Dexmedetomidine: The Science and Clinical Aspects in Adults and Children

  • Mohamed MahmoudEmail author


The unique sedative properties of dexmedetomidine (DEX) have created new interest in the use of alpha-2 adrenoceptor agonists and have led to its evaluation in a variety of pediatric and adult procedures. DEX has been shown to offer a beneficial pharmacological profile, with sedation which parallels natural sleep, sympatholysis, and anesthetic-sparing effect without relevant respiratory depression. In addition, there is increasing evidence supporting its organ protective effects against ischemic and hypoxic injury. The side effects of DEX including biphasic, dose-dependent blood pressure response, and bradycardia are predictable from the pharmacological profile of alpha-2 adrenoceptor agonists. A comprehensive understanding of the pharmacologic, pharmacokinetic, and pharmacodynamic effects of DEX is critical to maximize its safe application in adults and children.


Alpha-2 adrenoceptors Dexmedetomidine Anesthesia Perioperative use Procedural sedation Adverse events Pharmacology 


  1. 1.
    Belleville JP, Ward DS, Bloor BC, Maze M. Effects of intravenous dexmedetomidine in humans. I. Sedation, ventilation, and metabolic rate. Anesthesiology. 1992;77(6):1125–33.PubMedCrossRefGoogle Scholar
  2. 2.
    Correa-Sales C, Rabin BC, Maze M. A hypnotic response to dexmedetomidine, an alpha 2 agonist, is mediated in the locus coeruleus in rats. Anesthesiology. 1992;76(6):948–52.PubMedCrossRefGoogle Scholar
  3. 3.
    Petroz GC, Sikich N, James M, van Dyk H, Shafer SL, Schily M, et al. A phase I, two-center study of the pharmacokinetics and pharmacodynamics of dexmedetomidine in children. Anesthesiology. 2006;105(6):1098–110.PubMedCrossRefGoogle Scholar
  4. 4.
    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(2):428–36.PubMedCrossRefGoogle Scholar
  5. 5.
    Doze VA, Chen BX, Maze M. Dexmedetomidine produces a hypnotic-anesthetic action in rats via activation of central alpha-2 adrenoceptors. Anesthesiology. 1989;71(1):75–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Bloor BC, Ward DS, Belleville JP, Maze M. Effects of intravenous dexmedetomidine in humans. II. Hemodynamic changes. Anesthesiology. 1992;77(6):1134–42.PubMedCrossRefGoogle Scholar
  7. 7.
    Akeju O, Pavone KJ, Westover MB, Vazquez R, Prerau MJ, Harrell PG, et al. A comparison of propofol- and dexmedetomidine-induced electroencephalogram dynamics using spectral and coherence analysis. Anesthesiology. 2014;121(5):978–89.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Sanders RD, Sun P, Patel S, Li M, Maze M, Ma D. Dexmedetomidine provides cortical neuroprotection: impact on anaesthetic-induced neuroapoptosis in the rat developing brain. Acta Anaesthesiol Scand. 2010;54(6):710–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Li Y, Zeng M, Chen W, Liu C, Wang F, Han X, et al. Dexmedetomidine reduces isoflurane-induced neuroapoptosis partly by preserving PI3K/Akt pathway in the hippocampus of neonatal rats. PLoS One. 2014;9(4), e93639.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Tachibana K, Hashimoto T, Kato R, Uchida Y, Ito R, Takita K, et al. Neonatal administration with dexmedetomidine does not impair the rat hippocampal synaptic plasticity later in adulthood. Paediatr Anaesth. 2012;22(7):713–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Sanders RD, Xu J, Shu Y, Januszewski A, Halder S, Fidalgo A, et al. Dexmedetomidine attenuates isoflurane-induced neurocognitive impairment in neonatal rats. Anesthesiology. 2009;110(5):1077–85.PubMedCrossRefGoogle Scholar
  12. 12.
    Clarke KW, Hall LW. “Xylazine”--a new sedative for horses and cattle. Vet Rec. 1969;85(19):512–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Mason KP, Lerman J. Review article: Dexmedetomidine in children: current knowledge and future applications. Anesth Analg. 2011;113(5):1129–42.PubMedCrossRefGoogle Scholar
  14. 14.
    Mahmoud M, Mason KP. Dexmedetomidine: review, update, and future considerations of paediatric perioperative and periprocedural applications and limitations. Br J Anaesth. 2015;115(2):171–82.PubMedCrossRefGoogle Scholar
  15. 15.
    Bhana N, Goa KL, McClellan KJ. Dexmedetomidine. Drugs. 2000;59(2):263–8. discussion 9–70.PubMedCrossRefGoogle Scholar
  16. 16.
    Brede M, Philipp M, Knaus A, Muthig V, Hein L. alpha2-adrenergic receptor subtypes - novel functions uncovered in gene-targeted mouse models. Biol Cell. 2004;96(5):343–8.PubMedGoogle Scholar
  17. 17.
    Kobilka BK, Matsui H, Kobilka TS, Yang-Feng TL, Francke U, Caron MG, et al. Cloning, sequencing, and expression of the gene coding for the human platelet alpha 2-adrenergic receptor. Science. 1987;238(4827):650–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Virtanen R, Savola JM, Saano V, Nyman L. Characterization of the selectivity, specificity and potency of medetomidine as an alpha 2-adrenoceptor agonist. Eur J Pharmacol. 1988;150(1–2):9–14.PubMedCrossRefGoogle Scholar
  19. 19.
    Panzer O, Moitra V, Sladen RN. Pharmacology of sedative-analgesic agents: dexmedetomidine, remifentanil, ketamine, volatile anesthetics, and the role of peripheral mu antagonists. Crit Care Clin. 2009;25(3):451–69.PubMedCrossRefGoogle Scholar
  20. 20.
    Correa-Sales C, Reid K, Maze M. Pertussis toxin-mediated ribosylation of G proteins blocks the hypnotic response to an alpha 2-agonist in the locus coeruleus of the rat. Pharmacol Biochem Behav. 1992;43(3):723–7.PubMedCrossRefGoogle Scholar
  21. 21.
    Nacif-Coelho C, Correa-Sales C, Chang LL, Maze M. Perturbation of ion channel conductance alters the hypnotic response to the alpha 2-adrenergic agonist dexmedetomidine in the locus coeruleus of the rat. Anesthesiology. 1994;81(6):1527–34.PubMedCrossRefGoogle Scholar
  22. 22.
    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(5):1066–76.PubMedCrossRefGoogle Scholar
  23. 23.
    Ishii H, Kohno T, Yamakura T, Ikoma M, Baba H. Action of dexmedetomidine on the substantia gelatinosa neurons of the rat spinal cord. Eur J Neurosci. 2008;27(12):3182–90.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Roudet C, Mouchet P, Feuerstein C, Savasta M. Normal distribution of alpha 2-adrenoceptors in the rat spinal cord and its modification after noradrenergic denervation: a quantitative autoradiographic study. J Neurosci Res. 1994;39(3):319–29.PubMedCrossRefGoogle Scholar
  25. 25.
    Stone LS, Broberger C, Vulchanova L, Wilcox GL, Hokfelt T, Riedl MS, et al. Differential distribution of alpha2A and alpha2C adrenergic receptor immunoreactivity in the rat spinal cord. J Neurosci. 1998;18(15):5928–37.PubMedGoogle Scholar
  26. 26.
    Guo TZ, Jiang JY, Buttermann AE, Maze M. Dexmedetomidine injection into the locus ceruleus produces antinociception. Anesthesiology. 1996;84(4):873–81.PubMedCrossRefGoogle Scholar
  27. 27.
    Diaz SM, Rodarte A, Foley J, Capparelli EV. Pharmacokinetics of dexmedetomidine in postsurgical pediatric intensive care unit patients: preliminary study. Pediatr Crit Care Med. 2007;8(5):419–24.PubMedCrossRefGoogle Scholar
  28. 28.
    Vilo S, Rautiainen P, Kaisti K, Aantaa R, Scheinin M, Manner T, et al. Pharmacokinetics of intravenous dexmedetomidine in children under 11 yr of age. Br J Anaesth. 2008;100(5):697–700.PubMedCrossRefGoogle Scholar
  29. 29.
    Dextor (dexmedetomidine) package insert. Espo, Finland: Orion Corporation; 2014.Google Scholar
  30. 30.
    Wang SS, Zhang MZ, Sun Y, Wu C, Xu WY, Bai J, et al. The sedative effects and the attenuation of cardiovascular and arousal responses during anesthesia induction and intubation in pediatric patients: a randomized comparison between two different doses of preoperative intranasal dexmedetomidine. Paediatr Anaesth. 2014;24(3):275–81.PubMedCrossRefGoogle Scholar
  31. 31.
    Cimen ZS, Hanci A, Sivrikaya GU, Kilinc LT, Erol MK. Comparison of buccal and nasal dexmedetomidine premedication for pediatric patients. Paediatr Anaesth. 2013;23(2):134–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Anttila M, Penttila J, Helminen A, Vuorilehto L, Scheinin H. Bioavailability of dexmedetomidine after extravascular doses in healthy subjects. Br J Clin Pharmacol. 2003;56(6):691–3.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Iirola T, Vilo S, Manner T, Aantaa R, Lahtinen M, Scheinin M, et al. Bioavailability of dexmedetomidine after intranasal administration. Eur J Clin Pharmacol. 2011;67(8):825–31.PubMedCrossRefGoogle Scholar
  34. 34.
    Chrysostomou C, Di Filippo S, Manrique AM, Schmitt CG, Orr RA, Casta A, et al. Use of dexmedetomidine in children after cardiac and thoracic surgery. Pediatr Crit Care Med. 2006;7(2):126–31.PubMedCrossRefGoogle Scholar
  35. 35.
    Su F, Gastonguay MR, Nicolson SC, DiLiberto M, Ocampo-Pelland A, Zuppa AF. Dexmedetomidine pharmacology in neonates and infants after open heart surgery. Anesth Analg. 2016;122:1556–66.PubMedCrossRefGoogle Scholar
  36. 36.
    Iirola T, Aantaa R, Laitio R, Kentala E, Lahtinen M, Wighton A, et al. Pharmacokinetics of prolonged infusion of high-dose dexmedetomidine in critically ill patients. Crit Care. 2011;15(5):R257.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Eastwood PR, Platt PR, Shepherd K, Maddison K, Hillman DR. Collapsibility of the upper airway at different concentrations of propofol anesthesia. Anesthesiology. 2005;103(3):470–7.PubMedCrossRefGoogle Scholar
  38. 38.
    Dhonneur G, Combes X, Leroux B, Duvaldestin P. Postoperative obstructive apnea. Anesth Analg. 1999;89(3):762–7.PubMedGoogle Scholar
  39. 39.
    Brouillette RT, Thach BT. A neuromuscular mechanism maintaining extrathoracic airway patency. J Appl Physiol. 1979;46(4):772–9.PubMedGoogle Scholar
  40. 40.
    Mahmoud M, Gunter J, Donnelly LF, Wang Y, Nick TG, Sadhasivam S. A comparison of dexmedetomidine with propofol for magnetic resonance imaging sleep studies in children. Anesth Analg. 2009;109(3):745–53.PubMedCrossRefGoogle Scholar
  41. 41.
    Mahmoud M, Radhakrishman R, Gunter J, Sadhasivam S, Schapiro A, McAuliffe J, et al. Effect of increasing depth of dexmedetomidine anesthesia on upper airway morphology in children. Paediatr Anaesth. 2010;20(6):506–15.PubMedCrossRefGoogle Scholar
  42. 42.
    Mahmoud M, Jung D, Salisbury S, McAuliffe J, Gunter J, Patio M, et al. Effect of increasing depth of dexmedetomidine and propofol anesthesia on upper airway morphology in children and adolescents with obstructive sleep apnea. J Clin Anesth. 2013;25:529–41.PubMedCrossRefGoogle Scholar
  43. 43.
    Truong MT, Woo VG, Koltai PJ. Sleep endoscopy as a diagnostic tool in pediatric obstructive sleep apnea. Int J Pediatr Otorhinolaryngol. 2012;76(5):722–7.PubMedCrossRefGoogle Scholar
  44. 44.
    Chatterjee D, Friedman N, Shott S, Mahmoud M. Anesthetic dilemmas for dynamic evaluation of the pediatric upper airway. Semin Cardiothorac Vasc Anesth. 2014;18(4):371–8.PubMedCrossRefGoogle Scholar
  45. 45.
    Mahmoud M, Gunter J, Sadhasivam S. Cine MRI airway studies in children with sleep apnea: optimal images and anesthetic challenges. Pediatr Radiol. 2009;39(10):1034–7.PubMedCrossRefGoogle Scholar
  46. 46.
    Jooste EH, Muhly WT, Ibinson JW, Suresh T, Damian D, Phadke A, et al. Acute hemodynamic changes after rapid intravenous bolus dosing of dexmedetomidine in pediatric heart transplant patients undergoing routine cardiac catheterization. Anesth Analg. 2010;111(6):1490–6.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Potts AL, Anderson BJ, Holford NH, Vu TC, Warman GR. Dexmedetomidine hemodynamics in children after cardiac surgery. Paediatr Anaesth. 2010;20(5):425–33.PubMedCrossRefGoogle Scholar
  48. 48.
    Mason KP, Lonnqvist PA. Bradycardia in perspective-not all reductions in heart rate need immediate intervention. Paediatr Anaesth. 2015;25(1):44–51.PubMedCrossRefGoogle Scholar
  49. 49.
    Mason KP, Turner DP, Houle TT, Fontaine PJ, Lerman J. Hemodynamic response to fluid management in children undergoing dexmedetomidine sedation for MRI. AJR Am J Roentgenol. 2014;202(6):W574–9.PubMedCrossRefGoogle Scholar
  50. 50.
    Mason KP, Zgleszewski SE, Prescilla R, Fontaine PJ, Zurakowski D. Hemodynamic effects of dexmedetomidine sedation for CT imaging studies. Paediatr Anaesth. 2008;18(5):393–402.PubMedCrossRefGoogle Scholar
  51. 51.
    Mason KP, Zurakowski D, Zgleszewski SE, Robson CD, Carrier M, Hickey PR, et al. High dose dexmedetomidine as the sole sedative for pediatric MRI. Paediatr Anaesth. 2008;18(5):403–11.PubMedCrossRefGoogle Scholar
  52. 52.
    Jorden VS, Pousman RM, Sanford MM, Thorborg PA, Hutchens MP. Dexmedetomidine overdose in the perioperative setting. Ann Pharmacother. 2004;38(5):803–7.PubMedCrossRefGoogle Scholar
  53. 53.
    Ramsay MA, Luterman DL. Dexmedetomidine as a total intravenous anesthetic agent. Anesthesiology. 2004;101(3):787–90.PubMedCrossRefGoogle Scholar
  54. 54.
    Patel VJ, Ahmed SS, Nitu ME, Rigby MR. Vasovagal syncope and severe bradycardia following intranasal dexmedetomidine for pediatric procedural sedation. Paediatr Anaesth. 2014;24(4):446–8.PubMedCrossRefGoogle Scholar
  55. 55.
    Berkenbosch JW, Tobias JD. Development of bradycardia during sedation with dexmedetomidine in an infant concurrently receiving digoxin. Pediatr Crit Care Med. 2003;4(2):203–5.PubMedCrossRefGoogle Scholar
  56. 56.
    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(1):79–83.PubMedCrossRefGoogle Scholar
  57. 57.
    Chrysostomou C, Komarlu R, Lichtenstein S, Shiderly D, Arora G, Orr R, et al. Electrocardiographic effects of dexmedetomidine in patients with congenital heart disease. Intensive Care Med. 2010;36(5):836–42.PubMedCrossRefGoogle Scholar
  58. 58.
    Aantaa R, Kanto J, Scheinin M, Kallio A, Scheinin H. Dexmedetomidine, an alpha 2-adrenoceptor agonist, reduces anesthetic requirements for patients undergoing minor gynecologic surgery. Anesthesiology. 1990;73(2):230–5.PubMedCrossRefGoogle Scholar
  59. 59.
    Scheinin H, Aantaa R, Anttila M, Hakola P, Helminen A, Karhuvaara S. Reversal of the sedative and sympatholytic effects of dexmedetomidine with a specific alpha2-adrenoceptor antagonist atipamezole: a pharmacodynamic and kinetic study in healthy volunteers. Anesthesiology. 1998;89(3):574–84.PubMedCrossRefGoogle Scholar
  60. 60.
    Mason KP, Zgleszewski S, Forman RE, Stark C, DiNardo JA. An exaggerated hypertensive response to glycopyrrolate therapy for bradycardia associated with high-dose dexmedetomidine. Anesth Analg. 2009;108(3):906–8.PubMedCrossRefGoogle Scholar
  61. 61.
    Congdon JM, Marquez M, Niyom S, Boscan P. Evaluation of the sedative and cardiovascular effects of intramuscular administration of dexmedetomidine with and without concurrent atropine administration in dogs. J Am Vet Med Assoc. 2011;239(1):81–9.PubMedCrossRefGoogle Scholar
  62. 62.
    Subramanyam R, Cudilo EM, Hossain MM, McAuliffe J, Wu J, Patino M, et al. To pretreat or not to pretreat: prophylactic anticholinergic administration before dexmedetomidine in pediatric imaging. Anesth Analg. 2015;121(2):479–85.PubMedCrossRefGoogle Scholar
  63. 63.
    Peden CJ, Cloote AH, Stratford N, Prys-Roberts C. The effect of intravenous dexmedetomidine premedication on the dose requirement of propofol to induce loss of consciousness in patients receiving alfentanil. Anaesthesia. 2001;56(5):408–13.PubMedCrossRefGoogle Scholar
  64. 64.
    Ingersoll-Weng E, Manecke Jr GR, Thistlethwaite PA. Dexmedetomidine and cardiac arrest. Anesthesiology. 2004;100(3):738–9.PubMedCrossRefGoogle Scholar
  65. 65.
    Dawes J, Myers D, Gorges M, Zhou G, Ansermino JM, Montgomery CJ. Identifying a rapid bolus dose of dexmedetomidine (ED50) with acceptable hemodynamic outcomes in children. Paediatr Anaesth. 2014;24(12):1260–7.PubMedCrossRefGoogle Scholar
  66. 66.
    Ickeringill M, Shehabi Y, Adamson H, Ruettimann U. Dexmedetomidine infusion without loading dose in surgical patients requiring mechanical ventilation: haemodynamic effects and efficacy. Anaesth Intensive Care. 2004;32(6):741–5.PubMedGoogle Scholar
  67. 67.
    Nishibe S, Imanishi H, Mieda T, Tsujita M. The effects of dexmedetomidine administration on the pulmonary artery pressure and the transpulmonary pressure gradient after the bidirectional superior cavopulmonary shunt. Pediatr Cardiol. 2015;36(1):151–7.PubMedCrossRefGoogle Scholar
  68. 68.
    Kastner SB, Kull S, Kutter AP, Boller J, Bettschart-Wolfensberger R, Huhtinen MK. Cardiopulmonary effects of dexmedetomidine in sevoflurane-anesthetized sheep with and without nitric oxide inhalation. Am J Vet Res. 2005;66(9):1496–502.PubMedCrossRefGoogle Scholar
  69. 69.
    Lazol JP, Lichtenstein SE, Jooste EH, Shiderly D, Kudchadker NA, Tatum GH, et al. Effect of dexmedetomidine on pulmonary artery pressure after congenital cardiac surgery: a pilot study. Pediatr Crit Care Med. 2010;11(5):589–92.PubMedCrossRefGoogle Scholar
  70. 70.
    Friesen RH, Nichols CS, Twite MD, Cardwell KA, Pan Z, Pietra B, et al. The hemodynamic response to dexmedetomidine loading dose in children with and without pulmonary hypertension. Anesth Analg. 2013;117(4):953–9.PubMedCrossRefGoogle Scholar
  71. 71.
    Nathan AT, Nicolson SC, McGowan FX. A word of caution: dexmedetomidine and pulmonary hypertension. Anesth Analg. 2014;119(1):216–7.PubMedCrossRefGoogle Scholar
  72. 72.
    Venn RM, Bryant A, Hall GM, Grounds RM. Effects of dexmedetomidine on adrenocortical function, and the cardiovascular, endocrine and inflammatory responses in post-operative patients needing sedation in the intensive care unit. Br J Anaesth. 2001;86(5):650–6.PubMedCrossRefGoogle Scholar
  73. 73.
    Maze M, Virtanen R, Daunt D, Banks SJ, Stover EP, Feldman D. Effects of dexmedetomidine, a novel imidazole sedative-anesthetic agent, on adrenal steroidogenesis: in vivo and in vitro studies. Anesth Analg. 1991;73(2):204–8.PubMedCrossRefGoogle Scholar
  74. 74.
    Enomoto Y, Kudo T, Saito T, Hori T, Kaneko M, Matsui A, et al. Prolonged use of dexmedetomidine in an infant with respiratory failure following living donor liver transplantation. Paediatr Anaesth. 2006;16(12):1285–8.PubMedCrossRefGoogle Scholar
  75. 75.
    De Wolf AM, Fragen RJ, Avram MJ, Fitzgerald PC, Rahimi-Danesh F. The pharmacokinetics of dexmedetomidine in volunteers with severe renal impairment. Anesth Analg. 2001;93(5):1205–9.PubMedCrossRefGoogle Scholar
  76. 76.
    Villela NR, do Nascimento Junior P, de Carvalho LR, Teixeira A. Effects of dexmedetomidine on renal system and on vasopressin plasma levels. Experimental study in dogs. Rev Bras Anestesiol. 2005;55(4):429–40.PubMedCrossRefGoogle Scholar
  77. 77.
    Frumento RJ, Logginidou HG, Wahlander S, Wagener G, Playford HR, Sladen RN. Dexmedetomidine infusion is associated with enhanced renal function after thoracic surgery. J Clin Anesth. 2006;18(6):422–6.PubMedCrossRefGoogle Scholar
  78. 78.
    Billings FT, Chen SW, Kim M, Park SW, Song JH, Wang S, et al. alpha2-Adrenergic agonists protect against radiocontrast-induced nephropathy in mice. Am J Physiol Renal Physiol. 2008;295(3):F741–8.PubMedCrossRefGoogle Scholar
  79. 79.
    Greening A, Mathews L, Blair J. Apparent dexmedetomidine-induced polyuric syndrome in an achondroplastic patient undergoing posterior spinal fusion. Anesth Analg. 2011;113(6):1381–3.PubMedCrossRefGoogle Scholar
  80. 80.
    Leino K, Hynynen M, Jalonen J, Salmenpera M, Scheinin H, Aantaa R, et al. Renal effects of dexmedetomidine during coronary artery bypass surgery: a randomized placebo-controlled study. BMC Anesthesiol. 2011;11:9.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Ji F, Li Z, Young JN, Yeranossian A, Liu H. Post-bypass dexmedetomidine use and postoperative acute kidney injury in patients undergoing cardiac surgery with cardiopulmonary bypass. PLoS One. 2013;8(10), e77446.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Bayram A, Ulgey A, Baykan A, Narin N, Narin F, Esmaoglu A, et al. The effects of dexmedetomidine on early stage renal functions in pediatric patients undergoing cardiac angiography using non-ionic contrast media: a double-blind, randomized clinical trial. Paediatr Anaesth. 2014;24(4):426–32.PubMedCrossRefGoogle Scholar
  83. 83.
    Wilder RT, Flick RP, Sprung J, Katusic SK, Barbaresi WJ, Mickelson C, et al. Early exposure to anesthesia and learning disabilities in a population-based birth cohort. Anesthesiology. 2009;110(4):796–804.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Brambrink AM, Evers AS, Avidan MS, Farber NB, Smith DJ, Zhang X, et al. Isoflurane-induced neuroapoptosis in the neonatal rhesus macaque brain. Anesthesiology. 2010;112(4):834–41.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Slikker Jr W, Zou X, Hotchkiss CE, Divine RL, Sadovova N, Twaddle NC, et al. Ketamine-induced neuronal cell death in the perinatal rhesus monkey. Toxicol Sci. 2007;98(1):145–58.PubMedCrossRefGoogle Scholar
  86. 86.
    Satomoto M, Satoh Y, Terui K, Miyao H, Takishima K, Ito M, et al. Neonatal exposure to sevoflurane induces abnormal social behaviors and deficits in fear conditioning in mice. Anesthesiology. 2009;110(3):628–37.PubMedCrossRefGoogle Scholar
  87. 87.
    Cattano D, Williamson P, Fukui K, Avidan M, Evers AS, Olney JW, et al. Potential of xenon to induce or to protect against neuroapoptosis in the developing mouse brain. Can J Anaesth. 2008;55(7):429–36.PubMedCrossRefGoogle Scholar
  88. 88.
    Dahmani S, Stany I, Brasher C, Lejeune C, Bruneau B, Wood C, et al. Pharmacological prevention of sevoflurane- and desflurane-related emergence agitation in children: a meta-analysis of published studies. Br J Anaesth. 2010;104(2):216–23.PubMedCrossRefGoogle Scholar
  89. 89.
    Engelhard K, Werner C, Eberspacher E, Bachl M, Blobner M, Hildt E, et al. The effect of the alpha 2-agonist dexmedetomidine and the N-methyl-D-aspartate antagonist S(+)-ketamine on the expression of apoptosis-regulating proteins after incomplete cerebral ischemia and reperfusion in rats. Anesth Analg. 2003;96(2):524–31.PubMedCrossRefGoogle Scholar
  90. 90.
    Kuhmonen J, Pokorny J, Miettinen R, Haapalinna A, Jolkkonen J, Riekkinen Sr P, et al. Neuroprotective effects of dexmedetomidine in the gerbil hippocampus after transient global ischemia. Anesthesiology. 1997;87(2):371–7.PubMedCrossRefGoogle Scholar
  91. 91.
    Jolkkonen J, Puurunen K, Koistinaho J, Kauppinen R, Haapalinna A, Nieminen L, et al. Neuroprotection by the alpha2-adrenoceptor agonist, dexmedetomidine, in rat focal cerebral ischemia. Eur J Pharmacol. 1999;372(1):31–6.PubMedCrossRefGoogle Scholar
  92. 92.
    Degos V, Charpentier TL, Chhor V, Brissaud O, Lebon S, Schwendimann L, et al. Neuroprotective effects of dexmedetomidine against glutamate agonist-induced neuronal cell death are related to increased astrocyte brain-derived neurotrophic factor expression. Anesthesiology. 2013;118(5):1123–32.PubMedCrossRefGoogle Scholar
  93. 93.
    Laudenbach V, Mantz J, Lagercrantz H, Desmonts JM, Evrard P, Gressens P. Effects of alpha(2)-adrenoceptor agonists on perinatal excitotoxic brain injury: comparison of clonidine and dexmedetomidine. Anesthesiology. 2002;96(1):134–41.PubMedCrossRefGoogle Scholar
  94. 94.
    Ma D, Hossain M, Rajakumaraswamy N, Arshad M, Sanders RD, Franks NP, et al. Dexmedetomidine produces its neuroprotective effect via the alpha 2A-adrenoceptor subtype. Eur J Pharmacol. 2004;502(1–2):87–97.PubMedCrossRefGoogle Scholar
  95. 95.
    Hoffman WE, Kochs E, Werner C, Thomas C, Albrecht RF. Dexmedetomidine improves neurologic outcome from incomplete ischemia in the rat. Reversal by the alpha 2-adrenergic antagonist atipamezole. Anesthesiology. 1991;75(2):328–32.PubMedCrossRefGoogle Scholar
  96. 96.
    Altman JD, Trendelenburg AU, MacMillan L, Bernstein D, Limbird L, Starke K, et al. Abnormal regulation of the sympathetic nervous system in alpha2A-adrenergic receptor knockout mice. Mol Pharmacol. 1999;56(1):154–61.PubMedGoogle Scholar
  97. 97.
    Huang R, Chen Y, Yu AC, Hertz L. Dexmedetomidine-induced stimulation of glutamine oxidation in astrocytes: a possible mechanism for its neuroprotective activity. J Cereb Blood Flow Metab. 2000;20(6):895–8.PubMedCrossRefGoogle Scholar
  98. 98.
    van Oostrom H, Stienen PJ, Doornenbal A, Hellebrekers LJ. The alpha(2)-adrenoceptor agonist dexmedetomidine suppresses memory formation only at doses attenuating the perception of sensory input. Eur J Pharmacol. 2010;629(1–3):58–62.PubMedCrossRefGoogle Scholar
  99. 99.
    Ebert TJ, Hall JE, Barney JA, Uhrich TD, Colinco MD. The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology. 2000;93(2):382–94.PubMedCrossRefGoogle Scholar
  100. 100.
    Veselis RA, Pryor KO, Reinsel RA, Li Y, Mehta M, Johnson Jr R. Propofol and midazolam inhibit conscious memory processes very soon after encoding: an event-related potential study of familiarity and recollection in volunteers. Anesthesiology. 2009;110(2):295–312.PubMedPubMedCentralGoogle Scholar
  101. 101.
    Prielipp RC, Wall MH, Tobin JR, Groban L, Cannon MA, Fahey FH, et al. Dexmedetomidine-induced sedation in volunteers decreases regional and global cerebral blood flow. Anesth Analg. 2002;95(4):1052–9.PubMedGoogle Scholar
  102. 102.
    Zornow MH, Maze M, Dyck JB, Shafer SL. Dexmedetomidine decreases cerebral blood flow velocity in humans. J Cereb Blood Flow Metab. 1993;13(2):350–3.PubMedCrossRefGoogle Scholar
  103. 103.
    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(2):225–32.PubMedCrossRefGoogle Scholar
  104. 104.
    Cheung CW, Ng KF, Liu J, Yuen MY, Ho MH, Irwin MG. Analgesic and sedative effects of intranasal dexmedetomidine in third molar surgery under local anaesthesia. Br J Anaesth. 2011;107(3):430–7.PubMedCrossRefGoogle Scholar
  105. 105.
    Yuen VM, Hui TW, Irwin MG, Yuen MK. A comparison of intranasal dexmedetomidine and oral midazolam for premedication in pediatric anesthesia: a double-blinded randomized controlled trial. Anesth Analg. 2008;106(6):1715–21.PubMedCrossRefGoogle Scholar
  106. 106.
    Ghali AM, Mahfouz AK, Al-Bahrani M. Preanesthetic medication in children: a comparison of intranasal dexmedetomidine versus oral midazolam. Saudi J Anaesth. 2011;5(4):387–91.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Yuen VM, Hui TW, Irwin MG, Yao TJ, Wong GL, Yuen MK. Optimal timing for the administration of intranasal dexmedetomidine for premedication in children. Anaesthesia. 2010;65(9):922–9.PubMedCrossRefGoogle Scholar
  108. 108.
    Talon MD, Woodson LC, Sherwood ER, Aarsland A, McRae L, Benham T. Intranasal dexmedetomidine premedication is comparable with midazolam in burn children undergoing reconstructive surgery. J Burn Care Res. 2009;30(4):599–605.PubMedCrossRefGoogle Scholar
  109. 109.
    Schmidt AP, Valinetti EA, Bandeira D, Bertacchi MF, Simoes CM, Auler Jr JO. Effects of preanesthetic administration of midazolam, clonidine, or dexmedetomidine on postoperative pain and anxiety in children. Paediatr Anaesth. 2007;17(7):667–74.PubMedCrossRefGoogle Scholar
  110. 110.
    Pasin L, Febres D, Testa V, Frati E, Borghi G, Landoni G, et al. Dexmedetomidine vs midazolam as preanesthetic medication in children: a meta-analysis of randomized controlled trials. Paediatr Anaesth. 2016;25:468–76.CrossRefGoogle Scholar
  111. 111.
    Sun Y, Lu Y, Huang Y, Jiang H. Is dexmedetomidine superior to midazolam as a premedication in children? A meta-analysis of randomized controlled trials. Paediatr Anaesth. 2014;24(8):863–74.PubMedCrossRefGoogle Scholar
  112. 112.
    Hauber JA, Davis PJ, Bendel LP, Martyn SV, McCarthy DL, Evans MC, et al. Dexmedetomidine as a rapid bolus for treatment and prophylactic prevention of emergence agitation in anesthetized children. Anesth Analg. 2015;121(5):1308–15.PubMedCrossRefGoogle Scholar
  113. 113.
    Guler G, Akin A, Tosun Z, Eskitascoglu E, Mizrak A, Boyaci A. Single-dose dexmedetomidine attenuates airway and circulatory reflexes during extubation. Acta Anaesthesiol Scand. 2005;49(8):1088–91.PubMedCrossRefGoogle Scholar
  114. 114.
    Huupponen E, Maksimow A, Lapinlampi P, Sarkela M, Saastamoinen A, Snapir A, et al. Electroencephalogram spindle activity during dexmedetomidine sedation and physiological sleep. Acta Anaesthesiol Scand. 2008;52(2):289–94.PubMedCrossRefGoogle Scholar
  115. 115.
    Mason KP, O’Mahony E, Zurakowski D, Libenson MH. Effects of dexmedetomidine sedation on the EEG in children. Paediatr Anaesth. 2009;19(12):1175–83.PubMedCrossRefGoogle Scholar
  116. 116.
    Shukry M, Kennedy K. Dexmedetomidine as a total intravenous anesthetic in infants. Paediatr Anaesth. 2007;17(6):581–3.PubMedCrossRefGoogle Scholar
  117. 117.
    Seybold JL, Ramamurthi RJ, Hammer GB. The use of dexmedetomidine during laryngoscopy, bronchoscopy, and tracheal extubation following tracheal reconstruction. Paediatr Anaesth. 2007;17(12):1212–4.PubMedCrossRefGoogle Scholar
  118. 118.
    Chen KZ, Ye M, Hu CB, Shen X. Dexmedetomidine vs remifentanil intravenous anaesthesia and spontaneous ventilation for airway foreign body removal in children. Br J Anaesth. 2014;112(5):892–7.PubMedCrossRefGoogle Scholar
  119. 119.
    Abdelmalak B, Gutenberg L, Lorenz RR, Smith M, Farag E, Doyle DJ. Dexmedetomidine supplemented with local anesthesia for awake laryngoplasty. J Clin Anesth. 2009;21(6):442–3.PubMedCrossRefGoogle Scholar
  120. 120.
    Penttila J, Helminen A, Anttila M, Hinkka S, Scheinin H. Cardiovascular and parasympathetic effects of dexmedetomidine in healthy subjects. Can J Physiol Pharmacol. 2004;82(5):359–62.PubMedCrossRefGoogle Scholar
  121. 121.
    Tsai CJ, Chu KS, Chen TI, Lu DV, Wang HM, Lu IC. A comparison of the effectiveness of dexmedetomidine versus propofol target-controlled infusion for sedation during fibreoptic nasotracheal intubation. Anaesthesia. 2010;65(3):254–9.PubMedCrossRefGoogle Scholar
  122. 122.
    Stricker P, Fiadjoe JE, McGinnis S. Intubation of an infant with Pierre Robin sequence under dexmedetomidine sedation using the Shikani Optical Stylet. Acta Anaesthesiol Scand. 2008;52(6):866–7.PubMedCrossRefGoogle Scholar
  123. 123.
    Iravani M, Wald SH. Dexmedetomidine and ketamine for fiberoptic intubation in a child with severe mandibular hypoplasia. J Clin Anesth. 2008;20(6):455–7.PubMedCrossRefGoogle Scholar
  124. 124.
    Mahmoud M, Tyler T, Sadhasivam S. Dexmedetomidine and ketamine for large anterior mediastinal mass biopsy. Paediatr Anaesth. 2008;18(10):1011–3.PubMedCrossRefGoogle Scholar
  125. 125.
    Song J, Ji Q, Sun Q, Gao T, Liu K, Li L. The opioid-sparing effect of intraoperative dexmedetomidine infusion after craniotomy. J Neurosurg Anesthesiol. 2016;28:14–20.PubMedCrossRefGoogle Scholar
  126. 126.
    Tobias JD. Dexmedetomidine: applications in pediatric critical care and pediatric anesthesiology. Pediatr Crit Care Med. 2007;8(2):115–31.PubMedCrossRefGoogle Scholar
  127. 127.
    Mahmoud M, Sadhasivam S, Salisbury S, Nick TG, Schnell B, Sestokas AK, et al. Susceptibility of transcranial electric motor-evoked potentials to varying targeted blood levels of dexmedetomidine during spine surgery. Anesthesiology. 2010;112(6):1364–73.PubMedCrossRefGoogle Scholar
  128. 128.
    Tobias JD, Berkenbosch JW. Initial experience with dexmedetomidine in paediatric-aged patients. Paediatr Anaesth. 2002;12(2):171–5.PubMedCrossRefGoogle Scholar
  129. 129.
    Frost EA, Booij LH. Anesthesia in the patient for awake craniotomy. Curr Opin Anaesthesiol. 2007;20(4):331–5.PubMedCrossRefGoogle Scholar
  130. 130.
    Rozet I. Anesthesia for functional neurosurgery: the role of dexmedetomidine. Curr Opin Anaesthesiol. 2008;21(5):537–43.PubMedCrossRefGoogle Scholar
  131. 131.
    Ard J, Doyle W, Bekker A. Awake craniotomy with dexmedetomidine in pediatric patients. J Neurosurg Anesthesiol. 2003;15(3):263–6.PubMedCrossRefGoogle Scholar
  132. 132.
    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(1):38–44.PubMedCrossRefGoogle Scholar
  133. 133.
    Chaitanya G, Arivazhagan A, Sinha S, Reddy KR, Thennarasu K, Bharath RD, et al. Dexmedetomidine anesthesia enhances spike generation during intra-operative electrocorticography: a promising adjunct for epilepsy surgery. Epilepsy Res. 2015;109:65–71.PubMedCrossRefGoogle Scholar
  134. 134.
    Ellis JE, Drijvers G, Pedlow S, Laff SP, Sorrentino MJ, Foss JF, et al. Premedication with oral and transdermal clonidine provides safe and efficacious postoperative sympatholysis. Anesth Analg. 1994;79(6):1133–40.PubMedCrossRefGoogle Scholar
  135. 135.
    Muzi M, Goff DR, Kampine JP, Roerig DL, Ebert TJ. Clonidine reduces sympathetic activity but maintains baroreflex responses in normotensive humans. Anesthesiology. 1992;77(5):864–71.PubMedCrossRefGoogle Scholar
  136. 136.
    Curtis JA, Hollinger MK, Jain HB. Propofol-based versus dexmedetomidine-based sedation in cardiac surgery patients. J Cardiothorac Vasc Anesth. 2013;27(6):1289–94.PubMedCrossRefGoogle Scholar
  137. 137.
    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):538–45.PubMedCrossRefGoogle Scholar
  138. 138.
    Riha H, Kotulak T, Brezina A, Hess L, Kramar P, Szarszoi O, et al. 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.PubMedGoogle Scholar
  139. 139.
    Yoshitomi O, Cho S, Hara T, Shibata I, Maekawa T, Ureshino H, et al. Direct protective effects of dexmedetomidine against myocardial ischemia-reperfusion injury in anesthetized pigs. Shock. 2012;38(1):92–7.PubMedCrossRefGoogle Scholar
  140. 140.
    Tosun Z, Baktir M, Kahraman HC, 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):710–5.PubMedCrossRefGoogle Scholar
  141. 141.
    Talke P, Li J, Jain U, Leung J, Drasner K, Hollenberg M, et al. Effects of perioperative dexmedetomidine infusion in patients undergoing vascular surgery. The Study of Perioperative Ischemia Research Group. Anesthesiology. 1995;82(3):620–33.PubMedCrossRefGoogle Scholar
  142. 142.
    Roekaerts PM, Prinzen FW, De Lange S. Beneficial effects of dexmedetomidine on ischaemic myocardium of anaesthetized dogs. Br J Anaesth. 1996;77(3):427–9.PubMedCrossRefGoogle Scholar
  143. 143.
    Willigers HM, Prinzen FW, Roekaerts PM, de Lange S, Durieux ME. Dexmedetomidine decreases perioperative myocardial lactate release in dogs. Anesth Analg. 2003;96(3):657–64.PubMedCrossRefGoogle Scholar
  144. 144.
    Menda F, Koner O, Sayin M, Ture H, Imer P, Aykac B. Dexmedetomidine as an adjunct to anesthetic induction to attenuate hemodynamic response to endotracheal intubation in patients undergoing fast-track CABG. Ann Card Anaesth. 2010;13(1):16–21.PubMedCrossRefGoogle Scholar
  145. 145.
    Kunisawa T, Nagata O, Nagashima M, Mitamura S, Ueno M, Suzuki A, et al. Dexmedetomidine suppresses the decrease in blood pressure during anesthetic induction and blunts the cardiovascular response to tracheal intubation. J Clin Anesth. 2009;21(3):194–9.PubMedCrossRefGoogle Scholar
  146. 146.
    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):1576–84.PubMedPubMedCentralCrossRefGoogle Scholar
  147. 147.
    Mukhtar AM, Obayah EM, Hassona AM. The use of dexmedetomidine in pediatric cardiac surgery. Anesth Analg. 2006;103(1):52–6.PubMedCrossRefGoogle Scholar
  148. 148.
    Chrysostomou C, Beerman L, Shiderly D, Berry D, Morell VO, 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):1514–22.PubMedCrossRefGoogle Scholar
  149. 149.
    Chrysostomou C, Sanchez-de-Toledo J, Wearden P, Jooste EH, Lichtenstein SE, Callahan PM, et al. Perioperative use of dexmedetomidine is associated with decreased incidence of ventricular and supraventricular tachyarrhythmias after congenital cardiac operations. Ann Thorac Surg. 2011;92(3):964–72.PubMedPubMedCentralCrossRefGoogle Scholar
  150. 150.
    Ramsay MA, Saha D, Hebeler RF. Tracheal resection in the morbidly obese patient: the role of dexmedetomidine. J Clin Anesth. 2006;18(6):452–4.PubMedCrossRefGoogle Scholar
  151. 151.
    Tufanogullari B, White PF, Peixoto MP, Kianpour D, Lacour T, Griffin J, et al. Dexmedetomidine infusion during laparoscopic bariatric surgery: the effect on recovery outcome variables. Anesth Analg. 2008;106(6):1741–8.PubMedCrossRefGoogle Scholar
  152. 152.
    Sidorowicz M, Owczuk R, Kwiecinska B, Wujtewicz MA, Wojciechowski J, Wujtewicz M. Dexmedetomidine sedation for carotid endarterectomy. Anestezjol Intens Ter. 2009;41(2):78–83.PubMedGoogle Scholar
  153. 153.
    McCutcheon CA, Orme RM, Scott DA, Davies MJ, McGlade DP. A comparison of dexmedetomidine versus conventional therapy for sedation and hemodynamic control during carotid endarterectomy performed under regional anesthesia. Anesth Analg. 2006;102(3):668–75.PubMedCrossRefGoogle Scholar
  154. 154.
    Rich JM. 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):357–60.PubMedGoogle Scholar
  155. 155.
    Hitt JM, Corcoran T, Michienzi K, Creighton P, Heard C. An evaluation of intranasal sufentanil and dexmedetomidine for pediatric dental sedation. Pharmaceutics. 2014;6(1):175–84.PubMedPubMedCentralCrossRefGoogle Scholar
  156. 156.
    Sheta SA, Al-Sarheed MA, Abdelhalim AA. Intranasal dexmedetomidine vs midazolam for premedication in children undergoing complete dental rehabilitation: a double-blinded randomized controlled trial. Paediatr Anaesth. 2014;24(2):181–9.PubMedCrossRefGoogle Scholar
  157. 157.
    Surendar MN, Pandey RK, Saksena AK, Kumar R, Chandra G. A comparative evaluation of intranasal dexmedetomidine, midazolam and ketamine for their sedative and analgesic properties: a triple blind randomized study. J Clin Pediatr Dent. 2014;38(3):255–61.PubMedCrossRefGoogle Scholar
  158. 158.
    Farah GJ, de Moraes M, Filho LI, Pavan AJ, Camarini ET, Previdelli IT, et al. Induced hypotension in orthognathic surgery: a comparative study of 2 pharmacological protocols. J Oral Maxillofac Surg. 2008;66(11):2261–9.PubMedCrossRefGoogle Scholar
  159. 159.
    Ogawa S, Seino H, Ito H, Yamazaki S, Ganzberg S, Kawaai H. Intravenous sedation with low-dose dexmedetomidine: its potential for use in dentistry. Anesth Prog. 2008;55(3):82–8.PubMedPubMedCentralCrossRefGoogle Scholar
  160. 160.
    Hasan MS, Chan L. Dexmedetomidine and ketamine sedation for dental extraction in children with cyanotic heart disease. J Oral Maxillofac Surg. 2014;72(10):1920.e1–4.Google Scholar
  161. 161.
    Kim HS, Kim JW, Jang KT, Lee SH, Kim CC, Shin TJ. Initial experience with dexmedetomidine for dental sedation in children. J Clin Pediatr Dent. 2013;38(1):79–81.PubMedCrossRefGoogle Scholar
  162. 162.
    Xu L, Bao H, Si Y, Wang X. Effects of dexmedetomidine on early and late cytokines during polymicrobial sepsis in mice. Inflamm Res. 2013;62(5):507–14.PubMedCrossRefGoogle Scholar
  163. 163.
    Li S, Yang Y, Yu C, Yao Y, Wu Y, Qian L, et al. Dexmedetomidine analgesia effects in patients undergoing dental implant surgery and its impact on postoperative inflammatory and oxidative stress. Oxid Med Cell Longev. 2015;2015:186736.PubMedPubMedCentralCrossRefGoogle Scholar
  164. 164.
    Fan TW, Ti LK, Islam I. Comparison of dexmedetomidine and midazolam for conscious sedation in dental surgery monitored by bispectral index. Br J Oral Maxillofac Surg. 2013;51(5):428–33.PubMedCrossRefGoogle Scholar
  165. 165.
    Taniyama K, Oda H, Okawa K, Himeno K, Shikanai K, Shibutani T. Psychosedation with dexmedetomidine hydrochloride during minor oral surgery. Anesth Prog. 2009;56(3):75–80.PubMedPubMedCentralCrossRefGoogle Scholar
  166. 166.
    Singh C, Pandey RK, Saksena AK, Chandra G. A comparative evaluation of analgo-sedative effects of oral dexmedetomidine and ketamine: a triple-blind, randomized study. Paediatr Anaesth. 2014;24:1252–9.PubMedCrossRefGoogle Scholar
  167. 167.
    Eisenach JC, De Kock M, Klimscha W. alpha(2)-adrenergic agonists for regional anesthesia. A clinical review of clonidine (1984-1995). Anesthesiology. 1996;85(3):655–74.PubMedCrossRefGoogle Scholar
  168. 168.
    Wu HH, Wang HT, Jin JJ, Cui GB, Zhou KC, Chen Y, et al. Does dexmedetomidine as a neuraxial adjuvant facilitate better anesthesia and analgesia? A systematic review and meta-analysis. PLoS One. 2014;9(3), e93114.PubMedPubMedCentralCrossRefGoogle Scholar
  169. 169.
    Saadawy I, Boker A, Elshahawy MA, Almazrooa A, Melibary S, Abdellatif AA, et al. Effect of dexmedetomidine on the characteristics of bupivacaine in a caudal block in pediatrics. Acta Anaesthesiol Scand. 2009;53(2):251–6.PubMedCrossRefGoogle Scholar
  170. 170.
    El-Hennawy AM, Abd-Elwahab AM, Abd-Elmaksoud AM, El-Ozairy HS, Boulis SR. Addition of clonidine or dexmedetomidine to bupivacaine prolongs caudal analgesia in children. Br J Anaesth. 2009;103(2):268–74.PubMedCrossRefGoogle Scholar
  171. 171.
    Tong Y, Ren H, Ding X, Jin S, Chen Z, Li Q. Analgesic effect and adverse events of dexmedetomidine as additive for pediatric caudal anesthesia: a meta-analysis. Paediatr Anaesth. 2014;24(12):1224–30.PubMedCrossRefGoogle Scholar
  172. 172.
    Huang Y, Lu Y, Zhang L, Yan J, Jiang J, Jiang H. Perineural dexmedetomidine attenuates inflammation in rat sciatic nerve via the NF-kappaB pathway. Int J Mol Sci. 2014;15(3):4049–59.PubMedPubMedCentralCrossRefGoogle Scholar
  173. 173.
    Konakci S, Adanir T, Yilmaz G, Rezanko T. The efficacy and neurotoxicity of dexmedetomidine administered via the epidural route. Eur J Anaesthesiol. 2008;25(5):403–9.PubMedCrossRefGoogle Scholar
  174. 174.
    Lahdesmaki J, Sallinen J, MacDonald E, Sirvio J, Scheinin M. Alpha2-adrenergic drug effects on brain monoamines, locomotion, and body temperature are largely abolished in mice lacking the alpha2A-adrenoceptor subtype. Neuropharmacology. 2003;44(7):882–92.PubMedCrossRefGoogle Scholar
  175. 175.
    Quan N, Xin L, Ungar AL, Blatteis CM. Preoptic norepinephrine-induced hypothermia is mediated by alpha 2-adrenoceptors. Am J Physiol. 1992;262(3 Pt 2):R407–11.PubMedGoogle Scholar
  176. 176.
    Finkel JC, Quezado ZM. Hypothermia-induced bradycardia in a neonate receiving dexmedetomidine. J Clin Anesth. 2007;19(4):290–2.PubMedCrossRefGoogle Scholar
  177. 177.
    Pestieau SR, Quezado ZM, Johnson YJ, Anderson JL, Cheng YI, McCarter RJ, et al. The effect of dexmedetomidine during myringotomy and pressure-equalizing tube placement in children. Paediatr Anaesth. 2011;21(11):1128–35.PubMedCrossRefGoogle Scholar
  178. 178.
    Hammer GB, Sam WJ, Chen MI, Golianu B, Drover DR. Determination of the pharmacodynamic interaction of propofol and dexmedetomidine during esophagogastroduodenoscopy in children. Paediatr Anaesth. 2009;19(2):138–44.PubMedCrossRefGoogle Scholar
  179. 179.
    Makary L, Vornik V, Finn R, Lenkovsky F, McClelland AL, Thurmon J, et al. Prolonged recovery associated with dexmedetomidine when used as a sole sedative agent in office-based oral and maxillofacial surgery procedures. J Oral Maxillofac Surg. 2010;68(2):386–91.PubMedCrossRefGoogle Scholar
  180. 180.
    Jalowiecki P, Rudner R, Gonciarz M, Kawecki P, Petelenz M, Dziurdzik P. Sole use of dexmedetomidine has limited utility for conscious sedation during outpatient colonoscopy. Anesthesiology. 2005;103(2):269–73.PubMedCrossRefGoogle Scholar
  181. 181.
    Pestieau SR, Quezado ZM, Johnson YJ, Anderson JL, Cheng YI, McCarter RJ, et al. High-dose dexmedetomidine increases the opioid-free interval and decreases opioid requirement after tonsillectomy in children. Can J Anaesth. 2011;58(6):540–50.PubMedCrossRefGoogle Scholar
  182. 182.
    Olutoye OA, Glover CD, Diefenderfer JW, McGilberry M, Wyatt MM, Larrier DR, et al. The effect of intraoperative dexmedetomidine on postoperative analgesia and sedation in pediatric patients undergoing tonsillectomy and adenoidectomy. Anesth Analg. 2010;111(2):490–5.PubMedCrossRefGoogle Scholar
  183. 183.
    Mason KP. Sedation trends in the 21st century: the transition to dexmedetomidine for radiological imaging studies. Paediatr Anaesth. 2010;20(3):265–72.PubMedCrossRefGoogle Scholar
  184. 184.
    Koroglu A, Teksan H, Sagir O, Yucel A, Toprak HI, Ersoy OM. A comparison of the sedative, hemodynamic, and respiratory effects of dexmedetomidine and propofol in children undergoing magnetic resonance imaging. Anesth Analg. 2006;103(1):63–7, table of contents.Google Scholar
  185. 185.
    Mason KP, Zgleszewski SE, Dearden JL, Dumont RS, Pirich MA, Stark CD, et al. Dexmedetomidine for pediatric sedation for computed tomography imaging studies. Anesth Analg. 2006;103(1):57–62.PubMedCrossRefGoogle Scholar
  186. 186.
    Heard CM, Joshi P, Johnson K. Dexmedetomidine for pediatric MRI sedation: a review of a series of cases. Paediatr Anaesth. 2007;17(9):888–92.PubMedCrossRefGoogle Scholar
  187. 187.
    Alhashemi JA. Dexmedetomidine vs midazolam for monitored anaesthesia care during cataract surgery. Br J Anaesth. 2006;96(6):722–6.PubMedCrossRefGoogle Scholar
  188. 188.
    Munro HM, Tirotta CF, Felix DE, Lagueruela RG, Madril DR, Zahn EM, et al. Initial experience with dexmedetomidine for diagnostic and interventional cardiac catheterization in children. Paediatr Anaesth. 2007;17(2):109–12.PubMedCrossRefGoogle Scholar
  189. 189.
    Char D, Drover DR, Motonaga KS, Gupta S, Miyake CY, Dubin AM, et al. The effects of ketamine on dexmedetomidine-induced electrophysiologic changes in children. Paediatr Anaesth. 2013;23(10):898–905.PubMedCrossRefGoogle Scholar
  190. 190.
    Tobias JD. Dexmedetomidine and ketamine: an effective alternative for procedural sedation? Pediatr Crit Care Med. 2012;13(4):423–7.PubMedCrossRefGoogle Scholar
  191. 191.
    Koruk S, Mizrak A, Gul R, Kilic E, Yendi F, Oner U. Dexmedetomidine-ketamine and midazolam-ketamine combinations for sedation in pediatric patients undergoing extracorporeal shock wave lithotripsy: a randomized prospective study. J Anesth. 2010;24(6):858–63.PubMedCrossRefGoogle Scholar
  192. 192.
    McVey JD, Tobias JD. Dexmedetomidine and ketamine for sedation during spinal anesthesia in children. J Clin Anesth. 2010;22(7):538–45.PubMedCrossRefGoogle Scholar
  193. 193.
    Zor F, Ozturk S, Bilgin F, Isik S, Cosar A. Pain relief during dressing changes of major adult burns: ideal analgesic combination with ketamine. Burns. 2010;36(4):501–5.PubMedCrossRefGoogle Scholar
  194. 194.
    Shank ES, Sheridan RL, Ryan CM, Keaney TJ, Martyn JA. Hemodynamic responses to dexmedetomidine in critically injured intubated pediatric burned patients: a preliminary study. J Burn Care Res. 2013;34(3):311–7.PubMedCrossRefGoogle Scholar
  195. 195.
    Barton KP, Munoz R, Morell VO, Chrysostomou C. Dexmedetomidine as the primary sedative during invasive procedures in infants and toddlers with congenital heart disease. Pediatr Crit Care Med. 2008;9(6):612–5.PubMedCrossRefGoogle Scholar
  196. 196.
    Engelhard K, Werner C, Kaspar S, Mollenberg O, Blobner M, Bachl M, et al. Effect of the alpha2-agonist dexmedetomidine on cerebral neurotransmitter concentrations during cerebral ischemia in rats. Anesthesiology. 2002;96(2):450–7.PubMedCrossRefGoogle Scholar
  197. 197.
    Eckenhoff JE, Kneale DH, Dripps RD. The incidence and etiology of postanesthetic excitment. A clinical survey. Anesthesiology. 1961;22:667–73.PubMedCrossRefGoogle Scholar
  198. 198.
    Voepel-Lewis T, Malviya S, Tait AR. A prospective cohort study of emergence agitation in the pediatric postanesthesia care unit. Anesth Analg. 2003;96(6):1625–30.PubMedCrossRefGoogle Scholar
  199. 199.
    Sikich N, Lerman J. Development and psychometric evaluation of the pediatric anesthesia emergence delirium scale. Anesthesiology. 2004;100(5):1138–45.PubMedCrossRefGoogle Scholar
  200. 200.
    Kain ZN, Mayes LC, Caldwell-Andrews AA, Karas DE, McClain BC. Preoperative anxiety, postoperative pain, and behavioral recovery in young children undergoing surgery. Pediatrics. 2006;118(2):651–8.PubMedCrossRefGoogle Scholar
  201. 201.
    Kain ZN, Caldwell-Andrews AA, Maranets I, McClain B, Gaal D, Mayes LC, et al. Preoperative anxiety and emergence delirium and postoperative maladaptive behaviors. Anesth Analg. 2004;99(6):1648–54.PubMedCrossRefGoogle Scholar
  202. 202.
    Vlajkovic GP, Sindjelic RP. Emergence delirium in children: many questions, few answers. Anesth Analg. 2007;104(1):84–91.PubMedCrossRefGoogle Scholar
  203. 203.
    Ibacache ME, Munoz HR, Brandes V, Morales AL. Single-dose dexmedetomidine reduces agitation after sevoflurane anesthesia in children. Anesth Analg. 2004;98(1):60–3.PubMedCrossRefGoogle Scholar
  204. 204.
    Isik B, Arslan M, Tunga AD, Kurtipek O. Dexmedetomidine decreases emergence agitation in pediatric patients after sevoflurane anesthesia without surgery. Paediatr Anaesth. 2006;16(7):748–53.PubMedCrossRefGoogle Scholar
  205. 205.
    Guler G, Akin A, Tosun Z, Ors S, Esmaoglu A, Boyaci A. Single-dose dexmedetomidine reduces agitation and provides smooth extubation after pediatric adenotonsillectomy. Paediatr Anaesth. 2005;15(9):762–6.PubMedCrossRefGoogle Scholar
  206. 206.
    Shukry M, Clyde MC, Kalarickal PL, Ramadhyani U. Does dexmedetomidine prevent emergence delirium in children after sevoflurane-based general anesthesia? Paediatr Anaesth. 2005;15(12):1098–104.PubMedCrossRefGoogle Scholar
  207. 207.
    Patel A, Davidson M, Tran MC, Quraishi H, Schoenberg C, Sant M, et al. Dexmedetomidine infusion for analgesia and prevention of emergence agitation in children with obstructive sleep apnea syndrome undergoing tonsillectomy and adenoidectomy. Anesth Analg. 2010;111(4):1004–10.PubMedGoogle Scholar
  208. 208.
    Doufas AG, Lin CM, Suleman MI, Liem EB, Lenhardt R, Morioka N, et al. Dexmedetomidine and meperidine additively reduce the shivering threshold in humans. Stroke. 2003;34(5):1218–23.PubMedCrossRefGoogle Scholar
  209. 209.
    Talke P, Tayefeh F, Sessler DI, Jeffrey R, Noursalehi M, Richardson C. Dexmedetomidine does not alter the sweating threshold, but comparably and linearly decreases the vasoconstriction and shivering thresholds. Anesthesiology. 1997;87(4):835–41.PubMedCrossRefGoogle Scholar
  210. 210.
    Bicer C, Esmaoglu A, Akin A, Boyaci A. Dexmedetomidine and meperidine prevent postanaesthetic shivering. Eur J Anaesthesiol. 2006;23(2):149–53.PubMedCrossRefGoogle Scholar
  211. 211.
    Elvan EG, Oc B, Uzun S, Karabulut E, Coskun F, Aypar U. Dexmedetomidine and postoperative shivering in patients undergoing elective abdominal hysterectomy. Eur J Anaesthesiol. 2008;25(5):357–64.PubMedCrossRefGoogle Scholar
  212. 212.
    Blaine Easley R, Brady KM, Tobias JD. Dexmedetomidine for the treatment of postanesthesia shivering in children. Paediatr Anaesth. 2007;17(4):341–6.PubMedCrossRefGoogle Scholar
  213. 213.
    Frolich MA, Zhang K, Ness TJ. Effect of sedation on pain perception. Anesthesiology. 2013;118(3):611–21.PubMedPubMedCentralCrossRefGoogle Scholar
  214. 214.
    Schnabel A, Meyer-Friessem CH, Reichl SU, Zahn PK, Pogatzki-Zahn EM. Is intraoperative dexmedetomidine a new option for postoperative pain treatment? A meta-analysis of randomized controlled trials. Pain. 2013;154(7):1140–9.PubMedCrossRefGoogle Scholar
  215. 215.
    Schnabel A, Reichl SU, Poepping DM, Kranke P, Pogatzki-Zahn EM, Zahn PK. Efficacy and safety of intraoperative dexmedetomidine for acute postoperative pain in children: a meta-analysis of randomized controlled trials. Paediatr Anaesth. 2013;23(2):170–9.PubMedCrossRefGoogle Scholar
  216. 216.
    Riker RR, Shehabi Y, Bokesch PM, Ceraso D, Wisemandle W, Koura F, et al. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA. 2009;301(5):489–99.PubMedCrossRefGoogle Scholar
  217. 217.
    Pandharipande PP, Pun BT, Herr DL, Maze M, Girard TD, Miller RR, 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):2644–53.PubMedCrossRefGoogle Scholar
  218. 218.
    Tan JA, Ho KM. Use of dexmedetomidine as a sedative and analgesic agent in critically ill adult patients: a meta-analysis. Intensive Care Med. 2010;36(6):926–39.PubMedCrossRefGoogle Scholar
  219. 219.
    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(11):1151–60.PubMedCrossRefGoogle Scholar
  220. 220.
    Ruokonen E, Parviainen I, Jakob SM, Nunes S, Kaukonen M, Shepherd ST, et al. Dexmedetomidine versus propofol/midazolam for long-term sedation during mechanical ventilation. Intensive Care Med. 2009;35(2):282–90.PubMedCrossRefGoogle Scholar
  221. 221.
    Xia ZQ, Chen SQ, Yao X, Xie CB, Wen SH, Liu KX. Clinical benefits of dexmedetomidine versus propofol in adult intensive care unit patients: a meta-analysis of randomized clinical trials. J Surg Res. 2013;185(2):833–43.PubMedCrossRefGoogle Scholar
  222. 222.
    Turunen H, Jakob SM, Ruokonen E, Kaukonen KM, Sarapohja T, Apajasalo M, et al. Dexmedetomidine versus standard care sedation with propofol or midazolam in intensive care: an economic evaluation. Crit Care. 2015;19:67.PubMedPubMedCentralCrossRefGoogle Scholar
  223. 223.
    Guinter JR, Kristeller JL. Prolonged infusions of dexmedetomidine in critically ill patients. Am J Health Syst Pharm. 2010;67(15):1246–53.PubMedCrossRefGoogle Scholar
  224. 224.
    Shehabi Y, Ruettimann U, Adamson H, Innes R, Ickeringill M. Dexmedetomidine infusion for more than 24 hours in critically ill patients: sedative and cardiovascular effects. Intensive Care Med. 2004;30(12):2188–96.PubMedCrossRefGoogle Scholar
  225. 225.
    Gerlach AT, Murphy CV, Dasta JF. An updated focused review of dexmedetomidine in adults. Ann Pharmacother. 2009;43(12):2064–74.PubMedCrossRefGoogle Scholar
  226. 226.
    Dasta JF, Kane-Gill SL, Durtschi AJ. Comparing dexmedetomidine prescribing patterns and safety in the naturalistic setting versus published data. Ann Pharmacother. 2004;38(7–8):1130–5.PubMedCrossRefGoogle Scholar
  227. 227.
    Czaja AS, Zimmerman JJ. The use of dexmedetomidine in critically ill children. Pediatr Crit Care Med. 2009;10(3):381–6.PubMedCrossRefGoogle Scholar
  228. 228.
    Bejian S, Valasek C, Nigro JJ, Cleveland DC, Willis BC. Prolonged use of dexmedetomidine in the paediatric cardiothoracic intensive care unit. Cardiol Young. 2009;19(1):98–104.PubMedCrossRefGoogle Scholar
  229. 229.
    Hammer GB, Philip BM, Schroeder AR, Rosen FS, Koltai PJ. Prolonged infusion of dexmedetomidine for sedation following tracheal resection. Paediatr Anaesth. 2005;15(7):616–20.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of Anesthesia and PediatricsCincinnati Children’s Hospital Medical Center, University of CincinnatiCincinnatiUSA

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