Postoperative Cognitive Decline Noise or Signals? Jacqueline M. - - PDF document

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Postoperative Cognitive Decline – Noise or Signals?

Jacqueline M. Leung, MD, MPH

Professor & Vice Chair of Academic Affairs Department of Anesthesia & Perioperative Care University of California, San Francisco 1

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Disclosures

• Research funding from

– National Institutes of Health

Slide 1 1

Iris Solorzano, 3/16/2012

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Case #1

• 77 year old man
• Lost his job as a corporate accountant after

becoming “forgetful”

• He feels that his cognitive function was impaired

after colon surgery about one month before his memory difficulties were noted by his peers

• He continues to function very well and is trying to

research the problem

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• Patient e-mailed me back, gave me his medical record

number to check on his previous history

• Had multiple previous operations at our institution:

– Liver transplant 7 years ago for end stage liver disease secondary to primary sclerosing cholangitis – Colon CA – total colectomy with ileostomy in 2008, revised in 2009

Case #1 (cont.)

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• Problems with “memory loss” after the total prostatectomy
• Accounting errors while at work
• Sent to see a neuropsychologist who diagnosed cognitive

impairment

• “Requested” by his company to “retire”
• Felt that his memory has improved
• Did not want to “go down” like this in his professional

career, and searching for the answer to explain his apparent “transient” memory loss

Case #1 (cont.)

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Review of Anesthesia History

• Liver transplant – no anesthesia related problem
• Anesthetic in 2008 for prostatectomy – recovery protracted

with wound infection

• Anesthetic in 2009 for incontinence – uncomplicated
• All anesthetics were “balanced technique”

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Medications

• Tacrolimus
• Aspirin (81 mg)
• Sulfasalazine (ulcerative colitis)
• Bisphosphonate (alendronate)
• Pantoprazole (PPI)
• Naproxen
• Acetaminophen
• Ibuprofen

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Habits & Social History

• Non-smoker
• Non-drinker
• No other drug use
• College graduate
• Practicing accountant for 30+ years
• Physically active, plays golf 4x/week, doing well on

immunosuppressant

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Patient’s concern

Is/are the anesthetics contributory to his memory loss?

• 1. Yes
• 2. No
• 3. Uncertain

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What is POCD?

• The term POCD is used mostly in literature to represent a

decline in a variety of neuropsychological domains including memory, executive functioning, and speed of processing.

• A typical patient with POCD is oriented but exhibits significant

declines from his or her own baseline level of performance on

• ne or more neuropsychological domains
• POCD differs from dementia, which describes a chronic, often

insidious, decline in cognitive function

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Timing of POCD

One week 3 months 1-2 years Early Intermediate Long-term

Surgery

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How is POCD measured?

• Performance-based or self-report perceptions of changes in

memory, executive function, attention, learning, language, visual spatial skills, mathematics, motor function and anxiety

• r depression
• Selection of neurocognitive tests varies extensively between

studies

• Two most commonly assessed cognitive domains assessed

are learning and memory and attention and concentration

• Many studies use composite measures of cognitive

functioning to assess patients for the presence of POCD

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Low Intermediate High 0.0 5.0 10.0 15.0 20.0 25.0 30.0

0.0 0.0 0.0

4.6 2.3 0.8 11.6 5.0 0.0

Risk of Delirium per 100-Person Days

Delirium Risk Model Patient Factors + Extrinsic Factors

Baseline Risks:

• Vision, MMSE < 24,
• Apache > 16, Bun/CR > 18

Precipitating Factors: restraints, 3+ new meds, poor nutrition, bladder catheter, iatrogenic event Inouye SK, et al. JAMA. 1996;275:852-857.

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What Can Anesthesiologists Do to Minimize the Occurrence of POCD ?

• Baseline Risk Factors
• Preoperative risk identification
• Precipitating Factors

– Choice of anesthetics – Choice of medications – Postoperative management

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• Can we identify patients who may be at risk for

POCD preoperatively?

• If so, what are the risk factors?

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Risk Factors for Early/Intermediate POCD

• Age
• Education
• Burden of illness
• Preoperative cognitive status
• Pain and opioids use
• ApoE4?

Tsai TL, et al. Adv Anesth. 2010;28:269–284. Fong HK, et al. Anesth Analg. 2006;102:1255–1266. Leung JM, et al. Anesthesiology. 2007;107:406–411.

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Precipitating Factors for Early/Intermediate POCD

• Increased risk
• Second operation
• Postoperative infection
• Respiratory complications
• Role unclear
• Anesthetic type
• Intraoperative blood pressure

Moller JT, et al. Lancet. 1998;351:857–861.

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Question

Are there any medications that should be avoided in patients who are at risk for POCD?

1.

Midazolam

2.

Fentanyl

3.

Volatile agents

4.

N2O

5.

I don’t know

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• Is one anesthetic type (regional vs.

general) superior to another in minimizing POCD?

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GA vs. Regional Anesthesia

• “Cognitive effects after epidural vs general anesthetic in older

adults”

• 262 pts ≥ 40 yrs undergoing elective primary total knee

replacement

• Neuropsychological assessment preop and postop (1 week &

6 month)

Williams-Russo P, et al. JAMA 1995;274:44-50

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GA vs. Regional Anesthesia

• Cognitive outcome
• A generalized decline at 1 wk after surgery
• Return to or improvement over baseline at 6 months
• No difference between groups

Williams-Russo P, et al. JAMA 1995;274:44-50

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Multi-center trial

“No significant difference was found in the incidence of cognitive dysfunction 3 Months after either general

• r regional anesthesia in elderly patients. Thus, there seems to be no causative relationship between

general anaesthesia & long-term POCD.”

Acta Anaesthesiol Scand. 2003 Mar;47(3):260-6

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• At 7 days, POCD was found in 37/188 patients (19.7%)

after GA and in 22/176 (12.5%) after regional anesthesia, P = 0.06

• Sample size calculation: 1,400 patients (assuming a

drop-out of 20%) would allow a detection in difference in POCD (5% after regional and 10% after GA), a = 0.05, power 0.9

• Actual # patients studied = 364
• Calculated power 0.42

Multi-center trial

Acta Anaesthesiol Scand. 2003 Mar;47(3):260-6

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• Multi-center trial of patients ≥ 60 years of age undergoing

non-cardiac surgery

• Outcomes – POCD at one week and 3 months after surgery
• No relationship between GA & long-term POCD

GA vs. Regional Anesthesia

Rasmussen LS, et al. Acta Anaesthesiol Scand. 2003;47:260-6.

GA Regional P-value 7 days 37/188 (19.7%) 22/176 (12.5%) 0.06 7 days* 33/156 (21.2%) 20/158 (12.7%) 0.04 3 months 25/175 (14.3%) 23/165 (13.9%) 0.93

*Excluding patients who did not receive the allocated anesthetic

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• Isoflurane and sevoflurane induce apoptosis and

increases beta-amyloid protein levels in vitro and in mice1,2

• Isoflurane and nitrous oxide anesthesia produces a

sustained learning impairment in aged rats3

• Propofol anesthesia did not altered spatial memory in

aged rats4

• Clinical relevance?
• 1. Xie Z, et al. J Neurosci. 2007; 27(6):1247-1254.

2.

• 2. Dong Y, et al. Arch Neurol. 2009;66(5):620-631.
• 3. 3. Culley DJ, et al. Anesth Analg. 2003;96:1004-1009.
• 4. 4. Lee IH, et al. Anesth Analg. 2008;107:1211-1215.

Role of other anesthetic agents?

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Pain and POCD

• Multivariate regression analyses – only postoperative

analgesia was associated with POCD

• Oral opioids vs. PCA opioid (OR 0.22, P = 0.02)

Wang Y, et al. Am J Geriatr Psychiatry. 2007;15:50-59.

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• GA vs. regional – no definitive data to support superiority1
• Medications – no specific culprit2
• Postoperative pain management – increased risk with PCA
• pioid3
• 1. Tsai TL, et al. Adv Anesth. 2010;28:269–284.
• 2. Fong HK, et al. Anesth Analg. 2006;102:1255–1266.
• 3. Wang Y, et al. Am J Geriatr Psychiatry. 2007;15:50-59.

Anesthetics and Medications

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17/37 (54.1%,) patients developed POCD 1 day after surgery, and 3/37 (8.1%) developed POCD 7 days after surgery. Patients with POCD 1 day after surgery had significantly higher serum levels of IL-6 at 6 h (135 ± 32 pg/ml vs. 91 ± 29 pg/ml, P < 0.05) and S-100β at 1 h (1872 ± 385 pg/ml vs. 1289 ± 143 pg/ml, P < 0.05. No significant post-

• perative change was detected in levels of TNF-α, IL-1, or CRP.

The role of inflammation in POCD

Acta Anaesthesiol Scand. 2012:10.1111/j.1399-6576.2011

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• How can we advise patients as to how long

POCD may last?

• What is the temporal sequence of POCD?

Is POCD reversible?

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• 1. Williams-Russo P, et al. JAMA 1995;274:44-50. 2. Moller JT,

et al. Lancet. 1998;351:857-861. 3. Abildstrom H, et al. Acta Anaesthesiol Scand. 2000;44(10):1246-1251.

One week 3 months 1-2 years Early Intermediate Long-term

Surgery

26% (ISPOCD)1 5% (Williams-Russo)2 10% (ISPOCD)1 1- 4% (ISPOCD)3

ISPOCD = International Study for Postoperative Cognitive Dysfunction

Incidence of POCD

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Dijkstra JB, et al. J Am Geriatr Soc. 1998;46(10):1258-1265.

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• Are subjects already on a trajectory of decline before

surgery?

• What are the effects of surgery on cognitive function in

patients with pre-existent cognitive dysfunction or Alzheimer’s Disease?

Avidan MS, et al. Anesthesiology. 2009;111:964-970.

Surgery and long-term cognitive decline

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Avidan MS, et al. Anesthesiology. 2009;111:964-970.

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Acute illness and long-term cognitive decline

Preop Preop Postop Postop SURGERY

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• Retrospective cohort study, subjects recruited from ADRC
• Non-cardiac surgery, illness or neither
• N=575, 214 non demented, 361 had very mild or mild dementia @

recruitment

• Median years of follow up 3.1 years
• Those with Clinical Dementia Rating (CDR) 0.5 or 1 were recruited

(no or mild dementia)

• Novelties:
• Not recruited because of surgical status
• Substantial pre-event data

Avidan et al.

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• Cognitive trajectories did not differ among the three

groups (surgery, illness, control), although demented participants declined more markedly than nondemented.

• Of the initially nondemented participants, 23%

progressed to a clinical dementia rating greater than zero, but this was not more common following surgery

• r illness

Avidan et al.

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Acute illness and long-term cognitive decline

Preop Preop Postop Postop SURGERY

✔ ✗

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Question #1 Revisited

• Is/are the anesthetics contributory to memory loss in

this patient? and how can this be assessed?

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POCD and Anesthesia

• Noise or signals?
• To the patient and/or family – an important phenomenon

involving alteration in thinking and memory (self care and cognitive functioning affected)

• Associated with premature withdrawal from labor market
• Possibly associated with increased long-term mortality
• Acute POCD may in fact be marker of patients with MCI

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POCD and Anesthesia

• The anesthetics per se are not likely contributing to this

memory loss directly

• No preoperative cognitive assessment (unknown baseline)
• Postoperative events important and management important
• Most cases of early POCD do improve
• Relationship to long-term cognitive decline unclear

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• POCD – likely under-estimated in the

hospital setting

• Although short-live, can affect ADL, IADL,

ability to follow discharge instructions as

• utpatients
• Pain, opioids, preoperative cognitive

status, sensory impairment contributing factors

Summary