Organoprotective effects of the α2-adrenoreceptor agonist dexmedetomidine (literature review)

Vitik A.A.1, Shen N.P.2

Tyumen State Medical University, Tyumen

2 The branch of the Tomsk national research medical center “Tyumen Cardiology Research Center”, Tyumen

For correspondence: Shen N.P. — MD, Professor, head of Department of Obstetrics, Gynecology and critical care medicine with a course of KDL of the Institute of Continuing Professional Development of Tyumen State Medical University, Tyumen; e-mail:

For citation: Vitik A.A., Shen N.P. Organoprotective effects of the α2-adrenoreceptor agonist dexmedetomidine (literature review). Alexander Saltanov Intensive Care Herald. 2018;4:74–79.

DOI: 10.21320/1818-474X-2018-4-74-79

Currently, in experimental and clinical studies of critical states, scientists attend to the issues of protecting and preserving the functions of vital organs and systems. The pharmacological aspects of organoprotection with various drugs are considered separately. In this question, α2-adrenoreceptor agonists are of the greatest interest. The study is devoted to the analysis of domestic and foreign literature covering the efficacy of using dexmedetomidine adrenergic mimetic, its mechanisms of action and organ-preventive properties in ECMO patients with organic and mental disorders. Formulated aspects need to study the use of this drug in order to prevent neurocognitive and organ dysfunction in surgical and therapeutic patients who are in intensive care units.

Keywords: organoprotection, dexmedetomidine, α2-adrenoreceptor agonists, multiple organ dysfunction, delirium

Received: 05.10.2018


  1. Wu L., Zhao H., Wang T., Pac-Soo C., Ma D. Cellular signaling pathways and molecular mechanisms involving inhalational anesthetics-induced. J. Anesth. 2014; 28(5): 740–758. DOI: 10.1007/s00540-014-1805-y.
  2. Belleville J.P., Ward D.S., Bloor C., Maze M. Effects of intravenous dexmedetomidin e in humans. I. Sedation, ventilation, and metabolic rate. Anesthesiology. 1992; 77: 1125–1133.
  3. Chen X., Hu J., Zhang C., et al. Effect and mechanism of dexmedetomidine on lungs in patients of sepsis complicated with acute respiratory distress syndrome. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2018; 30(2): 151–155. DOI: 10.3760/cma.j.issn.2095-4352.2018.02.011.
  4. European Medicines Agency. European Public Assessment Report. 2016. Available from: 002268/WC500115631.pdf. Accessed 14 Nov 2016.
  5. Guo T.Z., Tinklenberg J., Oliker R., Maze M. Central alpha 1-adrenoceptor stimulation functionally antagonizes the hypnotic response to dexmedetomidine, an alpha 2-adrenoceptor agonist. Anesthesiology. 1991; 75: 252–256.
  6. Virtanen R., Savola J.M., Saano V., Nyman L. Characterization of the selectivity, specificity and potency of medetomidine as an alpha 2-adrenoceptor agonist. Eur. J. Pharmacol. 1988; 150: 9–14.
  7. Lobo F.A., Wagemakers M., Absalom A.R. Anaesthesia for awake craniotomy. Br. J. Anaesth. 2016; 116: 740–744.
  8. Riker R.R., Shehabi Y., Bokesch P.M., et al. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial (SEDCOM). JAMA. 2009; 301(5): 489–499.
  9. Bourenne J., Hraiech S., Roch A., et al. Sedation and neuromuscular blocking agents in acute respiratory distress syndrome. Ann. Transl. Med. 2017; 5(14): 291. DOI: 10.21037/atm.2017.07.19.
  10. Jakob S.M., Ruokonen E., Grounds R.M., et al. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA. 2012; 307(11): 1151–1160.
  11. Sulaiman S., Karthekeyan R.B., Vakamudi M., et al. The effects of dexmedetomidine on attenuation of stress response to endotracheal intubation in patients undergoing elective off-pump coronary artery bypass grafting. Ann. Card. Anaesth. 2012; 15: 39–43.
  12. Yildiz M., Tavlan A., Tuncer S., et al. Effect of dexmedetomidine on haemodynamic responses to laryngoscopy and intubation: perioperative haemodynamics and anaesthetic requirements. Drugs R.D. 2006; 7: 43–52.
  13. ЕременкоА.А., Чернова Е.В. Лечение делирия в раннем послеоперационном периоде у кардиохирургических пациентов. Анестезиология и реаниматология. 2014; 5: 30–34. [Yeremenko A.A., Chernova Ye.V. Lecheniye deliriya v rannem posleoperatsionnom iskusstve u kardiokhirurgicheskikh patsiyentov. Anesteziologiya i reanimatologiya. 2014; 5: 30–34. (In Russ)]
  14. ЕременкоА.А., Чернова Е.В. Применение дексмедетомидина для внутривенной седации и лечения делирия в раннем послеоперационном периоде у кардиохирургических пациентов. Анестезиология и реаниматология. 2013; 5: 4–7. [Yeremenko A.A., Chernova Ye.V. Primeneniye deksmedetomidina dlya vnutrivennogo sedatelʼstva i lecheniya v rannem posleoperatsionnom budushchem u kardiokhirurgicheskikh patsiyentov. Anesteziologiya i reanimatologiya. 2013; 5: 4–7. (In Russ)]
  15. Шевченко Ю.Л., Гороховатский Ю.И., Азизова О.А., Замятин М.Н. Системный воспалительный ответ при экстремальной хирургической агрессии. М.: РАЕН, 2009. [Shevchenko Yu.L., Gorokhovatskiy Yu.I., Azizova O.A., Zamyatin M.N. Sistemnyy vospalitelʼnyy otvet pri ekstremalʼnoy khirurgicheskoy agressii. Moscow: RAYEN, 2009. (In Russ)]
  16. Dahmani S., Paris A., Jannier V., et al. Dexmedetomidine increases hippocampal phosphorylated extracellular signal-regulated protein kinase 1 and 2 content by an alpha 2-adrenoceptor-independent mechanism: evidence for the involvement of imidazoline I1 receptors. Anesthesiology. 2008; 108(3): 457–466.
  17. Drummond J.C., Dao A. V., Roth D.M., et al. Effect of dexmedetomidine on cerebral blood flow velocity, cerebral metabolic rate, and carbon dioxide response in normal humans. Anesthesiology. 2008; 108(2): 225–232.
  18. Prielipp R.C., Wall M.H., Tobin J.R., et al. Dexmedetomidine-induced sedation in Volunteers decreases regional and global cerebral blood flow. Anesth. Analg. 2002; 95(4): 1052–1059.
  19. Talke P., Tong C., Lee H.W., et al. Effect of dexmedetomidine on lumbar cerebrospinal fluid pressure in humans. Anesth. Analg. 1997; 85(2): 358–364.
  20. Zhang Z., Ferretti V., Guntan I., et al. Neuronal ensembles sufficient for recovery sleep and the sedative actions of a2 adrenergic agonists. Nat. Neurosci. 2015; 18: 553–561.
  21. Virtanen R., Savola J.M., Saano V., Nyman L. Characterization of the selectivity, specificity and potency of medetomidine as an alpha 2-adrenoceptor agonist. Eur. J. Pharmacol. 1988; 150: 9–14.
  22. Abd-Ellatief R.B., Mohamed H.K., Kotb H.I. Reactive Astrogliosis in an Experimental Model of Fibromyalgia: Effect of Dexmedetomidine. Cells Tissues Organs. 2018; 205(2): 105–119. DOI: 10.1159/000488757.
  23. Reade M.C., O’Sullivan K., Bates S., et al. Dexmedetomidine vs. haloperidol in delirious, agitated, intubated patients: a randomised open-label trial. Crit. Care. 2009; 13(3): R75–R84.
  24. БершадскийФ.Ф., Улиткина О.Н., Скрипкин Ю.В., Лихванцев В.В. Седация дексмедетомидином сокращает сроки лечения делирия у пострадавших с тяжелой сочетанной травмой. Альманах клинической медицины. 2017; 45(8): 652–657. [Bershadskiy F.F., Ulitkina O.N., Skripkin Yu.V., Likhvantsev V.V. Sedatsiya deksmedetomidinom sokrashchayet sroki lecheniya s postradavshim s tyazheloy sochetannoy travmoy. Alʼmanakh klinicheskoy meditsiny. 2017; 45(8): 652–657. (In Russ)]
  25. Valitalo P.A., Ahtola-Satila T., Wighton A., et al. Population pharmacokinetics of dexmedetomidine in critically ill patients. Clin. Drug Invest. 2013; 33: 579–587.
  26. Lee S., Choi Y.S., Hong G.R., Oh Y.J. Echocardiographic evaluation of the effects of dexmedetomidine on cardiac function during total intravenous anaesthesia. Anaesthesia. 2015; 70: 1052–1059.
  27. КозловИ.А. Современные подходы к седации в отделениях реанимации и интенсивной терапии. Неотлож. Мед. 2013; 1: 22–32. [Kozlov I.A. Sovremennyye podkhody k sedatsii v otdeleniyakh reanimatsii i intensivnoy terapii. Neotlozh. Med. 2013; 1: 22–32. (In Russ)]
  28. Yoshikawa Y., Hirata N., Kawaguchi R., et al. Dexmedetomidine maintains its direct cardioprotective effect against ischemia/reperfusion injury in hypertensive hypertrophied myocardium. Anesth. Analg. 2017; 126(2): 443–452.
  29. Sun Y., Jiang C., Jiang J., et al. Dexmedetomidine protects mice against myocardium ischaemic/reperfusion injury by activating an A M PK/PI3K/Akt/eNO S pathway. Clin. Exp. Pharmacol. Physiol. 2017; 44(9): 946–953.
  30. Yang Y.F., Peng K., Liu H., et al. Dexmedetomidine preconditioning for myocardial protection in ischaemia-reperfusion injury in rats by down regulation of the high mobility group box 1-toll-like receptor 4-nuclear factor kB signalling pathway. Exp. Pharmacol. Physiol. 2017; 44(3): 353–361.
  31. Kunisawa T., Ueno M., Kurosawa A., et al. Dexmedetomidine can stabilize hemodynamics and spare anesthetics before cardiopulmonary bypass. J. Anesth. 2011; 25: 818–822.
  32. Maldonado J.R., Wysong A., van der Starre P.J.A., et al. Dexmedetomidine and the reduction of postoperative delirium after cardiac surgery. Psychosomatics. 2009; 50: 206–217.
  33. Geng J., Qian J., Cheng H., et al. The influence of perioperative dexmedetomidine on patients undergoing cardiac surgery: a meta-analysis. PLoS One. 2016; 11(4): e0152829.
  34. Kundra T.S., Nagaraja P.S., Singh N.G., et al. Effect of dexmedetomidine on diseased coronary vessel diameter and myocardial protection in percutaneous coronary interventional patients. Ann. Card. Anaesth. 2016; 19(3): 394–398.
  35. Ebert T.J., Hall J.E., Barney J.A., et al. The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology. 2000; 93: 382–394.
  36. Rui S., Hong-Tao T. Dexmedetomidine as a promising prevention strategy for cardiac surgery-associated acute kidney injury: a meta-analysis. Crit. Care. 2017; 21: 198.
  37. Cozzolino M., Franci A., Peris A., et al. Weaning from extracorporeal membrane oxygenation: experience with dexmedetomidine in seven adult ARDS patients. Critical Care. 2015; 19(Suppl. 1): P485.
  38. Constantin J.M., Momon A., Mantz J., et al. Efficacy and safety of sedation with dexmedetomidine in critical care patients: a meta-analysis of randomized controlled trials. Anaesth. Crit. Care Pain Med. 2016; 35(1): 7–15.
  39. Fang X.Z., Gao J., Ge Y.L., et al. Network Meta-Analysis on the Efficacy of Dexmedetomidine, Midazolam, Ketamine, Propofol, and Fentanyl for the Prevention of Sevoflurane-Related Emergence Agitation in Children. Am. J. Ther. 2016; 23(4): e1032–e1042.
  40. Pasin L., Greco T., Feltracco P., et al. Dexmedetomidine as a Sedative Agent in Critically Ill Patients: A Meta-Analysis of Randomized Controlled Trials. PLoS One. 2013; 8(12): e82913.