Dexmedetomidine as a Cardioprotector in Cardiac Surgery (Review)

The literature review presents an analysis of publications on the use of a selective α2-adrenergic receptor agonist (α2-AR) dexmedetomidine as a cardioprotector in cardiosurgical interventions. It summarizes historical aspects of the introduction of α2-AR agonists in the intensive care practice. It analyzes possible mechanisms of the cardioprotective effect of dexmedetomidine (central sympatholysis, favorable effects on the coronary circulation and relief of the coronary steal syndrome in originally ischemized areas of the myocardium, antiinflammatory and antioxidant effects, and prevention of apoptosis activation). Data from experimental studies of dexmedetomidine cardioprotection were analyzed. Results of clinical studies, including data of metanalyses, were discussed. It dwells on data on the favorable effect of dexmedetomidine on various parameters of the postoperative period, including a decreased risk of delirium, general complications of cardiosurgical interventions, and the mortality rate in patients. It presents data on cardioprotective properties of dexmedetomidine in surgical patients who undergo noncardiac interventions, particularly vascular ones, including high risk surgeries in the aorta. A comparative analysis of results of clinical trials studying the dexmedetomidine cardioprotection during surgeries with extracorporeal circulation was performed. A range of pharmacological effects of dexmedetomidine during anesthesiological support of cardiac surgeries, including those in elderly and senile patients, was described. It has been concluded that the dexmedetomidine cardioprotection in the various fields of surgery is obviously very promising.

dexmedetomidine, adjuvant cardioprotection, α2-adrenergic receptors agonists, sympatholysis, extracorporeal circulation, complications of cardiac surgery

1. Kozlov I.A., Klypa T.V. Glucoseinsulin mixture as a cardioprotective agent in cardiology and cardiac surgery (review). Obshchaya Reanimatologiya = General Reanimatology. 2017; 13 (1): 57-72. DOI: 10.15360/1813-9779-2017-1-57-72. [In Russ., In Engl.]

2. Dobson G.P., Faggian G., Onorati F., Vinten#Johansen J. Hyperkalemic cardioplegia for adult and pediatric surgery: end of an era? Front. Physiol. 2013; 4: 228. DOI: 10.3389/fphys.2013.00228. PMID: 24009586

3. Melrose D.G., Dreyer B., Bentall H.H., Baker J.B. Elective cardiac arrest. Lancet. 1955; 269 (6879): 21-22. DOI: 10.1016/S0140-6736(55)93381-X. PMID: 14382605

4. Lam C.R., Gahagan T., Sergeant C., Green E. Clinical experiences with induced cardiac arrest during intracardiac surgical procedures. Ann. Surg. 1957; 146 (3): 439-449. DOI: 10.1097/00000658-195709000-00012. PMID: 13459293

5. Cooley D.A., Reul G.J., Wukasch D.C. Ischemic contracture of the heart: «stone heart». Am. J. Cardiol. 1972; 29 (4): 575-577. DOI: 10.1016/0002-9149(72)90454-7. PMID: 5016840

6. Katz A.M., Tada M. The «stone heart»: a challenge to the biochemist. Am. J. Cardiol. 1972; 29 (4): 578-580. DOI: 10.1016/0002-9149(72)90455-9. PMID: 5016841

7. Hausenloy D.J., Yellon D.M. Ischaemic conditioning and reperfusion injury. Nat. Rev. Cardiol. 2016; 13 (4): 193-209. DOI: 10.1038/nrcardio.2016.5. PMID: 26843289

8. Horak J., Mohler E.R., Fleisher L.A. Assessment of cardiac risk and the cardiology consultation. In: Kaplan J.A., Reich D.L., Savino J.S. (eds.). Kaplan’s cardiac anesthesia: the echo era. 6th ed. St. Louis: Saunders; 2011: 2-15.

9. Pagel P.S. Cardiac physiology. In: Kaplan J.A., Reich D.L., Savino J.S. (eds.). Kaplan’s cardiac anesthesia: the echo era. 6th ed. St. Louis: Saunders; 2011: 98-131.

10. Sharma S., Durieux M.E. Molecular and genetic cardiovascular medicine. In: Kaplan J.A., Reich D.L., Savino J.S. (eds.). Kaplan’s cardiac anesthesia: the echo era. 6th ed. St. Louis: Saunders; 2011: 157-177.

11. Grocott H.P., Stafford#Smith M., Mora#Mangano C.T. Cardiopulmonary bypass management and organ protection. In: Kaplan J.A., Reich D.L., Savino J.S. (eds.). Kaplan’s cardiac anesthesia: the echo era. 6th ed. St. Louis: Saunders; 2011: 838-887.

12. Vinten#Johansen J., Thourani V.H. Myocardial protection: an overview. J. Extra Corpor. Technol. 2000; 32 (1): 38-48. PMID: 10947622

13. Cooley D.A., Reul G.J.J., Wukasch D.C. Ischemic myocardial contracture (“stone heart”). A complication of cardiac surgery. Isr. J. Med. Sci. 1975; 11 (2-3): 203-210. PMID: 1112706

14. Likhvantsev V.V., Ubasev Y.V., Skripkin Y.V., Zabelina T.S., Sungurov V.A., Lomivorotov V.V., Marchenko D.N. Preoperative prevention of heart failure in noncardiac surgery. Obshchaya Reanimatologiya = General Reanimatology. 2016; 12 (3): 48-61. DOI: 10.15360/1813-9779-2016-3-48-61. [In Russ., In Engl.]

15. Likhvantsev V.V., Grebenchikov O.A., Cherpakov R.A., Skripkin Y.V., Borisov K.Yu. Effect of preconditioning with desflurane on phosphorylated glycogen synthase kinase 3β contents in an experiment. Obshchaya Reanimatologiya = General Reanimatology. 2016; 12 (6): 8-15. DOI: 10.15360/1813-9779-2016-6-8-15. [In Russ., In Engl.]

16. Hillis L.D., Smith P.K., Anderson J.L., Bittl J.A., Bridges C.R., Byrne J.G., Cigarroa J.E., Disesa V.J., Hiratzka L.F., Hutter A.M.Jr., Jessen M.E., Keeley E.C., Lahey S.J., Lange R.A., London M.J., Mack M.J., Patel M.R., Puskas J.D., Sabik J.F., Selnes O., Shahian D.M., Trost J.C., Winniford M.D.; American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines; American Association for Thoracic Surgery; Society of Cardiovascular Anesthesiologists; Society of Thoracic Surgeons. 2011 ACCF/AHA guideline for coronary artery bypass graft surgery. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, Society of Cardiovascular Anesthesiologists, and Society of Thoracic Surgeons. J. Am. Coll. Cardiol. 2011; 58 (24): e123-e210. DOI: 10.1016/j.jacc.2011.08.009. PMID: 22070836

17. Ávalos R., MartinezSanz R., Jiménez J., Iribarren J., Montoto J., Lacruz A., Brouard M., Garrido P., Prada P., Pérez J. P., García-González M. Levosimendan preconditioning in patients undergoing elective cardiac surgery with poor ejection fraction. preliminary results. J. cardiothorac. Surg. 2015; 10 (1): A310. DOI: 10.1186/1749-8090-10-S1-A310

18. Landoni G., Zangrillo A., Lomivorotov V.V., Likhvantsev V., Ma J., De Simone F., Fominskiy E. Cardiac protection with phosphocreatine: a meta-analysis. Interact. Cardiovasc. Thorac. Surg. 2016; 23 (4): 637-646. DOI: 10.1093/icvts/ivw171. PMID: 27318357

19. Akselrod B.A., Meshcheryakov A.V., Babalyan G.V., Yavorovsky A.G., Guleshov V.A., Evdokimov M.E. Autonomic reactivity and intraoperative arterial hypertension in patients with ischemic heart disease. Anesteziologiya i Reanimatologiya. 2000; 5: 35-38. PMID: 11220932. [In Russ.]

20. Yavorovsky A.G., Meshcheryakov A.V., Grishin V.V., Akselrod B.A. Use of clofelin in the prevention of perioperative myocardial dysfunction in patients with ischemic heart disease. Anesteziologiya i Reanimatologiya. 2000; 5: 31-34. PMID: 11220931. [In Russ.]

21. Kristensen S.D., Knuuti J., Saraste A., Anker S., Bøtker H.E., Hert S.D., Ford I., Gonzalez-Juanatey J.R., Gorenek B., Heyndrickx G.R., Hoeft A., Huber K., Iung B., Kjeldsen K.P., Longrois D., Lüscher T.F., Pierard L., Pocock S., Price S., Roffi M., Sirnes P.A., Sousa-Uva M., Voudris V., Funck-Brentano C.; Authors/Task Force Members. 2014 ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management: The Joint Task Force on non-cardiac surgery: cardiovascular assessment and management of the European Society of Cardiology (ESC) and the European Society of Anaesthesiology (ESA). Eur. Heart J. 2014; 35 (35): 2383-2431. DOI: 10.1093/eurheartj/ehu282. PMID: 25086026

22. Devereaux P.J., Sessler D.I., Leslie K., Kurz A., Mrkobrada M., AlonsoCoello P., Villar J.C., Sigamani A., Biccard B.M., Meyhoff C.S., Parlow J.L., Guyatt G., Robinson A., Garg A.X., Rodseth R.N., Botto F., Lurati Buse G., Xavier D., Chan M.T., Tiboni M., Cook D., Kumar P.A., Forget P., Malaga G., Fleischmann E., Amir M., Eikelboom J., Mizera R., Torres D., Wang C. Y., VanHelder T., Paniagua P., Berwanger O., Srinathan S., Graham M., Pasin L., Le Manach Y., Gao P., Pogue J., Whitlock R., Lamy A., Kearon C., Chow C., Pettit S., Chrolavicius S., Yusuf S.; POISE#2 Investigators. Clonidine in patients undergoing noncardiac surgery. N. Engl. J. Med. 2014; 370 (16): 1504-1513. DOI: 10.1056/NEJMoa1401106. PMID: 24679061

23. Kozlov I.A. The alpha2-adrenoceptor agonist dexmedetomidine in current sedation practice. Obshchaya Reanimatologiya = General Reanimatology. 2013; 9 (2): 55-65. DOI: 10.15360/1813-9779-2013-2-55. [In Russ., In Engl.]

24. Kozlov I.A. Dexmedetomidine for anesthetic and resuscitative providing of cardiac surgery. Kardiologiya i Serdechno-Sosudistaya Khirurgiya. 2014; 7 (4): 100-108. [In Russ.]

25. Ji F., Li Z., Nguyen H., Young N., Shi P., Fleming N., Liu H. Perioperative dexmedetomidine improves outcomes of cardiac curgery. Circulation. 2013; 127 (15): 1576-1584. DOI: 10.1161/CIRCULATIONAHA.112.000936. PMID: 23513068

26. Zhang X., Zhao X., Wang Y. Dexmedetomidine: a review of applications for cardiac surgery during perioperative period. J. Anesth. 2015; 29 (1): 102-111. DOI: 10.1007/s00540-014-1857-z. PMID: 24913070

27. Soliman R., Zohry G. The myocardial protective effect of dexmedetomidine in high-risk patients undergoing aortic vascular surgery. Ann. Card. Anaesth. 2016; 19 (4): 606-613. DOI: 10.4103/0971-9784.191570. PMID: 27716690

28. Brandão P.G., Lobo F.R., Ramin S.L., Sakr Y., Machado M.N., Lobo S. M. Dexmedetomidine as an anesthetic adjuvant in cardiac surgery: a cohort study. Braz. J. Cardiovasc. Surg. 2016; 31 (3): 213-218. DOI: 10.5935/1678-9741.20160043. PMID: 27737403

29. Dygalo N.N. Receptors for hormones, neurotransmitters and tissue factors. Novosibirsk: NGU; 2001: 36. [In Russ.]

30. Kamibayashi T., Maze M. Clinical uses of alpha2 -adrenergic agonists. Anesthesiology. 2000; 93 (5): 1345-1349. DOI: 10.1097/00000542-200011000-00030. PMID: 11046225

31. Mizobe T., Maze M. Alpha 2-adrenoceptor agonists and anesthesia. Int. Anesthesiol. Clin. 1995; 33 (1): 81-102. DOI: 10.1097/00004311-199500000-00005. PMID: 7635559

32. Nelson L.E., Lu J., Guo T., Saper C.B., Franks N.P., Maze M. The alpha2-adrenoceptor agonist dexmedetomidine converges on an endogenous sleep-promoting pathway to exert its sedative effects. Anesthesiology. 2003; 98 (2): 428-436. DOI: 10.1097/00000542-200302000-00024. PMID: 12552203

33. Brown E.N., Lydic R., Schiff N.D. General anesthesia, sleep, and coma. N. Engl. J. Med. 2010; 363 (27): 2638-2650. DOI: 10.1056/NEJMra 0808281. PMID: 21190458

34. Geng J., Qian J., Cheng H., Ji F., Liu H. The influence of perioperative dexmedetomidine on patients undergoing cardiac surgery: a meta-analysis. PLoS One. 2016; 11 (4): e0152829. DOI: 10.1371/journal.pone.0152829. PMID: 27049318

35. Cheng H., Li Z., Young N., Boyd D., Atkins Z., Ji F., Liu H. The effect of dexmedetomidine on outcomes of cardiac surgery in elderly patients. J. Cardiothorac. Vasc. Anesth. 2016; 30 (6): 1502-1508. DOI: 10.1053/j.jvca.2016.02.026. PMID: 27435836

36. Eremenko A.A., Chernova E.V. Dexmedetomidine use for intravenous sedation and delirium treatment during early postoperative period in cardio-surgical patients. Anesteziologiya i Renimatologiya. 2013; 5: 4-8. PMID: 24624849. [In Russ.]

37. Bryant C.E., Clarke K.W., Thompson J. Cardiopulmonary effects of medetomidine in sheep and in ponies. Res. Vet. Sci. 1996; 60 (3): 267-271. DOI: 10.1016/S0034-5288(96)90052-1. PMID: 8735520

38. Pascoe P.J. The cardiopulmonary effects of dexmedetomidine infusions in dogs during isoflurane anesthesia. Vet. Anaesth. Analg. 2015; 42 (4): 360-368. DOI: 10.1111/vaa.12220. PMID: 25082327

39. Unal Y., Pampal H.K., Arslan M., Demirel C.B., Alkan M. The effects of dexmedetomidine on pulmonary artery pressure in experiment. Bratisl. Lek. Listy. 2014; 115 (5): 272-274. DOI: 10.4149/bll_2014_056. PMID: 25174057

40. Villela N.R., Nascimento Júnior Pd., Carvalho L.R. Cardiovascular effects of two dexmedetomidine doses: experimental study in dogs. Rev. Bras. Anestesiol. 2003; 53 (6): 784-796. DOI: 10.1590/S0034-70942003000600009. PMID: 19471697

41. Xu H., Aibiki M., Seki K., Ogura S., Ogli K. Effects of dexmedetomidine, an alpha2-adrenoceptor agonist, on renal sympathetic nerve activity, blood pressure, heart rate and central venous pressure in urethane-anesthetized rabbits. J. Auton. Nerv. Syst. 1998; 71 (1): 48-54. DOI: 10.1016/S0165-1838(98)00061-7. PMID: 9722194

42. Gozalo#Marcilla M., Steblaj B., Schauvliege S., Duchateau L., Gasthuys F. Comparison of the influence of two different constant-rate infusions (dexmedetomidine versus morphine) on anaesthetic requirements, cardiopulmonary function and recovery quality in isoflurane anaesthetized horses. Res. Vet. Sci. 2013; 95 (3): 1186-1194. DOI: 10.1016/j.rvsc.2013.09.014. PMID: 24148870

43. Pagel P.S., Hettrick D.A., Kersten J.R., Warltier D.C. Dexmedetomidine produces similar alterations in the determinants of left ventricular afterload in conscious dogs before and after the development of pacing-induced cardiomyopathy. Anesthesiology. 1998; 89 (3): 741-748. DOI: 10.1097/00000542-199809000-00026. PMID: 9743413

44. Roekaerts P.M., Prinzen F.W., De Lange S. Beneficial effects of dexmedetomidine on ischaemic myocardium of anaesthetized dogs. Br. J. Anaesth. 1996; 77 (3): 427-429. DOI: 10.1093/bja/77.3.427. PMID: 8949826

45. Nathan H.J., Feigl E.O. Adrenergic vasoconstriction lessens transmural steal during coronary hypoperfusion. Am. J. Physiol. 1986; 250 (4 Pt 2): H645-H653. PMID: 2870645

46. Guo H., Takahashi S., Cho S., Hara T., Tomiyasu S., Sumikawa K. The effects of dexmedetomidine on left ventricular function during hypoxia and reoxygenation in isolated rat hearts. Anesth. Analg. 2005; 100 (3): 629-635. DOI: 10.1213/01.ANE.0000145065.20816.B5. PMID: 15728042

47. Okada H., Kurita T., Mochizuki T., Morita K., Sato S. The cardioprotective effect of dexmedetomidine on global ischaemia in isolated rat hearts. Resuscitation. 2007; 74 (3): 538-545. DOI: 10.1016/j.resuscitation.2007.01.032. PMID: 17391832

48. Yoshitomi O., Cho S., Hara T., Shibata I., Maekawa T., Ureshino H., Sumikawa K. Direct protective effects of dexmedetomidine against myocardial ischemia-reperfusion injury in anesthetized pigs. Shock. 2012; 38 (1): 92-97. DOI: 10.1097/SHK.0b013e318254d3fb. PMID: 22552015.

49. Ibacache M., Sanchez G., Pedrozo Z., Galvez F., Humeres C., Echevarria G., Duaso J., Hassi M., Garcia L., Díaz-Araya G., Lavandero S. Dexmedetomidine preconditioning activates pro-survival kinases and attenuates regional ischemia/reperfusion injury in rat heart. Biochim. Biophys. Acta. 2012; 1822 (4): 537-545. DOI: 10.1016/j.bbadis.2011. 12.013. PMID: 22230708

50. Morishima N., Nakanishi K., Takenouchi H., Shibata T., Yasuhiko Y. An endoplasmic reticulum stress-specific caspase cascade in apoptosis. Cytochrome c-independent activation of caspase-9 by caspase-12. J. Biol. Chem. 2002; 277 (37): 34287-34294. DOI: 10.1074/jbc.M204973200. PMID: 12097332

51. Wang H., Zhang S., Xu S., Zhang L. The efficacy and mechanism of dexmedetomidine in myocardial apoptosis via the renin-angiotensin-aldosterone system. J. Renin Angiotensin Aldosterone Syst. 2015; 16 (4): 1274-1280. DOI: 10.1177/1470320314546941. PMID: 25172906

52. Guler L., Bozkirli F., Bedirli N., Unal Y., Guler A., Oztas Y., Balta S., Cakar M., Demirkol S., Arslan Z., Unlu M. Comparison of the effects of dexmedetomidine vs. ketamine in cardiac ischemia/reperfusion injury in rats — preliminary study. Adv. Clin. Exp. Med. 2014; 23 (5): 683-689. DOI: 10.17219/acem/37214. PMID: 25491680

53. Sukegawa S., Higuchi H., Inoue M., Nagatsuka H., Maeda S., Miyawaki T. Locally injected dexmedetomidine inhibits carrageenin-induced inflammatory responses in the injected region. Anesth. Analg. 2014; 118 (2): 473-480. DOI: 10.1213/ANE.0000000000000060. PMID: 24445644

54. Chang C., Uchiyama A., Ma L., Mashimo T., Fujino Y. A comparison of the effects on respiratory carbon dioxide response, arterial blood pressure, and heart rate of dexmedetomidine, propofol, and midazolam in sevoflurane-anesthetized rabbits. Anesth. Analg. 2009; 109 (1): 84-89. DOI: 10.1213/ane.0b013e3181a2ad5f. PMID: 19535698

55. Tamiya J., Ide R., Takahashi M., Saiki C. Effects of dexmedetomidine on cardiorespiratory regulation in spontaneously breathing newborn rats. Paediatr. Anaesth. 2014; 24 (12): 1245-1251. DOI: 10.1111/pan.12530. PMID: 25216395

56. De Monte V., Staffieri F., Di Meo A., Vannucci J., Bufalari A. Comparison of ketamine-dexmedetomidine-methadone and tiletamine-zolazepam-methadone combinations for short-term anaesthesia in domestic pigs. Vet. J. 2015; 205 (3): 364-368. DOI: 10.1016/j.tvjl.2015.05.011. PMID: 26070949

57. Gu J., Sun P., Zhao H., Watts H.R., Sanders R.D., Terrando N., Xia P., Maze M., Ma D. Dexmedetomidine provides renoprotection against ischemia-reperfusion injury in mice. Crit. Care. 2011; 15 (3): R153. DOI: 10.1186/cc10283. PMID: 21702944

58. Hoffman W.E., Kochs E., Werner C., Thomas C., Albrecht R.F. Dexmedetomidine improves neurologic outcome from incomplete ischemia in the rat. Reversal by the alpha 2-adrenergic antagonist atipamezole. Anesthesiology. 1991; 75 (2): 328-332. DOI: 10.1097/00000542-199108000-00022. PMID: 1677549

59. Kip G., Çelik A., Bilge M., Alkan M., Ali Kiraz H., Özer A., S¸ÞvgÞn V., Erdem Ö., Arslan M., Kavutçu M. Dexmedetomidine protects from post-myocardial ischaemia reperfusion lung damage in diabetic rats. Libyan J. Med. 2015; 10 (1): 27828. DOI: 10.3402/ljm.v10.27828. PMID: 28349789

60. Gertler R., Brown H.C., Mitchell D.H., Silvius E.N. Dexmedetomidine: a novel sedative-analgesic agent. Proc. (Bayl. Univ. Med. Cent.). 2001; 14 (1): 13-21. PMID: 16369581

61. Wijeysundera D.N., Bender J.S., Beattie W.S. Alpha-2 adrenergic agonists for the prevention of cardiac complications among patients undergoing surgery. Cochrane Database Syst. Rev. 2009; 4: CD004126. DOI: 10.1002/14651858.CD004126.pub2. PMID: 19821319

62. Wijeysundera D.N., Naik J.S., Beattie W.S. Alpha-2 adrenergic agonists to prevent perioperative cardiovascular complications: a meta-analysis. Am. J. Med. 2003; 114 (9): 742-752. DOI: 10.1016/S0002-9343(03)00165-7. PMID: 12829201

63. Biccard B.M., Goga S., de Beurs J. Dexmedetomidine and cardiac protection for non-cardiac surgery: a meta-analysis of randomised controlled trials. Anaesthesia. 2008; 63 (1): 4-14. DOI: 10.1111/j.1365-2044.2007.05306.x. PMID: 18086064

64. Talke P., Chen R., Thomas B., Aggarwall A., Gottlieb A., Thorborg P., Heard S., Cheung A., Son S.L., Kallio A. The hemodynamic and adrenergic effects of perioperative dexmedetomidine infusion after vascular surgery. Anesth. Analg. 2000; 90 (4): 834-839. DOI: 10.1213/00000539-200004000-00011. PMID: 10735784

65. Singh S., Singh A. Dexmedetomidine induced catecholamine suppression in pheochromocytoma. J. Nat. Sci. Biol. Med. 2014; 5 (1): 182-183. DOI: 10.4103/0976-9668.127323. PMID: 24678223

66. Xu L., Hu Z., Shen J., McQuillan P.M. Does dexmedetomidine have a cardiac protective effect during non-cardiac surgery? A randomised controlled trial. Clin. Exp. Pharmacol. Physiol. 2014; 41 (11): 879-883. DOI: 10.1111/1440-1681.12296. PMID: 25132247

67. Cho J.S., Kim S.H., Shin S., Pak H.N., Yang S.J., Oh Y.J. Effects of dexmedetomidine on changes in heart rate variability and hemodynamics during tracheal intubation. Am. J. Ther. 2016; 23 (2): e369-e376. DOI: 10.1097/MJT.0000000000000074. PMID: 24832388

68. Rich J.M. Dexmedetomidine as a sole sedating agent with local anesthesia in a high-risk patient for axillofemoral bypass graft: a case report. AANA J. 2005; 73 (5): 357-360. PMID: 16261851

69. Harsoor S.S., Rani D.D., Lathashree S., Nethra S.S., Sudheesh K. Effect of intraoperative Dexmedetomidine infusion on Sevoflurane requirement and blood glucose levels during entropy-guided general anesthesia. J. Anaesthesiol. Clin. Pharmacol. 2014; 30 (1): 25-30. DOI: 10.4103/0970-9185.125693. PMID: 24574589

70. Reddy S.V., Balaji D., Ahmed S.N. Dexmedetomidine versus esmolol to attenuate the hemodynamic response to laryngoscopy and tracheal intubation: a randomized double-blind clinical study. Int. J. Appl. Basic. Med. Res. 2014; 4 (2): 95-100. DOI: 10.4103/2229-516X.136788. PMID: 25143884

71. Jalonen J., Hynynen M., Kuitunen A., Heikkilä H., Perttilä J., Salmenperä M., Valtonen M., Aantaa R., Kallio A. Dexmedetomidine as an anesthetic adjunct in coronary artery bypass grafting. Anesthesiology. 1997; 86 (2): 331-345. DOI: 10.1097/00000542-199702000-00009. PMID: 9054252

72. Kunisawa T., Nagata O., Nagashima M., Mitamura S., Ueno M., Suzuki A., Takahata O., Iwasaki H. Dexmedetomidine suppresses the decrease in blood pressure during anesthetic induction and blunts the cardiovascular response to tracheal intubation. J. Clin. Anesth. 2009; 21 (3): 194-199. DOI: 10.1016/j.jclinane.2008.08.015. PMID: 19464613

73. Piao G., Wu J. Systematic assessment of dexmedetomidine as an anesthetic agent: a meta-analysis of randomized controlled trials. Arch. Med. Sci. 2014; 10 (1): 19-24. DOI: 10.5114/aoms.2014.40730. PMID: 24701209

74. Ji F., Li Z., Young N., Moore P., Liu H. Perioperative dexmedetomidine improves mortality in patients undergoing coronary artery bypass surgery. J. Cardiothorac. Vasc. Anesth. 2014; 28 (2): 267-273. DOI: 10.1053/j.jvca.2013.06.022. PMID: 24182835

75. Tosun Z., Baktir M., Kahraman H.C., Baskol G., Guler G., Boyaci A. Does dexmedetomidine provide cardioprotection in coronary artery bypass grafting with cardiopulmonary bypass? A pilot study. J. Cardiothorac. Vasc. Anesth. 2013; 27 (4): 710-715. DOI: 10.1053/j.jvca.2012.12.013. PMID: 23725681

76. Ríha H., Kotulák T., Brezina A., Hess L., Kramár P., Szárszoi O., Netuka I., Pirk J. Comparison of the effects of ketamine-dexmedetomidine and sevoflurane-sufentanil anesthesia on cardiac biomarkers after cardiac surgery: an observational study. Physiol. Res. 2012; 61 (1): 63-72. PMID: 22188112

77. Ammar A.S., Mahmoud K.M., Kasemy Z.A., Helwa M.A. Cardiac and renal protective effects of dexmedetomidine in cardiac surgeries: a randomized controlled trial. Saudi J. Anaesth. 2016; 10 (4): 395-401. DOI: 10.4103/1658-354X.177340. PMID: 27833481

78. Ueki M., Kawasaki T., Habe K., Hamada K., Kawasaki C., Sata T. The effects of dexmedetomidine on inflammatory mediators after cardiopulmonary bypass. Anaesthesia. 2014; 69 (7): 693-700. DOI: 10.1111/anae.12636. PMID: 24773263

79. Bulow N.M., Colpo E., Pereira R.P., Correa E.F., Waczuk E.P., Duarte M.F., Rocha J.B. Dexmedetomidine decreases the inflammatory response to myocardial surgery under mini-cardiopulmonary bypass. Braz. J. Med. Biol. Res. 2016; 49 (4): e4646. DOI: 10.1590/1414-431X20154646. PMID: 26909786

80. Abd Aziz N., Chue M.C., Yong C.Y., Hassan Y., Awaisu A., Hassan J., Kamarulzaman M.H. Efficacy and safety of dexmedetomidine versus morphine in post-operative cardiac surgery patients. Int. J. Clin. Pharm. 2011; 33 (2): 150-154. DOI: 10.1007/s11096-011-9480-7. PMID: 21744187

81. Yapici N., Coruh T., Kehlibar T., Yapici F., Tarhan A., Can Y., Ozler A., Aykac Z. Dexmedetomidine in cardiac surgery patients who fail extubation and present with a delirium state. Heart Surg. Forum. 2011; 14 (2): E93-E98. DOI: 10.1532/HSF98.201011102. PMID: 21521683

82. Liu H., Ji F., Peng K., Applegate R.L., Fleming N. Sedation after cardiac surgery: is one drug better than another? Anesth. Analg. 2017; 124 (4): 1061-1070. DOI: 10.1213/ANE.0000000000001588. PMID: 27984229

83. Liu X., Xie G., Zhang K., Song S., Song F., Jin Y., Fang X. Dexmedetomidine vs propofol sedation reduces delirium in patients after cardiac surgery: a meta-analysis with trial sequential analysis of randomized controlled trials. J. Crit. Care. 2017; 38: 190-196. DOI: 10.1016/j.jcrc.2016.10.026. PMID: 27936404

84. Lin Y.Y., He B., Chen J., Wang Z.N. Can dexmedetomidine be a safe and efficacious sedative agent in post-cardiac surgery patients? A metaanalysis. Crit. Care. 2012; 16 (5): R169. DOI: 10.1186/cc11646. PMID: 23016926

85. El Amrousy D.M., Elshmaa N.S., El#Kashlan M., Hassan S., Elsanosy M., Hablas N., Elrifaey S., El#Feky W. Efficacy of prophylactic dexmedetomidine in preventing postoperative junctional ectopic tachycardia after pediatric cardiac surgery. J. Am. Heart Assoc. 2017; 6 (3): e004780. DOI: 10.1161/JAHA.116.004780. PMID: 28249845

86. Anger K.E., Szumita P.M., Baroletti S.A., Labreche M.J., Fanikos J. Evaluation of dexmedetomidine versus propofol-based sedation therapy in mechanically ventilated cardiac surgery patients at a tertiary academic medical center. Crit. Pathw. Cardiol. 2010; 9 (4): 221-226. DOI: 10.1097/HPC.0b013e3181f4ec4a. PMID: 21119342

87. Torbic H., Papadopoulos S., Manjourides J., Devlin J.W. Impact of a protocol advocating dexmedetomidine over propofol sedation after robotic-assisted direct coronary artery bypass surgery on duration of mechanical ventilation and patient safety. Ann. Pharmacother. 2013; 47 (4): 441-446. DOI: 10.1345/aph.1S156. PMID: 23535816

88. Kabukçu H.K., Sahin N., Temel Y., Titiz T.A. Hemodynamics in coronary artery bypass surgery: effects of intraoperative dexmedetomidine administration. Anaesthesist. 2011; 60 (5): 427-431. DOI: 10.1007/s00101-010-1842-3. PMID: 21271232

89. Kunisawa T., Ueno M., Kurosawa A., Nagashima M., Hayashi D., Sasakawa T., Suzuki A., Takahata O., Iwasaki H. Dexmedetomidine can stabilize hemodynamics and spare anesthetics before cardiopulmonary bypass. J. Anesth. 2011; 25 (6): 818-822. DOI: 10.1007/s00540-011-1215-3. PMID: 21901330

90. But A.K., Ozgul U., Erdil F., Gulhas N., Toprak H.I., Durmus M., Ersoy M. O. The effects of pre-operative dexmedetomidine infusion on hemodynamics in patients with pulmonary hypertension undergoing mitral valve replacement surgery. Acta Anaesthesiol. Scand. 2006; 50 (10): 1207-1212. DOI: 10.1111/j.1399-6576.2006.01136.x. PMID: 16978159

91. Li X., Yang J., Nie X.#L., Zhang Y., Li X.#Y., Li L.#H., Wang D.#X., Ma D. Impact of dexmedetomidine on the incidence of delirium in elderly patients after cardiac surgery: a randomized controlled trial. PLoS One. 2017; 12 (2): e0170757. DOI: 10.1371/journal.pone.0170757. PMID: 28182690

92. Herr D.L., Sum#Ping S.T., England M. ICU sedation after coronary artery bypass graft surgery: dexmedetomidine-based versus propofolbased sedation regimens. J. Cardiothorac. Vasc. Anesth. 2003; 17 (5): 576-584. DOI: 10.1016/S1053-0770(03)00200-3. PMID: 14579210 93. Kozlov I.A. Modern approaches to sedation in intensive care units. Neotlozhnaya Meditsina. 2013; 1: 22-31. [In Russ.]