Postoperative Cognitive Dysfunction: The Next Challenge in Geriatric Anesthesia

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Postoperative Cognitive Dysfunction The Next
Challenge in Geriatric Anesthesia
Terri G. Monk, M.D. Professor Department of Ane
sthesiology University of Florida Gainesville, F
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Emery A. Rovenstine Memorial Lecture
October 13, 2003
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Geriatrics 1946 vol. 1, no. 1.
E.A. Rovenstine, M.D. New York City
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Table of Contents - Geriatrics 19461(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.

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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

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

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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 161454
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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

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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 2259
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Postoperative Cognitive Disorders
Delirium
POCD
Dementia

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

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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

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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
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Potential Mechanisms for POCD

• High-risk patients
• High-risk surgical procedures
• High-risk anesthetic techniques

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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.
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Continuum from Normal Aging through Mild
Cognitive Impairment to Dementia
Normal Aging
Mild cognitive impairment
Function
Dementia
Age
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Potential Mechanisms for POCD

• High-risk patients - Functional Cliff

• High-risk surgical procedures
• Cardiac Surgery
• Orthopedic Surgery

• High-risk anesthetic techniques

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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.

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POCD Attention in Lay Media
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POCD after CAB Longitudinal Assessment
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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 Graven
stein 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
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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

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Long-Term POCD in the ElderlyPhysiologic
Monitoring

• 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

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Incidence of POCD in Patients and Controls


p Lancet 1998 351857
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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 351857
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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)

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The Relationship Between Age and
POCDInclusion/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

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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
• Intraoperative Hemodynamics

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POCD After Major SurgeryBaseline 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) Year
s 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 differen
t from younger groups
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Incidence of POCD in Adult Patients Z Score
Definition
of Patients

p Monk et al. Anesthesiology 2001 95 A-50
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Predictors of POCD 3 Months After Surgery
Multivariate c-statistic 0.671 (p 0.003)
Monk et al. Anesthesiology 2001 95 A-50
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One-Year Mortality Rate by Cognitive Status


P 0.027 vs. No Decline P 0.014 vs. No
Decline
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Independent Multivariate Predictors of One-Year
Mortality
Multivariate c-statistic 0.806 (p

Beta blocker use was not protective

intraoperative beta-blockers hemodynamic
stability

chronic beta-blockers higher comorbidity

Weldon et al. Anesthesiology 2002 97 A-1097
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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

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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 99A-303
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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-statistic0.848
  (p
  
• Rank-ordered decrease in risk-adjusted mortality
  with increasing use of intraoperative BIS
  monitoring.

P et al. Anesthesiology 2003 99A-1361
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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.
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Research Support

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

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The POCO GroupPost-Operative Cognitive Outcomes
Group
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Mentors Make the Difference
Paul White, MD Washington University 1988 - 199
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Joachim S. Gravenstein, MD University of Florida
1998-2003
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Superman in his later years
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Society for the Advancement of Geriatric
Anesthesiawww.sagahq.org