Transcript File

Post Operative Cognitive
Dysfunction (POCD)
Sasikala Bimini Krishnamurthy, SRNA (J)
Objectives
• Understand the concept/definition of POCD.
• Identify the incidence & possible risk factors associated with POCD.
• Enlist the psychometric tests to assess POCD.
• Analyze the potential mechanisms for occurrence of POCD.
• Discuss the possible interventions for management/prevention of
POCD.
Why?
• ISPOCD study by Moller et al. in 1998.
• Steinmetz et al. found POCD to be associated with higher mortality,
earlier retirement and greater utilization of social financial assistance.
• Monk et al. found that the risk of death within one year was greater
among patients who had POCD when they were discharged from the
hospital.
• Harten et al. – POCD associated with decreased quality of life, early
withdrawal from workforce, loss of independence and increased
dependence on society.
Concepts
• Delirium:
• It is an acute confusional state featuring disturbances in attention
and decreased awareness of the environment. The patient is often
disoriented, symptoms fluctuate during the course of the day and
hallucinations may be observed.
• Dementia:
• It is a chronic, often insidious, irreversible, global decline in
cognitive function in the absence of clouding of consciousness.
Concepts
• Cognition:
• It is defined as the mental processing of perception, memory, and
information that allows an individual to acquire knowledge, solve
problems and plan for the future. It comprises functions required
for everyday living and should not be confused with intelligence.
• POCD
• It is a new cognitive impairment arising after a surgical procedure.
Its diagnosis requires both pre- and post operative psychometric
testing. Its manifestations are subtle and manifold depending on
the particular cognitive domains that are affected. The most
commonly affected are memory impairment and impaired
performance on intellectual tasks.
Concepts
• POCD:
• It is a decline in mental capabilities such as concentration, memory,
perception and problem solving abilities which last for weeks or months
following surgical procedures.
• It is an impairment of recent memory, concentration, language
comprehension and social integration. It is described as deterioration of
cognition associated with memory.
Incidence
Incidence
• Canet et al. – cognitive
dysfunction after
minor/ambulatory surgery in the
elderly.
• Rohan et al reported that 47% of
patients undergoing minor noncardiac surgery were found to
have POCD before discharge.
• 15.9% of older adult patients
developed POCD 3 months after
major non-cardiac surgery.
Incidence
• POCD after cardiac surgery is more frequent than non-cardiac surgery.
• According to Funder et al.,
•
•
•
•
•
•
53% at discharge
36% in 6 weeks
24% in 6 months
21% - off pump surgeries in 3 months
29% - on pump surgeries in 3 months
POCD on QOL: 37% at 1 year and 42% at 5 years
Incidence
• GA
• Post 1 week – 19.7%
• Post 3 months – 14.3%
• 37/188 patients; 25/175 patients;
p=0.06
• Mortality is higher (4/217 vs
0/211; p < 0.05)
• RA
• Post 1 week – 12.5%
• Post 3 months – 13.9%
• 22/176 patients; 23/165 patients;
p=0.93
Risk factors
Types
• ACC & AHA classified neurological complications post cardiac surgery
• Type 1 – deficits due to stroke, TIA, coma and fatal cerebral injury
• Type 2 – diffuse and not well-defined; includes delirium and POCD
• POCD is broadly divided into:
• Acute – cognitive decline detected within 1 week after surgery
• Intermediate – cognitive decline within 3 months
• Long term – cognitive changes after 1 to 2 years after surgery
Diagnosis
Criteria:
Score:
Age greater than or equal to 70
Criteria:
History of alcohol abuse
Age greater than or equal to 70
History of alcohol abuse
Baseline cognitive impairment
Baseline cognitive impairment
Severe physical impairment (reduced ability to walk or perform
Severe physical impairment (reduced ability to walk or perform daily activities)
daily activities)
Abnormal blood levels of electrolytes or glucose
Abnormal blood levels of electrolytes or glucose
Thoracic (non-cardiac surgery of the chest or lungs) surgery
Thoracic (non-cardiac Abdominal
surgery
ofAneurysm
the chest
or lungs) surgery
Aortic
(AAA) surgery
Score:
Abdominal Aortic Aneurysm
(AAA) surgery
Score:
0
1
Score:
1
1
1
1
1
1
1
1
1
1
1
1
Risk of POCD:
1
0
2%
1-2
11%
3 or more
T50%
Risk of POCD:
2%
1-2
11%
3 or more
50%
Psychometric testing
• A consensus recommendations on core tests used for diagnosis of
POCD was issued in 1995.
• One stated criterion specified that there must significant changes in
several of cognitive domains: learning and memory, attention,
executive functioning and language.
• Testing should be conducted by the same person – qualified and
trained individual and performed in a standardized manner.
• No general consensus has been established regarding optimum
timing of assessments after surgery.
Psychometric tests
• Mini-Mental Status Examination:
• Has questions r/o temporal and spatial orientation, tasks r/o retentiveness,
recollection, attention and correctness, assessment of language and ability to
write and draw.
• Five minutes to administer.
• Basically intended to assess dementia but sometimes may be used to quantify
POCD
• It was used in 21% of reviewed studies.
Psychometric tests
• Cognitive Failure Questionnaire:
• Is a suitable means of documenting the subjective symptoms of patients who
are at risk.
• Self-assessment questionnaire.
• It has 25 different items to assess the frequency of cognitive errors in
everyday life (relating to conceptualization, memory, and motor skills) on a
verbal scale.
• Erzigkeit’s Short Cognitive Performance Test:
• Shorter alternative consisting of 9 subtests.
• Administered in 15 mins.
• Suitable for perioperative use.
Erzigkeit’s Test
Psychometric tests
• Grooved Pegboard Test (manual
dexterity)
• Measures complete visual motor coordination.
• Pegs must be rotated before they are
inserted.
• Found sensitive to general slowing due
to medication or disease progression.
• Age: 5 years and up.
• Takes 10 – 15 minutes.
Psychometric tests
• Rey Auditory Verbal Learning Test (word learning test):
• Is a measure of immediate recall.
• A list of 15 unrelated words via audio recording and is asked to recall as many
words as the person can.
• Three trials are done and score is equal to total number of words recalled
across three trials.
• Ages 8 – 85 years.
Psychometric tests
• Trail Making Tests, Parts A & B
• Assess the ability to perform
combined tasks.
• Part A – Connect the numbers in
ascending order, with a line.
• Part B – Connect the number in
ascending order and letters in
alphabetical order with a line.
• The time needed to do each part
is measured in seconds.
• This is a test of dexterity and
ability to combine tasks.
Psychometric tests
• Digit Span Test
• The numbers are
presented in a particular
sequence.
• The test measures ability
to remember the
number sequence.
Psychometric tests
• Stroop test:
• This is a test of attention and
concentration in the presence of
distractors.
• The printed words must be read
out loud and the color they
printed in must be named.
• If the word is a color word that is
printed in a different color, the
reaction time and error rate are
higher.
Psychometric tests
• Other tests:
• Paper and Pencil Memory Test – a test of sensorimotor speed and of the
speed of recall.
• Letter – Number Replacement Test – a test of speed of general information
processing.
• Four – Field Test – a test of psychomotor reaction time.
Possible pathogenesis/mechanisms
Possible Pathogenesis/Mechanisms
• Immune response to surgery
• Terrando et al. showed that a peripheral surgical procedure in mice  activates inflammatory
TNF/NF-kB signal cascades  cytokines release  impaired BBB integrity 
neuroinflammation  macrophages migrate into hippocampus  memory impairment.
• Central cytokines: Presence of microglial cells is indicator of chronic inflammation. Astrocytes
and microglial cells secrete cytokines  hippocampal dysfunction  cognitive dysfunction.
Cerebral endothelial cells also secrete cytokines and chemokines.
• Peripheral cytokines: Acts on CNS through direct and indirect means. Enters periventricular
area via BBB (permeable) or binds with cognate receptors on endothelial cells within brain
vessels  central inflammatory response.
• Cyclooxygenase-2: Marked and sustained expression of inflammation-related enzymes 
amplify cerebral injury after ischemia.
• ? POCD associated: Matrix metalloproteinase (MMPs) – early breakdown of BBB in
neuroinflammatory diseases; IL 8 – neuroinflammation in brain trauma.
• Tau (a microtubule-associated protein) phosphorylation changes; excessive beta-amyloid.
Possible pathogenesis/mechanisms
• Genetic predisposition
• Not well understood.
• The apolipoprotein E (4) is a polymorphic protein which is involved in the
mobilization and redistribution of cholesterol in repair, growth and
maintenance of myelin and neuronal membranes during development or
after injury.
• Surgery related
• Reduced systemic pressure and cerebral blood flow and /or increase in ICP 
decreased CPP when auto-regulation fails  impaired cerebral perfusion and
oxygenation.
• Cerebral micro emboli  more diffusely spread very small cerebral emboli
could cause more subtle deficits associated with POCD.
Possible pathogenesis/mechanisms
• Age
• Normal ageing  structural cerebral changes (reduction in grey matter
volume and myelinated axon length)  loss of neuronal dendrites, spines and
myelin, as well as alterations in synaptic transmission and receptors 
normal decline in cognitive reserve with aging or exaggerated response
(neuronal dysfunction or losses) to cerebral insult.
• Volatile agents
• Controversial.
• One hypothesis is that volatile agents may enhance the susceptibility of
neurons to apoptosis and also neurodegenerative processes.
Possible pathogenesis/mechanisms
• Cognitive reserve
• A hypothetical construed word “cognitive reserve” has been used to describe
cognitive aging/decline.
• This includes educational level, occupational attainment and performance on
tests of cognitive domains.
• Plays a protective role against POCD but more research needed.
• Stress response to surgery
• Persistent high levels of stress  increased secretions of cortisol and catechol
amines  interfere with hippocampal function  memory impairment.
Potential strategies - Management/Prevention
Pre-operative
• Critical evaluation of the potential benefit of surgery weighed against
its potential harm including cognitive impairment.
• Perioperative geriatric consultation for high-risk patients.
• Improve cognitive reserve (Hippocampus enhancement techniques
such as physical exercise, intellectual exercise, good nutrition).
• Pre-procedure neurological consultation/psychometric testing.
• Education/awareness about POCD to patients and family members.
• Premedication (e.g., Midazolam) – measurable memory impairment
one day after surgery (pts had GA with propofol & remifentanil).
Intraoperative
• Neurotransmitters influences conscience, memory and learning
through the central cholinergic system.
• The agonists of central mAChRs and nAChRs may improve, while
antagonists could impair cognitive function.
• Induction agents:
• Barbiturates – antagonists of mAChRs.
• Propofol – act on both nAChRs & mAChRs but in higher concentrations.
• Ketamine – Inhibitors of nAChRs. (Controversial). Hudetz et al., found that
single administration of ketamine at 0.5 mg/kg during induction – reduced
POCD incidence 1 week after cardiac surgery – anti-inflammatory
properties of ketamine10. Has acute effect on cognitive function.
Intraoperative
• Opioids
• Fentanyl and morphine – inhibit signals carried by both receptors.
• Remifentanil – no change.
• Inhalational agents
•
•
•
•
Desflurane – M1 subtype. Has less harmful neurotoxic profile.
Sevoflurane – M1 and M2 subtype.
Isoflurane – M3 subtype.
Zhang et al., Isoflurane - increase in human CSF amyloid – B40 at 24 hours
after; Desflurane – decrease in amyloid B 42 at 2 hours after; both did not
affect tau concentration.
Intraoperative
• Xenon – noble
gas. Patients
wake up early
after GA; has
neuroprotective
effects in
cerebral
ischemia.
• However,
studies does
not show any
significant
difference.
Intraoperative
• Appropriate level of anesthesia
• Farag et al., found that patients with lower BIS had fewer cognitive dysfunction (esp.
information processing) at 4 and 6 weeks after surgery.
• Chan et al., concluded that BIS guided anesthesia reduced anesthetic exposure, thus
incidence of POCD.
• Steinmetz et al., found no association between deep (CSI < 40) and light (CSI >60) Cerbral
State Index monitoring and POCD.
• EEG monitoring for control depth of anesthesia and effect on POCD – short term benefit in
one hour after post propofol/remifentanil. More studies needed.
• Cerebral oxygen monitoring
• Papadopoulos et al., found association between cognitive decline in elderly patients with
hip fracture and low cerebral oxygenation.
• Homeostasis maintenance
• Fluid and electrolyte balance; glucose control, normothermia.
• Puskas et al. – intraoperative BS >200 mg/dl – significant cognitive dysfunction – 6 weeks
after surgery.
Post-operative
• Pain management:
• Associated with higher risk of POCD regardless of parenteral route (IV, IM or
epidural).
• IV opioids have higher incidence than oral drugs.
• IV or epidural – use of Morphine has more risk of POCD than Fentanyl.
• Epidural with LA and/or opioids better than PCA.
• Other pain management strategies – use of NSAIDS; peripheral blocks –
decreased use of opioids and POCD.
The Future
• Atorvastatin – under clinical trials for treatment of POCD.
• Near - infrared spectroscopy – noninvasive cerebral oxygen
monitoring.
• Continue efforts to identify biochemical markers specific to neuronal
damage and relate their level to the severity and prognosis.
• Newer MRI sequences such as diffusion weighted imaging used with
higher resolution – potential to detect smaller micro embolic infarcts.
• Positron-emission tomography scanning with C-PK11195 –
quantitative assay of cerebral inflammation and PET tracers useful for
assessing amyloid plaque and tau concentrations.
• Further work required to determine the benefit of immune
modulators which may exert beneficial balance between pro and
anti-inflammatory mediators.
To summarize ……
• POCD is an impairment of cognitive function arising after surgical
procedure.
• The incidence and causes are varied making it a complex phenomenon.
• Advanced age, pre-existing cerebral, cardiac and vascular disease, low
educational level and extensive surgery increase the risk of POCD.
• The pathogenesis is multifactorial, with the immune response
(inflammatory process) to surgery probably serving as a trigger.
• Meticulous planning and care by the anesthesia and surgical teams to
prevent intra and post operative complications can reduce the risk of
POCD.
• It is still an evolving phenomenon with continuing research to reduce the
occurrence of POCD.
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