Post on 22-Mar-2022
10/18/2021
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Cognitive Dysfunction:
Anesthesia’s Silent Side
Effect
Disclaimer
� I have no actual or potential conflict of
interest in relation to this
program/presentation.
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And We Never Knew…..
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Objectives
� Define what is Post Operative Cognitive
Dysfunction(POCD)
� Understand the physiology behind POCD
� Identify the difference between Cognitive
Dysfunction and Delirium
� Understand the role of anesthesia in
cognitive dysfunction
� Identify ways to reduce cognitive
dysfunction
Definition:
� Cognitive dysfunction is the loss of
intellectual functions such as thinking,
remembering, and reasoning of
sufficient severity to interfere with daily
functioning. Patients with cognitive
dysfunction have trouble with verbal
recall, basic arithmetic, and
concentration
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Do YOU Know the Answer?
� What condition is noted in 10-25% of all
patients undergoing anesthesia?
Postoperative Cognitive Dysfunction
� From highest to lowest list the incidence
of POCD? Age 18-39 or 40-59 or >60?
1. > 60
2. 18-39
3. 40-59
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What symptoms will you see:
� change in mental status characterized
by a reduced awareness of the
environment and a disturbance in
attention.
� hypoactive, hyperactive, or mixed
psychomotor behaviors
� disorientation or temporary memory
dysfunction.
IS this YOUR PATIENT?
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History and Statistics
� 1955: Described in the “LANCET” as
“adverse cerebral effects of anesthesia
on old people”
� 50% of patients suffer some form of
POCD or PD within 1 week of surgery
� 10-15% of all patients display symptoms
up to 3 months post surgery
� 26-33% of all Geriatric patients (>65yr)
experience.
The Neuro Physiology� Inflammatory Cytokines which are
released as a result of injury to the CNS
� Interleukin 6(IL-6) and IL-1β○ Found in the plasma (crosses BBB)
○ Cause of Neuronal Apoptosis
� Tumor Necrosis Factor α-8
○ Inflammatory Cytokine
○ Released into plasma as a result of acute cerebral injury.
○ Released in the presence of Inhalation agents
� Protein S-100β
○ Acidic Calcium Binding Protein
○ Considered a Bio-Marker for acute brain injury
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Neuro Physiology (cont.)
� Integrity of the Blood-Barrier is
comprimised by the release of cytokines
� Macrophages enter the hippocampus
leading to memory impairment.
� Alzhiemiers and POCD
� Neuro Markers
○ Beta-Amyloid Protein
○ Tau Protein
� Modulates stability if axonal microtubles
Pre-existing Conditions:
� Geriatric (age >65)
� Cerebral Disease
� Cardiac Disease
� Vascular Disease
� ETOH Abuse
� History of IntraOperative Complications
� History of Post-Operative Complications
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Non-Anesthesia POCD
Triggers
� Major surgery >Minor Surgery
� Type of Surgery
� Old>Young
� ASA Class 4>1
� Education Level
� Hx of CVA
� Pre-existing MCI
� Length of Surgery
Anesthesia Triggers?
� Hyperventilation�Pre-Frontal Dysfunction
� Residual Inhalation Agents
� Residual IV Drugs�Opoids
�Propofol
�Steroids
� Hyper-metabolic state during surgery
� PTSD
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Delirium vs. POCD
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Delirium…..
� Medical-underlying neurologic disorder
� Medication-pharmaceutical related
� Medication Withdrawal
� Not related to Emergence Delirium which is usually seen in pediatrics
� Hallucinations
� Abnormal State of Consciousness� Hyperactive
� Hypoactive
� Mixed
Delirium (cont)
� Cognitive Deficits are usually seen from
post-op to weeks out.
� Reversible, only if underlying condition
is treatable
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Cognitive Dysfunction…
� Not related to emergence and no
underlying issue prior to surgery
� Impaired memory
� Decreased ability to perform tasks
� Decreased psychomotor dexterity skills.
� Symptoms appear from post-op to
months post-operatively
� Requires pre-op testing to confirm.
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Triggers of Other Etiology
� Medial prefrontal cortex (mPFC)
� Significant change in mRNA expression in
aged subjects vs non-aged.
� Propofol > Precedex
� Fentanyl > Remifentanil
� Postsynaptic density-95 (PSD95)
� Decreased expression in presence of
sevoflurane.
� Most significant change was at 36 hour mark
POCD Testing (not the CPC)
� Pre and Post Procedural Mental
examinations
� Mini Mental State Examination (MMSE)
� Logical Memory Testing
� Boston Naming Test
� Category Fluency Test
� Digit Span Test
� Trail Making Test
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Testing and Research??
� Testing performed at day 1, 3, 7 &
3 months.
� Significant increase in IL-6, TNF, and S-
100β in those patients with
POCD(especially Day 1 and 3)
� Neuroinflammatory and peripheral
inflammatory response as evidenced by
increased plasma cytokines present in
patients exhibiting POCD. Possibly due
to activation of microglia
POCD Research
110
277
100103 103
135
THJR CABG CA
Incidence of POCD
Post-Op Day 7 Post-Op 3 Months
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The Arrow Points to…..
� Mast Cell Release
� Periphral
� Central- Meniges and Choroid Plexus
� Promotes destruction of the BBB further
allowing inflammation
� Nuclear Transferase NF-kB allow for
cytokines to damage
� Also Mitochondria function is altered
Anesthesia:What is your
Plan?
� What do feel is the best approach to
anesthesia in patients predisposed for
POCD?
� Short-acting drugs
� Low potency metabolite of primary drug
� Minimal cognitive effects
� What drugs do you feel are best for
individuals at risk for POCD?
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Inhaled Anesthetics
� Isoflurane causes and increase in
amyloid β and induces apoptosis.
These are key findings in Alzheimer's
Disease
� Sevoflurane appears cause increased
levels of IL-1β, IL-6, and TNF-α
� Desflurane shows smallest percentage
of POCD, especially in patients elderly
patients
Comparison of TIVA and Inhaled
Anesthetics on POCD
Association between the Apolipoprotein E4 and Postoperative Cognitive Dysfunction in Elderly Patients
Undergoing Intravenous Anesthesia and Inhalation Anesthesia
Anesthesiology. 2012;116(1):84-93. doi:10.1097/ALN.0b013e31823da7a2
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Research Comparing TIVA to
Inhalation Anesthesia� Comparative Study
� Propofol
� Sevoflurane
� Sevoflurane and Solumedrol
� MMSE scores significantly higher in the Propofoland Sevo/MP Groups
� Plasma Concentrations of TNF-α, IL-6, and S100β were significantly increased at week 1 in the Sevoflurane Group.
� Direct Correlation between increased TNF-α, IL-6, and S100β levels and decreased MMSE Scores
� Propofol Anesthesia shown to be superior to Sevoflurane, although when combined with Solumedrol neuroprotection was noted.
Statistics regarding
Inhalation vs. Intravenous
0
5
10
15
20
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Pre Day 1 Day 3 Day 7
Group C
Group S
Group S +MP
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Regional vs. GA
� According to Davis, N. et al in the Neurosurgery Anesthesiology a retrospective study looking at general vsregional in noncardiac cases.� 45 studies were reviewed (16utilized)
� Compared GA to SAB, Epidural or LA
� 12 studies showed no difference in POCD at 7 days
� 2 studies showed RA superior to GA
� 2 studies showed GA superior to RA
Now What?
� Inhalation Anesthesia with Sevoflurane
leads to increased POCD in patients
>60yr old vs TIVA and Regional.
� Elevated plasma concentration of
cytokines with Inhalation Anesthesia vs
TIVA.
� Protein S-100β is a biomarker for acute
Brain Injury and is why POCD is seen in
both GA and Regional Anesthesia.
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POCD and Elderly Patients
� 41% of patients age >60 show signs of
POCD from day 1 to 3 months
� 12% of patients >60 show signs of
POCD 3 months post surgery.
Drugs and POCD
� Benzodiazepines
� 48.6% elderly patients experience after
receiving for abdominal surgery.
� POCD at 1 week was similiar with POCD
rates for other anesthetic drugs
� Precedex is shown to reduce POCD
� Most likely due to suppression of cytokine
release
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So What is the Ideal
Anesthetic?� TIVA
� Precedex
� Propofol
� Remifentanil○ Metabolized by nonspecific esterases
� Remimazolam (New?)
� Inhalation Agents� Desflurane
○ Lowest Blood/Muscle and Blood/Fat Coefficient.
� Use Regional Anesthesia � Limit Opioid Use
� Limit Benzodiazepine
� Use ERAS
We haven’t reached the tip of the
ICEBERG…...
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Summary
� Pre-Assessment � Question wake-ups with previous surgeries
� Listen to the family
� Consider Age, Surgery, and Co-existing Disease
� Maintain hemodynamic stability, Acid-Base Balance, and proper anesthetic technique
� Pharmacologic Agents with short half-life, post-op Regional
� Educate your PACU Nurses
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Questions and Answers
Bibliography
� Davis, N. et al, “Postoperative Cognitive Dysfunction Following General versus Regional Anesthesia, A Systematic Review”; Neurosurgery Anesthesiology: Oct. 2014; 26(4): 369-76.
� Therapeutic Medicine: Nov. 2015; 10(5): 1635-42.
� Kotekar, N. et al. “Post-operative Cognitive Dysfunction-Current Preventative Strategies”; Clinical Interventions in Aging: Nov. 8, 2018; (13): 2267-2273.
� Li, Y. et al. “Effect of Dexmedetomidine on Early Postoperative Dysfunction and Perioperative Inflammation in Elderly Patients Undergoing Laparoscopic Cholecystectomy”; Experimental and
� Lin, X. et al. “The Potential Mechanism of Postoperative Cognitive Dysfunction in Older People”; ExperimntalGerontology: Feb. 2020
� Ling, Y. et al. “Decreased PSD95 Expression in Medial Prefrontal Cortex was Associatied with Cogntive Impairment Induced by Sevoflurane Anesthesia”; Journal of AheijiangUniversity Science: Sept. 2015; 16(9): 763-71.
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Bibliography (Cont.)
� Qiao, Y. et al. “ Postoperative Cognitive Dysfunction After Inhalational Anesthesia in Elderly Patients Undergoing Major Surgery: The Influence of Anesthestic Technique, Cerebral Injury and Systematic Inflammation”; BMC Anesthesiology: Oct. 2015; 15: 154-63
� Rundshagen, I, “Postoperative Cognitive Dysfunction”; Deutches Arzteblatt International: 2014; 111(8):119-25.
� Vlisides, P. et al. “Anesthesia and Postoperative Cognitive Dysfunction”, Journal of Anesthesia and Perioperative Medicine. Sept. 2014; 1(1): 60-62.
� Zywiel, M. et al. “The Influence of Anesthesia and Pain Management on Cognitive Dysfunction after Joint Arthroplasty: A Systematic Review”, Clinical Orthopaedicsand Related Research. May 2014; 472(5): 1453-66.
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