Skip to main content
SpringerLink
Log in

Does Dexmedetomidine Ameliorate Postoperative Cognitive Dysfunction? A Brief Review of the Recent Literature

  • Critical Care (SA Mayer, Section Editor)
  • Published:
Current Neurology and Neuroscience Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Postoperative cognitive dysfunction (POCD) occurs in 20–50% of postsurgical patients with a higher prevalence in elderly patients and patients with vascular disease and heart failure. In addition, POCD has been associated with many negative outcomes, such as increased hospital length of stay, increased rates of institutionalization, and higher patient mortality. This brief review discusses select evidence suggesting an association between neuroinflammation and POCD and whether the use of dexmedetomidine, a short-acting alpha 2 agonist, may ameliorate the incidence of POCD. We review the recent evidence for neuroinflammation in POCD, dexmedetomidine’s properties in reducing inflammatory-mediated brain injury, and clinical studies of dexmedetomidine and POCD.

Recent Findings

There is evidence to support the anti-inflammatory and immunomodulatory effects of dexmedetomidine in animal models. Several clinical investigations have demonstrated favorable outcomes using dexmedetomidine over placebo for the reduction of postoperative delirium. Few studies have used high-quality endpoints for the assessment of POCD and no demonstrable evidence supports the use of dexmedetomidine for the prevention of POCD.

Summary

While evidence exists for the neural anti-inflammatory properties of dexmedetomidine, human trials have yielded incomplete results concerning its use for the management of POCD. Dexmedetomidine may reduce acute postoperative delirium, but further studies are needed prior to recommending the use of dexmedetomidine for the direct reduction of POCD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major Importance

  1. Feinkohl I, Winterer G, Spies CD, Pischon T. Cognitive reserve and the risk of postoperative cognitive dysfunction. Deutsch Arztebl Int. 2017;114(7):110–7.

    Google Scholar 

  2. • Needham MJ, Webb CE, Bryden DC. Postoperative cognitive dysfunction and dementia: what we need to know and do. Br J Anaesth. 2017;119(suppl_1):i115–i25. An excellent analysis of the definition and diagnosis of postoperative dysfunction.

    Article  CAS  PubMed  Google Scholar 

  3. Rasmussen LS. Postoperative cognitive dysfunction: incidence and prevention. Best Pract Res Clin Anaesthesiol. 2006;20(2):315–30.

    Article  PubMed  Google Scholar 

  4. Coburn M, Fahlenkamp A, Zoremba N, Schaelte G. Postoperative cognitive dysfunction: incidence and prophylaxis. Anaesthesist. 2010;59(2):177–84. quiz 85

    Article  CAS  PubMed  Google Scholar 

  5. Moskowitz EE, Overbey DM, Jones TS, Jones EL, Arcomano TR, Moore JT, et al. Post-operative delirium is associated with increased 5-year mortality. Am J Surg. 2017;214(6):1036–8.

    Article  PubMed  Google Scholar 

  6. Radtke FM, Franck M, Herbig TS, Papkalla N, Kleinwaechter R, Kork F, et al. Incidence and risk factors for cognitive dysfunction in patients with severe systemic disease. J Int Med Res. 2012;40(2):612–20.

    Article  CAS  PubMed  Google Scholar 

  7. Robinson TN, Raeburn CD, Tran ZV, Angles EM, Brenner LA, Moss M. Postoperative delirium in the elderly: risk factors and outcomes. Ann Surg. 2009;249(1):173–8.

    Article  PubMed  Google Scholar 

  8. Feinkohl I, Winterer G, Pischon T. Diabetes is associated with risk of postoperative cognitive dysfunction: a meta-analysis. Diabetes Metab Res Rev. 2017;33(5).

    Article  CAS  Google Scholar 

  9. Plas M, Rotteveel E, Izaks GJ, Spikman JM, van der Wal-Huisman H, van Etten B, et al. Cognitive decline after major oncological surgery in the elderly. Eur J Cancer (Oxford, England: 1990). 2017;86:394–402.

    Article  CAS  Google Scholar 

  10. Devore EE, Fong TG, Marcantonio ER, Schmitt EM, Travison TG, Jones RN, et al. Prediction of long-term cognitive decline following postoperative delirium in older adults. J Gerontol A Biol Sci Med Sci. 2017;72(12):1697–702.

    Article  PubMed  Google Scholar 

  11. Singh-Manoux A, Fayosse A, Sabia S, Canonico M, Bobak M, Elbaz A, et al. Atrial fibrillation as a risk factor for cognitive decline and dementia. Eur Heart J. 2017;38(34):2612–8.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Celutkiene J, Vaitkevicius A, Jakstiene S, Jatuzis D. Expert opinion-cognitive decline in heart failure: more attention is needed. Card Fail Rev. 2016;2(2):106–9.

    PubMed  PubMed Central  Google Scholar 

  13. Langer SZ, Hicks PE. Alpha-adrenoreceptor subtypes in blood vessels: physiology and pharmacology. J Cardiovasc Pharmacol. 1984;6(Suppl 4):S547–58.

    Article  PubMed  Google Scholar 

  14. Dawson LF, Phillips JK, Finch PM, Inglis JJ, Drummond PD. Expression of alpha1-adrenoceptors on peripheral nociceptive neurons. Neuroscience. 2011;175:300–14.

    Article  CAS  PubMed  Google Scholar 

  15. Arnsten AF, Pliszka SR. Catecholamine influences on prefrontal cortical function: relevance to treatment of attention deficit/hyperactivity disorder and related disorders. Pharmacol Biochem Behav. 2011;99(2):211–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Di Cesare Mannelli L, Micheli L, Crocetti L, Giovannoni MP, Vergelli C, Ghelardini C. alpha2 Adrenoceptor: a target for neuropathic pain treatment. Mini Rev Med Chem. 2017;17(2):95–107.

    Article  PubMed  CAS  Google Scholar 

  17. Langer SZ. alpha2-Adrenoceptors in the treatment of major neuropsychiatric disorders. Trends Pharmacol Sci. 2015;36(4):196–202.

    Article  CAS  PubMed  Google Scholar 

  18. Virtanen R. Pharmacological profiles of medetomidine and its antagonist, atipamezole. Acta Vet Scand Suppl. 1989;85:29–37.

    CAS  PubMed  Google Scholar 

  19. Song AH, Kucyi A, Napadow V, Brown EN, Loggia ML, Akeju O. Pharmacological modulation of noradrenergic arousal circuitry disrupts functional connectivity of the locus ceruleus in humans. J Neurosci. 2017;37(29):6938–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Akeju O, Loggia ML, Catana C, Pavone KJ, Vazquez R, Rhee J, et al. Disruption of thalamic functional connectivity is a neural correlate of dexmedetomidine-induced unconsciousness. elife. 2014;3:e04499.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Hamilton C, Ma Y, Zhang N. Global reduction of information exchange during anesthetic-induced unconsciousness. Brain Struct Funct. 2017;222(7):3205–16.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Funai Y, Pickering AE, Uta D, Nishikawa K, Mori T, Asada A, et al. Systemic dexmedetomidine augments inhibitory synaptic transmission in the superficial dorsal horn through activation of descending noradrenergic control: an in vivo patch-clamp analysis of analgesic mechanisms. Pain. 2014;155(3):617–28.

    Article  CAS  PubMed  Google Scholar 

  23. Zhang B, Wang G, Liu X, Wang TL, Chi P. The opioid-sparing effect of perioperative dexmedetomidine combined with oxycodone infusion during open hepatectomy: a randomized controlled trial. Front Pharmacol. 2017;8:940.

    Article  PubMed  Google Scholar 

  24. Sharma R, Gupta R, Choudhary R, Singh Bajwa SJ. Postoperative analgesia with intravenous paracetamol and dexmedetomidine in laparoscopic cholecystectomy surgeries: a prospective randomized comparative study. Int J Appl Basic Med Res. 2017;7(4):218–22.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Sun S, Wang J, Bao N, Chen Y. Comparison of dexmedetomidine and fentanyl as local anesthetic adjuvants in spinal anesthesia: a systematic review and meta-analysis of randomized controlled trials. Drug Des Devel Ther. 2017;11:3413–24.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Schomer KJ, Sebat CM, Adams JY, Duby JJ, Shahlaie K, Louie EL. Dexmedetomidine for refractory intracranial hypertension. J Intensive Care Med. 2017; https://doi.org/10.1177/0885066616689555.

  27. Aouad MT, Zeeni C, Al Nawwar R, Siddik-Sayyid SM, Barakat HB, Elias S, et al. Dexmedetomidine for improved quality of emergence from general anesthesia: a dose-finding study. Anesth Analg. 2017.

  28. Elbakry AE, Sultan WE, Ibrahim E. A comparison between inhalational (desflurane) and total intravenous anaesthesia (propofol and dexmedetomidine) in improving postoperative recovery for morbidly obese patients undergoing laparoscopic sleeve gastrectomy: a double-blinded randomised controlled trial. J Clin Anesth. 2017;45:6–11.

    Article  PubMed  CAS  Google Scholar 

  29. Davy A, Fessler J, Fischler M. M LEG. Dexmedetomidine and general anesthesia: a narrative literature review of its major indications for use in adults undergoing non-cardiac surgery. Minerva Anestesiol. 2017;83(12):1294–308.

    PubMed  Google Scholar 

  30. Perry EC. Inpatient management of acute alcohol withdrawal syndrome. CNS Drugs. 2014;28(5):401–10.

    Article  CAS  PubMed  Google Scholar 

  31. Muzyk AJ, Kerns S, Brudney S, Gagliardi JP. Dexmedetomidine for the treatment of alcohol withdrawal syndrome: rationale and current status of research. CNS Drugs. 2013;27(11):913–20.

    Article  CAS  PubMed  Google Scholar 

  32. Skvarc DR, Berk M, Byrne LK, Dean OM, Dodd S, Lewis M, et al. Post-operative cognitive dysfunction: an exploration of the inflammatory hypothesis and novel therapies. Neurosci Biobehav Rev. 2018;84:116–33.

    Article  PubMed  Google Scholar 

  33. •• Hovens IB, Schoemaker RG, van der Zee EA, Absalom AR, Heineman E, van Leeuwen BL. Postoperative cognitive dysfunction: involvement of neuroinflammation and neuronal functioning. Brain Behav Immun. 2014;38:202–10. A comprehensive review of neuroinflammation.

    Article  CAS  PubMed  Google Scholar 

  34. •• Terrando N, Eriksson LI, Ryu JK, Yang T, Monaco C, Feldmann M, et al. Resolving postoperative neuroinflammation and cognitive decline. Ann Neurol. 2011;70(6):986–95. An elegant series of experiments detailing the effects of surgical related inflammation on the blood brain barrier and cognition.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Yang N, Liang Y, Yang P, Wang W, Zhang X, Wang J. TNF-alpha receptor antagonist attenuates isoflurane-induced cognitive impairment in aged rats. Exp Ther Med. 2016;12(1):463–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Bi J, Shan W, Luo A, Zuo Z. Critical role of matrix metallopeptidase 9 in postoperative cognitive dysfunction and age-dependent cognitive decline. Oncotarget. 2017;8(31):51817–29.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Zhang S, Dong H, Zhang X, Li N, Sun J, Qian Y. Cerebral mast cells contribute to postoperative cognitive dysfunction by promoting blood brain barrier disruption. Behav Brain Res. 2016;298(Pt B):158–66.

    Article  CAS  PubMed  Google Scholar 

  38. Xu J, Dong H, Qian Q, Zhang X, Wang Y, Jin W, et al. Astrocyte-derived CCL2 participates in surgery-induced cognitive dysfunction and neuroinflammation via evoking microglia activation. Behav Brain Res. 2017;332:145–53.

    Article  CAS  PubMed  Google Scholar 

  39. Willner AE, Rabiner CJ. Psychopathology and cognitive dysfunction five years after open-heart surgery. Compr Psychiatry. 1979;20(5):409–18.

    Article  CAS  PubMed  Google Scholar 

  40. Westaby S, Saatvedt K, White S, Katsumata T, van Oeveren W, Halligan PW. Is there a relationship between cognitive dysfunction and systemic inflammatory response after cardiopulmonary bypass? Ann Thorac Surg. 2001;71(2):667–72.

    Article  CAS  PubMed  Google Scholar 

  41. Smith PL. The systemic inflammatory response to cardiopulmonary bypass and the brain. Perfusion. 1996;11(3):196–9.

    Article  CAS  PubMed  Google Scholar 

  42. Peng L, Xu L, Ouyang W. Role of peripheral inflammatory markers in postoperative cognitive dysfunction (POCD): a meta-analysis. PLoS One. 2013;8(11):e79624.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Li YC, Xi CH, An YF, Dong WH, Zhou M. Perioperative inflammatory response and protein S-100beta concentrations - relationship with post-operative cognitive dysfunction in elderly patients. Acta Anaesthesiol Scand. 2012;56(5):595–600.

    Article  CAS  PubMed  Google Scholar 

  44. Kline R, Wong E, Haile M, Didehvar S, Farber S, Sacks A, et al. Peri-operative inflammatory cytokines in plasma of the elderly correlate in prospective study with postoperative changes in cognitive test scores. Int J Anesthesiol Res. 2016;4(8):313–21.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Steinberg BE, Sundman E, Terrando N, Eriksson LI, Olofsson PS. Neural control of inflammation: implications for perioperative and critical care. Anesthesiology. 2016;124(5):1174–89.

    Article  PubMed  Google Scholar 

  46. Qiao Y, Feng H, Zhao T, Yan H, Zhang H, Zhao X. Postoperative cognitive dysfunction after inhalational anesthesia in elderly patients undergoing major surgery: the influence of anesthetic technique, cerebral injury and systemic inflammation. BMC Anesthesiol. 2015;15:154.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Forsberg A, Cervenka S, Jonsson Fagerlund M, Rasmussen LS, Zetterberg H, Erlandsson Harris H, et al. The immune response of the human brain to abdominal surgery. Ann Neurol. 2017;81(4):572–82.

    Article  CAS  PubMed  Google Scholar 

  48. Wang L, Liu H, Zhang L, Wang G, Zhang M, Yu Y. Neuroprotection of dexmedetomidine against cerebral ischemia-reperfusion injury in rats: involved in inhibition of NF-kappaB and inflammation response. Biomol Ther. 2017;25(4):383–9.

    Article  Google Scholar 

  49. Xiong B, Shi Q, Fang H. Dexmedetomidine alleviates postoperative cognitive dysfunction by inhibiting neuron excitation in aged rats. Am J Transl Res. 2016;8(1):70–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. • Yamanaka D, Kawano T, Nishigaki A, Aoyama B, Tateiwa H, Shigematsu-Locatelli M, et al. Preventive effects of dexmedetomidine on the development of cognitive dysfunction following systemic inflammation in aged rats. J Anesth. 2017;31(1):25–35. Yamanaka demonstrates that pre-systemic insult treatment with dexmedetomidine may mitigate neuroinflammation in a rat model of cognitive dysfunction.

    Article  PubMed  Google Scholar 

  51. Zhu YJ, Peng K, Meng XW, Ji FH. Attenuation of neuroinflammation by dexmedetomidine is associated with activation of a cholinergic anti-inflammatory pathway in a rat tibial fracture model. Brain Res. 2016;1644:1–8.

    Article  CAS  PubMed  Google Scholar 

  52. Xu KL, Liu XQ, Yao YL, Ye MR, Han YG, Zhang T, et al. Effect of dexmedetomidine on rats with convulsive status epilepticus and association with activation of cholinergic anti-inflammatory pathway. Biochem Biophys Res Commun. 2017.

  53. Lannes N, Eppler E, Etemad S, Yotovski P, Filgueira L. Microglia at center stage: a comprehensive review about the versatile and unique residential macrophages of the central nervous system. Oncotarget. 2017;8(69):114393–413.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Peng M, Wang YL, Wang CY, Chen C. Dexmedetomidine attenuates lipopolysaccharide-induced proinflammatory response in primary microglia. J Surg Res. 2013;179(1):e219–25.

    Article  CAS  PubMed  Google Scholar 

  55. Liu H, Davis JR, Wu ZL, Faez Abdelgawad A. Dexmedetomidine attenuates lipopolysaccharide induced MCP-1 expression in primary astrocyte. Biomed Res Int. 2017;2017:6352159.

    PubMed  PubMed Central  Google Scholar 

  56. Chen C, Qian Y. Protective role of dexmedetomidine in unmethylated CpG-induced inflammation responses in BV2 microglia cells. Folia Neuropathol. 2016;54(4):382–91.

    Article  PubMed  Google Scholar 

  57. Zhang X, Wang J, Qian W, Zhao J, Sun L, Qian Y, et al. Dexmedetomidine inhibits inducible nitric oxide synthase in lipopolysaccharide-stimulated microglia by suppression of extracellular signal-regulated kinase. Neurol Res. 2015;37(3):238–45.

    Article  PubMed  CAS  Google Scholar 

  58. Choi S-H, Lee H, Chung T-S, Park K-M, Jung Y-C, Kim SI, et al. Neural network functional connectivity during and after an episode of delirium. Am J Psychiatr. 2012;169(5):498–507.

    Article  PubMed  Google Scholar 

  59. Zhou C, Zhu Y, Liu Z, Ruan L. Effect of dexmedetomidine on postoperative cognitive dysfunction in elderly patients after general anaesthesia: a meta-analysis. J Int Med Res. 2016;44(6):1182–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Palsetia D, Rao GP, Tiwari SC, Lodha P, De Sousa A. The clock drawing test versus mini-mental status examination as a screening tool for dementia: a clinical comparison. Indian J Psychol Med. 2018;40(1):1–10.

    PubMed  PubMed Central  Google Scholar 

  61. Man Y, Guo Z, Cao J, Mi W. Efficacy of perioperative dexmedetomidine in postoperative neurocognitive function: a meta-analysis. Clin Exp Pharmacol Physiol. 2015;42(8):837–42.

    Article  CAS  PubMed  Google Scholar 

  62. •• Deiner S, Luo X, Lin HM, Sessler DI, Saager L, Sieber FE, et al. Intraoperative infusion of dexmedetomidine for prevention of postoperative delirium and cognitive dysfunction in elderly patients undergoing major elective noncardiac surgery: a randomized clinical trial. JAMA Surg. 2017;152(8):e171505. The most comprehensive clinical trial of dexemedetomidine for the treatment of postoperative cognitive dysfunction to date.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Weintraub S, Besser L, Dodge HH, Teylan M, Ferris S, Goldstein FC, et al. Version 3 of the Alzheimer disease centers’ neuropsychological test battery in the uniform data set (UDS). Alzheimer Dis Assoc Disord. 2017.

  64. Su X, Meng ZT, Wu XH, Cui F, Li HL, Wang DX, et al. Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery: a randomised, double-blind, placebo-controlled trial. Lancet (London, England). 2016;388(10054):1893–902.

    Article  CAS  Google Scholar 

  65. Li X, Yang J, Nie XL, Zhang Y, Li XY, Li LH, et al. Impact of dexmedetomidine on the incidence of delirium in elderly patients after cardiac surgery: a randomized controlled trial. PLoS One. 2017;12(2):e0170757.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Inouye SK, Marcantonio ER, Kosar CM, Tommet D, Schmitt EM, Travison TG, et al. The short-term and long-term relationship between delirium and cognitive trajectory in older surgical patients. Alzheimers Dement. 2016;12(7):766–75.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Krogseth M, Watne LO, Juliebo V, Skovlund E, Engedal K, Frihagen F, et al. Delirium is a risk factor for further cognitive decline in cognitively impaired hip fracture patients. Arch Gerontol Geriatr. 2016;64:38–44.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anesthesiology & Perioperative Medicine, Penn State Health Milton S. Hershey Medical Center, 500 University Dr., Hershey, PA, 17033, USA

    Zyad J. Carr, Theodore J. Cios, Kenneth F. Potter & John T. Swick

Authors
  1. Zyad J. Carr
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Theodore J. Cios
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kenneth F. Potter
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. John T. Swick
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zyad J. Carr.

Ethics declarations

Conflict of Interest

Zyad J. Carr, Theodore J. Cios, Kenneth F. Potter, and John T. Swick declare no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Critical Care

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Carr, Z.J., Cios, T.J., Potter, K.F. et al. Does Dexmedetomidine Ameliorate Postoperative Cognitive Dysfunction? A Brief Review of the Recent Literature. Curr Neurol Neurosci Rep 18, 64 (2018). https://doi.org/10.1007/s11910-018-0873-z

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11910-018-0873-z

Keywords

Search

Navigation