#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Dexmedetomidine and its use in anaesthesia and intensive care


Authors: B. Bilý 1;  F. Sabol 1;  P. Török 2;  P. Čandík 2
Authors‘ workplace: Klinika srdcovej chirurgie Lekárskej fakulty Univerzity Pavla Jozefa Šafárika a VÚSCH a. s., Košice 1;  Klinika anestéziológie a intenzívnej medicíny Lekárskej fakulty Univerzity Pavla Jozefa Šafárika a VÚSCH a. s., Košice 2
Published in: Anest. intenziv. Med., 28, 2017, č. 2, s. 114-126
Category:

Overview

Dexmedetomidine is a potent, highly selective and specific α2-adrenergic agonist with sedative, analgesic and sympatholytic effect. It is characterized by high selectivity of α21 at a ratio of 1600:1. Dexmedetomidine acts through the G-protein coupled receptor, which induces inhibition of adenylate cyclase, which in turn leads to a decrease in cAMP. The result is inhibition of the release of norepinephrine, which leads to a decrease of excitation in particular in the locus coeruleus. It also reduces the release of norepinephrine into the systemic circulation, thereby improving the haemodynamic stability, and has a positive effect on the myocardial oxygen supply, which contributes to the protection of the myocardium. α2-adrenergic agonists alleviate the stress response of the organism to the surgical intervention, thus during heart surgery they reduce the number of ischemic episodes and their administration is associated with a decreased risk of myocardial infarction. By its anti-inflammatory effect, stabilization of the sympathetic nervous system and the mitigation of ischemia-reperfusion damage, dexmedetomidine is characterized by a protective effect on the function of the heart, brain, kidney and the immune system. Although dexmedetomidine has sedative, analgesic and anxiolytic effects, in contrast to other sedatives it does not cause respiratory depression and provides respiratory stability during anaesthesia. The primary site of action of α2-adrenergic agonists is the locus coeruleus and not the cortex, like it is in the case of GABA-mimetics. The unusual subcortical form of sedation induced by dexmedetomidine is characterized by quickly and easily reached loss of consciousness, which resembles natural sleep.

KEYWORDS:
dexmedetomidine – α2-adrenergic agonist – sedation – surgical trauma – cardiac surgery – cardio-protective effect


Sources

1. Arcangeli, A., D’Alò, C., Gaspari, R. Dexmedetomidine use in general anaesthesia. Current. Drug. Targets., 2009, 10, 8, p. 687–695.

2. Philipp, M., Hein, L. Adrenergic receptor knockout mice: distinct functions of 9 receptor subtypes. Pharmacol. Ther., 2004, 101, 1, p. 65–74.

3. Riker, R. R., Shehabi, Y., Bokesch, P. M., Ceraso, D., Wisemandle, W., Koura, F. et al. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. SEDCOM (Safety and Efficacy of Dexmedetomidine Compared with Midazolam) Study Group. JAMA, 2009, 301, 5, p. 489–499.

4. Ibacache, M., Sanchez, G., Pedrozo, Z., Galvez, F., Humeres, C., Echevarria, G. et al. Dexmedetomidine preconditioning activates pro-survival kinases and attenuates regional ischemia/reperfusion injury in rat heart. Biochimica. Biophysica. Acta, 2012, 1822, 4, p. 537–545.

5. Bloor, B. C., Ward, D. S., Belleville, J. P., Maze, M. Effects of intravenous dexmedetomidine in humans. II. Hemodynamic changes. Anesthesiology, 1992, 77, 6, p. 1134–1142.

6. Ebert, T. J., Hall, J. E., Barney, J. A., Uhrich, T. D., Colinco, M. D. The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology, 2000, 93, 2, p. 382–394.

7. Venn, R. M., Bradshaw, C. J., Spencer, R., Brealey, D., Caudwell, E., Naughton, C. et al. Preliminary UK experience of dexmedetomidine: a novel agent for postoperative sedation in the intensive care unit. Anaesthesia, 1999, 54, 12, p. 1136–1142.

8. Arain, S. R., Ruehlow, R. M., Uhrich, T. D., Ebert, T. J. The efficacy of dexmedetomidine versus morphine for postoperative analgesia after major inpatient surgery. Anesth. Analg., 2004, 98, 1, p. 153–158.

9. Phan, H., Nahata, M. C. Clinical uses of dexmedetomidine in pediatric patients. Paediatr. Drugs., 2008, 10, 1, p. 49–69.

10. Málek, J., Mareček, F., Hess, L., Votava, M., Kurzová, A., Očadlík, M. Dexmedetomidin v premedikaci před laparoskopickou cholecystektomií – prospektivní randomizovaná studie. Anest. intenziv. Med., 2010, 21, 4, p. 179–184.

11. Jaakola, M. L. Dexmedetomidine premedication before intravenous regional anesthesia in minor outpatient hand surgery. J. Clin. Anesth., 1994, 6, 3, p. 204–211.

12. Bergese, S. D., Khabiri, B., Roberts, W. D., Howie, M. B., McSweeney, T. D., Gerhardt, M. A. Dexmedetomidine for con­scious sedation in difficult awake fiberoptic intubation cases. J. Clin. Anesth., 2007, 19, 2, p. 141–144.

13. Abdelmalak, B., Makary, L., Hoban, J., Doyle, D. J. Dexmedetomidine as sole sedative for awake intubation in management of the critical airway. J. Clin. Anesth., 2007, 19, 5, p. 370–373.

14. Uzümcügil, F., Canbay, O., Celebi, N., Karagoz, A. H., Ozgen, S. Comparison of dexmedetomidine-propofol vs. fentanyl-propofol for laryngeal mask insertion. Eur. J. Anaesthesiol., 2008, 25, 8, p. 675–680.

15. Málek, J., Hess, L., Hrehorová, Z., Šklíba, V. Intravenózní sedace kombinací dexmedetomidinu a ketaminu u operací v místní anestezii. Anest. intenziv. Med., 2008, 19, 2, p. 87–90.

16. Aho, M., Erkola, O., Kallio, A. et al. Dexmedetomidine infusion for maintenance of anesthesia in patients undergoing abdominal hysterectomy. Anesth. Analg., 1992, 75, 6, p. 940–946.

17. Khan, Z. P., Munday, I. T., Jones, R. M., Thornton, C., Mant, T. G., Amin, D. Effects of dexmedetomidine on isoflurane requirements in healthy volunteers. 1: Pharmacodynamic and pharmacokinetic interactions. Br. J. Anaesth., 1999, 83, 3, p. 372–380.

18. Ohtani, N., Kida, K., Shoji, K., Yasui, Y., Masaki, E. Recovery profiles from dexmedetomidine as a general anesthetic adjuvant in patients undergoing lower abdominal surgery. Anesth. Analg., 2008, 107, 6, p. 1871–1874.

19. Ramsay, M. A., Luterman, D. L. Dexmedetomidine as a total intravenous anesthetic agent. Anesthesiology, 2004, 101, 3, p. 787–790.

20. Ebert, T., Maze, M. Dexmedetomidine: another arrow for the clinician’s quiver. Anesthesiology, 2004, 101, 3, p. 568–570.

21. Wahlander, S., Frumento, R. J., Wagener, G., Saldana-Ferretti, B., Joshi, R. R., Playford, H.R. et al. A prospective, double-blind, randomized, placebo-controlled study of dexmedetomidine as an adjunct to epidural analgesia after thoracic surgery. J. Cardiothorac. Vasc. Anesth., 2005, 19, 5, p. 630–635.

22. 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, 34, 4. CD004126. doi: 10.1002/14651858.CD004126.pub2.

23. Chrysostomou, C., Beerman, L., Shiderly, D., Berry, D., Morell, V. O., Munoz, R. Dexmedetomidine: a novel drug for the treatment of atrial and junctional tachyarrhythmias during the perioperative period for congenital cardiac surgery: a preliminary study. Anesth. Analg., 2008, 107, 5, p. 1514–1522.

24. Ji, F., Li, Z., Nguyen, H., Young, N., Shi, P., Fleming, N. et al. Perioperative dexmedetomidine improves outcomes of cardiac surgery. Circulation, 2013, 127, 15, p. 1576–1584.

25. Lin, Y. Y., He. B., Chen, J., Wang, Z. N. Can dexmedetomidine be safe and efficacious sedative agent in post-cardiac surgery patients? A meta-analysis. Critical Care, 2012, 16, 5, R169. doi: 10.1186/cc11646.

26. Pandharipande, P. P., Pun, B. T., Herr, D. L., Maze, M., Girard, T. D., Miller, R. R. et al. Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA, 2007, 298, 22, p. 2644–2653.

27. Jackson, D. L., Proudfoot, C. W., Cann, K. F., Walsh, T. A systemic review of the impact of sedation practice in the ICU on resource use, costs and patient safety. Crit. Care, 2010, 14, 2, R59. doi: 10.1186/cc8956. Epub 2010 Apr 9.

28. Girard, T. D., Jackson, J. C., Pandharipande, P. P., Pun, B. T., Thompson, J. L., Shintani, A. K. et al. Delirium as a predictor of long-term cognitive impairment in survivors of critical illness. Crit. Care. Med., 2010, 38, 7, p. 1513–1520.

29. Roberts, R. J., Barletta, J. F., Fong, J. J., Schumaker, G., Kuper, P. J., Papadopoulos, S. et al. Incidence of propofol-related infusion syndrome in critically ill adults: a prospective, multicenter study. Crit. Care, 2009, 13, 5, R169. doi: 10.1186/cc8145. Epub 2009 Oct 29.

30. Jakob, S. M., Ruokonen, E., Grounds, R. M., Sarapohja, T., Garratt, C., Pocock, S. J. et al. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA, 2012, 307, 11, p. 1151–1160.

31. Mirski, M. A., Lewin, J. J. 3rd, Ledroux, S., Thompson, C., Murakami, P., Zink, E. K. et al. Cognitive improvement during continuous sedation in critically ill, awake and responsive patients: the Acute Neurological ICU Sedation Trial (ANIST). Intensive Care Med., 2010, 36, 9, p. 1505–1513.

32. Seaman, J. S., Schillerstrom, J., Carroll, D., Brown, T. M. Impaired oxidative metabolism precipitates delirium: a study of 101 ICU patients. Psychosomatics, 2006, 47, 1, p. 56–61.

33. Aakerlund, L. P., Rosenberg, J. Postoperative delirium: treatment with supplementary oxygen. Br. J. Anaesth., 1994, 72, 3, p. 286–290.

34. van Dijk, D., Jansen, E. W., Hijman, R., Nierich, A. P., Diephuis, J. C., Moons, K. G. et al. Cognitive outcome after off-pump and on-pump coronary artery bypass graft surgery: a randomized trial. Octopus Study Group, JAMA, 2002, 287, 11, p. 1405–1412.

35. Maldonado, J. R., Wysong, A., van der Starre, P. J., Block, T., Miller, C., Reitz, B. A. Dexmedetomidine and the reduction of postoperative delirium after cardiac surgery. Psychosomatics, 2009, 50, 3, p. 206–217.

Labels
Anaesthesiology, Resuscitation and Inten Intensive Care Medicine
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#