Postoperative
Cognitive
Dysfunction:
Can we prevent
it?
Postoperative Cognitive
Dysfunction
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Michael Rieker, DNP, CRNA
Director, Nurse Anesthesia Program
Wake Forest University Baptist Medical Center
Types of postoperative cognitive
dysfunction
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Emergence delirium- immediate postop
confusion, restlessness. Affects all ages, but
prominent in elderly, emergency surgery
Interval delirium- POD 2-7; fluctuating
impairment of cognition, memory, emotional
lability
Characteristic postoperative cognitive
dysfunction- lasts 3 months to years
Synonyms of POCD
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Postoperative psychosis
Mild neurocognitive disorder.
Acute confusional state
Mental dysfunction
Acute brain syndrome
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Impairment of Memory
Impairment of Attention
D l
Delayed
d functional
f
ti
l recovery
(psychomotor function)
Symes E et al. Issues associated with the identification of
cognitive change following coronary artery bypass
grafting. Aust NZ J Psychiatry 2000;34(5):770-84.
Postoperative Delirium
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Brief, fluctuating
Impaired cognition
Fl t ti llevels
Fluctuating
l off consciousness
i
Altered psychomotor activity (pulling out
IVs, etc.)
Emotional lability (crying, anger)
History of POCD
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Postoperative psychosis
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Historical term. Various forms of cognitive
disorder recognized
g
since 1819
Bedford- retrospective review of > 4,200 elderly
patients
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(Bedford PD Adverse cerebral effects of anaesthesia
on old people. Lancet 1955;2:259-63.)
1
Sequelae of Postoperative
Cognitive Dysfunction
History of POCD
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Shaw PJ et al. Early intellectual dysfunction
following coronary bypass surgery. Q J
Medicine 1986;58(225):59
1986;58(225):59-68.
68.
Savageau JA et al. Neuropsychological
dysfunction following elective cardiac
operation I. Early Assessment. J Thoracic
Cardiovascular Surgery 1982;84(4):585-94.
Increased morbidity
„ Prolonged hospitalization
„ Necessitates long-term care
„ Loss of functional ability
„ Cost!
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Sequelae of Postoperative Cognitive
Dysfunction
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Sequelae
Patients with POCD at hospital discharge were
more likely to die in the first 3 months after
surgery (P = 0.02).
Patients who had POCD at both hospital
discharge and 3 months after surgery were
more likely to die in the first year after surgery
(P = 0.02).
Monk TG. Et. al. Predictors of cognitive dysfunction after major
noncardiac surgery. Anesthesiology. 108(1):18-30, 2008 Jan.
Sequelae
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720 patients enrolled in multicenter studies of POCD
1995-2000
Cognitive
g
function assessed before, 1 week and 30
days after non-cardiac surgery
patients with POCD at 3 months showed higher
rates of mortality and lower rates of return to
function
Steinmetz, Jacob; Christensen, Karl Bang; Lund, Thomas; Lohse,
Nicolai; Rasmussen, Lars S. the ISPOCD Group Anesthesiology
2009;110(3):548-555.
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Monk TG. Et. al. Predictors of cognitive dysfunction after major
noncardiac surgery. Anesthesiology. 108(1):18-30, 2008 Jan.
Incidence of Cognitive Dysfunction
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Age is a prominent risk factor.
„ Affects 10% overall elderly surgical patients
Can occur in any age group; delirium (immediate
post-op) more common in young.
Incidence highest in days-weeks postop. (50-80%)
Declines to 5-60% at 3 months
After six months may also be due to depression or
awareness of age related changes. Dighstra JB et al Br J
Anaesth 1999;82(6))
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Risk Factors
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The independent risk factors for POCD at 3
months after surgery were:
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Advanced age is a consistent, independent
predictor
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increasing age
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lower educational level
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Age as a major risk factor
history of previous cerebral vascular accident with
no residual impairment
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Decreased lean body mass
Decrease total body water
Increase in body fat
Thus, increase in dose-response variability.
POCD at hospital discharge.
Monk TG. Et. al. Predictors of cognitive dysfunction after major
noncardiac surgery. Anesthesiology. 108(1):18-30, 2008 Jan.
Theory on Aging
Older patients are at a functional cliff, and if
they have a major stress, such as loss of
cognitive function after surgery, some of
them will functionally decline. This decline is
associated with increased mortality, loss of
independence and further declines in health
and independence.
Incidence of Cognitive Dysfunction
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25-50% following ortho procedures
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30% following cardiac surgery post-op, 7% after 5
days.
days
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Galanakis et al. Int J Geriatric Psych. 2001;16:349-355.
Silber et al. J Cardiothoracic Vasc Anesth 2001;15(1):20-4.
Low incidence with minimally-invasive procedures
(~1-3% with Cataract ext.)
Meta-analysis of 80 studies showed incidence as
high as 75%
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Dyer. Ann Int Med. 1995;155:461-465.
Characteristics of POCD
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Temporal association with surgery
Fluctuating symptoms
Impairment of
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Memory
Learning
Sensory and language processing
Concentration
Social integration
Sleep-wake cycle
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Characteristics of POCD
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Hallucinations
Delusions
Motor dysfunctiondysfunction tremor
Lability of mood, anger, depression
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Diagnosis is difficult!
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Standardized Understanding is Elusive
Concentration
Memory
Cognitive
Function
Attention
Function/ADLs
Standardized Understanding is Elusive
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Mahanna et al. applied different criteria to
same sample
Found rates of POCD to vary 20% - 70%
Pathophysiology Hypotheses
Metabolic encephalopathy
Neurological injury
1.
2.
Mahanna EP et al. Defining neuropsychological dysfunction
after coronary artery bypass grafting. Annals of Thoracic
Surgery 1996 61(5):1342-7.
Metabolic encephalopathy
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Hypoxia
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Ach synthesis sensitive to hypoxia (would alter memory,
alertness, motor function)
Hypoglycemia
Hypothermia
Surgical trauma (factors may alter amino acids and
neurtransmitters)
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Neurological Injury
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Cerebral infarction
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Fat or air embolism
Thrombus
Decreases thyroid hormone
Increases cortisol
Releases cytokines
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International Study of POCD
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1218 patients over 60 yoa
Tested pre-op, 1 week, and 3 months after
major non-cardiac surgery
Surgery
Control
1 week
25.8 %
3.4
3 months
9.9%
2.8
p value
0.0001
0.0037
Moller, J et al Long-term postoperative cognitive dysfunction in the elderly:
ISPOCD1 study. Lancet 1998; 351:857-861.
International Study of POCD
International Study of POCD
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Risk factors:
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Age
Duration of anesthesia
Lower education
Second operation
Postoperative infections
Respiratory complications
No relation of POCD to:
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ASA status, lung, heart, PVD, HTN, head inj.,
stroke,, a-fib,, delirium,, cancer,, anesthetic
technique, smoking, ETOH, EBL, periop fluids,
type of operation, gender, long-term ICU stay,
hypoxemia, hypotension
Moller, J et al Long-term postoperative cognitive dysfunction in the elderly:
ISPOCD1 study. Lancet 1998; 351:857-861.
International Study of POCD; More
questions than answers
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If known insults are not corollaries, what is
etiology?
Is it more common in some operations than
others?
Will it improve over additional postoperative
time?
Does it occur in younger patients or after
short procedures?
Long-term cognitive decline in older subjects was not
attributable to noncardiac surgery or major illness.
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Retrospective cohort study of 575 participants tested
annually at the Washington University Alzheimer’s
Disease Research Center
Three cohorts: surgical, no surgery/no illness, no
surgery/illness
Retrospective, matched-control group. Long-term
annual testing.
Attempted to overcome methodological/statistical
deficiencies of previous studies.
Avidan MS et al. Anesthesiology 2009;111:964-970.
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Long-term cognitive decline in older subjects was not
attributable to noncardiac surgery or major illness.
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Failed to find correlation between surgery and long-term
decline.
Suggests that accounting for pre-surgery cognitive trajectory
removes association between surgery/illness and POCD
POCD.
Unclear how to account for inevitable crossover
Unclear how many were lost to follow-up to arrive at the
final sample
If incidence not different on annual testing, isn’t it still
important in shorter-term?
Avidan MS et al. Anesthesiology 2009;111:964-970.
Is there a connection we are missing?
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“…thyroid hormones negatively regulate
expression of the amyloid-beta protein
precursor (AbetaPP), which plays a key role
in the development of AD.”
Is there a connection we are missing?
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Cellular injury
Reduced ability to regenerate new cells
Impaired cell-to-cell communication
Auditory deficits
(Rat model at developmental stage
equivalent to 0-2 year-old human brain)
Is there a connection we are missing?
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Within hours of exposure to NMDA blocker,
developing rat brains show:
Mafrica F. Fodale V. Thyroid function, Alzheimer's disease and
postoperative cognitive dysfunction: a tale of dangerous liaisons? Journal
Hypoxia, hypocapnia, and anesthetics trigger
Alzhemier’s Disease.
Could this be a similar molecular trigger for
POCD?
Zie, Z & Tanzi, RE. Alzheimer’s disease and post-operative
cognitive dysfunction. Experimental Gerontology
2006;41:346-359.
of Alzheimer's Disease. 14(1):95-105, 2008 May.
Is it all about beta-amyloid
protein?
Possible Etiologic Factors
Preoperative
„ Intraoperative
„ Postoperative
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Preoperative
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Preoperative- theories
Psychiatric disorder
„ Psychosis
„ Dementia
„ Depression
„ Personality disorder
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Nutritional deficiency
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Thiamine, etc.
Drug influences
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Alcohol abuse
Benzodiazepine abuse or withdrawal
Anticholinergic pre-med
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Intraoperative
Hyperglycemia
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Previous surgery
Sensory impairment
Intraoperative
Type of surgery (esp ortho, cardiac)
Duration of surgery
Hypoglycemia
Electrolyte disturbance (esp. sodium)
Temperature disturbance (hypo or hyperthermia have
been implicated)
Drugs: anticholinergics, inhalational anesthetics,
polypharmacy
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Parkinson’s disease
Cerebrovascular disease
Hypoalbuminemia
Ancelin, et al Exposure to anaesthetic agents, cognitive
functioning and depressive symptomatology in the elderly.
British journal of psychiatry 2001;178:360.
Preoperative
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Poor medical status
hyperglycemic = POCD incidence of 40% vs 29% in
the normoglycemic
gy
group
g p (P = 0.01).
)
Hyperglycemia was the strongest factor associated
with POCD
Puskas F, et al. Intraoperative hyperglycemia and cognitive
decline after CABG. Ann Thorac Surg 2007; 84:1467–73.
Meperidine, long-acting BNZ, BNZ withdrawal
Intraoperative
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Hypoxemia
CBF
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Cerebral oximetry?
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CBF found to be decreased after bypass.
Hong SW.
SW et al
al. Prediction of cognitive
dysfunction and patients' outcome following valvular heart surgery and the
role of cerebral oximetry. European Journal of Cardio-Thoracic Surgery.
33(4):560-5, 2008 Apr.
Hypotension
Although these are good theoretical bases, no-one has been able to show a
direct correlation to POCD.
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Anemia (hemorrhage). This has been correlated to
POCD
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Is it a lingering effect of the
anesthetic drugs?
Cardiopulmonary Bypass
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Temporary depression of CBF
Microembolization of vessels
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(arterial filtration reduces incidence)
Fall below limits of autoregulation
Prolonged focal changes on EEG correlate with
POCD; while increasing perfusion pressure reduced
it.
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Bekker AY. Cognitive dysfunction after anaesthesia in the
elderly. Best Prac Research in Clin Anaes.
2003;17(2):259-272.
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Does anesthetic type make a
difference?
The use of volatile anesthetics that are rapidly
eliminated with minimal metabolic
breakdown may reduce postoperative
cognitive dysfunction and postoperative
delirium by facilitating a faster recovery
The down-regulation of nerve growth factor (NGF) mRNA and
protein expression in the cortex and thalamus after the propofol
treatment, as well as a decrease of phosphorylated Akt were
observed. The extrinsic apoptotic pathway was induced by overover
expression of tumor necrosis factor (TNF) which led to the
activation of caspase-3 in both examined structures.
Neurodegeneration was confirmed by Fluoro-Jade B staining. Our
findings provide direct experimental evidence that the anesthetic
dose (25mg/kg) of propofol induces complex changes that are
accompanied by cell death in the cortex and thalamus of the
developing rat brain.
Pesić, Vesna V. Potential mechanism of cell death in the developing rat brain induced by propofol
anesthesia. International journal of developmental neuroscience, 2009;27 (3): 279.
General vs. Regional
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Rasmussen, Moller et. al. as part of
International Study of POCD repeated earlier
study in 2003. Included researchers in US,
UK, Europe, and Netherlands.
Looked at 438 elderly (>60) patients.
Chen X et al.Anesth Analg 2001;93:1489-94.
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ISPOCD follow-up
Does anesthetic type make a
difference?
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Findings:
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Mostly ortho procedures
POCD occurred in 10-20% of all patients at 1 week and 3
months.
No difference based on anesthesia type.
Limitations:
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High refusal/drop-out rate
Regional group received propofol sedation
GA group- didn’t specify technique
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Rasmussen LS, Johnson T, Kuipers M, et. al. Does
anaesthesia cause postoperative cognitive dysfunction? A
randomised study of regional versus general anaesthesia in
438 elderly patients. Acta Anaes Scand 2003;47:260-266.
No difference in POCD according to type of
anesthetic.
Overall 5% long-term POCD.
POCD
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Williams-Russo, et. al. Cognitive effects after
epidural versus general anesthesia in older
adults. JAMA. 1995;274:44-50.
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Does anesthetic type make a
difference?
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Does anesthetic type make a
difference?
Comparison of rates of POCD in patients
having CEA with regional are similar to those
of patients having CEA under general, in
comparison to controls.
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Heyer, Eric J EJ (08/2008). "A study of cognitive dysfunction in
patients having carotid endarterectomy performed with regional
anesthesia". Anesthesia and analgesia. 107 (2), p. 636.
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Does anesthetic type make a
difference?
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P
Percentage
t
with
ith POCD att X interval
i t
l
6 Days
30 Days
Propofol
50%
18%
12%
Xenon
44%
12%
6%
Does anesthetic type make a
difference?
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Other factors are likely to contribute to the
pathogenesis of POCD:
„ inflammatory processes triggered by the surgical
procedure.
procedure
„ Animal studies demonstrate a correlation
between the inflammatory response in the
hippocampus and the development of POCD in
rodents.
Caza N. Taha R. Qi Y. Blaise G. The effects of surgery and anesthesia on
memory and cognition. Progress in Brain Research. 169:409-22, 2008.
130 ortho patients 64-87 years old
POCD duration General anes > regional +
sedation > regional without sedation
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Höcker, Jan J Postoperative neurocognitive dysfunction in elderly patients after
xenon versus propofol anesthesia for major noncardiac surgery: a doubleblinded randomized controlled pilot study. Anesthesiology 2009;110(5):1068.
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Nishikawa et. al. Recovery characteristics and postoperative delirium after long-duration laparoscopeassisted surgery in elderly… Acta Anaes Scand.
2004;48:162-168.
Does anesthetic type make a
difference?
100 patients ASA status I-III; age 65-83, undergoing
elective abdominal or urologic surgery > 2 hours
1 Day
Comparison of propofol and sevo.
Very weak differences noted.
Sevo caused faster initial emergence and less early
delirium.
No difference in POCD.
Ancelin, et al Exposure to anaesthetic agents,
cognitive functioning and depressive
symptomatology in the elderly. British journal of
psychiatry 2001;178:360.
Postoperative Factors
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Pain
Hypoxia
Hypocarbia
Sepsis
Sensory deprivation or overload (ICU
environment)
Electrolyte or metabolic derangement
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Prevention
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Preoperative assessment
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Prevention
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Detailed history of drugs
Medical problem evaluation
Detection of sensory or perceptual deficits
Mental preparation prior to surgery
Neuropsychologic testing
Adequate oxygenation and perfusion
Correct the electrolyte imbalance
„ Adjust drug dose (BIS, etc. to minimize
doses)
„ Minimize the variety of drugs
„ Avoid atropine, diazepam, scopolamine
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Thrombus prophylaxis
Optimize medical condition
Tailor anesthetic plan…
Geriatric-Anesthesiologic
Intervention Program
Prevention
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Postoperative care
„ Frequent orientation
„ Early
y mobilization
„ Environmental support (noise
reduction, glasses/hearing aids
used)
„ Treat pain
„ Identify risk-associated drugs
„ Reassure patient and family
Treatment of POCD
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Recognize and prevent causes
Rule out organic cause
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Hypo/hyperglycemia
yp yp g y
Hypoxemia
Electrolytes
Anemia
Sepsis
Dehydration
Malnutrition
Intraoperative precautions
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Preop and postop assessment
Early surgery
Thrombus prophylaxis
Tight BP control
Oxygen therapy
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Parikh SS & Chung F. Postoperative delirium in the
elderly Anesthesia & Analgesia, 1995;80:1223-1232
Treatment of POCD
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Remove contributing factors
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Encourage patterned rest
Opioids/BNZ/DA antagonists
Pain
Polypharmacy
Control with drugs only if necessary
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Narcoleptics (buterophenones/chlorpromazine) better
than BNZ, unless BNZ withdrawal
Physostigmine
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Summary
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POCD is variable in definition, but affects a
significant number of patients
May be associated with increased cost and
functional decline
Awareness of risk factors and measures to
avoid those that are preventable may benefit
the patient.
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