Anesth Pain Med.  2017 Oct;12(4):306-319. 10.17085/apm.2017.12.4.306.

Current clinical application of dexmedetomidine for sedation and anesthesia

• Kim DS
• Na HS
• Lee JH
• Shin YD
• Shim JK
• Shin HW
• Kang H
• Joung KW

• KMID: 2405847
• DOI: http://doi.org/10.17085/apm.2017.12.4.306

Abstract

Many sedatives are used clinically and include benzodiazepines, barbiturates, antihistamines, propofol, and alpha-2-agonist. Benzodiazepines activate GABA neuronal receptors in the brain and present sedating, hypnotic, anxiolytic, amnestic, and anticonvulsant effects, but low analgesic effects. Propofol induce sedative, anxiolytic, and amnestic effects but no analgesic effects. However, risks such as cardiopulmonary instability and hypotension must be considered during administration. Dexmedetomidine is a high selective alpha-2 agonist and has many advantages as a sedative. Patients under dexmedetomidine sedation awaken easily and are more likely to be cooperative. Risk of respiratory depression and cardiopulmonary instability is low as well. Additionally, dexmedetomidine decreases amount of analgesic needed during and after surgery, presenting analgesic effects. Dexmedetomidine also decreases risk of delirium. However, bradycardia may occur and biphasic effects on blood pressure may be observed during beginning of administration. Because of lengthy symptom onset and offset time, physicians should carefully control administration at the beginning and end of dexmedetomidine administration. The purpose of this review is to evaluate the efficacy and availability of dexmedetomidine in various clinical fields including sedation for critically ill patients, regional anesthesia, monitored anesthesia care for some invasive procedures, stabilization of heart in cardiac surgery or endoscopic procedures.

Keyword

Dexmedetomidine; Procedure; Regional anesthesia; Sedation

MeSH Terms

Anesthesia*
Anesthesia, Conduction
Barbiturates
Benzodiazepines
Blood Pressure
Bradycardia
Brain
Critical Illness
Delirium
Dexmedetomidine*
GABAergic Neurons
Heart
Histamine Antagonists
Humans
Hypnotics and Sedatives
Hypotension
Propofol
Respiratory Insufficiency
Thoracic Surgery
Barbiturates
Benzodiazepines
Dexmedetomidine
Histamine Antagonists
Hypnotics and Sedatives
Propofol

Reference

1. Lee YK, Yang HS, Jeong SM, Jun GW, Um SJ. Clinical survey of sedation and analgesia procedures in intensive care units. Korean J Anesthesiol. 2009; 56:295–302. DOI: 10.4097/kjae.2009.56.3.295.

2. Gertler R, Brown HC, Mitchell DH, Silvius EN. Dexmedetomidine:a novel sedative-analgesic agent. Proc (Bayl Univ Med Cent). 2001; 14:13–21. PMID: 16369581. PMCID: PMC1291306.

3. Yu SB. Dexmedetomidine sedation in ICU. Korean J Anesthesiol. 2012; 62:405–11. DOI: 10.4097/kjae.2012.62.5.405. PMID: 22679535. PMCID: PMC3366305.

4. Philipp M, Brede M, Hein L. Physiological significance of alpha(2)-adrenergic receptor subtype diversity:one receptor is not enough. Am J Physiol Regul Integr Comp Physiol. 2002; 283:R287–95. DOI: 10.1152/ajpregu.00123.2002. PMID: 12121839.

5. Ebert TJ, Hall JE, Barney JA, Uhrich TD, Colinco MD. The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology. 2000; 93:382–94. DOI: 10.1097/00000542-200008000-00016. PMID: 10910487.

6. Barr J, Fraser GL, Puntillo K, Ely EW, Gélinas C, Dasta JF, et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013; 41:263–306. DOI: 10.1097/CCM.0b013e3182783b72. PMID: 23269131.

7. Djaiani G, Silverton N, Fedorko L, Carroll J, Styra R, Rao V, et al. Dexmedetomidine versus propofol sedation reduces delirium aftercardiac surgery:a randomized controlled trial. Anesthesiology. 2016; 124:362–8. DOI: 10.1097/ALN.0000000000000951. PMID: 26575144.

8. Patanwala AE, Erstad BL. Comparison of dexmedetomidine versus propofol on hospital costs and length of stay. J Intensive Care Med. 2016; 31:466–70. DOI: 10.1177/0885066614544452. PMID: 25061063.

9. Mıngır T, Ervatan Z, Turgut N. Spinal anaesthesia and perioperative anxiety. Turk J Anaesthesiol Reanim. 2014; 42:190–5. DOI: 10.5152/TJAR.2014.99705. PMID: 27366419. PMCID: PMC4894147.

10. Höhener D, Blumenthal S, Borgeat A. Sedation and regional anaesthesia in the adult patient. Br J Anaesth. 2008; 100:8–16. DOI: 10.1093/bja/aem342. PMID: 18070783.

11. Chernik DA, Gillings D, Laine H, Hendler J, Silver JM, Davidson AB, et al. Validity and reliability of the Observer's Assessment of Alertness/Sedation Scale:study with intravenous midazolam. J Clin Psychopharmacol. 1990; 10:244–51. PMID: 2286697.

12. Némethy M, Paroli L, Williams-Russo PG, Blanck TJ. Assessing sedation with regional anesthesia:inter-rater agreement on a modified Wilson sedation scale. Anesth Analg. 2002; 94:723–8. DOI: 10.1097/00000539-200203000-00045. PMID: 11867405.

13. Ramsay MA, Savege TM, Simpson BR, Goodwin R. Controlled sedation with alphaxalone-alphadolone. Br Med J. 1974; 2:656–9. DOI: 10.1136/bmj.2.5920.656. PMID: 4835444. PMCID: PMC1613102.

14. Shah PJ, Dubey KP, Sahare KK, Agrawal A. Intravenous dexmedetomidine versus propofol for intraoperative moderate sedation during spinal anesthesia:a comparative study. J Anaesthesiol Clin Pharmacol. 2016; 32:245–9. DOI: 10.4103/0970-9185.168172. PMID: 27275058. PMCID: PMC4874083.

15. Arain SR, Ebert TJ. The efficacy, side effects, and recovery characteristics of dexmedetomidine versus propofol when used for intraoperative sedation. Anesth Analg. 2002; 95:461–6. DOI: 10.1097/00000539-200208000-00042.

16. Ok HG, Baek SH, Baik SW, Kim HK, Shin SW, Kim KH. Optimal dose of dexmedetomidine for sedation during spinal anesthesia. Korean J Anesthesiol. 2013; 64:426–31. DOI: 10.4097/kjae.2013.64.5.426. PMID: 23741565. PMCID: PMC3668104.

17. Dinesh CN, Sai Tej NA, Yatish B, Pujari VS, Mohan Kumar RM, Mohan CV. Effects of intravenous dexmedetomidine on hyperbaric bupivacaine spinal anesthesia:a randomized study. Saudi J Anaesth. 2014; 8:202–8. DOI: 10.4103/1658-354X.130719. PMID: 24843333. PMCID: PMC4024677.

18. Kaya FN, Yavascaoglu B, Turker G, Yildirim A, Gurbet A, Mogol EB, et al. Intravenous dexmedetomidine, but not midazolam, prolongs bupivacaine spinal anesthesia. Can J Anaesth. 2010; 57:39–45. DOI: 10.1007/s12630-009-9231-6. PMID: 20039221.

19. Strebel S, Gurzeler JA, Schneider MC, Aeschbach A, Kindler CH. Small-dose intrathecal clonidine and isobaric bupivacaine for orthopedic surgery:a dose-response study. Anesth Analg. 2004; 99:1231–8. DOI: 10.1213/01.ANE.0000133580.54026.65. PMID: 15385382.

20. Dobrydnjov I, Axelsson K, Thörn SE, Matthiesen P, Klockhoff H, Holmström B, et al. Clonidine combined with small-dose bupivacaine during spinal anesthesia for inguinal herniorrhaphy:a randomized double-blinded study. Anesth Analg. 2003; 96:1496–503. DOI: 10.1213/01.ANE.0000061110.62841.E9. PMID: 12707157.

21. Giovannitti JA Jr, Thoms SM, Crawford JJ. Alpha-2 adrenergic receptor agonists:a review of current clinical applications. Anesth Prog. 2015; 62:31–9. DOI: 10.2344/0003-3006-62.1.31. PMID: 25849473. PMCID: PMC4389556.

22. Bonnet F. Mechanisms of the analgesic effect of alpha 2 adrenergic agonists. Cah Anesthesiol. 1994; 42:723–5. PMID: 7767720.

23. Cohen LB, Wecsler JS, Gaetano JN, Benson AA, Miller KM, Durkalski V, et al. Endoscopic sedation in the United States:results from a nationwide survey. Am J Gastroenterol. 2006; 101:967–74. DOI: 10.1111/j.1572-0241.2006.00500.x. PMID: 16573781.

24. Wu W, Chen Q, Zhang LC, Chen WH. Dexmedetomidine versus midazolam for sedation in upper gastrointestinal endoscopy. J Int Med Res. 2014; 42:516–22. DOI: 10.1177/0300060513515437. PMID: 24514431.

25. Kim N, Yoo YC, Lee SK, Kim H, Ju HM, Min KT. Comparison of the efficacy and safety of sedation between dexmedetomidine-remifentanil and propofol-remifentanil during endoscopic submucosal dissection. World J Gastroenterol. 2015; 21:3671–8. DOI: 10.3748/wjg.v21.i12.3671. PMID: 25834336. PMCID: PMC4375593.

26. Jeurnink SM, Steyerberg E, Kuipers E, Siersema P. The burden of endoscopic retrograde cholangiopancreatography (ERCP) performed with the patient under conscious sedation. Surg Endosc. 2012; 26:2213–9. DOI: 10.1007/s00464-012-2162-2. PMID: 22302536.

27. Kilic N, Sahin S, Aksu H, Yavascaoglu B, Gurbet A, Turker G, et al. Conscious sedation for endoscopic retrograde cholangiopancreatography:dexmedetomidine versus midazolam. Eurasian J Med. 2011; 43:13–7. DOI: 10.5152/eajm.2011.03. PMID: 25610153. PMCID: PMC4261372.

28. Lee BS, Ryu J, Lee SH, Lee MG, Jang SE, Hwang JH, et al. Midazolam with meperidine and dexmedetomidine vs. midazolam with meperidine for sedation during ERCP:prospective, randomized, double-blinded trial. Endoscopy. 2014; 46:291–8. DOI: 10.1055/s-0033-1358909. PMID: 24671858.

29. Dere K, Sucullu I, Budak ET, Yeyen S, Filiz AI, Ozkan S, et al. A comparison of dexmedetomidine versus midazolam for sedation, pain and hemodynamic control, during colonoscopy under conscious sedation. Eur J Anaesthesiol. 2010; 27:648–52. DOI: 10.1097/EJA.0b013e3283347bfe. PMID: 20531094.

30. Poon RT, Fan ST, Tsang FH, Wong J. Locoregional therapies for hepatocellular carcinoma:a critical review from the surgeon's perspective. Ann Surg. 2002; 235:466–86. DOI: 10.1097/00000658-200204000-00004. PMID: 11923602. PMCID: PMC1422461.

31. Lee S, Rhim H, Kim YS, Choi D, Lee WJ, Lim HK, et al. Percutaneous radiofrequency ablation of hepatocellular carcinomas:factors related to intraprocedural and postprocedural pain. AJR Am J Roentgenol. 2009; 192:1064–70. DOI: 10.2214/AJR.08.1350. PMID: 19304715.

32. Rhim H. Complications of radiofrequency ablation in hepatocellular carcinoma. Abdom Imaging. 2005; 30:409–18. DOI: 10.1007/s00261-004-0255-7. PMID: 15688113.

33. Joung KW, Choi SS, Jang DM, Kong YG, Lee HM, Shim JH, et al. Comparative effects of dexmedetomidine and propofol on us-guidedradiofrequency ablation of hepatic neoplasm under monitoredanesthesia care:a randomized controlled study. Medicine (Baltimore). 2015; 94:e1349. DOI: 10.1097/MD.0000000000001349. PMID: 26266387. PMCID: PMC4616670.

34. Gaitan BD, Trentman TL, Fassett SL, Mueller JT, Altemose GT. Sedation and analgesia in the cardiac electrophysiology laboratory:a national survey of electrophysiologists investigating the who, how, and why? J Cardiothorac Vasc Anesth. 2011; 25:647–59. DOI: 10.1053/j.jvca.2010.11.006. PMID: 21251850.

35. January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation:a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014; 64:e1–76. DOI: 10.1016/j.jacc.2014.03.022. PMID: 24685669.

36. Bhatt HV, Syros G, Greco M, Miller M, Fischer GW. Ablation therapy for atrial fibrillation:implications for the anesthesiologist. J Cardiothorac Vasc Anesth. 2015; 29:1341–56. DOI: 10.1053/j.jvca.2015.05.197.

37. Kottkamp H, Hindricks G, Eitel C, Müller K, Siedziako A, Koch J, et al. Deep sedation for catheter ablation of atrial fibrillation:a prospective study in 650 consecutive patients. J Cardiovasc Electrophysiol. 2011; 22:1339–43. DOI: 10.1111/j.1540-8167.2011.02120.x. PMID: 21692895.

38. Hummel JD, Elsayed-Awad H. Walking the tightrope between deep sedation and general anesthesia:by whom can this safely be done? J Cardiovasc Electrophysiol. 2011; 22:1344–5. DOI: 10.1111/j.1540-8167.2011.02151.x. PMID: 21848634.

39. Trentman TL, Fassett SL, Mueller JT, Altemose GT. Airway interventions in the cardiac electrophysiology laboratory:a retrospective review. J Cardiothorac Vasc Anesth. 2009; 23:841–5. DOI: 10.1053/j.jvca.2009.01.027. PMID: 19362493.

40. Cho JS, Shim JK, Na S, Park I, Kwak YL. Improved sedation with dexmedetomidine-remifentanil compared with midazolam-remifentanil during catheter ablation of atrial fibrillation:a randomized, controlled trial. Europace. 2014; 16:1000–6. DOI: 10.1093/europace/eut365. PMID: 24381332.

41. Sairaku A, Yoshida Y, Hirayama H, Nakano Y, Ando M, Kihara Y. Procedural sedation with dexmedetomidine during ablation of atrial fibrillation:a randomized controlled trial. Europace. 2014; 16:994–9. DOI: 10.1093/europace/eut363. PMID: 24351886.

42. Hsu YW, Cortinez LI, Robertson KM, Keifer JC, Sum-Ping ST, Moretti EW, et al. Dexmedetomidine pharmacodynamics:part I:crossover comparison of the respiratory effects of dexmedetomidine and remifentanil in healthy volunteers. Anesthesiology. 2004; 101:1066–76. DOI: 10.1097/00000542-200411000-00005. PMID: 15505441.

43. Ingersoll-Weng E, Manecke GR Jr, Thistlethwaite PA. Dexmedetomidine and cardiac arrest. Anesthesiology. 2004; 100:738–9. DOI: 10.1097/00000542-200403000-00040. PMID: 15108994.

44. Hammer GB, Drover DR, Cao H, Jackson E, Williams GD, Ramamoorthy C, et al. The effects of dexmedetomidine on cardiac electrophysiology in children. Anesth Analg. 2008; 106:79–83. DOI: 10.1213/01.ane.0000297421.92857.4e. PMID: 18165557.

45. Shepard SM, Tejman-Yarden S, Khanna S, Davis CK, Batra AS. Dexmedetomidine-related atrial standstill and loss of capture in a pediatric patient after congenital heart surgery. Crit Care Med. 2011; 39:187–9. DOI: 10.1097/CCM.0b013e3181feb4b3. PMID: 20959781.

46. Bloor BC, Ward DS, Belleville JP, Maze M. Effects of intravenous dexmedetomidine in humans. II. Hemodynamic changes. Anesthesiology. 1992; 77:1134–42. DOI: 10.1097/00000542-199212000-00014. PMID: 1361311.

47. Housmans PR. Effects of dexmedetomidine on contractility, relaxation, and intracellular calcium transients of isolated ventricular myocardium. Anesthesiology. 1990; 73:919–22. DOI: 10.1097/00000542-199011000-00020. PMID: 1978616.

48. Mester R, Easley RB, Brady KM, Chilson K, Tobias JD. Monitored anesthesia care with a combination of ketamine and dexmedetomidine during cardiac catheterization. Am J Ther. 2008; 15:24–30. DOI: 10.1097/MJT.0b013e3180a72255. PMID: 18223350.

49. Motov S, Rosenbaum S, Vilke GM, Nakajima Y. Is there a role for intravenous subdissociative-dose ketamine administered as an adjunct to opioids or as a single agent for acute pain management in the emergency department? J Emerg Med. 2016; 51:752–7. DOI: 10.1016/j.jemermed.2016.07.087. PMID: 27693070.

50. Nelson LE, Lu J, Guo T, Saper CB, Franks NP, Maze M. The alpha2-adrenoceptor agonist dexmedetomidine converges on an endogenous sleep-promoting pathway to exert its sedative effects. Anesthesiology. 2003; 98:428–36. DOI: 10.1097/00000542-200302000-00024. PMID: 12552203.

51. Levänen J, Mäkelä ML, Scheinin H. Dexmedetomidine premedication attenuates ketamine-induced cardiostimulatory effects and postanesthetic delirium. Anesthesiology. 1995; 82:1117–25. DOI: 10.1097/00000542-199505000-00005. PMID: 7741286.

52. Hogendoorn W, Schlösser FJ, Muhs BE, Popescu WM. Surgical and anesthetic considerations for the endovascular treatment of ruptured descending thoracic aortic aneurysms. Curr Opin Anaesthesiol. 2014; 27:12–20. DOI: 10.1097/ACO.0000000000000028. PMID: 24256918.

53. Lhommet P, Espitalier F, Merlini T, Marchand E, Aupart M, Martinez R. Tolerance of rapid right ventricular pacing during thoracic endovascular aortic repair. Ann Vasc Surg. 2015; 29:578–85. DOI: 10.1016/j.avsg.2014.10.023. PMID: 25595106.

54. Brown BJ, Zakhary S, Rogers L, Ellis-Stoll C, Gable D, Ramsay MA. Use of dexmedetomidine versus general anesthesia for endovascular repair of abdominal aortic aneurysms. Proc (Bayl Univ Med Cent). 2006; 19:213–5. PMID: 17252035. PMCID: PMC1484526.

55. Rüger LJ, Irnich D, Abahji TN, Crispin A, Hoffmann U, Lang PM. Characteristics of chronic ischemic pain in patients with peripheral arterial disease. Pain. 2008; 139:201–8. DOI: 10.1016/j.pain.2008.03.027. PMID: 18472216.

56. Morris-Stiff G, Lewis MH. Gabapentin (Neurontin) improves pain scores of patients with critical limb ischaemia:an observational study. Int J Surg. 2010; 8:212–5. DOI: 10.1016/j.ijsu.2009.12.009. PMID: 20060939.

57. Rokyta R, Yamamotová A, Sulc R, Trefil L, Racek J, Treska V. Assessment of biochemical markers in patients with pain of vascular origin. Clin Exp Med. 2008; 8:199–206. DOI: 10.1007/s10238-008-0001-5. PMID: 18806929.

58. Rajan S, Hutcherson MT, Sessler DI, Kurz A, Yang D, Ghobrial M, et al. The effects of dexmedetomidine and remifentanil on hemodynamic stability and analgesic requirement after craniotomy:a randomized controlled trial. J Neurosurg Anesthesiol. 2016; 28:282–90. DOI: 10.1097/ANA.0000000000000221. PMID: 26325514.

59. Li Y, Liu S. The effect of dexmedetomidine on oxidative stress responsefollowing cerebral ischemia-reperfusion in rats and the expression of intracellular adhesion molecule-1 (ICAM-1) and S100B. Med Sci Monit. 2017; 23:867–73. DOI: 10.12659/MSM.899855. PMID: 28212354. PMCID: PMC5328199.

60. Zhong WG, Ge XY, Zhu H, Liang X, Gong HX, Zhong M, et al. Dexmedetomidine for antiemesis in gynecologic surgery:a meta-analysis of randomized controlled trials. Int J Clin Exp Med. 2015; 8:14566–76. PMID: 26628940. PMCID: PMC4658829.

61. Elvan EG, Oç B, Uzun S, Karabulut E, Coşkun F, Aypar U. Dexmedetomidine and postoperative shivering in patients undergoing elective abdominal hysterectomy. Eur J Anaesthesiol. 2008; 25:357–64. DOI: 10.1017/S0265021507003110. PMID: 18205960.

62. Palanisamy A, Klickovich RJ, Ramsay M, Ouyang DW, Tsen LC. Intravenous dexmedetomidine as an adjunct for labor analgesia and cesarean delivery anesthesia in a parturient with a tethered spinal cord. Int J Obstet Anesth. 2009; 18:258–61. DOI: 10.1016/j.ijoa.2008.10.002. PMID: 19188060.

63. Toyama H, Wagatsuma T, Ejima Y, Matsubara M, Kurosawa S. Cesarean section and primary pulmonary hypertension:the role of intravenous dexmedetomidine. Int J Obstet Anesth. 2009; 18:262–7. DOI: 10.1016/j.ijoa.2008.08.001. PMID: 19157850.

64. Ala-Kokko TI, Pienimäki P, Lampela E, Hollmén AI, Pelkonen O, Vähäkangas K. Transfer of clonidine and dexmedetomidine across the isolated perfused human placenta. Acta Anaesthesiol Scand. 1997; 41:313–9. DOI: 10.1111/j.1399-6576.1997.tb04685.x. PMID: 9062619.

65. Yousef AA, Salem HA, Moustafa MZ. Effect of mini-dose epidural dexmedetomidine in elective cesarean section using combined spinal-epidural anesthesia:a randomized double-blinded controlled study. J Anesth. 2015; 29:708–14. DOI: 10.1007/s00540-015-2027-7. PMID: 26006222.

66. El-Tahan MR, Mowafi HA, Al Sheikh IH, Khidr AM, Al-Juhaiman RA. Efficacy of dexmedetomidine in suppressing cardiovascular and hormonal responses to general anaesthesia for caesarean delivery:a dose-response study. Int J Obstet Anesth. 2012; 21:222–9. DOI: 10.1016/j.ijoa.2012.04.006. PMID: 22681971.

67. Li C, Li Y, Wang K, Kong X. Comparative evaluation of remifentanil and dexmedetomidine in general anesthesia for cesarean delivery. Med Sci Monit. 2015; 21:3806–13. DOI: 10.12659/MSM.895209. PMID: 26638888. PMCID: PMC4676355.

68. Danylkova NO, Alcala SR, Pomeranz HD, McLoon LK. Neuroprotective effects of brimonidine treatment in a rodent model of ischemic optic neuropathy. Exp Eye Res. 2007; 84:293–301. DOI: 10.1016/j.exer.2006.10.002. PMID: 17113077.

69. Ma D, Rajakumaraswamy N, Maze M. Alpha2-Adrenoceptor agonists:shedding light on neuroprotection? Br Med Bull. 2005; 71:77–92. DOI: 10.1093/bmb/ldh036. PMID: 15684247.

70. Karlsson BR, Forsman M, Roald OK, Heier MS, Steen PA. Effect of dexmedetomidine, a selective and potent alpha 2-agonist, on cerebral blood flow and oxygen consumption during halothane anesthesia in dogs. Anesth Analg. 1990; 71:125–9. DOI: 10.1213/00000539-199008000-00003. PMID: 1973880.

71. McPherson RW, Koehler RC, Kirsch JR, Traystman RJ. Intraventricular dexmedetomidine decreases cerebral blood flow during normoxia and hypoxia in dogs. Anesth Analg. 1997; 84:139–47. DOI: 10.1213/00000539-199701000-00026. PMID: 8989015.

72. Iida H, Ohata H, Iida M, Watanabe Y, Dohi S. Direct effects of alpha1- and alpha2-adrenergic agonists on spinal and cerebral pial vessels in dogs. Anesthesiology. 1999; 91:479–85. DOI: 10.1097/00000542-199908000-00023. PMID: 10443612.

73. Ogawa Y, Iwasaki K, Aoki K, Kojima W, Kato J, Ogawa S. Dexmedetomidine weakens dynamic cerebral autoregulation as assessed by transfer function analysis and the thigh cuff method. Anesthesiology. 2008; 109:642–50. DOI: 10.1097/ALN.0b013e3181862a33. PMID: 18813043.

74. Drummond JC, Dao AV, Roth DM, Cheng CR, Atwater BI, Minokadeh A, et al. Effect of dexmedetomidine on cerebral blood flow velocity, cerebral metabolic rate, and carbon dioxide response in normal humans. Anesthesiology. 2008; 108:225–32. DOI: 10.1097/01.anes.0000299576.00302.4c. PMID: 18212567.

75. Bekker A, Gold M, Ahmed R, Kim J, Rockman C, Jacobovitz G, et al. Dexmedetomidine does not increase the incidence of intracarotid shunting in patients undergoing awake carotid endarterectomy. Anesth Analg. 2006; 103:955–8. DOI: 10.1213/01.ane.0000237288.46912.39. PMID: 17000811.

76. Samuels ER, Hou RH, Langley RW, Szabadi E, Bradshaw CM. Modulation of the acoustic startle response by the level of arousal:comparison of clonidine and modafinil in healthy volunteers. Neuropsychopharmacology. 2007; 32:2405–21. DOI: 10.1038/sj.npp.1301363. PMID: 17342169.

77. Mahmoud M, Sadhasivam S, Sestokas AK, Samuels P, McAuliffe J. Loss of transcranial electric motor evoked potentials during pediatric spine surgery with dexmedetomidine. Anesthesiology. 2007; 106:393–6. DOI: 10.1097/00000542-200702000-00027. PMID: 17264733.

78. Li Y, Meng L, Peng Y, Qiao H, Guo L, Han R, et al. Effects of Dexmedetomidine on motor- and somatosensory-evoked potentials in patients with thoracic spinal cord tumor:a randomized controlled trial. BMC Anesthesiol. 2016; 16:51. DOI: 10.1186/s12871-016-0217-y. PMID: 27484701. PMCID: PMC4970285.

79. Tobias JD, Goble TJ, Bates G, Anderson JT, Hoernschemeyer DG. Effects of dexmedetomidine on intraoperative motor and somatosensory evoked potential monitoring during spinal surgery in adolescents. Paediatr Anaesth. 2008; 18:1082–8. DOI: 10.1111/j.1460-9592.2008.02733.x. PMID: 18717802.

80. Souter MJ, Rozet I, Ojemann JG, Souter KJ, Holmes MD, Lee L, et al. Dexmedetomidine sedation during awake craniotomy for seizure resection:effects on electrocorticography. J Neurosurg Anesthesiol. 2007; 19:38–44. DOI: 10.1097/01.ana.0000211027.26550.24. PMID: 17198099.

81. Vesper J, Haak S, Ostertag C, Nikkhah G. Subthalamic nucleus deep brain stimulation in elderly patients--analysis of outcome and complications. BMC Neurol. 2007; 7:7. DOI: 10.1186/1471-2377-7-7. PMID: 17367531. PMCID: PMC1847528.

82. Khatib R, Ebrahim Z, Rezai A, Cata JP, Boulis NM, John Doyle D, et al. Perioperative events during deep brain stimulation:the experience at cleveland clinic. J Neurosurg Anesthesiol. 2008; 20:36–40. DOI: 10.1097/ANA.0b013e318157a15a. PMID: 18157023.

83. Lakatta EG. Arterial and cardiac aging:major shareholders in cardiovascular disease enterprises:Part III:cellular and molecular clues to heart and arterial aging. Circulation. 2003; 107:490–7. DOI: 10.1161/01.CIR.0000048894.99865.02. PMID: 12551876.

84. Jakob SM, Ruokonen E, Grounds RM, Sarapohja T, Garratt C, Pocock SJ, et al. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation:two randomized controlled trials. JAMA. 2012; 307:1151–60. DOI: 10.1001/jama.2012.304. PMID: 22436955.

85. Park SH, Shin YD, Yu HJ, Bae JH, Yim KH. Comparison of two dosing schedules of intravenous dexmedetomidine in elderly patients during spinal anesthesia. Korean J Anesthesiol. 2014; 66:371–6. DOI: 10.4097/kjae.2014.66.5.371.

86. Lee JM, Lee SK, Lee SJ, Hwang WS, Jang SW, Park EY. Comparison of remifentanil with dexmedetomidine for monitored anaesthesia care in elderly patients during vertebroplasty and kyphoplasty. J Int Med Res. 2016; 44:307–16. DOI: 10.1177/0300060515607385. PMID: 26912506. PMCID: PMC5580066.

87. Rozet I, Muangman S, Vavilala MS, Lee LA, Souter MJ, Domino KJ, et al. Clinical experience with dexmedetomidine for implantation of deep brain stimulators in Parkinson's disease. Anesth Analg. 2006; 103:1224–8. DOI: 10.1213/01.ane.0000239331.53085.94. PMID: 17056959.

88. Deogaonkar A, Deogaonkar M, Lee JY, Ebrahim Z, Schubert A. Propofol-induced dyskinesias controlled with dexmedetomidine during deep brain stimulation surgery. Anesthesiology. 2006; 104:1337–9. DOI: 10.1097/00000542-200606000-00029. PMID: 16732105.

89. Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet. 2014; 383:911–22. DOI: 10.1016/S0140-6736(13)60688-1.

90. Fraser GL, Devlin JW, Worby CP, Alhazzani W, Barr J, Dasta JF, et al. Benzodiazepine versus nonbenzodiazepine-based sedation for mechanically ventilated, critically ill adults:a systematic review and meta-analysis of randomized trials. Crit Care Med. 2013; 41(9 Suppl 1):S30–8. DOI: 10.1097/CCM.0b013e3182a16898. PMID: 23989093.

91. Su X, Meng ZT, Wu XH, Cui F, Li HL, Wang DX. Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery:a randomised, double-blind, placebo-controlled trial. Lancet. 2016; 388:1893–902. DOI: 10.1016/S0140-6736(16)30580-3.

92. 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; 44:1182–90. DOI: 10.1177/0300060516671623. PMID: 27913743. PMCID: PMC5536774.