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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

Postoperative Cognitive Dysfunction: The Next Challenge in Geriatric Anesthesia

Terri G. Monk, M.D.


Department of Anesthesiology

University of Florida

Gainesville, FL

Emery A. Rovenstine Memorial Lecture

October 13, 2003


Geriatrics 1946 vol. 1, no. 1.

E.A. Rovenstine, M.D. New York City

table of contents geriatrics 1946 1 1
Table of Contents - Geriatrics 1946;1(1)
  • 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
orthopedic surgery in the elderly
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

realities for the practicing anesthesiologist
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

adverse cerebral effects of anesthesia on old people
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

postoperative cognitive disorders
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




postoperative cognitive dysfunction
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
implications of postoperative neurocognitive disorder
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

potential mechanisms for pocd
Potential Mechanisms for POCD
  • High-risk patients
  • High-risk surgical procedures
  • High-risk anesthetic techniques
threshold theory for cognitive decline





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.

continuum from normal aging through mild cognitive impairment to dementia
Continuum from Normal Aging through Mild Cognitive Impairment to Dementia

Normal Aging

Mild cognitive impairment




potential mechanisms for pocd16
Potential Mechanisms for POCD
  • High-risk patients - “Functional Cliff”
  • High-risk surgical procedures
    • Cardiac Surgery
    • Orthopedic Surgery
  • High-risk anesthetic techniques
anesthetic risk factors for pocd
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.
international study of postoperative cognitive dysfunction
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

long term pocd in the elderly hypotheses
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
long term pocd in the elderly physiologic 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

Long-Term POCD in the ElderlyPhysiologic Monitoring
incidence of pocd in patients and controls
Incidence of POCD in Patients and Controls



* p < 0.004

Lancet 1998; 351:857

long term pocd in the elderly conclusions and questions
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

a prospective study evaluating the relationship between age and pocd
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)
the relationship between age and pocd inclusion exclusion criteria
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
evaluation of factors affecting outcome
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
pocd after major surgery baseline characteristics
POCD After Major Surgery:Baseline Characteristics

Baseline Characteristics of the Patients


( 60 yrs)


(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)


13.4 (2.2)

29.3 (1.1)

1.0 (1.5)

379 (36%)

49.9 (5.6)


13.7 (2.8)

29.2 (1.2)

1.4 (1.8)

354 (33%)

69.5 (6.5)


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

incidence of pocd in adult patients z score definition
Incidence of POCD in Adult Patients: Z Score Definition

% of Patients


*p < 0.05

Monk et al. Anesthesiology 2001; 95: A-50

predictors of pocd 3 months after surgery

Risk Factors for POCD

Univariate P value

Multivariate Odds Ratio

Years of Education

< 0.001

0.86 (p=0.028)



2.51 (p=0.057)

History of Stroke



ASA Physical Status



Baseline Comorbidity



NYHA Status



History of MI



Surgery Type






Baseline MMSE



Anesthesia Time



Predictors of POCD: 3 Months After Surgery

Multivariate c-statistic = 0.671 (p = 0.003)

Monk et al. Anesthesiology 2001; 95: A-50

one year mortality rate by cognitive status
One-Year Mortality Rate by Cognitive Status



* P = 0.027 vs. No Decline; ** P = 0.014 vs. No Decline

independent multivariate predictors of one year mortality
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

outcomes following major surgery conclusions
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
is anesthesia associated with one year mortality
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

additional investigation
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

  • “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.

research support
Research Support
  • Anesthesia Patient Safety Foundation (APSF)
  • I Heermann Anesthesia Foundation
  • NIA K01 award
  • Aspect Medical Systems
mentors make the difference
Mentors Make the Difference

Paul White, MD

Washington University

1988 - 1992

Joachim S. Gravenstein, MD

University of Florida