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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.
E.A. Rovenstine, M.D. New York City
Table of Contents - Geriatrics 1946;1(1)
 GERIATRIC ANESTHESIA
E. A. Rovenstine, M.D.
 SPECIAL PROBLEMS
OF POOR SURGICAL
RISKS AMONG THE AGED
William B. Kountz, M.D., and Louis H. Jorstad, M.D.
 MENTAL DISORDERS OF
Harold D. Palmer, M.D.
OLD AGE
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
Projection of the U.S. Population by Age:
1995-2050
Population in millions
70
60
50
40
30
20
10
0
1995 2000 2005 2010 2015 2020 2025 2030 2035 2040 2045 2050
Ages 85+
Ages 75-84
Ages 65-74
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

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
 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
Delirium
POCD
Dementia
 Delirium

10-15% of elderly patients after GA
 Mild neurocognitive disorder
 Dementia (rare)


- POCD
Multiple cognitive deficits
Impairment in occupational and social function
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
 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

High-risk patients

High-risk surgical procedures

High-risk anesthetic techniques
Brain Reserve Capacity
Threshold Theory for Cognitive Decline
Lesion
Protective
Factor
Case A
Lesion
Case B
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
Function
Normal Aging
Mild cognitive impairment
Dementia
Age
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

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.
POCD: Attention in Lay Media
POCD after CAB: Longitudinal Assessment
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

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
 Noninvasive blood
continuous pulse oximetry pressure

One night preop

Every 3 min in OR

Operating room

Every 15 min in PACU

24 hrs postop


Nights of POD 2-3
Every 30 min for 24 hrs
after PACU discharge
Incidence of POCD in Patients and Controls
30
Percentage (%)
25
*
20
15
*
10
Controls
Patients
5
0
Early
Late
* p < 0.004
Lancet 1998; 351:857
Long-Term POCD in the Elderly
Conclusions 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
 Single
 1200



site - University of Florida: 1999 - 2002
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
 Study


- primary family members
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
 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
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
Baseline Characteristics of the Patients
Young
(18-39 yrs)
Middle Aged
(40-59 yrs)
Elderly
( 60 yrs)
Number of Patients
331 (31%)
Age (yrs)†
30.7 (6.0)
Gender (M/F)
30/70%
Years of Education†
13.4 (2.2)
Baseline MMSE†
29.3 (1.1)
Baseline Charlson Comorbidity Index† 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
Incidence of POCD in Adult Patients:
Z Score Definition
60
Young (18-39 yrs)
50
Patients
%%ofofPatients
Middle Aged (40-59 yrs)
Elderly (60 yrs and older)
40
30
20
*
10
0
Early (At Hospital Discharge)
Late (3 mo PO)
*p < 0.05
Monk et al. Anesthesiology 2001; 95: A-50
Predictors of POCD:
3 Months After Surgery
Risk Factors for POCD
Years of Education
Age
History of Stroke
ASA Physical Status
Baseline Comorbidity
NYHA Status
History of MI
Surgery Type
Gender
Baseline MMSE
Anesthesia Time
Univariate P value
< 0.001
0.001
0.003
0.009
0.021
0.028
0.046
Multivariate Odds Ratio
0.86 (p=0.028)
2.51 (p=0.057)
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
Multivariate c-statistic = 0.671 (p = 0.003)
Monk et al. Anesthesiology 2001; 95: A-50
One-Year Mortality Rate by Cognitive Status
10%
8.1%
8%
6.5%
6%
4%
*
3.4%
2.4%
2%
0%
Hospital Discharge
No Decline
Three Months
Cognitive Decline
* P = 0.027 vs. No Decline; ** P = 0.014 vs. No Decline
**
Independent Multivariate Predictors
of One-Year Mortality
Risk Factors
Baseline Comorbidity
Volatile vs. TIVA
Intraoperative Beta Blocker
Chronic Beta Blocker
Cumulative Deep Anesthesia Time (BIS < 45, per hour)
Systolic Blood Pressure < 80 mmHg (per minute)
Relative Risk
16.86
2.97
1.67
1.53
1.34
1.04
P Value
< 0.001
0.022
0.004
0.019
0.007
0.008
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
 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?

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
vs.
Relative Risk: 19.7% / Hr
34.1% in our POCD/Mortality Study
Lennmarken et al, Anesthesiology 2003; 99:A-303
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.
BIS Utilization Rate
(% Procedures Monitored)
None
1-25%
26-75%
> 75%
Total
* P < 0.001 for Trend
# of Sites
# of Cases
3,774
350
308
101
1,087,061
262,180
191,462
80,804
1,621,507
Risk-Adjusted
Mortality Rate
9.33%
8.89%*
8.95%*
8.69%*
Monk, et al. Anesthesiology 2003; 99:A-1361
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.
Research Support

Anesthesia Patient Safety Foundation (APSF)
 I Heermann Anesthesia Foundation
 NIA K01 award
 Aspect Medical Systems
The POCO Group:Post-Operative Cognitive Outcomes Group
Mentors Make the Difference
Paul White, MD
Joachim S. Gravenstein, MD
Washington University
University of Florida
1988 - 1992
1998-2003
Superman in his later years
Society for the Advancement of Geriatric Anesthesia
www.sagahq.org