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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

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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

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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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