAL PROBLEMS OF POOR SURGICAL RISKS AMONG THE AGEDWilliam B. Kountz, M.D., and Louis H. Jorstad, M.D. • MENTAL DISORDERS OF OLD AGEHarold D. Palmer, M.D.

  4. Objectives • Importance of Geriatric Anesthesia • Definition of Postoperative Cognitive Dysfunction (POCD) • Historical evidence for POCD • Potential Mechanisms for POCD • Current evidence for POCD following • Coronary Artery Bypass Surgery • Non-Cardiac Surgery • Long-Term Implications of POCD and Anesthetic Management

  5. Projection of the U.S. Population by Age: 1995-2050

  6. Orthopedic Surgery in the Elderly • In past, hesitancy to perform hip and knee replacement in elderly  80 years • Prospective study comparing pain, functional outcome and quality of life outcomes in young (55-79 yrs) and elderly ( 80 yrs): • No difference in outcomes between groups at 6 months after surgery • Age should not be a limiting factor for this type of surgery Jones et al. Arch Intern Med 2001; 161:454

  7. Realities for the Practicing Anesthesiologist • Half of all individuals  65 years will have at least 1 surgery in the remainder of their lifetime • Over 7,000,000 inpatient surgeries per year in people over 65 years Most anesthesiologists will become geriatric anesthesiologists

  8. Adverse Cerebral Effects of Anesthesia on Old People • Review of records of 1193 patients: • Age 50 years or older • Operation under GA • Mental deterioration in 120 (10%) patients • Conclusions • Cognitive decline related to anesthetic agents and hypotension • “Operations on elderly people should be confined to unequivocally necessary cases” Bedford. The Lancet 1955; 2:259

  9. Postoperative Cognitive Disorders • Delirium • 10-15% of elderly patients after GA • Mild neurocognitive disorder - POCD • Dementia (rare) • Multiple cognitive deficits • Impairment in occupational and social function Delirium POCD Dementia

  10. Postoperative Cognitive Dysfunction • Deterioration of intellectual function presenting as impaired memory or concentration. • Not detected until days or weeks after anesthesia • Duration of several weeks to permanent • Diagnosis is only warranted if: • corroborated with neuropsychological testing • evidence of greater memory loss than one would expect due to normal aging

  11. Implications of Postoperative Neurocognitive Disorder • Abrupt decline in cognitive function heralds: • Loss of independence • Withdrawal from society • Death Seattle Longitudinal Study of Aging Berlin Aging Study

  12. Potential Mechanisms for POCD • High-risk patients • High-risk surgical procedures • High-risk anesthetic techniques

  13. Lesion Lesion Protective Factor Brain Reserve Capacity Case A Case B Threshold Theory for Cognitive Decline A: Protective factor (greater brain reserve capacity), lower test sensitivity, no impairment B: Vulnerability factor (less brain reserve capacity), higher test sensitivity, impairment Satz Neuropsychology 1993:(7);273.

  14. Continuum from Normal Aging through Mild Cognitive Impairment to Dementia Normal Aging Mild cognitive impairment Function Dementia Age

  15. Potential Mechanisms for POCD • High-risk patients - “Functional Cliff” • High-risk surgical procedures • Cardiac Surgery • Orthopedic Surgery • High-risk anesthetic techniques

  16. Anesthetic Risk Factors for POCD • Cholinergic neurons in the basal forebrain regulate normal memory • Choline reserves  with aging • Anesthetic agents affect release of CNS neurotransmitter • acetylcholine, dopamine, norepinephrine • Difficult to postulate effects of anesthesia on memory, since mechanisms of general anesthesia are poorly understood.

  17. POCD: Attention in Lay Media

  18. POCD after CAB: Longitudinal Assessment

  19. International Study of Postoperative Cognitive Dysfunction Long-term postoperative cognitive dysfunction in the elderly: ISPOCD1 study JT Moller P Cluitmans LS Rasmussen P Houx H Rasmussen J Canet P Rabbitt J Jolles K Larsen CD Hanning O Langeron T Johnson PM Lauven PA Kristensen A Biedler H van Beem O Fraidakis, JH Silverstein JEW Beneken JS Gravenstein for the ISPOCD investigators • Collaborative research effort: • Members from 8 European countries and USA • 13 hospitals • Research conducted from 1994 - 1996 THE LANCET Saturday 21 March 1998 Vol. 351 No. 9106 Pages 857-861

  20. Long-Term POCD in the ElderlyHypotheses • Anesthesia and surgery in elderly patients cause prolonged cognitive dysfunction • The incidence of prolonged POCD increases with age • Potential mechanisms of POCD • Hypoxemia is a major cause of POCD • Hypotension is a major cause of POCD

  21. O2 saturation by continuous pulse oximetry One night preop Operating room 24 hrs postop Nights of POD 2-3 Noninvasive blood pressure Every 3 min in OR Every 15 min in PACU Every 30 min for 24 hrs after PACU discharge Long-Term POCD in the ElderlyPhysiologic Monitoring

  22. Incidence of POCD in Patients and Controls * * * p < 0.004 Lancet 1998; 351:857

  23. Long-Term POCD in the ElderlyConclusions and Questions • Anesthesia and surgery cause long-term POCD • Hypotension and/or hypoxemia not related to occurrence of POCD • Variable incidence of early POCD at different centers • Differences in anesthetics, procedures, patients? • Are results generalizable to single institutions? Lancet 1998; 351:857

  24. A Prospective Study Evaluating The Relationship Between Age and POCD • Single site - University of Florida: 1999 - 2002 • 1200 patients undergoing elective surgery • Young - 18 to 39 years of age • Middle-aged - 40 to 59 years of age • Elderly - 60 years and older • Controls - primary family members • Study design identical to ISPOCD study • Same psychometric test battery • Outcome Endpoints: • POCD (primary) and mortality (secondary)

  25. The Relationship Between Age and POCD:Inclusion/Exclusion Criteria • Inclusion criteria • Aged 18 years or older • General anesthesia > 2 hrs • Major abdominal/thoracic or orthopedic surgery • Mini-Mental State Exam (MMSE) ≥ 24 • Exclusion criteria • Cardiac or neurosurgical procedures • CNS disease • Alcoholism or drug dependence • Major depression • Patients not expected to live 3 months or longer

  26. Evaluation of Factors Affecting Outcome Effect of patient, procedure and anesthetic variables on outcome was evaluated using multivariate modeling • Co-morbidity Scores, Demographics, Patient History • Medications, Anesthetic Agents / Duration, Surgery Type • Cumulative Deep Anesthesia Time (BIS < 45) • Intraoperative Hemodynamics

  27. POCD After Major Surgery:Baseline Characteristics Baseline Characteristics of the Patients Elderly ( 60 yrs) Young (18-39 yrs) Middle Aged (40-59 yrs) Number of Patients Age (yrs)† Gender (M/F) Years of Education† Baseline MMSE† Baseline Charlson Comorbidity Index† 331 (31%) 30.7 (6.0) 30/70% 13.4 (2.2) 29.3 (1.1) 1.0 (1.5) 379 (36%) 49.9 (5.6) 35%/65% 13.7 (2.8) 29.2 (1.2) 1.4 (1.8) 354 (33%) 69.5 (6.5) 43%/57% 13.5 (2.8) 28.8 (1.4) 1.9 (2.1)* † Numbers are expressed as Mean (standard deviation) * Elderly group significantly different from younger groups

  28. Incidence of POCD in Adult Patients: Z Score Definition % of Patients * *p < 0.05 Monk et al. Anesthesiology 2001; 95: A-50

  29. Risk Factors for POCD Univariate P value Multivariate Odds Ratio Years of Education < 0.001 0.86 (p=0.028) Age 0.001 2.51 (p=0.057) History of Stroke 0.003 NS ASA Physical Status 0.009 NS Baseline Comorbidity 0.021 NS NYHA Status 0.028 NS History of MI 0.046 NS Surgery Type NS NS Gender NS NS Baseline MMSE NS NS Anesthesia Time NS NS Predictors of POCD: 3 Months After Surgery Multivariate c-statistic = 0.671 (p = 0.003) Monk et al. Anesthesiology 2001; 95: A-50

  30. One-Year Mortality Rate by Cognitive Status ** * * P = 0.027 vs. No Decline; ** P = 0.014 vs. No Decline

  31. Independent Multivariate Predictors of One-Year Mortality Multivariate c-statistic = 0.806 (p < 0.001) • Beta blocker use was not protective • intraoperative beta-blockers – hemodynamic stability • chronic beta-blockers – higher comorbidity Weldon et al. Anesthesiology 2002; 97: A-1097

  32. Outcomes Following Major Surgery: Conclusions • POCD • Common in all age groups at hospital discharge • 3 months after surgery, POCD is more common in adults age 60 years or older, with lower educational achievement • Associated with increased one-year mortality • Mortality • Increased by comorbidity • Anesthetic management has a significant effect • volatile agent use • cumulative deep anesthesia time • systolic hypotension

  33. Is Anesthesia Associated with One-Year Mortality? • Multi-center Prospective Trial (Sweden) • 5,057 General Anesthetics, Non-cardiac Surgery • 1 Year Mortality Rate = 5.6% • vs. 5.4% in our POCD/Mortality Study • Deep Anesthesia Time: Significant Independent Predictor Of Mortality • Increased Relative Risk: 19.7% / Hr • vs. 34.1% in our POCD/Mortality Study Lennmarken et al, Anesthesiology 2003; 99:A-303

  34. Additional Investigation Medicare Data Analysis • 2001 MEDPAR Inpatient File (1.6 Million Surgeries) • Prediction of Risk-Adjusted Post-Surgical Mortality Rate • Cox Proportional Hazards Model: c-statistic=0.848 (p < 0.001) • Rank-ordered decrease in risk-adjusted mortality with increasing use of intraoperative BIS monitoring. * P < 0.001 for Trend Monk, et al. Anesthesiology 2003; 99:A-1361

  35. Summary • “Anesthetic management, directly or indirectly, may contribute to the biology of remote adverse events” • “Practicing anesthesiologists may be able to influence long-term outcomes by adjusting anesthetic and adjuvant regimens” • “Reducing one-year mortality in the elderly by just 5% would translate to 40,000 - 50,000 lives saved each year” Meiler, Monk et al. APSF Newsletter 2003; 18(3):33.

  36. Research Support • Anesthesia Patient Safety Foundation (APSF) • I Heermann Anesthesia Foundation • NIA K01 award • Aspect Medical Systems

  37. The POCO Group:Post-Operative Cognitive Outcomes Group

  38. Mentors Make the Difference Paul White, MD Washington University 1988 - 1992 Joachim S. Gravenstein, MD University of Florida 1998-2003

  39. Superman in his later years

  40. Society for the Advancement of Geriatric Anesthesiawww.sagahq.org

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