1 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 Disclosures • Research funding from – National Institutes of Health 2 1
Slide 1 1 Iris Solorzano, 3/16/2012
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 3 Case #1 (cont.) • 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 4 2
Case #1 (cont.) P roblems 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 5 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” 6 3
Medications • Tacrolimus • Aspirin (81 mg) • Sulfasalazine (ulcerative colitis) • Bisphosphonate (alendronate) • Pantoprazole (PPI) • Naproxen • Acetaminophen • Ibuprofen 7 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 8 4
Patient’s concern Is/are the anesthetics contributory to his memory loss? 1. Yes 2. No 3. Uncertain 9 10 5
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 one or more neuropsychological domains • POCD differs from dementia, which describes a chronic, often insidious, decline in cognitive function 11 Timing of POCD Surgery One week 3 months 1-2 years Early Intermediate Long-term 12 6
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 or 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 13 Delirium Risk Model Patient Factors + Extrinsic Factors Risk of Delirium per 100-Person Days 30.0 25.0 20.0 11.6 15.0 10.0 5.0 4.6 0.0 5.0 High 2.3 0.8 Baseline Risks: 0.0 Intermediate 0.0 0.0 • Vision, MMSE < 24, 0.0 Low • 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 . 14 7
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 15 • Can we identify patients who may be at risk for POCD preoperatively? • If so, what are the risk factors? 16 8
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. 17 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. 18 9
Question Are there any medications that should be avoided in patients who are at risk for POCD? Midazolam 1. Fentanyl 2. Volatile agents 3. N 2 O 4. I don’t know 5. 19 • Is one anesthetic type (regional vs. general) superior to another in minimizing POCD? 20 10
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 21 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 22 11
Multi-center trial “ No significant difference was found in the incidence of cognitive dysfunction 3 Months after either general or 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 23 Multi-center trial 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 • Acta Anaesthesiol Scand. 2003 Mar;47(3):260-6 24 12
GA vs. Regional Anesthesia • Multi-center trial of patients ≥ 60 years of age undergoing non-cardiac surgery • Outcomes – POCD at one week and 3 months after surgery GA Regional P-value 37/188 (19.7%) 22/176 (12.5%) 0.06 7 days 7 days * 33/156 (21.2%) 20/158 (12.7%) 0.04 25/175 (14.3%) 23/165 (13.9%) 0.93 3 months • No relationship between GA & long-term POCD *Excluding patients who did not receive the allocated anesthetic Rasmussen LS, et al. Acta Anaesthesiol Scand. 2003;47:260-6. 25 Role of other anesthetic agents? • Isoflurane and sevoflurane induce apoptosis and increases beta-amyloid protein levels in vitro and in mice 1,2 • Isoflurane and nitrous oxide anesthesia produces a sustained learning impairment in aged rats 3 • Propofol anesthesia did not altered spatial memory in aged rats 4 • 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. 26 13
27 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 . 28 14
Anesthetics and Medications • GA vs. regional – no definitive data to support superiority 1 • Medications – no specific culprit 2 • Postoperative pain management – increased risk with PCA opioid 3 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 . 29 The role of inflammation in POCD 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-100 β at 1 h (1872 ± 385 pg/ml vs. 1289 ± 143 pg/ml, P < 0.05. No significant post- operative change was detected in levels of TNF- α , IL-1, or CRP. Acta Anaesthesiol Scand. 2012:10.1111/j.1399-6576.2011 30 15
Is POCD reversible? • How can we advise patients as to how long POCD may last? • What is the temporal sequence of POCD? 31 Incidence of POCD Surgery One week 3 months 1-2 years Early Intermediate Long-term 26% (ISPOCD) 1 5% (Williams-Russo) 2 1- 4% (ISPOCD) 3 10% (ISPOCD) 1 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 ISPOCD = International Study for Postoperative Cognitive Dysfunction Anaesthesiol Scand . 2000;44(10):1246-1251. 32 16
Dijkstra JB, et al. J Am Geriatr Soc . 1998;46(10):1258-1265. 33 Surgery and long-term cognitive decline • 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. 34 17
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