Anesthesia: Essays and Researches

REVIEW ARTICLE
Year
: 2011  |  Volume : 5  |  Issue : 2  |  Page : 128--133

Current role of dexmedetomidine in clinical anesthesia and intensive care


Manpreet Kaur1, PM Singh2,  
1 Department of Anaesthesia and Critical Care, All India Institute of Medical Sciences, J.P.N.A Trauma Centre, New Delhi, India
2 Department of Anaesthesia and Critical Care, All India Institute of Medical Sciences, New Delhi, India

Correspondence Address:
Manpreet Kaur
Department of Anaesthesia, All India Institute of Medical Sciences, J.P.N.A Trauma Centre, New Delhi - 110 029
India

Abstract

Dexmedetomidine is a new generation highly selective α 2-adrenergic receptor (α 2-AR) agonist that is associated with sedative and analgesic sparing effects, reduced delirium and agitation, perioperative sympatholysis, cardiovascular stabilizing effects, and preservation of respiratory function. The aim of this review is to present the most recent topics regarding the advantages in using dexmedetomidine in clinical anesthesia and intensive care, while discussing the controversial issues of its harmful effects.



How to cite this article:
Kaur M, Singh P M. Current role of dexmedetomidine in clinical anesthesia and intensive care.Anesth Essays Res 2011;5:128-133


How to cite this URL:
Kaur M, Singh P M. Current role of dexmedetomidine in clinical anesthesia and intensive care. Anesth Essays Res [serial online] 2011 [cited 2021 Nov 27 ];5:128-133
Available from: https://www.aeronline.org/text.asp?2011/5/2/128/94750


Full Text

 Introduction



α 2-adrenergic receptor (α 2-AR) agonists have been successfully used in several clinical settings in view of diverse actions which include sedation, analgesia, anxiolysis, perioperative sympatholysis, cardiovascular stabilizing effects, reduced anesthetic requirements, and preservation of respiratory function. [1] Dexmedetomidine is a relatively new drug approved at the end of 1999 by the Food and Drug Administration (FDA) for humans use for short-term sedation and analgesia (<24 hours) in the intensive care unit (ICU). Dexmedetomidine is a useful sedative agent with analgesic properties, hemodynamic stability and ability to recover respiratory function in mechanically ventilated patients facilitating early weaning. [2] Besides being a new modality of sedation and analgesia in ICU patient management, [3] it has been studied in several other perioperative settings, which will be discussed.

 Chemical Structure



Dexmedetomidine is the dextrorotatory S-enantiomer of medetomidine, an agent used in veterinary medicine. [4] It is chemically (S)-4-[1-(2,3-dimethylphenyl) ethyl]-3H-imidazole [Figure 1].{Figure 1}

 Mechanism of Action



α 2-AR agonists produce clinical effects after binding to G-Protein-coupled α 2-AR, of which there are three subtypes (α 2A, α 2B, and α 2C) with each having different physiological functions and pharmacological activities. These receptor subtypes are found ubiquitously in the central, peripheral, and autonomic nervous systems, as well as in vital organs and blood vessels. [5] Dexmedetomidine is 8 to 10 times more selective towards α 2-AR than clonidine. [6] Neither clonidine nor dexmedetomidine is totally selective for any one of the α 2-AR subtypes, but dexmedetomidine seems to have higher α2A-AR and α 2C-AR affinity than clonidine. [7] Major differences in the pharmacology of clonidine and dexmedetomidine have been described in [Table 1].{Table 1}

Locus ceruleus of the brain stem is the principal site for the sedative action and spinal cord is the principal site for the analgesic action, both acting through α 2A-AR. In the heart, the dominant action of α 2-AR agonists is a decrease in tachycardia (through blocking cardioaccelerator nerve) and bradycardia via α 2A-AR (through a vagomimetic action). In the peripheral vasculature, there is sympatholysis-mediated vasodilatation and smooth muscle cells receptor-mediated vasoconstriction. [8] The mechanism for the antishivering and diuretic actions has yet to be established firmly [9] [Figure 2].{Figure 2}

The responses to activation of the receptors in other areas include decreased salivation, decreased secretion, and decreased bowel motility in the gastrointestinal tract; contraction of vascular and other smooth muscle; inhibition of renin release, increased glomerular filtration, and increased secretion of sodium and water in the kidney; decreased intraocular pressure; and decreased insulin release from the pancreas. [10] Combining all these effects, dexmedetomidine avoids some of the side effects of multiagent therapies.

 Pharmacokinetics



Absorption and distribution

Dexmedetomidine exhibits linear pharmacokinetics in the recommended dose range of 0.2 to 0.7 μg/ kg/ hr administered as intravenous infusion up to 24 hours. The distribution phase is rapid, with a half-life of distribution of approximately 6 minutes and elimination half life of 2 hours. The steady-state volume of distribution is 118 L. The average protein binding is 94% and is constant across the different plasma concentrations and also similar in males and females. It has negligible protein binding displacement by drugs commonly used during anesthesia and in the ICU like fentanyl, ketorolac, theophylline, digoxin, and lidocaine. [10] Context-sensitive half life ranges from 4 minutes after a 10-minute infusion to 250 minutes after an 8-hour infusion. Oral bioavailability is poor because of extensive first-pass metabolism. However, bioavailability of sublingually administered dexmedetomidine is high (84%), offering a potential role in pediatric sedation and premedication. [11]

Metabolism and excretion

Dexmedetomidine undergoes almost complete biotransformation through direct N-glucuronidation and cytochrome P-450 (CYP 2A6)-mediated aliphatic hydroxylation to inactive metabolites. Metabolites are excreted in the urine (about 95%) and in the feces (4%). [10] Dose adjustments are required in patients with hepatic failure because of lower rate of metabolism.

 Clinical Pharmacology



Cardiovascular system

Dexmedetomidine evokes a biphasic blood pressure response: A short hypertensive phase and subsequent hypotension. The two phases are considered to be mediated by two different α 2-AR subtypes: the α -2B AR is responsible for the initial hypertensive phase, whereas hypotension is mediated by the α 2A-AR. [12] In younger patients with high levels of vagal tone, bradycardia and sinus arrest have been described which were effectively treated with anticholinergic agents (atropine, glycopyrrolate).

Central nervous system

Dexmedetomidine reduces cerebral blood flow and cerebral metabolic requirement of oxygen but its effect on intracranial pressure (ICP) is not yet clear. Dexmedetomidine modulates spatial working memory, enhancing cognitive performance besides having sedative, analgesic, and anxiolytic action through the α 2-AR. [13] Studies suggest the likelihood of its neuroprotective action by reducing the levels of circulating and brain catecholamines and thus balancing the ratio between cerebral oxygen supplies, reducing excitotoxicity, and improving the perfusion in the ischemic penumbra. It reduces the levels of the glutamate responsible for cellular brain injury, especially in subarachnoid hemorrhage. [14] It has been shown to limit the morphologic and functional effects after ischemic (focal and global) and traumatic injury to the nervous system.

Respiratory effects

Dexmedetomidine affect on respiration appears to be similar in order of magnitude to those seen in the heavy sleep state. [15] Dexmedetomidine does not suppress respiratory function, even at high doses. [16] It has no adverse effects on respiratory rate and gas exchange when used in spontaneously breathing ICU patients after surgery. [15] It helps in maintaining sedation without cardiovascular instability or respiratory drive depression and hence may facilitate weaning and extubation in trauma/surgical ICU patients who have failed previous attempts at weaning because of agitation and hyperdynamic cardiopulmonary response. [2],[17]

Endocrine and renal effects

Dexmedetomidine activates peripheral presynaptic α 2- AR which reduces the release of catecholamines, and hence reduces sympathetic response to surgery. [18] Animal studies have demonstrated the occurrence of natriuresis and diuresis. Dexmedetomidine is an imidazole agent but unlike etomidate, it does not appear to inhibit steroidogenesis when used as an infusion for short-term sedation. [19]

 Adverse Effects



The various reported side effects are hypotension, hypertension, nausea, vomiting, dry mouth, bradycardia, atrial fibrillation, pyrexia, chills, pleural effusion, atelectasis, pulmonary edema, hyperglycemia, hypocalcaemia, acidosis, etc. Rapid administration of dexmedetomidine infusion (Loading dose of 1 μ/ kg/ hr if given in less than 10 minutes) may cause transient hypertension mediated by peripheral α 2B- AR vasoconstriction. [5] But hypotension and bradycardia may occur with ongoing therapy mediated by central α 2A-AR, causing decreased release of noradrenaline from the sympathetic nervous system. Long-term use of dexmedetomidine leads to super sensitization and upregulation of receptors; so, with abrupt discontinuation, a withdrawal syndrome of nervousness, agitation, headaches, and hypertensive crisis can occur. [20] Dexmedetomidine is not recommended in patients with advanced heart block and ventricular dysfunction. [5] FDA has classified it as a category C pregnancy risk, so the drug should be used with extreme caution in women who are pregnant.

 Clinical Applications of Dexmedetomidine



Premedication

Dexmedetomidine is used as an adjuvant for premedication, especially in patients susceptible to preoperative and perioperative stress because of its sedative, anxiolytic, analgesic, sympatholytic, and stable hemodynamic profile. Dexmedetomidine decreases oxygen consumption in intraoperative period (up to 8%) and in postoperative period (up to 17%). [21] Premedication dose is 0.33 to 0.67 mg/kg IV given 15 minutes before surgery (this dose minimizes side effects of hypotension and bradycardia).

Intraoperative use

Dexmedetomidine attenuates hemodynamic stress response to intubation and extubation by sympatholysis. [15],[22],[23],[24] In view of absent respiratory depression, it can be continued at extubation period unlike other drugs. Dexmedetomidine potentiates anesthetic effect of all the anesthetic agents irrespective of the mode of administration (intravenous, inhalation, regional block). Intraoperative administration of dexmedetomidine in lower concentrations has reduced the requirement of other anesthetic agents; fewer interventions to treat tachycardia; and a reduction in the incidence of myocardial ischemia. [23] However, side effects like bradycardia and hypotension are limitations to its use necessitating need for pharmacological rescue therapy. These effects may be attributed to the combined properties of volatile anesthetics such as vasodilatation and myocardial depression. Dexmedetomidine administered in high concentrations may cause systemic and pulmonary hypertension because of direct peripheral vascular effects or may compromise myocardial function and blood pressure.

Locoregional analgesia

Highly lipophilic nature of dexmedetomidine allows rapid absorption into the cerebrospinal fluid and binding to α 2-AR of spinal cord for its analgesic action. It prolongs the duration of both sensory and motor blockade induced by local anesthetics irrespective of the route of administration (e.g., epidural, [25] caudal, [26] or spinal [27] ). Dexmedetomidine though enhances both central and peripheral neural blockade by local anesthetics; [27] however, the peripheral neural blockade is due to its binding to α 2A-AR. [28] Dexmedetomidine has been successfully used in intravenous regional anesthesia (IVRA), [29] brachial plexus block, [30] and intraarticularly. [31],[32] Addition of 0.5 μg/kg dexmedetomidine to lidocaine for IVRA improves quality of anesthesia and improves intraoperative-postoperative analgesia without causing side effects. [29] Dexmedetomidine added to levobupivacaine for axillary brachial plexus block shortens the onset time and prolongs the duration of the block and postoperative analgesia. [30] Intraarticular dexmedetomidine in patients undergoing arthroscopic knee surgery improves the quality and duration of postoperative analgesia. [31],[32]

Sedation in intensive care unit

Dexmedetomidine has become popular sedative agent in ICU because of its ability to produce cooperative sedation, i.e., patients remain awake, calm, and are able to communicate their needs. It does not interfere with the respiratory drive or produce any agitation, hence facilitating early weaning from ventilator, thereby reducing overall ICU stay costs. [33] The maintenance of natural sleep during sedation might speed recovery time in the ICU. Dexmedetomidine currently is approved by FDA for use in ICU for not more than 24 hours; though many studies have reported its safe use for longer duration. [34] Dexmedetomidine, when compared with conventional sedatives and opiates [Table 2], has been demonstrated to be associated with both sedative and analgesic sparing effects, reduced delirium and agitation, minimal respiratory depression, and desirable cardiovascular effects. [2],[35],[36] {Table 2}

Procedural sedation

Dexmedetomidine is an attractive agent for short-term procedural sedation and has been safely used in transesophageal echocardiography, [37] colonoscopy, [38] awake carotid endarterectomy, [39] shockwave lithotripsy, [34] vitreoretinal surgery, [40] elective awake fiberoptic intubation, [41] pediatric patients undergoing tonsillectomy, [42] and pediatric MRI. [43] The usual dose of dexmedetomidine for procedural sedation is 1 μg/ kg, followed by an infusion of 0.2 μg/kg/h. Its onset of action is less than 5 minutes and the peak effect occur within 15 minutes. As the pharmacologic effects of dexmedetomidine can be reversed by the α 2-AR antagonist atipamezole, [44] dexmedetomidine provides a titratable form of hypnotic sedation that can be readily reversed.

Controlled hypotension

Dexmedetomidine is an effective and safe agent for controlled hypotension mediated by its central and peripheral sympatholytic action. Its easy administration, predictability with anesthetic agents, and lack of toxic side effect while maintaining adequate perfusion of the vital organs makes it a near-ideal hypotensive agent. Spinal fusion surgery for idiopathic scoliosis, [45] septoplasty and tympanoplasty operations, [46] and maxillofacial surgery [47] have been safely done with dexmedetomidine-controlled hypotension.

Analgesia

Dexmedetomidine activates α 2-AR in the spinal cord reducing transmission of nociceptive signals like substance P. It has significant opioid sparing effect and is useful in intractable neuropathic pain. [14]

Cardiac surgery

Dexmedetomidine in addition to blunting the hemodynamic response to endotracheal intubation also reduces the extent of myocardial ischemia during cardiac surgery. [48] Dexmedetomidine has been successfully used to manage patients with pulmonary hypertension undergoing mitral valve replacement, with reduction in pulmonary vascular resistance, pulmonary artery pressure, and pulmonary capillary wedge pressures. [5]

Neurosurgery

Dexmedetomidine provides stable cerebral hemodynamics without sudden increase in ICP during intubation, extubation, and head pin insertion. It attenuates neurocognitive impairment (delirium and agitation) allowing immediate postoperative neurological evaluation. It exerts its neuroprotective effects through several mechanisms which make the usage of this drug a promising tool during cerebral ischemia. [14] It does not interfere with neurological monitors [5] and has an upcoming role in "functional" neurosurgery. This includes awake craniotomy for the resection of tumors or epileptic foci in eloquent areas, and the implantation of deep brain stimulators for Parkinson's disease. [5]

Obesity

Dexmedetomidine does not cause respiratory depression and has been infused at a dose of 0.7 μg/kg intraoperatively to avoid respiratory depression due to narcotic usage in a morbidly obese patient. [49]

Obstetrics

Dexmedetomidine has been successfully used as an adjunct to unsatisfactory analgesia by systemic opioids in laboring parturients who could not benefit from epidural analgesia. [50] It provides maternal hemodynamic stability, anxiolysis, and stimulation of uterine contractions. It is retained in placental tissue and passes less readily into the fetal circulation than clonidine because of high lipophilicity and thereby has less susceptibility to cause fetal bradycardia.

Pediatrics

It is currently being used off-label as an adjunctive agent in pediatric patients for sedation and analgesia in the critical care unit and for sedation during noninvasive procedures in radiology like computed tomography and magnetic resonance imaging. [43]

Other uses

The literature suggests other potential uses for dexmedetomidine, for example



Dexmedetomidine has been used successfully in the treatment of withdrawal from benzodiazepines, opioids, alcohol, and recreational drugs.As an adjunct in otorhinolaryngology anesthesia for middle ear surgery and rhinoplasty.As an adjunct in the repair of aortic aneurysms.Management of tetanus in ICU.As an antishivering agent.Dexmedetomidine is effective in preventing ethanol-induced neurodegeneration.

 Conclusion



Dexmedetomidine because of its unique properties offers its promising use in wide spectrum of clinical settings and ICUs. It is a part of fast-tracking anesthesia regimens and offers anesthetic sparing and hemodynamic stabilizing effects. As pharmacological effects of dexmedetomidine can be reversed by α 2-AR antagonist atipamezole, combination of dexmedetomidine and atipamezole can provide titratable form of sedation in the future.

References

1Kemp KM, Henderlight L, Neville M. Precedex: Is it the future of cooperative sedation? Nursing 2008;38 Suppl Critical:7-8.
2Takrouri MS, Seraj MA, Channa AB, el-Dawlatly AA, Thallage A, Riad W, et al. Dexmedetomidine in intensive care unit: A study of hemodynamic changes. Middle East J Anesthesiol 2002;16:587-95.
3Takrouri MS. New concepts in intensive care: Dexmedetomidine and immunonutrition. Middle East J Anesthesiol 2002;16:567-72.
4Dexmedetomidine. Available from: http://en.wikipedia.org/wiki/Dexmedetomidine [Last accessed on 2011 March 18].
5Afsani N. Clinical application of dexmedetomidine. S Afr J Anaesthesiol Analg 2010;16:50-6.
6Wagner DS, Brummett CM. Dexmedetomidine: As safe as safe can be. Semin Anesth Perioper Med Pain 2006;25:77-83.
7Fairbanks CA, Stone LS, Wilcox GL. Pharmacological profiles of alpha 2 adrenergic receptor agonists identified using genetically altered mice and isobolographic analysis. Pharmacol Ther 2009;123:224-38.
8Macdonald E, Koblka BK, Scheinin M. Gene targeting-homing in on alpha 2-adrenoceptor-subtype function. Trends Pharmacol Sci 1997;18:211-9.
9Kamibayashi T, Maze M. Clinical Uses of a2-Adrenergic Agonists. Anesthesiology 2000;93:1345-9.
10Gertler R, Brown HC, Mitchell DH, Silvius EN. Dexmedetomidine: A novel sedative-analgesic agent. Proc (Bayl Univ Med Cent) 2001;14:13-21.
11Anttila M, Penttilä J, Helminen A, Vuorilehto L, Scheinin H. Bioavailability of dexmedetomidine after extravascular doses in healthy subjects. Br J Clin Pharmacol 2003;56:691-3.
12Philipp 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.
13Franowicz JS, Arnsten AF. The alpha-2a noradrenergic agonist, guanfacine, improves delayed response performance in young adult rhesus monkeys. Psychopharmacology (Berl) 1998;136:8-14.
14Bekker A, Sturaitis MK. Dexmedetomidine for neurological surgery. Neurosurgery 2005;57:1-10.
15Venn RM, Hell J, Grounds RM. Respiratory effects of dexmedetomidine in the surgical patient requiring intensive care. Crit Care 2000;4:302-8.
16Hsu YW, Cortinez LI, Robertson KM, Keifer JC, Sum-Ping ST, Moretti EW, et al. Dexmedetomidine pharmacodynamics: Part I: Cross-over comparison of the respiratory effects of dexmedetomidine and remifentanil in healthy volunteers. Anesthesiology 2004;101:1066-76.
17Siobal MS, Kallet RH, Kivett VA, Tang JF. Use of dexmedetomidine to facilitate extubation in surgical intensive-care-unit patients who failed previous weaning attempts following prolonged mechanical ventilation: A pilot study. Respir Care 2006;51:492-6.
18Ebert TJ, Hall JE, Barney JA, Uhrich TD, Colinco MD. The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology 2000;93:382-94.
19Venn R, 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;86:650-6.
20Morgan GE, Mikhail MS, Murray MJ. Preoperative Medication in Clinical Anaethesia. In: Morgan GE, Mikhail MS, Murray MJ, Editors. 4 th ed. New York: Mc graw Hill; 2006. p. 248.
21Taittonen MT, Kirvela OA, Aantaa R, Kanto JH. Effect of clonidine and dexmedetomidine premedication on perioperative oxygen consumption and haemodynamic state. Br J Anaesth 1997;78:400-6.
22Scheinin B, Lindgren L, Randell T, Scheinin H, Scheinin M. Dexmedetomidine attenuates sympathoadrenal responses to tracheal intubation and reduces the need for thiopentone and peroperative fentanyl. Br J Anaesth 1992;68:126-31.
23Aho M, Lehtinen AM, Erkola O, Kallio A, Korttila K. The effect of intravenously administered dexmedetomidine on perioperative hemodynamics and isoflurane requirements in patients undergoing abdominal hysterectomy. Anesthesiology 1991;74:997-1002.
24Guler G, Akin A, Tosun E, Eskitafloglu E, Mizrak A, Boyaci A. Single-dose dexmedetomidine attenuates airway and circulatory reflexes during extubation. Acta Anaesthesiol Scand 2005;49:1088-91.
25Schnaider TB, Vieira AM, Brandao AC, Lobo MV. Intraoperative analgesic effect of epidural ketamine, clonidine or dexmedetomidine for upper abdominal surgery. Rev Bras Anestesiol 2005;55:525-31.
26El-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;103:268-74.
27Kanazi GE, Aouad MT, Jabbour-Khoury SI, Al Jazzar MD, Alameddine MM, Al-Yaman R, et al. Effect of low-dose dexmedetomidine or clonidine on the characteristics of bupivacaine spinal block. Acta Anaesthesiol Scand 2006;50:222-7.
28Yoshitomi T, Kohjitani A, Maeda S, Higuchi H, Shimada M, Miyawaki T. Dexmedetomidine enhances the local anesthetic action of lidocaine via an alpha-2A adrenoceptor. Anesth Analg 2008;107:96-101.
29Memiº D, Turan A, Karamanlıog¢lu B, Pamukçu Z, Kurt I. Adding Dexmedetomidine to Lidocaine for Intravenous Regional Anesthesia. Anesth Analg 2004;98:835-40.
30Esmaoglu A, Yegenoglu F, Akin A, Turk CY. Dexmedetomidine added to levobupivacaine prolongs axillary brachial plexus block. Anesth Analg 2010;111:1548-51.
31Al-Metwalli RR, Mowafi HA, Ismail SA, Siddiqui AK, Al-Ghamdi AM, Shafi MA, et al. Effect of intra-articular dexmedetomidine on postoperative analgesia after arthroscopic knee surgery. Br J Anaesth 2008;101:395-9.
32Paul S, Bhattacharjee DP, Ghosh S, Dawn S, Chatterjee N. Efficacy of intra-articular dexmedetomidine for postoperative analgesia in arthroscopic knee surgery. Ceylon Med J 2010;55:111-5.
33Short J. Use of Dexmedetomidine for Primary Sedation in a General Intensive Care Unit. Crit Care Nurse 2010;30:29-38.
34Kaygusuz K, Gokce G, Gursoy S, Ayan S, Mimaroglu C, Gultekin Y. A comparison of sedation with dexmedetomidine or propofol during shockwave lithotripsy: A randomized controlled trial. Anesth Analg 2008;106:114-9.
35Shehabi Y, Botha JA, Ernest D, Freebairn RC, Reade M, Roberts BL, et al. Clinical application, the use of dexmedetomidine in intensive care sedation. Crit Care Shock 2010;13:40-50.
36Pandharipande 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;298:2644-53.
37Cooper L, Candiotti K, Gallagher C, Grenier E, Arheart KL, Barron ME. A Randomized, Controlled Trial on Dexmedetomidine for Providing Adequate Sedation and Hemodynamic Control for Awake, Diagnostic Transesophageal Echocardiography. J Cardiothorac Vasc Anesth 2011;25:233-7.
38Jalowiecki 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;103:269-73.
39Bekker AY, Basile J, Gold M, Riles T, Adelman M, Cuff G, et al. Dexmedetomidine for awake carotid endarterectomy: Efficacy, hemodynamic profile, and side effects. J Neurosurg Anesthesiol 2004;16:126-35.
40Ghali A, Mahfouz AK, Ihanamäki T, El Btarny AM. Dexmedetomidine versus propofol for sedation in patients undergoing vitreoretinal surgery under sub-Tenon's anesthesia. Saudi J Anaesth 2011;5:36-41.
41Bergese SD, Khabiri B, Roberts WD, Howie MB, McSweeney TD, Gerhardt MA, et al. Dexmedetomidine for conscious sedation in difficult awake fiberoptic intubation cases. J Clin Anesth 2007;19:141-4.
42Olutoye 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;111:490-5.
43Phan H, Nahata MC. Clinical uses of dexmedetomidine in pediatric patients. Paediatr Drugs 2008;10:49-69.
44Aho M, Erkola O, Kallio A, Scheinin H, Korttila K. Comparison of dexmedetomidine and midazolam sedation and antagonism of dexmedetomidine with atipamezole. J Clin Anesth 1993;5:194-203.
45El-Gohary MM, Arafa AS. Dexmedetomidine as a hypotensive agent: Efficacy and hemodynamic response during spinal surgery for idiopathic scoliosis in adolescents. Egyp J Anaesth 2010;26:305-11.
46Ayoglu H, Yapakci O, Ugur MB, Uzun L, Altunkaya H, Ozer Y, et al. Effectiveness of dexmedetomidine in reducing bleeding during septoplasty and tympanoplasty operations. J Clin Anesth 2008;20:437-41.
47Richa F, Yazigi A, El Hage C, Jebara S, Hokayem N, Antakly MC. Dexmedetomidine: An agent for controlled hypotension in maxilla-facial surgery. Eur J Anaesthesiol 2004;21:902-6.
48Wijeysundera DN, Naik JS, Beattie WS. Alpha-2 adrenergic agonists to prevent perioperative cardiovascular complications: A meta analysis. Am J Med 2003;114:742-52.
49Hofer RE, Sprung J, Sarr MG, Wedel DJ. Anesthesia for a patient with morbid obesity using dexmedetomidine without narcotics. Can J Anesth 2005;52:176-80.
50Abu-Halaweh SA, Al Oweidi AK, Abu-Malooh H, Zabalawi M, Alkazaleh F, Abu-Ali H, et al. Intravenous dexmedetomidine infusion for labour analgesia in patient with preeclampsia. Eur J Anaesthesiol 2009;26:86-7.