Pathogenesis and treatment of post-operative cognitive dysfunction
Keywords:
Memory deterioration, Pathogenesis, Post-operative cognitive dysfunction, Post-operative mental disorderAbstract
Cognitive disorders common in the post-operative period, are the post-operative delirium (POD) and the post-operative cognitive dysfunction (POCD). The Diagnostic and Statistical Manual of Mental Disorders (DSM) does not mention POCD as a separate disease entity, and thus little is known about the pathogenesis of this disorder. The aim of this study was to review, detect and highlight the most important data cited, regarding pathogenesis mechanisms and treatment of the post-operative cognitive dysfunction (POCD). The study was carried out from March 2015 to June 2015. Literature review was achieved by searching a number of bibliographic databases including PubMed, Google Scholar and SCOPUS, surveying published articles from 1955 to 2014. As far as the selection criteria, the material consists of scientific articles published mainly over the last fifteen years, while material published before 2000 was selected because it was considered to be important. This review showed that deficits are observed in one or more discrete areas of the patient's mental state, such as attention, concentration, memory, psychomotor speed and more. This condition is usually developed over a period of more than a week or month after surgery and is more common in elderly patients. Mechanisms that have been proposed to explain this phenomenon are hyperventilation, hypotension, cerebral microemboli and inflammatory mechanisms. Its differential diagnosis will be made mainly from delirium. POCD treatment will first include the exclusion of any other serious diseases that can cause organic psychosyndrome and then focus on the actual symptoms.
References
Rudra A, Chatterjee S, Kirtania J, Sengupta S, Moitra G, Sirohia S, et al. Postoperative delirium. Indian J
Crit Care Med. 2006; 10(4): 235-40. doi: 10.4103/0972-5229.29842.
Blumenthal JA, Mahanna EP, Madden DJ, White WD, Croughwell ND, Newman MF. Methodological
issues in the assessment of neuropsychologic function after cardiac surgery. Ann Thorac Surg. 1995; 59(5):
-50. doi: 10.1016/0003-4975(95)00055-P. PMID: 7733766.
Mackensen GB, Gelb AW. Postoperative cognitive deficits: more questions than answers. Eur J
Anaesthesiol. 2004; 21(2): 85-8. doi: 10.1097/00003643-200402000-00001. PMID: 14977337.
Wu CL, Hsu W, Richman JM, Raja SN. Postoperative Cognitive Function as an Outcome of Regional
Anesthesia and Analgesia. Reg Anesth Pain Med. 2004; 29(3): 257-68. doi: 10.1097/00115550-200405000- 00013. PMID: 15138912.
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington,
VA: American Psychiatric Publishing; 2013.
Krenk L, Rasmussen LS, Kehlet H. New insights into the pathophysiology of postoperative cognitive
dysfunction. Acta Anaesthesiol Scand. 2010; 54(8): 951-6. doi: 10.1111/j.1399-6576.2010.02268. PMID:
Rasmussen LS, Larsen K, Houx P, Skovgaard LT, Hanning CD, Moller JT. The assessment of
postoperative cognitive function. Acta Anaesthesiol Scand. 2001; 45(3): 275-89. doi: 10.1034/j.1399- 6576.2001.045003275.x. PMID: 11207462.
Krenk L, Rasmussen LS. Postoperative delirium and postoperative cognitive dysfunction in the elderly
what are the differences? Minerva Anestesiol. 2011; 77(7): 742-9. PMID: 21709661.
Monk TG, Weldon BC, Garvan CW, Dede DE, Van der Aa MT, Heilman KM, et al. Predictors of
Cognitive Dysfunction After Major Noncardiac Surgery. Anesthesiology. 2008; 108(1): 18-30. doi:
1097/01.anes.0000296071.19434.1e. PMID: 18156878.
Steinmetz J, Christensen KB, Lund T, Lohse N, Rasmussen LS. Long-term Consequences of Postoperative
Cognitive Dysfunction. Anesthesiology. 2009; 110(3): 548-55. doi: 10.1097/ALN.0b013e318195b569.
PMID: 19225398.
Price CC, Garvan CW, Monk TG. Type and Severity of Cognitive Decline in Older Adults after
Noncardiac Surgery. Anesthesiology. 2008; 108(1): 8-17. doi: 10.1097/01.anes.0000296072.02527.18.
PMID: 18156877, PMCID: PMC2911011.
Weiser TG, Regenbogen SE, Thompson KD, Haynes AB, Lipsitz SR, Berry WR, et al. An estimation of
the global volume of surgery: a modelling strategy based on available data. Lancet. 2008; 372(9633): 139- 44. doi: 10.1016/S0140-6736(08)60878-8. PMID: 18582931.
Etzioni DA, Liu JH, Maggard MA, Ko CY. The Aging Population and Its Impact on the Surgery
Workforce. Ann Surg. 2003; 238(2): 170-7. doi: 10.1097/01.SLA.0000081085.98792.3d. PMID:
, PMCID: PMC1422682.
Wollman SB, Orkin LR. Postoperativehuman reaction time and hypocarbia during anaesthesia. Br J
Anaesth. 1968; 40(12): 920-6. doi: 10.1093/bja/40.12.920. PMID: 5710909.
Blenkarn GD, Briggs G, Bell J, Sugioka K. Cognitive Function after Hypocapnic Hyperventilation.
Anesthesiology. 1972; 37(4): 381-6. doi: 10.1097/00000542-197210000-00004. PMID: 5074717.
Murrin KR, Nagarajan TM. Hyperventilation and psychometric testing. A preliminary study. Anaesthesia.
; 29(1): 50-8. doi: 10.1111/j.1365-2044.1974.tb00582.x. PMID: 4808805.
Bedford P. Adverse cerebral effects of anaesthesia on old people. Lancet. 1955; 266(6884): 259-63. doi:
1016/S0140-6736(55)92689-1. PMID: 13243706.
Gruvstad M, Kebbon L, Lof BA. Changes in mental functions after induced hypotension. Acta Psychiatr
Scand Suppl. 1962; 163(1): 1-112. PMID: 13902478.
Eckenhoff JE, Compton JR, Larson A, Davies RM. Assessment of cerebral effects of deliberate
hypotension by psychological measurements. The Lancet. 1964; 284(7362): 711-4. doi: 10.1016/S0140- 6736(64)92539-5. PMID: 14193942.
Rollason WN, Robertson GS, Cordiner CM, Hall DJ. A comparison of mental function in relation to
hypotensive and normotensive anaesthesia in the elderly. Br J Anaesth. 1971; 43(6): 561-6. doi:
1093/bja/43.6.561. PMID: 5089934.
Thompson GE, Miller RD, Stevens WC, Murray WR. Hypotensive Anesthesia for Total Hip Arthroplasty.
Anesthesiology. 1978; 48(2): 91-6. doi: 10.1097/00000542-197802000-00003. PMID: 655457.
Moller JT, Cluitmans P, Rasmussen LS, Houx P, Rasmussen H, Canet J, et al. Long-term postoperative
cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post- Operative Cognitive Dysfunction. Lancet. 1998; 351(9106): 857-61. doi: 10.1016/S0140-6736(97)07382-0.
PMID: 9525362.
Stump DA, Rogers AT, Hammon JW, Newman SP. Cerebral emboli and cognitive outcome after cardiac
surgery. J Cardiothorac Vasc Anesth. 1996; 10(1): 113-8. doi: 10.1016/S1053-0770(96)80186-8. PMID:
Knipp SC, Matatko N, Wilhelm H, Schlamann M, Thielmann M, Lösch C, et al. Cognitive Outcomes Three
Years After Coronary Artery Bypass Surgery: Relation to Diffusion-Weighted Magnetic Resonance
Imaging. Ann Thorac Surg. 2008; 85(3): 872-9. doi: 10.1016/j.athoracsur.2007.10.083. PMID: 18291160.
Moody DM, Brown WR, Challa VR, Stump DA, Reboussin DM, Legault C. Brain microemboli associated
with cardiopulmonary bypass: A histologic and magnetic resonance imaging study. Ann Thorac Surg.
; 59(5): 1304-7. doi: 10.1016/0003-4975(95)00057-R. PMID: 7733757.
Liu YH, Wang DX, Li LH, Wu XM, Shan GJ, Su Y, et al. The Effects of Cardiopulmonary Bypass on the
Number of Cerebral Microemboli and the Incidence of Cognitive Dysfunction After Coronary Artery
Bypass Graft Surgery. Anesth Analg. 2009; 109(4): 1013-22. doi: 10.1213/ane.0b013e3181aed2bb. PMID:
Knipp SC, Matatko N, Schlamann M, Wilhelm H, Thielmann M, Forsting M, et al. Small ischemic brain
lesions after cardiac valve replacement detected by diffusion-weighted magnetic resonance imaging:
relation to neurocognitive function. Eur J Cardiothor Surg. 2005; 28(1): 88-96. doi:
1016/j.ejcts.2005.02.043. PMID: 15922616.
Barber PA, Hach S, Tippett LJ, Ross L, Merry AF, Milsom P. Cerebral Ischemic Lesions on Diffusion- Weighted Imaging Are Associated With Neurocognitive Decline After Cardiac Surgery. Stroke. 2008;
(5): 1427-33. doi: 10.1161/STROKEAHA.107.502989. PMID: 18323490.
Roach GW, Newman MF, Murkin JM, Martzke J, Ruskin A, Li J, et al. Ineffectiveness of burst
suppression therapy in mitigating perioperative cerebrovascular dysfunction. Multicenter Study of
Perioperative Ischemia (McSPI) Research Group. Anesthesiology. 1999; 90(5): 1255-64. doi:
1097/00000542-199905000-00006. PMID: 10319770.
Grigore AM, Mathew J, Grocott HP, Reves JG, Blumenthal JA, White WD, et al. Prospective Randomized
Trial of Normothermic versus Hypothermic Cardiopulmonary Bypass on Cognitive Function after
Coronary Artery Bypass Graft Surgery. Anesthesiology. 2001; 95(5): 1110-9. doi: 10.1097/00000542- 200111000-00014. PMID: 11684979.
Hindman BJ. Emboli, inflammation, and CNS impairment: an overview. Heart Surg Forum. 2002; 5(3):
-53. PMID: 12538140.
Hudetz JA, Gandhi SD, Iqbal Z, Patterson KM, Pagel PS. Elevated postoperative inflammatory biomarkers
are associated with short- and medium-term cognitive dysfunction after coronary artery surgery. J Anesth.
; 25(1): 1-9. doi: 10.1007/s00540-010-1042-y. PMID: 21061037.
Hudetz JA, Iqbal Z, Gandhi SD, Patterson KM, Byrne AJ, Hudetz AG. Ketamine attenuates post-operative
cognitive dysfunction after cardiac surgery. Acta Anaesthesiol Scand. 2009; 53(7): 864-72. doi:
1111/j.1399-6576.2009.01978.x. PMID: 19422355.
Gao L, Taha R, Gauvin D, Othmen LB, Wang Y, Blaise G. Postoperative Cognitive Dysfunction After
Cardiac Surgery. Chest. 2005; 128(5): 3664-70. doi: 10.1378/chest.128.5.3664. PMID: 16304328.
Day JR, Taylor KM. The systemic inflammatory response syndrome and cardiopulmonary bypass. Int J
Surg. 2005; 3(2): 129-40. doi: 10.1016/j.ijsu.2005.04.002. PMID: 17462274.
Jungwirth B, Kellermann K, Qing M, Mackensen GB, Blobner M, Kochs EF. Cerebral tumor necrosis
factor α expression and long-term neurocognitive performance after cardiopulmonary bypass in rats. J
Thorac Cardiovasc Surg. 2009; 138(4): 1002-7. doi: 10.1016/j.jtcvs.2009.06.022. PMID: 19660347.
Parolari A, Camera M, Alamanni F, Naliato M, Polvani GL, Agrifoglio M, et al. Systemic Inflammation
After On-Pump and Off-Pump Coronary Bypass Surgery: A One-Month Follow-Up. Ann Thorac Surg.
; 84(3): 823-8. doi: 10.1016/j.athoracsur.2007.04.048. PMID: 17720383.
Börgermann J, Scheubel RJ, Simm A, Silber RE, Friedrich I. Inflammatory Response in On- Versus Off- Pump Myocardial Revascularization: Is ECC Really the Culprit? Thorac Cardiovasc Surg. 2007; 55(8):
-80. doi: 10.1055/s-2007-965631. PMID: 18027331.
Jungwirth B, Eckel B, Blobner M, Kellermann K, Kochs EF, Mackensen GB. The Impact of
Cardiopulmonary Bypass on Systemic Interleukin-6 Release, Cerebral Nuclear Factor-kappa B Expression,
and Neurocognitive Outcome in Rats. Anesth Analg. 2010; 110(2): 312-20. doi:
1213/ANE.0b013e3181bbc42e. PMID: 19861361.
Tomic V, Russwurm S, Möller E, Claus RA, Blaess M, Brunkhorst F, et al. Transcriptomic and proteomic
patterns of systemic inflammation in on-pump and off-pump coronary artery bypass grafting. Circulation.
; 112(19): 2912-20. doi: 10.1161/CIRCULATIONAHA.104.531152. PMID: 16275880.
Ma CX, Yin WN, Cai BW, He M, Wu J, Wang JY, et al. Activation of TLR4/NF kappaB signaling
pathway in early brain injury after subarachnoid hemorrhage. Neurol Res. 2009. doi:
1179/016164109X12445616596283. PMID: 19703340.
Clemens JA, Stephenson DT, Smalstig EB, Dixon EP, Little SP. Global Ischemia Activates Nuclear Factor- B in Forebrain Neurons of Rats. Stroke. 1997; 28(5): 1073-80. doi: 10.1161/01.STR.28.5.1073. PMID:
Dhawan J, Benveniste H, Nawrocky M, Smith SD, Biegon A. Transient focal ischemia results in persistent
and widespread neuroinflammation and loss of glutamate NMDA receptors. Neuroimage. 2010; 51(2): 599- 605. doi: 10.1016/j.neuroimage.2010.02.073. PMID: 20206701, PMCID: PMC2856923.
Young G, Bolton C, Archibald Y, Austin T, Wells G. The Electroencephalogram in Sepsis-Associated
Encephalopathy. J Clin Neurophysiol. 1992; 9(1): 145-52. doi: 10.1097/00004691-199201000-00016.
PMID: 1552002.
Davies DC. Blood-brain barrier breakdown and oedema formation in systemic sepsis and human brain
tumours. J Anat. 2002; 200(5): 523-34. doi: 10.1046/j.1469-7580.2002.00047_17.x. PMID: 12162731,
PMCID: PMC1570705.
Kurtel H, Fujimoto K, Zimmerman BJ, Granger DN, Tso P. Ischemia-reperfusion-induced mucosal
dysfunction: role of neutrophils. Am J Physiol. 1991; 261(3 Pt 1): G490-6. PMID: 1887895.
McMillen MA, Huribal M, Sumpio B. Common pathway of endothelial-leukocyte interaction in shock,
ischemia, and reperfusion. Am J Surg. 1993; 166(5): 557-62. doi: 10.1016/S0002-9610(05)81153-5. PMID:
Meisel SR, Shapiro H, Radnay J, Neuman Y, Khaskia AR, Gruener N, et al. Increased expression of
neutrophil and monocyte adhesion molecules LFA-1 and Mac-1 and their ligand ICAM-1 and VLA-4
throughout the acute phase of myocardial infarction: possible implications for leukocyte aggregation and
microvascular plugging. J Am Coll Cardiol. 1998; 31(1): 120-5. doi: 10.1016/S0735-1097(97)00424-5.
PMID: 9426029.
Korthuis RJ, Smith JK, Carden DL. Hypoxic reperfusion attenuates postischemic microvascular injury. Am
J Physiol. 1989; 256(1 Pt 2): H315-9. PMID: 2912194.
Allan SM, Rothwell NJ. Cytokines and acute neurodegeneration. Nat Rev Neurosci. 2001; 2(10): 734-44.
doi: 10.1038/35094583. PMID: 11584311.
González-Scarano F, Baltuch G. Microglia as mediators of inflammatory and degenerative diseases. Annu
Rev Neurosci. 1999; 22: 219-40. doi: 10.1146/annurev.neuro.22.1.219. PMID: 10202538.
Gahtan E, Overmier JB. Inflammatory pathogenesis in Alzheimer's disease: biological mechanisms and
cognitive sequeli. Neurosci Biobehav Rev. 1999; 23(5): 615-33. doi: 10.1016/S0149-7634(98)00058-X.
PMID: 10392655.
Dietrich WD, Alonso O, Halley M, Busto R. Delayed Posttraumatic Brain Hyperthermia Worsens Outcome
after Fluid Percussion Brain Injury: A Light and Electron Microscopic Study in Rats. Neurosurgery. 1996;
(3): 533-41. PMID: 8837806.
Azzimondi G, Bassein L, Nonino F, Fiorani L, Vignatelli L, Re G, et al. Fever in Acute Stroke Worsens
Prognosis: A Prospective Study. Stroke. 1995; 26(11): 2040-3. doi: 10.1161/01.STR.26.11.2040. PMID:
Lipowski ZJ. Transient Cognitive Disorders (Delirium, Acute Confusional Sates) in the Elderly. Am J
Psychiatry. 1983; 140(11): 1426-36. doi: 10.1176/ajp.140.11.1426. PMID: 6624987.
Michota FA, Frost SD. Perioperative management of the hospitalized patient. Med Clin North Am. 2002;
(4): 731-48. doi: 10.1016/S0025-7125(02)00020-2. PMID: 12365338.
Ansaloni L, Catena F, Chattat R, Fortuna D, Franceschi C, Mascitti P, et al. Risk factors and incidence of
postoperative delirium in elderly patients after elective and emergency surgery. Br J Surg. 2010; 97(2):
-80. doi: 10.1002/bjs.6843. PMID: 20069607.
Inouye SK, Zhang Y, Han L, Leo-Summers L, Jones R, Marcantonio E. Recoverable cognitive dysfunction
at hospital admission in older persons during acute illness. J Gen Intern Med. 2006; 21(12): 1276-81. doi:
1111/j.1525-1497.2006.00613.x. PMID: 16965558, PMCID: PMC1924736.
Inouye SK, Ferrucci L. Introduction: Elucidating the Pathophysiology of Delirium and the Interrelationship
of Delirium and Dementia. J Gerontol A Biol Sci Med Sci. 2006; 61(12): 1277-80. doi:
1093/gerona/61.12.1277. PMID: 17234820, PMCID: PMC2645654.
Lynch EP, Lazor MA, Gellis JE, Orav J, Goldman L, Marcantonio ER. The Impact of Postoperative Pain
on the Development of Postoperative Delirium. Anesth Analg. 1998; 86(4): 781-5. doi: 10.1213/00000539- 199804000-00019. PMID: 9539601.
Wang W, Wang Y, Wu H, Lei L, Xu S, Shen X, et al. Postoperative Cognitive Dysfunction: Current
Developments in Mechanism and Prevention. Med Sci Monit. 2014; 20: 1908-12. doi:
12659/MSM.892485. PMID: 25306127, PMCID: PMC4206478.
Attard A, Ranjith G, Taylor D. Delirium and its treatment. CNS Drugs. 2008; 22(8): 631-44. doi:
2165/00023210-200822080-00002. PMID: 18601302.
Joshi S. Current concepts in the management of delirium. Mo Med. 2007; 104(1): 58-62. PMID: 17410827.
Kirshner HS. Delirium: a focused review. Curr Neurol Neurosci Rep. 2007; 7(6): 479-82. doi:
1007/s11910-007-0074-7. PMID: 17999893.
Published
Issue
Section
License
Copyright (c) 2020 KNOWLEDGE KINGDOM PUBLISHING
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.