Preventing Postoperative Preventing Postoperative Cognitive Decline Cognitive Decline

in the Elderlyin the Elderly

Alex Bekker, M.D., Ph.DAlex Bekker, M.D., Ph.DProfessor and ChairProfessor and Chair

Department of AnesthesiologyDepartment of AnesthesiologyRutgers New Jersey Medical SchoolRutgers New Jersey Medical School

"My brain, that's my second favorite organ"

Subtle Perioperative Brain InjurySubtle Perioperative Brain Injury

Emergence DeliriumEmergence Delirium

Postoperative DeliriumPostoperative Delirium

Postoperative Cognitive DeclinePostoperative Cognitive Decline

Postoperative DeliriumPostoperative Delirium

An acute brain disorder An acute brain disorder that has a fluctuating that has a fluctuating course and course and characterized by characterized by disturbance of disturbance of attention, memory, attention, memory, orientation, and orientation, and perceptionperception

Incidence (in elderly) Incidence (in elderly) Noncardiac surgery: Noncardiac surgery: 10%-40%10%-40%Cardiac surgery: 20%-Cardiac surgery: 20%-70% 70%

Interplay of Factors Leading to DeliriumInterplay of Factors Leading to Delirium

Steiner L, Eur J Anaesth, 2011

Predisposing FactorsPredisposing Factors

AgeAge Functional impairmentFunctional impairment Cognitive impairmentCognitive impairment Medical co-morbidityMedical co-morbidity DrugsDrugs Genetic factors (sigma 4 allele of Genetic factors (sigma 4 allele of

apolipoprotein E4)apolipoprotein E4)

Precipitating FactorsPrecipitating Factors

Admission to ICUAdmission to ICU DrugsDrugs Concomitant illnessConcomitant illness Primary neurologic diseasePrimary neurologic disease PainPain Use of physical restraintsUse of physical restraints Prolonged sleep deprivationProlonged sleep deprivation

Can Delirium be Prevented in the Can Delirium be Prevented in the Postoperative Period?Postoperative Period?

Pharmacological preventionPharmacological prevention Non-pharmacologic multicomponent Non-pharmacologic multicomponent

strategiesstrategies– Good nursing careGood nursing care– Regular orientationRegular orientation– Early mobilizationEarly mobilization– Reduce modifiable risk factorsReduce modifiable risk factors

Inouye S, JAMA, 1998

Pain Management and Pain Management and Postoperative Delirium Postoperative Delirium

Vaurio L, Anesth Analg 2006

Pharmacologic StrategiesPharmacologic Strategies

Dopamine HaloperidolDopamine Haloperidol Serotonin Risperidone/QuetiapineSerotonin Risperidone/Quetiapine Acetylcholine Rivastigmine/DonazepilAcetylcholine Rivastigmine/Donazepil Norepinephrine DexmedetomidineNorepinephrine Dexmedetomidine

GABA BenzodiazepinesGABA Benzodiazepines

MENDS: Dexmedetomidine vs Lorazepam MENDS: Dexmedetomidine vs Lorazepam

Pandharipande PP, et al. JAMA. 2007;298:2644-2653.

Dexmedetomidine resulted Dexmedetomidine resulted in more days alive without in more days alive without delirium or coma (delirium or coma (P P = = 0.01) and a lower 0.01) and a lower prevalence of coma (prevalence of coma (P P < < 0.001) than lorazepam0.001) than lorazepam

Dexmedetomidine resulted Dexmedetomidine resulted in more time spent within in more time spent within sedation goals than sedation goals than lorazepam (lorazepam (P P = 0.04)= 0.04)

Differences in 28-day Differences in 28-day mortality and delirium-free mortality and delirium-free days were not significantdays were not significant

Days

Lorazepam n = 51Dexmedetomidine n = 520

24

68

10

12 P = 0.011

Delirium/Coma-Free

Days

Delirium-Free Days

P = 0.086 P < 0.001

Coma-Free Days

Midazolam

Dexmedetomidine

Dexmedetomidine versus Midazolam, P < 0.001

Reduced Delirium Prevalence with Dexmedetomidine Reduced Delirium Prevalence with Dexmedetomidine vs Midazolamvs Midazolam

SEDCOMSEDCOM

Sample Size 118 229 109 206 92 175 77 134 57 92 42 60 44 34Treatment Day

0

20

40

60

80

100

Baseline 1 2 3 4 5 6

Pati

en

ts W

ith

Deliri

um

, %

Riker RR, et al. JAMA. 2009;301:489-499.

Monitoring Depth of Anesthesia Monitoring Depth of Anesthesia and Postoperative Deliriumand Postoperative Delirium

Study Routine Care BIS-Guided P-Value

Radtke F, Br J Anaesth, 2013

124/580 (21.4%)

95/575 (16.7%)

0.036

Chan M, J Neurosurg Anesth, 2013

109/452 (24.1%)

70/450 (15.6%)

0.01

Delirium PreventionDelirium Prevention Multicomponent targeted intervention strategyMulticomponent targeted intervention strategy

Optimizing medical conditionOptimizing medical condition

Continue antidepressant treatmentContinue antidepressant treatment

Postoperative pain control Postoperative pain control

Avoid benzodiazepinesAvoid benzodiazepines

Dexmedetomidine Dexmedetomidine

Use of brain function monitors (?)Use of brain function monitors (?)

Grandma Never Was The Same…Grandma Never Was The Same…

“He’s become so forgetful since…”

“He can’t concentrate on anything since…”

“She’s become childish and unreliable since…”

“He’s not just the same person since…”

CONCLUSION: Operations on elderly people should be confined to unequivocally necessary cases

Postoperative Cognitive Postoperative Cognitive Dysfunction (POCD):Dysfunction (POCD):

An impairment of functioning An impairment of functioning in several cognitive in several cognitive domains: memory, domains: memory, executive functioning, executive functioning, attention, and attention, and comprehensioncomprehension

POCD Following Cardiac SurgeryPOCD Following Cardiac Surgery

Study Follow-up Incidence

Newman M, NEJM, 2001

6 months & 5 years 45% & 42%

Van Dijk D, Ann Thor Surg, 2008

5 years 34% versus 16 % in control

Selnes O, Ann Neurol, 2008

3 and 6 years No difference

Wahrborg P, Circulation, 2004

1 No difference

POCD following Non-Cardiac SurgeryPOCD following Non-Cardiac Surgery

Study Follow-up Incidence

Molner J, Lancet, 1998 3 months 9.8%

Abidstrom H, Acta Anaest Scand, 2000

1-2 years No difference

Avidan M, Anesthesiology, 2009

3.1 years(median) No difference

McDonagh, Anesthesiology, 2010

1 year 46%

Kline R, Anesthesiology, 2012

9 month (median) Only patients with MCI

Methodological Challenges Methodological Challenges

Definition of POCDDefinition of POCD What tests should we use?What tests should we use? ControlsControls Learning effectLearning effect Cognitive trajectoryCognitive trajectory

There are no laboratory test or imaging study which can be used to predict or diagnose POCD

Preoperative and Postoperative Preoperative and Postoperative Cognitive TrajectoriesCognitive Trajectories

Sanders R, Neurologic outcomes of Surgery & Anesthesia, 2013

Predisposing Factors : POCDPredisposing Factors : POCD

AgeAge

Preoperative cognitionPreoperative cognition

Type of surgeryType of surgery

Vascular risk factorsVascular risk factors

Apolipoprotein E genotype (?)Apolipoprotein E genotype (?)

Possible causes of POCD Possible causes of POCD Related to SurgeryRelated to Surgery

Altered cerebral perfusionAltered cerebral perfusion AnestheticsAnesthetics Cerebral microemboliCerebral microemboli InflammationInflammation

– Surgery relatedSurgery related– Patient relatedPatient related

Conceptual Model of POCDConceptual Model of POCD

Eckenhoff R, Prog Neuro-Psychopharm & Bio Psych, 2012

MCI: DiagnosisMCI: Diagnosis

MCI is diagnosed when there is:MCI is diagnosed when there is:

– Evidence of memory impairmentEvidence of memory impairment– Preservation of general cognitive and Preservation of general cognitive and

functional abilitiesfunctional abilities– Absence of diagnosed dementiaAbsence of diagnosed dementia

Morris J, Arch Neurol, 2001

Diagnostic and Treatment Possibilities Along Diagnostic and Treatment Possibilities Along the Evolution of Dementiathe Evolution of Dementia

Cedazo-Minguez A et al., Exp Gerontology, 2010

Does MCI Increases the Risk of POCD?Does MCI Increases the Risk of POCD?

Baseline Follow-up

Visit

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MCI no surgery

MCI surgery

Baseline Follow up

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MCI no surgery

MCI surgery

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MCI no surgery

MCI surgery

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MCI no surgery

MCI surgery

Bekker A , Am J Surg, 2010

Brain Images from Age Matched Cognitively Brain Images from Age Matched Cognitively Intact Individuals and AD PatientsIntact Individuals and AD Patients

Cedazo-Minguez A et al., Exp Gerontology, 2010

Study Design: Longitudinal Study Design: Longitudinal Examination of Structural MRI Examination of Structural MRI

From ADNI DatabaseFrom ADNI Database Apply MRI to study perioperative cortical Apply MRI to study perioperative cortical

volume change in surgical subjects volume change in surgical subjects

Examine hippocampus, gray matter, white Examine hippocampus, gray matter, white matter and lateral ventricle. matter and lateral ventricle.

Examine composite cognitive scoreExamine composite cognitive score

LV Volume Changes in a Surgical LV Volume Changes in a Surgical Patient with MCIPatient with MCI

Bekker A, Anesthesiology 2012

Atrophy of Hippocampus in the Atrophy of Hippocampus in the Perioperative PeriodPerioperative Period

Kline R, Anesthesiology 2012

POCD: Concluding RemarksPOCD: Concluding Remarks

Standardization of diagnostic criteria Standardization of diagnostic criteria NeuroinflammationNeuroinflammation Low intraoperative cerebral Low intraoperative cerebral

oxygenationoxygenation Patient-related factors:Patient-related factors:

– AgeAge– Pre-existing cognitive impairmentPre-existing cognitive impairment– Cognitive reserveCognitive reserve– Priming of the immune systemPriming of the immune system

Low Tech Prescriptions for Low Tech Prescriptions for LongevityLongevity

““Swim, dance a little, go to Paris every Swim, dance a little, go to Paris every August and live within walking distance of August and live within walking distance of two hospitals”two hospitals”

Horatio Lure, at 80Horatio Lure, at 80

““Stay busy, get plenty of exercise and don’t Stay busy, get plenty of exercise and don’t drink too much.drink too much.

Then again, don’t drink too little”Then again, don’t drink too little”Herman ”Jack Rabbit” Smith-Johannsen, at Herman ”Jack Rabbit” Smith-Johannsen, at

103103

““The secret to longevity is to keep breathing” The secret to longevity is to keep breathing” My observationMy observation