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Meta-Analysis
. 2018 Mar 6;3(3):CD004126.
doi: 10.1002/14651858.CD004126.pub3.

Alpha-2 adrenergic agonists for the prevention of cardiac complications among adults undergoing surgery

Dallas Duncan  1 , Ashwin Sankar, W Scott Beattie, Duminda N Wijeysundera
Affiliations
Meta-Analysis

Alpha-2 adrenergic agonists for the prevention of cardiac complications among adults undergoing surgery

Dallas Duncan et al. Cochrane Database Syst Rev. .

Abstract

Background: The surgical stress response plays an important role on the pathogenesis of perioperative cardiac complications. Alpha-2 adrenergic agonists attenuate this response and may help prevent postoperative cardiac complications.

Objectives: To determine the efficacy and safety of α-2 adrenergic agonists for reducing mortality and cardiac complications in adults undergoing cardiac surgery and non-cardiac surgery.

Search methods: We searched CENTRAL (2017, Issue 4), MEDLINE (1950 to April Week 4, 2017), Embase (1980 to May 2017), the Science Citation Index, clinical trial registries, and reference lists of included articles.

Selection criteria: We included randomized controlled trials that compared α-2 adrenergic agonists (i.e. clonidine, dexmedetomidine or mivazerol) against placebo or non-α-2 adrenergic agonists. Included trials had to evaluate the efficacy and safety of α-2 adrenergic agonists for preventing perioperative mortality or cardiac complications (or both), or measure one or more relevant outcomes (i.e. death, myocardial infarction, heart failure, acute stroke, supraventricular tachyarrhythmia and myocardial ischaemia).

Data collection and analysis: Two authors independently assessed trial quality, extracted data and independently performed computer entry of abstracted data. We contacted study authors for additional information. Adverse event data were gathered from the trials. We evaluated included studies using the Cochrane 'Risk of bias' tool, and the quality of the evidence underlying pooled treatment effects using GRADE methodology. Given the clinical heterogeneity between cardiac and non-cardiac surgery, we analysed these subgroups separately. We expressed treatment effects as pooled risk ratios (RR) with 95% confidence intervals (CI).

Main results: We included 47 trials with 17,039 participants. Of these studies, 24 trials only included participants undergoing cardiac surgery, 23 only included participants undergoing non-cardiac surgery and eight only included participants undergoing vascular surgery. The α-2 adrenergic agonist studied was clonidine in 21 trials, dexmedetomidine in 24 trials and mivazerol in two trials.In non-cardiac surgery, there was high quality evidence that α-2 adrenergic agonists led to a similar risk of all-cause mortality compared with control groups (1.3% with α-2 adrenergic agonists versus 1.7% with control; RR 0.80, 95% CI 0.61 to 1.04; participants = 14,081; studies = 16). Additionally, the risk of cardiac mortality was similar between treatment groups (0.8% with α-2 adrenergic agonists versus 1.0% with control; RR 0.86, 95% CI 0.60 to 1.23; participants = 12,525; studies = 5, high quality evidence). The risk of myocardial infarction was probably similar between treatment groups (RR 0.94, 95% CI 0.69 to 1.27; participants = 13,907; studies = 12, moderate quality evidence). There was no associated effect on the risk of stroke (RR 0.93, 95% CI 0.55 to 1.56; participants = 11,542; studies = 7; high quality evidence). Conversely, α-2 adrenergic agonists probably increase the risks of clinically significant bradycardia (RR 1.59, 95% CI 1.18 to 2.13; participants = 14,035; studies = 16) and hypotension (RR 1.24, 95% CI 1.03 to 1.48; participants = 13,738; studies = 15), based on moderate quality evidence.There was insufficient evidence to determine the effect of α-2 adrenergic agonists on all-cause mortality in cardiac surgery (RR 0.52, 95% CI 0.26 to 1.04; participants = 1947; studies = 16) and myocardial infarction (RR 1.01, 95% CI 0.43 to 2.40; participants = 782; studies = 8), based on moderate quality evidence. There was one cardiac death in the clonidine arm of a study of 22 participants. Based on very limited data, α-2 adrenergic agonists may have reduced the risk of stroke (RR 0.37, 95% CI 0.15 to 0.93; participants = 1175; studies = 7; outcome events = 18; low quality evidence). Conversely, α-2 adrenergic agonists increased the risk of bradycardia from 6.4% to 12.0% (RR 1.88, 95% CI 1.35 to 2.62; participants = 1477; studies = 10; moderate quality evidence), but their effect on hypotension was uncertain (RR 1.19, 95% CI 0.87 to 1.64; participants = 1413; studies = 9; low quality evidence).These results were qualitatively unchanged in subgroup analyses and sensitivity analyses.

Authors' conclusions: Our review concludes that prophylactic α-2 adrenergic agonists generally do not prevent perioperative death or major cardiac complications. For non-cardiac surgery, there is moderate-to-high quality evidence that these agents do not prevent death, myocardial infarction or stroke. Conversely, there is moderate quality evidence that these agents have important adverse effects, namely increased risks of hypotension and bradycardia. For cardiac surgery, there is moderate quality evidence that α-2 adrenergic agonists have no effect on the risk of mortality or myocardial infarction, and that they increase the risk of bradycardia. The quality of evidence was inadequate to draw conclusions regarding the effects of alpha-2 agonists on stroke or hypotension during cardiac surgery.

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Conflict of interest statement

DD: no conflict of interest.

AS: no conflicts of interest.

WSB: the senior author of one included study (Wijeysundera 2014a); however, he had no involvement in either the data abstraction or quality assessment process. This author had no other relevant conflicts of interest.

DNW: the lead author of one included study (Wijeysundera 2014a); however, he had no involvement in either the primary data abstraction or quality assessment process. This author had no other relevant conflicts of interest.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Funnel plot of comparison: 1 Alpha‐2 adrenergic agonists versus control in non‐cardiac surgery, outcome: 1.1 All‐cause mortality.
5
5
Funnel plot of comparison: 1 Alpha‐2 adrenergic agonists versus control in non‐cardiac surgery, outcome: 1.3 Myocardial infarction.
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References

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    1. Ayoglu H, Yapakci O, Ugur MB, Uzun L, Altunkaya H, Ozer Y, et al. Effectiveness of dexmedetomidine in reducing bleeding during septoplasty and tympanoplasty operations. Journal of Clinical Anesthesia 2008;20(6):437‐41. [EMBASE: 2008461522; PUBMED: 18929284] - PubMed
Babu 2013 {published data only}
    1. Babu M, Verma A, Agarwal A, Tyagi C, Upadhyay M, Tripathi S. A comparative study in the post‐operative spine surgeries: Epidural ropivacaine with dexmedetomidine and ropivacaine with clonidine for post‐operative analgesia. Indian Journal of Anaesthesia 2013;57(4):371‐6. [EMBASE: 2013673831; PUBMED: 24163451] - PMC - PubMed
Bajwa 2011 {published data only}
    1. Bajwa SJS, Arora V, Kaur J, Singh A, Parmar SS. Comparative evaluation of dexmedetomidine and fentanyl for epidural analgesia in lower limb orthopedic surgeries. Saudi Journal of Anaesthesia 2011;5(4):365‐70. [EMBASE: 2011640719; PUBMED: 22144922] - PMC - PubMed
Bajwa 2012 {published data only}
    1. Bajwa S, Kaur J, Singh A, Parmar S, Singh G, Kulshrestha A, et al. Attenuation of pressor response and dose sparing of opioids and anaesthetics with pre‐operative dexmedetomidine. Indian Journal of Anaesthesia 2012;56(2):123‐8. [EMBASE: 2012406418; PUBMED: 22701201] - PMC - PubMed
Bakan 2015 {published data only}
    1. Bakan M, Umutoglu T, Topuz U, Uysal H, Bayram M, Kadioglu H, et al. Opioid‐free total intravenous anesthesia with propofol, dexmedetomidine and lidocaine infusions for laparoscopic cholecystectomy: a prospective, randomized, double‐blinded study. [Portuguese]. Revista Brasileira de Anestesiologia 2015;65(3):191‐9. [EMBASE: 2015796275; PUBMED: 25990496] - PubMed
Bakhamees 2007 {published data only}
    1. Bakhamees HS, El‐Halafawy YM, El‐Kerdawy HM, Gouda NM, Altemyatt S. Effects of dexmedetomidine in morbidly obese patients undergoing laparoscopic gastric bypass. Middle East Journal of Anesthesiology 2007;19:537‐51. [PUBMED: 18044282] - PubMed
Bakri 2015 {published data only}
    1. Bakri MH, Ismail EA, Ibrahim A. Comparison of dexmedetomidine and dexamethasone for prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy. Korean Journal of Anesthesiology 2015;68(3):254‐60. [EMBASE: 2015102998; PUBMED: 26045928] - PMC - PubMed
Balaraju 2013 {published data only}
    1. Balaraju TC, Ramdas B, Thomas R, Garg A, Sreekantha, Yogish B, et al. Comparative evaluation of oral clonidine and intravenous clonidine premedication in functional endoscopic sinus surgery. International Journal of Pharma and Bio Sciences 2013;4(1):B587‐91. [EMBASE: 2013473514]
Basar 2008 {published data only}
    1. Basar H, Akpinar S, Doganci N, Buyukkocak U, Kaymak C, Sert O, et al. The effects of preanesthetic, single‐dose dexmedetomidine on induction, hemodynamic, and cardiovascular parameters. Journal of Clinical Anesthesia 2008;20(6):431‐6. [EMBASE: 2008461521; PUBMED: 18929283] - PubMed
Batista 2015 {published data only}
    1. Batista HMT, Bezerra IMP, Abreu LC. Effect of clonidine on the target dose of propofol: Bispectral index evaluation. International Archives of Medicine 2015;8(1):1‐9. [CENTRAL: CN‐01074279; EMBASE: 2015058251]
Bayram 2011 {published data only}
    1. Bayram A, Esmaoglu A, Akin A, Baskol G, Aksu R, Bicer C, et al. The effects of intraoperative infusion of dexmedetomidine on early renal function after percutaneous nephrolithotomy. Acta Anaesthesiologica Scandinavica 2011;55(5):539‐44. [EMBASE: 2011204716; PUBMED: 21827441] - PubMed
Bayram 2012 {published data only}
    1. Bayram A, Altuntas R, Ulgey A, Gunes I, Akin A, Esmaoglu A, et al. Comparison between dexmedetomidine and remifentanil for controlled hypotension in patients scheduled for tympanoplasty. Erciyes Tip Dergisi 2012;34(2):65‐8. [EMBASE: 2012410017]
Beg 2001 {published data only}
    1. Beg AA, Saleena K, Naqeeb AJ, Dar BA, Sofi FA. Effect of oral clonidine premedication on anxiety and sedation in patients undergoing TURP under spinal anaesthesia. JK Practitioner : a Journal of Current Clinical Medicine & Surgery 2001;8:15‐7. [EMBASE: 2001101034]
Beigh 2003 {published data only}
    1. Beigh A, Naqeeb A, Khan FA. Haemodynamic and analgesic effect of oral clonidine on subarachanoid block with lidocaine. Journal of Anaesthesiology Clinical Pharmacology 2003;19:389‐93. [EMBASE: 2005003169]
Bekker 2008 {published data only}
    1. Bekker A, Sturaitis M, Bloom M, Moric M, Golfinos J, Parker E, et al. The effect of dexmedetomidine on perioperative hemodynamics in patients undergoing craniotomy. Anesthesia and Analgesia 2008;107(4):1340‐7. [EMBASE: 2009306675; PUBMED: 18806050] - PubMed
Bekker 2013 {published data only}
    1. Bekker A, Haile M, Kline R, Didehvar S, Babu R, Martiniuk F, et al. The effect of intraoperative infusion of dexmedetomidine on the quality of recovery after major spinal surgery. Journal of Neurosurgical Anesthesiology 2013;25(1):16‐24. [EMBASE: 2013041174; PUBMED: 22824921] - PMC - PubMed
Benhamou 1994 {published data only}
    1. Benhamou D, Narchi P, Hamza J, Marx M, Peyrol MT, Sembeil F. Addition of oral clonidine to postoperative patient‐controlled analgesia with i.v. morphine. British Journal of Anaesthesia 1994;72(5):537‐40. [PUBMED: 8198904] - PubMed
Bernard 1991a {published data only}
    1. Bernard JM, Hommeril J‐L, Passuti N, Pinaud M. Postoperative analgesia by intravenous clonidine. Anesthesiology 1991;75(4):577‐82. [PUBMED: 1928767] - PubMed
Bernard 1991b {published data only}
    1. Bernard JM, Bourreli B, Hommeril JL, Pinaud M. Effects of oral clonidine premedication and postoperative i.v. infusion on haemodynamic and adrenergic responses during recovery from anaesthesia. Acta Anaesthesiologica Scandinavica 1991;35(1):54‐9. [PUBMED: 2006600] - PubMed
Bernard 1993 {published data only}
    1. Bernard JM, Hommeril JL, Legendre MP, Passuti N, Pinaud M. Spinal or systemic analgesia after extensive spinal surgery: comparison between intrathecal morphine and intravenous fentanyl plus clonidine. Journal of Clinical Anesthesia 1993;5(3):231‐6. [PUBMED: 8318243] - PubMed
Bernard 1994 {published data only}
    1. Bernard JM, Lagarde D, Souron R. Balanced postoperative analgesia: effect of intravenous clonidine on blood gases and pharmacokinetics of intravenous fentanyl. Anesthesia and Analgesia 1994;79(6):1126‐32. [PUBMED: 7978437] - PubMed
Bhanderi 2014 {published data only}
    1. Bhanderi D, Shah C, Shah B, Mandowara N. Comparison of iv dexmedetomidine V/S iv clonidine In hemodynamic stability in laparoscopic surgery. Research Journal of Pharmaceutical, Biological and Chemical Sciences 2014;5(4):910‐7. [EMBASE: 2014495017]
Bharti 2010 {published data only}
    1. Bharti N, Bala SDI, Singh G. Effect of clonidine on postoperative pain: comparison of intravenous administration versus wound infiltration. Anaesthesia and Intensive Care 2010;38(6):1110‐1. [EMBASE: 71053337]
Bharti 2013 {published data only}
    1. Bharti N, Dontukurthy S, Bala I, Singh G. Postoperative analgesic effect of intravenous (i.v.) clonidine compared with clonidine administration in wound infiltration for open cholecystectomy. British Journal of Anaesthesia 2013;111(4):656‐61. [PUBMED: 23704191] - PubMed
Bhattacharjee 2010 {published data only}
    1. Bhattacharjee DP, Nayek SK, Dawn S, Bandopadhyay G, Gupta K. Effects of dexmedetomidine on haemodynamics in patients undergoing laparoscopic cholecystectomy‐ A comparative study. Journal of Anaesthesiology Clinical Pharmacology 2010;26(1):45‐8. [EMBASE: 2010114400]
Bicer 2006 {published data only}
    1. Bicer C, Esmaoglu A, Akin A, Boyaci A. Dexmedetomidine and meperidine prevent postanaesthetic shivering. European Journal of Anaesthesiology 2006;23:149‐53. [PUBMED: 16426470] - PubMed
Bindu 2013 {published data only}
    1. Bindu B, Pasupuleti S, Gowd UP, Gorre V, Murthy RR, Laxmi MB. A double blind, randomized, controlled trial to study the effect of dexmedetomidine on hemodynamic and recovery responses during tracheal extubation. Journal of Anaesthesiology Clinical Pharmacology 2013;29(2):162‐7. [EMBASE: 2013349348; PUBMED: 23878434] - PMC - PubMed
Boldt 1996 {published data only}
    1. Boldt J, Rothe G, Schindler E, Doll C, Gorlach G, Hempelmann G. Can clonidine, enoximone, and enalaprilat help to protect the myocardium against ischaemia in cardiac surgery?. Heart 1996;76(3):207‐13. [PUBMED: 8868976] - PMC - PubMed
Bouslama 2013 {published data only}
    1. Bouslama A, Echehoumi H, Smairi S, Ben Jazia K. A single intravenous dose of clonidine (4 mug/kg) given before induction reduces postoperative nausea and vomiting in patients after myomectomy under general anesthesia. European Journal of Anaesthesiology 2013;30:148. [EMBASE: 71315902]
Bozgeyik 2014 {published data only}
    1. Bozgeyik S, Mizrak A, Kilic E, Yendi F, Ugur B. The Effects of Preemptive Tramadol and Dexmedetomidine on Shivering during Arthroscopy. Saudi Journal of Anaesthesia 2014;8(2):238‐43. [EMBASE: 2014306876; PUBMED: 24843340] - PMC - PubMed
Buggy 1997 {published data only}
    1. Buggy D, Higgins P, Moran C, O'Donovan F, McCarroll M. Clonidine at induction reduces shivering after general anaesthesia. Canadian Journal of Anaesthesia 1997;44(3):263‐7. [PUBMED: 9067044] - PubMed
Bulow 2007 {published data only}
    1. Bulow NM, Barbosa NV, Rocha JB. Opioid consumption in total intravenous anesthesia is reduced with dexmedetomidine: a comparative study with remifentanil in gynecologic videolaparoscopic surgery. Journal of Clinical Anesthesia 2007;19(4):280‐5. [PUBMED: 17572323] - PubMed
Bulow 2016 {published data only}
    1. Bulow NMH, Colpo E, Pereira RP, Correa EFM, Waczuk EP, Duarte MF, et al. Dexmedetomidine decreases the inflammatory response to myocardial surgery under mini‐cardiopulmonary bypass. Brazilian Journal of Medical and Biological Research 2016;49(4):e4646. [EMBASE: 20160167871; PUBMED: 26909786] - PMC - PubMed
But 2006 {published data only}
    1. But AK, Ozgul U, Erdil F, Gulhas N, Toprak HI, Durmus M, et al. The effects of pre‐operative dexmedetomidine infusion on hemodynamics in patients with pulmonary hypertension undergoing mitral valve replacement surgery. Acta Anaesthesiologica Scandinavica 2006;50(10):1207‐12. [PUBMED: 16978159] - PubMed
Campagni 1999 {published data only}
    1. Campagni MA, Howie MB, White PF, McSweeney TD. Comparative effects of oral clonidine and intravenous esmolol in attenuating the hemodynamic response to epinephrine injection. Journal of Clinical Anesthesia 1999;11(3):208‐15. [PUBMED: 10434216] - PubMed
Carabine 1991a {published data only}
    1. Carabine UA, Milligan KR, Moore JA. Adrenergic modulation of preoperative anxiety: a comparison of temazepam, clonidine, and timolol. Anesthesia and Analgesia 1991;73(5):633‐7. [PUBMED: 1683183] - PubMed
Carabine 1991b {published data only}
    1. Carabine UA, Wright PMC, Moore J. Preanaesthetic medication with clonidine: a dose‐response study. British Journal of Anaesthesia 1991;67(1):79‐83. [PUBMED: 1859765] - PubMed
Carabine 1992 {published data only}
    1. Carabine UA, Allen RW, Moore J. Partial attenuation of the pressor response to endotracheal intubation. A comparison of the effects of intravenous clonidine and fentanyl. European Journal of Anaesthesiology 1992;9(4):325‐9. [PUBMED: 1628636] - PubMed
Caumo 2009 {published data only}
    1. Caumo W, Levandovski R, Hidalgo MPL. Preoperative anxiolytic effect of melatonin and clonidine on postoperative pain and morphine consumption in patients undergoing abdominal hysterectomy: a double‐blind, randomized, placebo‐controlled study. Journal of Pain 2009;10(1):100‐8. [EMBASE: 2009000997; PUBMED: 19010741] - PubMed
Ceballos 2011 {published data only}
    1. Ceballos Caballero M, Osorio Rodriguez G. Anesthesia for bariatric surgery: fentanyl versus fentanyl and dexmedetomidina. [Spanish]. Neurologia, Neurocirugia y Psiquiatria 2011;44(4):114‐21. [EMBASE: 2012108220]
Celebi 2013 {published data only}
    1. Celebi N, Canbay O, Cil H, Ayaz A. Effects of dexmedetomidine on succinylcholine‐induced myalgia in the early postoperative period. Saudi Medical Journal 2013;34(4):369‐73. [EMBASE: 2013229731; PUBMED: 23552589] - PubMed
Chadha 1992 {published data only}
    1. Chadha R, Padmanabhan V, Joseph A, Mohandas K. Oral clonidine pretreatment for haemodynamic stability during craniotomy. Anaesthesia and Intensive Care 1992;20(3):341‐4. [PUBMED: 1524175] - PubMed
Chaoba 2011 {published data only}
    1. Singh CL, Devi AN, Singh RN, Laithangbam P, Singh MK. The effect of intrathecal clonidine on hyperbaric bupivacaine for postoperative analgesia. JMS ‐ Journal of Medical Society 2011;25(3):29‐33. [EMBASE: 2013558752]
Chaturvedi 2014 {published data only}
    1. Chaturvedi A, Jain V, Pandaya MP. Effect of dexmedetomidine on postoperative pain and recovery in patients undergoing cervical spine surgery. Pain Practice 2014;14:88. [EMBASE: 71512674]
Chen 2013 {published data only}
    1. Chen J, Yan J, Han X. Dexmedetomidine may benefit cognitive function after laparoscopic cholecystectomy in elderly patients. Experimental and Therapeutic Medicine 2013;5(2):489‐94. [EMBASE: 2012742995; PUBMED: 23403854] - PMC - PubMed
Chen 2014 {published data only}
    1. Chen J, Zhou JQ, Chen ZF, Huang Y, Jiang H. Efficacy and safety of dexmedetomidine versus propofol for the sedation of tube‐retention after oral maxillofacial surgery. Journal of Oral and Maxillofacial Surgery 2014;72(2):285.e1‐7. [EMBASE: 2014044109; PUBMED: 24438599] - PubMed
Chen 2014a {published data only}
    1. Chen J, Tong XG. Application of dexmedetomidine with total intravenous anesthesia on perioperative period of carotid endarterectomy. [Chinese]. Chinese Journal of Contemporary Neurology and Neurosurgery 2014;14(2):87‐92. [EMBASE: 2014252119]
Cheung 2011 {published data only}
    1. Cheung CW, Ng KF, Choi WS, Chiu WK, Aaron Ying CL, et al. Evaluation of the analgesic efficacy of local dexmedetomidine application. Clinical Journal of Pain 2011;27(5):377‐82. [EMBASE: 2011258679; PUBMED: 21317777] - PubMed
Cheung 2014 {published data only}
    1. Cheung CW, Qiu Q, Ying AC, Choi SW, Law WL, Irwin MG. The effects of intra‐operative dexmedetomidine on postoperative pain, side‐effects and recovery in colorectal surgery. Anaesthesia 2014;69(11):1214‐21. [PUBMED: 24915800] - PubMed
Cho 2015 {published data only}
    1. Cho JS, Kim HI, Lee KY, An JY, Bai SJ, Cho JY, et al. Effect of intraoperative dexmedetomidine infusion on postoperative bowel movements in patients undergoing laparoscopic gastrectomy: a prospective, randomized, placebo‐controlled study. Medicine 2015;94(24):e959. [PUBMED: 26091461] - PMC - PubMed
Chua 2010 {published data only}
    1. Chua KS, Wang FY, Hsu HT, Lua IC, Wang HM, Tsai CJ. The effectiveness of dexmedetomidine infusion for sedating oral cancer patients undergoing awake fibreoptic nasal intubation. European Journal of Anaesthesiology 2010;27(1):36‐40. [EMBASE: 2010345545; PUBMED: 19550337] - PubMed
Cindea 2012 {published data only}
    1. Cindea I, Balcan A, Samoila B, Gherghina V, Popescu R, Iordache I. The impact of intravenous clonidine on management of acute postoperative pain following colorectal surgery. European Journal of Anaesthesiology 2012;29:204. [EMBASE: 71084666]
Curtis 2002 {published data only}
    1. Curtis FG, Castiglia YMM, Stolf AA, Ronzella E, Vanni SMD, Do Nascimento P Jr. Dexmedetomidine and sufentanil as intraoperative analgesics. Comparative study. Revista Brasileira de Anestesiologia 2002;52(5):525‐34. [EMBASE: 2002342279; PUBMED: 19475222] - PubMed
De Deyne 2000 {published data only}
    1. Deyne C, Struys M, Heylen R, Jongh R, Laenen M, Buyse L, et al. Influence of intravenous clonidine pretreatment on anesthetic requirements during bispectral EEG‐guided sevoflurane anesthesia. Journal of Clinical Anesthesia 2000;12(1):52‐7. [PUBMED: 10773509] - PubMed
De Kock 1992 {published data only}
    1. Kock MF, Pichon G, Scholtes JL. Intraoperative clonidine enhances postoperative morphine patient‐controlled analgesia. Canadian Journal of Anaesthesia 1992;39(6):537‐44. [PUBMED: 1643675] - PubMed
De Kock 1994 {published data only}
    1. Kock M, Lavandhomme P, Scholtes JL. Intraoperative and postoperative analgesia using intravenous opioid, clonidine and lignocaine. Anaesthesia and Intensive Care 1994;22(1):15‐21. [PUBMED: 8160943] - PubMed
De Kock 1995 {published data only}
    1. Kock M, Merello L, Pendeville P, Maiter D, Scholtes JL. Effects of intravenous clonidine on the secretion of growth hormone in the perioperative period. Acta Anaesthesiologica Belgica 1995;45(4):167‐74. [PUBMED: 7887119] - PubMed
De la Mora‐Gonzalez 2012 {published data only}
    1. Mora‐Gonzalez JF, Robles‐Cervantes JA, Mora‐Martinez JM, Barba‐Alvarez F, Cruz Llontop‐Pisfil E, Gonzalez‐Ortiz M, et al. Hemodynamic effects of dexmedetomidine‐fentanyl vs. nalbuphine‐propofol in plastic surgery. Middle East Journal of Anesthesiology 2012;21(4):553‐7. [PUBMED: 23327028] - PubMed
Delaunay 1991 {published data only}
    1. Delaunay L, Bonnet F, Duvaldestin P. Clonidine decreases postoperative oxygen consumption in patients recovering from general anaesthesia. British Journal of Anaesthesia 1991;67(4):397‐401. [PUBMED: 1931396] - PubMed
Demirhan 2011 {published data only}
    1. Demirhan A, Gul R, Ganidagli S, Koruk S, Mizrak A, Sanli M, et al. Combination of dexmedetomidine and tramadol in the treatment of pain after thoracotomy. [Turkish]. Gogus‐Kalp‐Damar Anestezi ve Yogun Bakim Dernegi Dergisi 2011;17(2):34‐41. [EMBASE: 2012130652]
Dhorigol 2010 {published data only}
    1. Dhorigol MG, Dhulkhed VK, Biyani A, Desai N. Randomized controlled, double‐blind study to evaluate oral clonidine to prevent post‐subarachnoid block shivering in patients undergoing elective urological surgery. Journal of Anaesthesiology Clinical Pharmacology 2010;26(1):15‐8. [EMBASE: 2010114394]
Dimou 2003 {published data only}
    1. Dimou P, Paraskeva A, Papilas K, Fassooulaki A. Transdermal clonidine: does it affect pain after abdominal hysterectomy?. Acta Anaesthesiologica Belgica 2003;54:227‐32. [PUBMED: 14598620] - PubMed
Doak 1993 {published data only}
    1. Doak GJ, Duke PC. Oral clonidine premedication attenuates the haemodynamic effects associated with ketamine anaesthetic induction in humans. Canadian Journal of Anaesthesia 1993;40(7):612‐8. [PUBMED: 8403135] - PubMed
Dobrydniov 1999 {published data only}
    1. Dobrydniov I, Samarutel J. Enhancement of intrathecal lidocaine by addition of local and systemic clonidine. Acta Anaesthesiologica Scandinavica 1999;43(5):556‐62. [PUBMED: 10342005] - PubMed
Dobrydnjov 2002 {published data only}
    1. Dobrydnjov I, Axelsson K, Samarutel J, Holmstrom B. Postoperative pain relief following intrathecal bupivacaine combined with intrathecal or oral clonidine. Acta Anaesthesiologica Scandinavica 2002;46(7):806‐14. [PUBMED: 12139535] - PubMed
Dogan 2008 {published data only}
    1. Dogan Y, Alptekin A, Ozkan D, Arik E, Gumus H. Comparison of the effect of dexmedetomidine and remifentanyl on the hemodynamic response to intubation. Anestezi Dergisi 2008;16(3):136‐41. [EMBASE: 2008557577]
Dorman 1997 {published data only}
    1. Dorman T, Clarkson K, Rosenfeld BA, Shanholtz C, Lipsett PA, Breslow MJ. Effects of clonidine on prolonged postoperative sympathetic response. Critical Care Medicine 1997;25(7):1147‐52. [PUBMED: 9233740] - PubMed
Durmus 2007 {published data only}
    1. Durmus M, But AK, Dogan Z, Yucel A, Miman MC, Ersoy MO. Effect of dexmedetomidine on bleeding during tympanoplasty or septorhinoplasty. European Journal of Anaesthesiology 2007;24(5):447‐53. [PUBMED: 17241505] - PubMed
Eberhart 2000 {published data only}
    1. Dorman T, Clarkson K, Rosenfeld BA, Shanholtz C, Lipsett PA, Breslow MJ. Effects of clonidine on prolonged postoperative sympathetic response. Critical Care Medicine 1997;25(7):1147‐52. [PUBMED: 9233740] - PubMed
    1. Eberhart LH, Novatchkov N, Schricker T, Georgieff M, Baur CP. Intravenous premedication with clonidine and midazolam before ambulatory surgery. A controlled double‐blind study in ASA 1 patients. Anasthesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie 2000;35(6):388‐93. [PUBMED: 10900497] - PubMed
El 2012 {published data only}
    1. Ayad AE, Masry A. Epidural steroid and clonidine for chronic intractable post‐thoracotomy pain: a pilot study. Pain Practice 2012;12(1):7‐13. [PUBMED: 21615856] - PubMed
Elkassem 2008 {published data only}
    1. Elkassem SA. Dexmedetomidine vs remifentanil in abdominoplasty surgery (BIS guided): a comparative study. Egyptian Journal of Anaesthesia 2008;24(3):261‐9. [EMBASE: 2010651443]
Elliott 1997 {published data only}
    1. Elliott S, Eckersall S, Fligelstone L, Jothilingam S. Does the addition of clonidine affect duration of analgesia of bupivacaine wound infiltration in inguinal hernia surgery?. British Journal of Anaesthesia 1997;79(4):446‐9. [PUBMED: 9389260] - PubMed
Ellis 1998 {published data only}
    1. Ellis JE, Pedlow S, Bains J. Premedication with clonidine does not attenuate suppression of certain lymphocyte subsets after surgery. Anesthesia and Analgesia 1998;87(6):1426‐30. [PUBMED: 9842842] - PubMed
ElSheikh 2010 {published data only}
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Elvan 2008 {published data only}
    1. Elvan EG, Oc B, Uzun S, Karabulut E, Coskun F, Aypar U. Dexmedetomidine and postoperative shivering in patients undergoing elective abdominal hysterectomy. European Journal of Anaesthesiology 2008;25(5):357‐64. [PUBMED: 18205960] - PubMed
Engelman 1989 {published data only}
    1. Engelman E, Lipszyc M, Gilbart E, Linden P, Bellens B, Romphey A, et al. Effects of clonidine on anesthetic drug requirements and hemodynamic response during aortic surgery. Anesthesiology 1989;71(2):178‐87. [PUBMED: 2502935] - PubMed
Eremenko 2014a {published data only}
    1. Eremenko AA, Chemova EV. Comparison of dexmedetomidine and propofol for short‐term sedation in early postoperative period after cardiac surgery. Anesteziologiia i Reanimatologiia 2014;Mar‐Apr(2):37‐41. [PUBMED: 25055491] - PubMed
Eremenko 2014b {published data only}
    1. Eremenko AA, Chernova EV. Treatment of delirium in the early postoperative period after cardiac surgery. Anesteziologiia i Reanimatologiia 2014;May‐Jun(3):30‐4. [PUBMED: 25306681] - PubMed
Erkola 1994 {published data only}
    1. Erkola O, Korttila K, Aho M, Haasio J, Aantaa R, Kallio A. Comparison of intramuscular dexmedetomidine and midazolam premedication for elective abdominal hysterectomy. Anesthesia and Analgesia 1994;79(4):646‐53. [PUBMED: 7943770] - PubMed
Ezri 1998 {published data only}
    1. Ezri T, Szmuk P, Shklar B, Katz J, Geva D. Oral clonidine premedication does not prolong analgesia after herniorrhaphy under subarachnoid anesthesia. Journal of Clinical Anesthesia 1998;10(6):474‐81. [PUBMED: 9793811] - PubMed
Favre 1995 {published data only}
    1. Favre JB, Gardaz JP, Ravussin P. Effect of clonidine on ICP and on the hemodynamic responses to nociceptive stimuli in patients with brain tumors. Journal of Neurosurgical Anesthesiology 1995;7(3):159‐67. [PUBMED: 7549366] - PubMed
Fehr 2001 {published data only}
    1. Fehr SB, Zalunardo MP, Seifert B, Rentsch KM, Rohling RG, Pasch T, et al. Clonidine decreases propofol requirements during anaesthesia: effect on bispectral index. British Journal of Anaesthesia 2001;86(5):627‐32. [PUBMED: 11575336] - PubMed
Feld 2003 {published data only}
    1. Feld JM, Laurito CE, Beckerman M, Vincent J, Hoffman WE. Non‐opioid analgesia improves pain relief and decreases sedation after gastric bypass surgery. Canadian Journal of Anaesthesia 2003;50(4):336‐41. [PUBMED: 12670809] - PubMed
Feld 2006 {published data only}
    1. Feld JM, Hoffman WE, Stechert MM, Hoffman IW, Ananda RC. Fentanyl or dexmedetomidine combined with desflurane for bariatric surgery. Journal of Clinical Anesthesia 2006;18(1):24‐8. [PUBMED: 16517328] - PubMed
Feld 2007 {published data only}
    1. Feld J, Hoffman WE, Paisansathan C, Park H, Ananda RC. Autonomic activity during dexmedetomidine or fentanyl infusion with desflurane anesthesia. Journal of Clinical Anesthesia 2007;19(1):30‐6. [PUBMED: 17321924] - PubMed
Flacke 1987 {published data only}
    1. Flacke JW, Bloor BC, Flacke WE, Wong D, Dazza S Stead SW, et al. Reduced narcotic requirement by clonidine with improved hemodynamic and adrenergic stability in patients undergoing coronary bypass surgery. Anesthesiology 1987;67(1):11‐9. [PUBMED: 3496811] - PubMed
Frank 1999 {published data only}
    1. Frank T, Thieme V, Olthoff D. Preoperative clonidine comedication within the scope of balanced inhalation anesthesia with sevoflurane in oral surgery procedures. Anaesthesiologie und Reanimation 1999;24(3):65‐70. [PUBMED: 10472699] - PubMed
Frank 2000a {published data only}
    1. Frank T, Thieme V, Olthoff D. Clonidine within the scope of balanced inhalation anesthesia with sevoflurane ‐ effects on pEEG parameters. Anaesthesiologie und Reanimation 2000;25(2):32‐6. [PUBMED: 10816895] - PubMed
Frank 2000b {published data only}
    1. Frank T, Thieme V, Radow L. Premedication in maxillofacial surgery under total intravenous anesthesia. Effects of clonidine compared to midazolam on the perioperative course. Anasthesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie 2000;35(7):428‐34. [PUBMED: 10949680] - PubMed
Frank 2002 {published data only}
    1. Frank T, Wehner M, Heinke W, Schmadicke L. Clonidine vs. midazolam for premedication ‐ comparison of the anxiolytic effect by using the STAI‐test. Anasthesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie 2002;37(2):89‐93. [PUBMED: 11865386] - PubMed
Galindo 2008 {published data only}
    1. Galindo Palazuelos M, Diaz Setien NA, Rodriguez Cundin P, Manso Marin FJ, Castro Ugalde A. Premedication with intraoperative clonidine and low‐dose ketamine in outpatient laparoscopic cholecystectomy. [Spanish]. Revista Espanola de Anestesiologia y Reanimacion 2008;55(7):414‐7. [PUBMED: 18853679] - PubMed
Gandhi 2017 {published data only}
    1. Gandhi KA, Panda NB, Vellaichamy A, Mathew PJ, Sahni N, Batra YK. Intraoperative and postoperative administration of dexmedetomidine reduces anesthetic and postoperative analgesic requirements in patients undergoing cervical spine surgeries. Journal of Neurosurgical Anesthesiology 2017;29(3):258‐63. [EMBASE: 609460791] - PubMed
Ganter 2005 {published data only}
    1. Ganter MT, Hofer CK, Spahn DR, Bruggisser M, Bombeli T, Seifert B, et al. The effect of clonidine on perioperative blood coagulation. Journal of Clinical Anesthesia 2005;17(6):456‐62. [PUBMED: 16171667] - PubMed
Gao 2012 {published data only}
    1. Gao GJ, Xu YY, Wang B, Lv HM, Yang WY, Shang Y. Feasibility of dexmedetomidine assisting sevoflurane for controlled hypotension in endoscopic sinus surgery. [Chinese]. Medical Journal of Chinese People's Liberation Army 2012;37(1):45‐8. [EMBASE: 2014601501]
Garcia‐Guiral 1994 {published data only}
    1. Garcia‐Guiral M, Carrera A, Lora‐Tamayo JI, Luengo C, Pascual E, Quintana B, et al. Premedication with clonidine in the neurosurgical patient: sedation, anesthetic requirements and hemodynamic perfusion. Revista Española de Anestesiología y Reanimación 1994;41(2):77‐81. [PUBMED: 8041979] - PubMed
Ghatak 2010 {published data only}
    1. Ghatak T, Chandra G, Malik A, Singh D, Bhatia VK. Evaluation of the effect of magnesium sulphate vs. clonidine as adjunct to epidural bupivacaine. Indian Journal of Anaesthesia 2010;54(4):308‐13. [EMBASE: 2011056851; PUBMED: 20882172] - PMC - PubMed
Ghosh 2008 {published data only}
    1. Ghosh I, Bithal PK, Dash HH, Chaturvedi A, Prabhakar H. Both clonidine and metoprolol modify anesthetic depth indicators and reduce intraoperative propofol requirement. Journal of Anesthesia 2008;22(2):131‐4. [EMBASE: 2008262464; PUBMED: 18500609] - PubMed
Gomez‐Vazquez 2007 {published data only}
    1. Gomez‐Vazquez ME, Hernandez‐Salazar E, Hernandez‐Jimenez A, Perez‐Sanchez A, Zepeda‐Lopez VA, Salazar‐Paramo M. Clinical analgesic efficacy and side effects of dexmedetomidine in the early postoperative period after arthroscopic knee surgery. Journal of Clinical Anesthesia 2007;19(8):576‐82. [PUBMED: 18083469] - PubMed
Goyagi 1996 {published data only}
    1. Goyagi T, Nishikawa T. Oral clonidine premedication enhances the quality of postoperative analgesia by intrathecal morphine. Anesthesia and Analgesia 1996;82(6):1192‐6. [PUBMED: 8638790] - PubMed
Grottke 2003 {published data only}
    1. Grottke O, Muller J, Dietrich PJ, Krause TH, Wappler F. Comparison of premedication with clonidine and midazolam combined with TCI for orthopaedic shoulder surgery. Anasthesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie 2003;38(12):772‐80. [PUBMED: 14666440] - PubMed
Grundmann 1997 {published data only}
    1. Grundmann U, Berg K, Stamminger U, Juckenhofel S, Wilkem W. Comparison of pethidine and clonidine in the prevention of postoperative shivering. A prospective, randomized, placebo‐controlled, double‐blind study. Anasthesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie 1997;32(1):36‐42. [PUBMED: 9138543] - PubMed
Guglielminotti 1998 {published data only}
    1. Guglielminotti J, Descraques C, Petitmaire S, Almenza L, Grenapin O, Mantz J. Effects of premedication on dose requirements for propofol: comparison of clonidine and hydroxyzine. British Journal of Anaesthesia 1998;80(6):733‐6. [PUBMED: 9771298] - PubMed
Gupta 2011a {published data only}
    1. Gupta D, Srivastava S, Dubey R, Prakash P, Singh P, Singh U. Comparative evaluation of atenolol and clonidine premedication on cardiovascular response to nasal speculum insertion during trans‐sphenoid surgery for resection of pituitary adenoma: A prospective, randomised, double‐blind, controlled study. Indian Journal of Anaesthesia 2011;55(2):135‐40. [EMBASE: 2012059701; PUBMED: 21712869] - PMC - PubMed
Gupta 2011b {published data only}
    1. Gupta K, Sharma D, Gupta PK. Oral premedication with pregabalin or clonidine for hemodynamic stability during laryngoscopy and laparoscopic cholecystectomy: A comparative evaluation. Saudi Journal of Anaesthesia 2011;5(2):179‐84. [EMBASE: 2011405481; PUBMED: 21804800] - PMC - PubMed
Gupta 2011c {published data only}
    1. Gupta R, Verma R, Bogra J, Kohli M, Raman R, Kushwaha JK. A comparative study of intrathecal dexmedetomidine and fentanyl as adjuvants to bupivacaine. Journal of Anaesthesiology Clinical Pharmacology 2011;27(3):339‐43. [EMBASE: 2011448409; PUBMED: 21897504] - PMC - PubMed
Gupta 2012 {published data only}
    1. Gupta K, Jain M, Gupta PK, Rastogi B, Saxena SK, Manngo A. Dexmedetomidine premedication for fiberoptic intubation in patients of temporomandibular joint ankylosis: A randomized clinical trial. Saudi Journal of Anaesthesia 2012;6(3):219‐23. [EMBASE: 2012596318; PUBMED: 23162393] - PMC - PubMed
Guven 2011 {published data only}
    1. Guven DG, Demiraran Y, Sezen G, Kepek O, Iskender A. Evaluation of outcomes in patients given dexmedetomidine in functional endoscopic sinus surgery. Annals of Otology, Rhinology and Laryngology 2011;120(9):586‐92. [EMBASE: 2011502324; PUBMED: 22032072] - PubMed
Hahm 2002 {published data only}
    1. Hahm TS, Cho HS, Lee KH, Chung IS, Kim JA, Kim MH. Clonidine premedication prevents preoperative hypokalemia. Journal of Clinical Anesthesia 2002;14(1):6‐9. [PUBMED: 11880014] - PubMed
Hall 2006 {published data only}
    1. Hall DL, Rezvan E, Tatakis DN, Walters JD. Oral clonidine pretreatment prior to venous cannulation. Anesthesia Progress 2006;53(2):34‐42. [PUBMED: 16863391] - PMC - PubMed
Handa 2000 {published data only}
    1. Handa F, Tanaka M, Nishikawa T, Toyooka H. Effects of oral clonidine premedication on side effects of intravenous ketamine anesthesia: a randomized, double‐blind, placebo‐controlled study. Journal of Clinical Anesthesia 2000;12(1):19‐24. [PUBMED: 10773503] - PubMed
Harsoor 2013 {published data only}
    1. Harsoor SS, Rani DD, Yalamuru B, Sudheesh K, Nethra SS. Effect of supplementation of low dose intravenous dexmedetomidine on characteristics of spinal anaesthesia with hyperbaric bupivacaine. Indian Journal of Anaesthesia 2013;57(3):265‐9. [EMBASE: 2013477136; PUBMED: 23983285] - PMC - PubMed
Harsoor 2014 {published data only}
    1. Harsoor S, Rani D, Lathashree S, Nethra S, Sudheesh K. Effect of intraoperative dexmedetomidine infusion on sevoflurane requirement and blood glucose levels during entropy‐guided general anesthesia. Journal of Anaesthesiology Clinical Pharmacology 2014;30(1):25‐30. [EMBASE: 2014095808; PUBMED: 24574589] - PMC - PubMed
Hashemian 2017 {published data only}
    1. Hashemian M, Ahmadinejad M, Mohajerani SA, Mirkheshti A. Impact of dexmedetomidine on hemodynamic changes during and after coronary artery bypass grafting. Annals of Cardiac Anaesthesia 2017;20(2):152‐7. - PMC - PubMed
Hazra 2014 {published data only}
    1. Hazra R, Manjunatha SM, Babrak Manuar MD, Basu R, Chakraborty S. Comparison of the effects of intravenously administered dexmedetomidine with clonidine on hemodynamic responses during laparoscopic cholecystectomy. Anaesthesia, Pain and Intensive Care 2014;18(1):25‐30. [EMBASE: 2015025031]
Hidalgo 2005 {published data only}
    1. Hidalgo MP, Auzani JA, Rumpel LC, Moreira NL Jr, Cursino AW, Caumo W. The clinical effect of small oral clonidine doses on perioperative outcomes in patients undergoing abdominal hysterectomy. Anesthesia and Analgesia 2005;100(3):795‐802. [PUBMED: 15728070] - PubMed
Higuchi 2002 {published data only}
    1. Higuchi H, Adachi Y, Dahan A, Olofsen E, Arimura S, Mori T, et al. The interaction between propofol and clonidine for loss of consciousness. Anesthesia and Analgesia 2002;94(4):886‐91. [PUBMED: 11916791] - PubMed
Honarmand 2007 {published data only}
    1. Honarmand A, Safavi MR. Preoperative oral dextromethorphan vs. clonidine to prevent tourniquet‐induced cardiovascular responses in orthopaedic patients under general anaesthesia. European Journal of Anaesthesiology 2007;24(6):511‐5. [PUBMED: 17202010] - PubMed
Horn 1997 {published data only}
    1. Horn EP, Werner C, Sessler DI, Steinfath M, Schulte am Esch J. Late intraoperative clonidine administration prevents postanesthetic shivering after total intravenous or volatile anesthesia. Anesthesia and Analgesia 1997;84(3):613‐7. [PUBMED: 9052312] - PubMed
Horng 2007 {published data only}
    1. Horng HC, Wong CS, Hsiao KN, Huh BK, Kuo CP, Cherng CH, et al. Pre‐medication with intravenous clonidine suppresses fentanyl‐induced cough. Acta Anaesthesiologica Scandinavica 2007;51(7):862‐5. [PUBMED: 17578464] - PubMed
Hwang 2015 {published data only}
    1. Hwang W, Lee J, Park J, Joo J. Dexmedetomidine versus remifentanil in postoperative pain control after spinal surgery: a randomized controlled study. BMC Anesthesiology 2015;15:21. [EMBASE: 2015845589; PUBMED: 25750586] - PMC - PubMed
Ishiyama 2006 {published data only}
    1. Ishiyama T, Kashimoto S, Oguchi T, Furuya A, Fukushima H, Kumazawa T. Clonidine‐ephedrine combination reduces pain on injection of propofol and blunts hemodynamic stress responses during the induction sequence. Journal of Clinical Anesthesia 2006;18(3):211‐5. [PUBMED: 16731324] - PubMed
Jaakola 1994 {published data only}
    1. Jaakola ML, Kanto J, Scheinin H, Kallio A. Intramuscular dexmedetomidine premedication ‐ an alternative to midazolam‐fentanyl‐combination in elective hysterectomy?. Acta Anaesthesiologica Scandinavica 1994;38(3):238‐43. [PUBMED: 7912877] - PubMed
Jabalameli 2005 {published data only}
    1. Jabalameli M, Hashemi M, Soltani H, Hashemi J. Oral clonidine premedication decreases intraoperative bleeding in patients undergoing endoscopic sinus surgery. Journal of Research in Medical Sciences 2005;10(1):25‐30. [EMBASE: 2005178855]
Javaherfroosh 2009 {published data only}
    1. Javaherfroosh F, Pipelzadeh MR, Namazi M. Clonidine reduces post operative nausea and vomiting in laparoscopic gynecological surgery. Pakistan Journal of Medical Sciences 2009;25(5):782‐5. [EMBASE: 2009571437]
Jeffs 2002 {published data only}
    1. Jeffs SA, Hall JE, Morris S. Comparison of morphine alone with morphine plus clonidine for postoperative patient‐controlled analgesia. British Journal of Anaesthesia 2002;89(3):424‐7. [PUBMED: 12402720] - PubMed
Jellish 2001 {published data only}
    1. Jellish WS, Theard MA, Cheng MA, Leonetti JP, Crowder CM, Tempelhoff R. The effects of clonidine premedication and scalp infiltration of lidocaine on hemodynamic responses to laryngoscopy and skull pin head‐holder insertion during skull base procedures. Skull Base 2001;11(3):169‐76. [PUBMED: 17167618] - PMC - PubMed
Ji 2013 {published data only}
    1. Ji F, Li Z, Nguyen H, Young N, Shi P, Fleming N, et al. Perioperative dexmedetomidine improves outcomes of cardiac surgery. Circulation 2013; Vol. 127, issue 15:1576‐84. [EMBASE: 2013243940; PUBMED: 23513068] - PMC - PubMed
Joao 2014 {published data only}
    1. Joao BB, do Amaral JL, Bueno RM, Ferez D, Falcao LF, Perez MV, et al. Intravenous clonidine administration and its ability to reduce pulmonary arterial pressure in patients undergoing heart surgery. Brazilian Journal of Anesthesiology 2014;64(1):40‐8. [PUBMED: 24565387] - PubMed
Joris 1993 {published data only}
    1. Joris J, Banache M, Bonnet F, Sessler DI, Lamy M. Clonidine and ketanserin both are effective treatment for postanesthetic shivering. Anesthesiology 1993;79(3):532‐9. [PUBMED: 8363079] - PubMed
Joris 1998 {published data only}
    1. Joris JL, Chiche JD, Canivet JL, Jacquet NJ, Legros JJ, Lamy LL. Hemodynamic changes induced by laparoscopy and their endocrine correlates: effects of clonidine. Journal of the American College of Cardiology 1998;32(5):1389‐96. [PUBMED: 9809953] - PubMed
Joshi 2012 {published data only}
    1. Joshi SA, Khadke VV, Subhedar RD, Patil AW, Motghare VM. Comparative evaluation of intrathecal midazolam and low dose clonidine: efficacy, safety and duration of analgesia. A randomized, double blind, prospective clinical trial. Indian Journal of Pharmacology 2012; Vol. 44, issue 3:357‐61. [EMBASE: 2012322476; PUBMED: 22701246] - PMC - PubMed
Juarez‐Pichardo 2009 {published data only}
    1. Juarez‐Pichardo JS, Avila‐Lopez A, Serrano‐Herrera MA. Preventive postoperative analgesia with dexmetomidine iv compared to lidocaine iv in cholecystectomy. [Spanish]. Revista Mexicana de Anestesiologia 2009;32(2):81‐8. [EMBASE: 2009468805]
Kajiyama 2009 {published data only}
    1. Kajiyama S, Nakagawa I, Hidaka S, Okada H, Kubo T, Nao Y. Effect of dexmedetomidine on intraoperative somatosensory evoked potential monitoring. [Japanese]. Japanese Journal of Anesthesiology 2009;58(8):966‐70. [EMBASE: 2009464313] - PubMed
Kalajdzija 2011 {published data only}
    1. Kalajdzija M, Cero I, Prnjavorac B, Ljuca S. Influence of clonidine on the chemodynamic stability and stress response in the course of surgery on general anesthesia. Medicinski arhiv 2011;65(4):210‐2. [PUBMED: 21950225] - PubMed
Kang 2012 {published data only}
    1. Kang WS, Kim SY, Son JC, Kim JD, Muhammad HB, Kim SH, et al. The effect of dexmedetomidine on the adjuvant propofol requirement and intraoperative hemodynamics during remifentanil‐based anesthesia. Korean Journal of Anesthesiology 2012;62(2):113‐8. [EMBASE: 2012125528; PUBMED: 22379564] - PMC - PubMed
Kang 2013 {published data only}
    1. Kang SH, Kim YS, Hong TH, Chae MS, Cho ML, Her YM, et al. Effects of dexmedetomidine on inflammatory responses in patients undergoing laparoscopic cholecystectomy. Acta Anaesthesiologica Scandinavica 2013;57(4):480‐7. [EMBASE: 2013243000; PUBMED: 23240685] - PubMed
Kang 2015 {published data only}
    1. Kang MH, Lee HJ, Lim YJ, Jeon YT, Hwang JW, Park HP. Preoperative dexmedetomidine attenuates hemodynamic responses to hydrodissection in patients undergoing robotic thyroidectomy. Journal of Anesthesia 2015;29(2):191‐7. [PUBMED: 25262475] - PubMed
Karaman 2013 {published data only}
    1. Karaman S, Gunusen I, Ceylan MA, Karaman Y, Cetin EN, Derbent A, et al. Dexmedetomidine infusion prevents postoperative shivering in patients undergoing gynecologic laparoscopic surgery. Turkish Journal of Medical Sciences 2013;43(2):232‐7. [EMBASE: 2013171247]
Karaman 2015 {published data only}
    1. Karaman Y, Abud B, Tekgul ZT, Cakmak M, Yildiz M, Gonullu M. Effects of dexmedetomidine and propofol on sedation in patients after coronary artery bypass graft surgery in a fast‐track recovery room setting. Journal of Anesthesia 2015;29(4):522‐8. [PUBMED: 25617159] - PubMed
Kawasaki 2014 {published data only}
    1. Kawasaki T, Kawasaki C, Sata T. Dexmedetomidine suppresses inflammatory mediators level in patients of cardiac surgery using cardiopulmonary bypass. Shock 2014;41:59. [EMBASE: 71497732]
Kaya 2010 {published data only}
    1. Kaya FN, Yavascaoglu B, Turker G, Yildirim A, Gurbet A, Mogol EB, et al. Intravenous dexmedetomidine, but not midazolam, prolongs bupivacaine spinal anesthesia. Canadian Journal of Anesthesia 2010;57(1):39‐45. [EMBASE: 2010046678; PUBMED: 20039211] - PubMed
Kaymak 2008 {published data only}
    1. Kaymak C, Basar H, Doganci N, Sert O, Apan A. The effects of perioperative low ‐ moderate doses of dexmedetomidine infusion on hemodynamic and neuroendocrine parameters. Turkish Journal of Medical Sciences 2008;38(1):65‐71. [EMBASE: 2008051508]
Ke 2013 {published data only}
    1. Ke J, Pen X. The effect of dexmedetomidine on post‐operative blood pressure after controlled hypotension in endoscopic sinus surgery. [Chinese]. Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke za Zhi [Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery] 2013;27(10):478‐80. [PUBMED: 23937012] - PubMed
Keniya 2011 {published data only}
    1. Keniya VM, Ladi S, Naphade R. Dexmedetomidine attenuates sympathoadrenal response to tracheal intubation and reduces perioperative anaesthetic requirement. Indian Journal of Anaesthesia 2011;55(4):352‐7. [EMBASE: 2011568239; PUBMED: 22013250] - PMC - PubMed
Khafagy 2012 {published data only}
    1. Khafagy HF, Ebied RS, Osman ES, Ali MZ, Samhan YM. Perioperative effects of various anesthetic adjuvants with TIVA guided by bispectral index. Korean Journal of Anesthesiology 2012;63(2):113‐9. [EMBASE: 2012524970; PUBMED: 22949977] - PMC - PubMed
Kim 2012 {published data only}
    1. Kim WO, Yoon Y, Choi Y, Kim SH, Kil HK. Effects of intravenous dexmedetomidine on low‐dose bupivacaine spinal anaesthesia in elderly patients. Acta Anaesthesiologica Scandinavica 2012;56(3):382‐7. [PUBMED: 22220945] - PubMed
Kim 2013a {published data only}
    1. Kim SH, Oh YJ, Park BW, Sim J, Choi YS. Effects of single‐dose dexmedetomidine on the quality of recovery after modified radical mastectomy: a randomised controlled trial. Minerva Anestesiologica 2013;79(11):1248‐58. [EMBASE: 2014029902; PUBMED: 23698545] - PubMed
Kim 2013b {published data only}
    1. Kim SY, Kim JM, Lee JH, Song BM, Koo BN. Efficacy of intraoperative dexmedetomidine infusion on emergence agitation and quality of recovery after nasal surgery. British Journal of Anaesthesia 2013;111(2):222‐8. [EMBASE: 2013463896; PUBMED: 23524149] - PubMed
Kim 2013c {published data only}
    1. Kim Y‐I, Seo K‐H, Kang H‐R. Optimal dose of prophylactic dexmedetomidine for preventing postoperative shivering. International Journal of Medical Sciences 2013;10(10):1327‐32. [PUBMED: 23983593] - PMC - PubMed
Kim 2014b {published data only}
    1. Kim WH, Shim HS, Kim G, Lee JE, Lee YT, Cho HS. A comparison of the infusion of dexmedetomidine versus remifentanil in patients undergoing off‐pump coronary artery bypass graft: a randomized trial. Experimental and Clinical Cardiology 2014;20(6):4234‐51. [EMBASE: 2014448289]
Korkmaz 2013 {published data only}
    1. Korkmaz Disli Z, Celebi N, Canbay O, Celebioglu B. Comparison of morphine and dexmedetomidine delivered by patient‐controlled analgesia device during the postoperative period of coronary artery bypass surgery. [Turkish]. Anestezi Dergisi 2013;21(1):29‐36. [EMBASE: 2013167966]
Koyuncu 2009 {published data only}
    1. Koyuncu O, Alagol A, Turan A. Comparison of dexmedetomidine and ketamine infusions in patients undergoing lower extremity surgery with regional anesthesia. European Journal of Anaesthesiology 2009;26:122. [EMBASE: 70162271]
Kulka 1996 {published data only}
    1. Kulka PJ, Tryba M, Zenz M. Preoperative alpha2‐adrenergic receptor agonists prevent the deterioration of renal function after cardiac surgery: results of a randomized, controlled trial. Critical Care Medicine 1996;24(6):947‐52. [PUBMED: 8681596] - PubMed
Kumari 2012 {published data only}
    1. Kumari I, Naithni U, Bedi V, Gupta S, Gupta R, Bhuie. Comparison of clonidine versus midazolam in monitored anesthesia care during ENT surgery ‐ a prospective, double blind, randomized clinical study. Anaesthesia, Pain and Intensive Care 2012;16(2):157‐64. [EMBASE: 2012643410]
Lang 2011 {published data only}
    1. Lang Y, Wang TL, Wu XM, Ding LG. Application of sedation with a low dose of dexmedetomidine during intrathecal anesthesia in elderly patients. [Chinese]. Zhonghua yi xue hui 2011; Vol. 91, issue 28:1953‐6. [EMBASE: 2012710260; PUBMED: 22093888] - PubMed
Lattermann 2001 {published data only}
    1. Lattermann R, Schricker T, Georgieff M, Schreiber M. Low dose clonidine premedication accentuates the hyperglycemic response to surgery. Canadian Journal of Anaesthesia 2001;48(8):755‐9. [PUBMED: 11546715] - PubMed
Launo 1991 {published data only}
    1. Launo C, Palermo S, Germi MR, Lanfrit C, Frasca A, Simonetti F. Clonidine and postoperative shivering. Minerva Anestesiologica 1991;57(7‐8):427‐31. [PUBMED: 1944967] - PubMed
Laurito 1991 {published data only}
    1. Laurito CE, Baughman VL, Becker GL, DeSilva TW, Carranza CJ. The effectiveness of oral clonidine as a sedative/anxiolytic and as a drug to blunt the hemodynamic responses to laryngoscopy. Journal of Clinical Anesthesia 1991;3(3):186‐93. [PUBMED: 1878231] - PubMed
Laurito 1993 {published data only}
    1. Laurito CE, Baughman VL, Becker GL, Cunnigham F, Pygon BH, Citron GM. Oral clonidine blunts the hemodynamic responses to brief but not prolonged laryngoscopy. Journal of Clinical Anesthesia 1993;5(1):54‐7. [PUBMED: 8442970] - PubMed
Lawrence 1997 {published data only}
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Lee 2012 {published data only}
    1. Lee HK, Kim YC, Yim JY. Assessment of the effect of dexmedetomidine in the management of postoperative pain when combined with fentanyl in the patient‐controlled analgesia. European Journal of Anaesthesiology 2012;29:196‐7. [EMBASE: 71084641]
Lee 2013b {published data only}
    1. Lee J, Kim Y, Park C, Jeon Y, Kim D, Joo J, et al. Comparison between dexmedetomidine and remifentanil for controlled hypotension and recovery in endoscopic sinus surgery. Annals of Otology, Rhinology and Laryngology 2013;122(7):421‐6. [EMBASE: 2013495596; PUBMED: 23951692] - PubMed
Le Guen 2014 {published data only}
    1. Guen M, Liu N, Tounou F, Auge M, Tuil O, Chazot T, et al. Dexmedetomidine reduces propofol and remifentanil requirements during bispectral index‐guided closed‐loop anesthesia: a double‐blind, placebo‐controlled trial. Anesthesia and Analgesia 2014;118(5):946‐55. [PUBMED: 24722260] - PubMed
Leino 2011 {published data only}
    1. Leino K, Hynynen M, Jalonen J, Salmenpera M, Scheinin H, Aantaa R. Renal effects of dexmedetomidine during coronary artery bypass surgery: a randomized placebo‐controlled study. BMC Anesthesiology 2011; Vol. 11:9. [EMBASE: 2011348574; PUBMED: 21605394] - PMC - PubMed
Levanen 1995 {published data only}
    1. Levanen J, Makela M‐L, Scheinin H. Dexmedetomidine premedication attenuates ketamine‐induced cardiostimulatory effects and postanesthetic delirium. Anesthesiology 1995;82(5):1117‐25. [PUBMED: 7741286] - PubMed
Li 2010 {published data only}
    1. Li H, She S, Yan Y, Zhu S. [Effect of dexmedetomidine on bispectral index and auditory evoked potential index during anesthesia with target controlled infusion of propofol and remifentanyl]. Zhejiang da Xue Xue Bao. Yi Xue Ban = Journal of Zhejiang University. Medical Sciences 2010;39(1):84‐8. [PUBMED: 20175241] - PubMed
Li 2013 {published data only}
    1. Li H, Chen YH, Gong HJ. Effects of dexmedetomidine on inflammatory cytokines and renal function in patients underwent radical nephrectomy during perioperative period. [Chinese]. Journal of Jilin University Medicine Edition 2013;39(3):588‐91. [EMBASE: 2013391674]
Liu 2013 {published data only}
    1. Liu HL, Qian YN. [Effects of dexmedetomidine on perioperative inflammatory response in patients undergoing valve replacement]. [Chinese]. Zhongguo Ying Yong Sheng li Xue Za Zhi = Zhongguo Yingyong Shenglixue Zazhi = Chinese Journal of Applied Physiology 2013; Vol. 29, issue 4:316‐7. [PUBMED: 24175551] - PubMed
Lu 2013 {published data only}
    1. Lu Y, Zhang Y, Dong CS, Yu JM, Wong GT. Preoperative dexmedetomidine prevents tourniquet‐induced hypertension in orthopedic operation during general anesthesia. Kaohsiung Journal of Medical Sciences 2013;29(5):271‐4. [EMBASE: 2013279941; PUBMED: 23639514] - PMC - PubMed
Lyons 1997 {published data only}
    1. Lyons FM, Bew S, Sheeran P, Hall GM. Effects of clonidine on the pituitary hormonal response to pelvic surgery. British Journal of Anaesthesia 1997;78(2):134‐7. [PUBMED: 9068327] - PubMed
Ma 2013 {published data only}
    1. Ma PP, Piao MH, Wang YS, Ma HC, Feng CS. Influence of dexmedetomidine and sub‐anesthetic dose of ketamine on postoperative delirium in elderly orthopedic patients under total intravenous anesthesia. [Chinese]. Journal of Jilin University Medicine Edition 2013;39(1):128‐32. [EMBASE: 2013147857]
Mahendru 2013 {published data only}
    1. Mahendru V, Tewari A, Katyal S, Grewal A, Singh MR, Katyal R. A comparison of intrathecal dexmedetomidine, clonidine, and fentanyl as adjuvants to hyperbaric bupivacaine for lower limb surgery: a double blind controlled study. Journal of Anaesthesiology Clinical Pharmacology 2013;29(4):496‐502. [EMBASE: 2013651749] - PMC - PubMed
Maldonado 2009 {published data only}
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Malek 2009 {published data only}
    1. Malek J, Hess L, Votava M, Marecek F, Kurzova A. The combination of dexmedetomidine, fentanyl, midazolam and atropine may result in dangerous respiratory depression and hypoxemia. European Journal of Anaesthesiology 2009;26:136. [EMBASE: 70162317]
Malek 2010a {published data only}
    1. Malek J, Marecek F, Hess L, Votava M, Kurzova A. Dexmedetomidine in combination with fentanyl and midazolam can induce serious respiratory depression. [Czech]. Bolest 2010;13(2):80‐7. [EMBASE: 2010397845]
Malek 2010b {published data only}
    1. Malek J, Marecek F, Hess L, Kurzova A, Ocadlik M, Votava M. A combination of dexmedetomidine with ketamine and opioids results in significant inhibition of hemodynamic changes associated with laparoscopic cholecystectomy and in prolongation of postoperative analgesia. [Czech]. Rozhledy v Chirurgii : Mesicnik Ceskoslovenske Chirurgicke Spolecnosti 2010;89(5):275‐81. [EMBASE: 20666328] - PubMed
Manne 2014 {published data only}
    1. Manne GR, Upadhyay MR, Swadi VN. Effects of low dose dexmedetomidine infusion on haemodynamic stress response, Sedation and post‐operative analgesia requirement in patients undergoing laparoscopic cholecystectomy. Indian Journal of Anaesthesia 2014;58(6):726‐31. [PUBMED: 25624537] - PMC - PubMed
Mannion 2005 {published data only}
    1. Mannion S, Hayes I, Loughnane F, Murphy DB, Shorten GD. Intravenous but not perineural clonidine prolongs postoperative analgesia after psoas compartment block with 0.5% levobupivacaine for hip fracture surgery. Anesthesia and Analgesia 2005;100(3):873‐8. [PUBMED: 15728081] - PubMed
Marangoni 2005 {published data only}
    1. Marangoni MA, Castiglia YM, Pechutti TP. Analgesic efficacy of dexmedetomidine as compared to sufentanil in intraperitoneal surgeries. Comparative study. Revista Brasileira de Anestesiologia 2005;55(1):19‐27. [EMBASE: 2005078359; PUBMED: 19471805] - PubMed
Marchal 2001 {published data only}
    1. Marchal JM, Gomez‐Luque A, Martos‐Crespo F, Sanchez De La Cuesta F, Martinez‐Lopez MC, Delgado‐Martinez AD. Clonidine decreases intraoperative bleeding in middle ear microsurgery. Acta Anaesthesiologica Scandinavica 2001;45(5):627‐33. [PUBMED: 11309017] - PubMed
Mariappan 2014 {published data only}
    1. Mariappan R, Ashokkumar H, Kuppuswamy B. Comparing the effects of oral clonidine premedication with intraoperative dexmedetomidine infusion on anesthetic requirement and recovery from anesthesia in patients undergoing major spine surgery. Journal of Neurosurgical Anesthesiology 2014;26(3):192‐7. [EMBASE: 2014397409; PUBMED: 23887684] - PubMed
Marinangeli 2002 {published data only}
    1. Marinangeli F, Ciccozzi A, Donatelli F, Pietro A, Iovinelli G, Rawal G, et al. Clonidine for treatment of postoperative pain: a dose‐finding study. European Journal of Pain 2002;6(1):35‐42. [PUBMED: 11888226] - PubMed
Martin 2003 {published data only}
    1. Mantz J, French Dexmedetomidine Phase III Group. Phase III study on dexmedetomidine used for postoperative sedation of patients requiring mechanical ventilation for less than 24 hours: the French experience. Middle East Journal of Anesthesiology 2002;16(6):597‐606. [PUBMED: 12503263] - PubMed
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Massad 2009 {published data only}
    1. Massad IM, Mohsen WA, Basha AS, Al‐Zaben KR, Al‐Mustafa MM, Alghanem SM. A balanced anesthesia with dexmedetomidine decreases postoperative nausea and vomiting after laparoscopic surgery. Saudi Medical Journal 2009;30(12):1537‐41. [EMBASE: 2010055533; PUBMED: 19936416] - PubMed
Mishra 2012 {published data only}
    1. Mishra S. Prospective, randomized study to assess the role of dexmedetomidine in patients with posterior fossa tumors undergoing craniotomy and requiring post operative ventilation in ICU. Intensive Care Medicine 2012;38:S36‐7. [EMBASE: 71013335]
Mizrak 2010 {published data only}
    1. Mizrak A, Koruk S, Bilgi M, Kocamer B, Erkutlu I, Ganidagli S, et al. Pretreatment with dexmedetomidine or thiopental decreases myoclonus after etomidate: a randomized, double‐blind controlled trial. Journal of Surgical Research 2010;159(1):e11‐6. [EMBASE: 2010115952; PUBMED: 20018300] - PubMed
Mizrak 2012 {published data only}
    1. Mizrak A, Sanli M, Bozgeyik S, Gul R, Ganidagli S, Baysal E, et al. Dexmedetomidine use in direct laryngoscopic biopsy under TIVA. Middle East Journal of Anesthesiology 2012;21(4):605‐12. [PUBMED: 23327034] - PubMed
Mizrak 2013 {published data only}
    1. Mizrak A, Ganidagli S, Cengiz MT, Oner U, Saricicek V. The effects of DEX premedication on volatile induction of mask anesthesia (VIMA) and sevoflurane requirements. Journal of Clinical Monitoring and Computing 2013;27(3):329‐34. [EMBASE: 2013337331; PUBMED: 23400425] - PubMed
Moghadam 2012 {published data only}
    1. Moghadam MJ, Ommi D, Mirkheshti A, Shadnoush M, Dabbagh A. The effect of pretreatment with clonidine on propofol consumption in opium abuser and non‐abuser patients undergoing elective leg surgery. Journal of Research in Medical Sciences 2012;17(8):728‐31. [EMBASE: 2012537334; PUBMED: 23798938] - PMC - PubMed
Mohamed 2012 {published data only}
    1. Mohamed AA, Fares KM, Mohamed SA. Efficacy of intrathecally administered dexmedetomidine versus dexmedetomidine with fentanyl in patients undergoing major abdominal cancer surgery. Pain Physician 2012;15(4):339‐48. [EMBASE: 2012453151; PUBMED: 22828688] - PubMed
Mohamed 2013 {published data only}
    1. Mohamed HS, Asida SM, Salman OH. Dexmedetomidine versus nimodipine for controlled hypotension during spine surgery. Egyptian Journal of Anaesthesia 2013;29(4):325‐31. [EMBASE: 2013684468]
Mohammadi 2007 {published data only}
    1. Mohammadi SS, Seyedi M. Effects of oral clonidine in preventing postoperative shivering after general anesthesia. International Journal of Pharmacology 2007;3(5):441‐3. [EMBASE: 2008112839]
Mohammadi 2008 {published data only}
    1. Mohammadi SS, Seyedi M. Comparing oral gabapentin versus clonidine as premedication on early postoperative pain, nausea and vomiting after general anesthesia. International Journal of Pharmacology 2008;4(2):153‐6. [EMBASE: 2009077239]
Mousa 2013 {published data only}
    1. Mousa SA, Abd Elfatah Alsobky H. Efficacy and effect of TIVA with propofol or dexmedetomidine versus sevoflurane without muscle relaxant during repair of the brachial plexus. Egyptian Journal of Anaesthesia 2013;29(1):31‐40. [EMBASE: 2013099363]
Muhammad 2012 {published data only}
    1. Muhammad HB, Esa N, Idris NH, Sidik H. Is dexmedetomidine with patient controlled analgesia morphine better than continuous morphine infusion as a post operative analgesia in off pump coronary artery bypass grafting surgery? A preliminary study. British Journal of Anaesthesia 2012;108:ii398‐9. [EMBASE: 70719618]
Murari Sudre 2004 {published data only}
    1. Murari Sudre EC, MDo Salvador C, Elena Bruno G, Valentim Vassallo D, Rocha Lauretti G, Sudre Filho GN. Remifentanil versus dexmedetomidine as coadjutants of standardized anesthetic technique in morbidly obese patients. Revista Brasileira de Anestesiologia 2004;54(2):178‐89. [EMBASE: 2004138134; PUBMED: 19471725] - PubMed
Myatra 2010 {published data only}
    1. Myatra SN, Dalvi N, Divatia JV, Mohite S, Pethkar T, Patil V, et al. A observer blind, randomized, parallel group, comparative, study to evaluate safety and efficacy of dexmedetomidine hcl versus propofol for postoperative sedation in the intensive care unit. Intensive Care Medicine 2010;36:S327. [EMBASE: 70291183]
Nader 2001 {published data only}
    1. Nader ND, Ignatowski TA, Kurek CJ, Knight PR, Spengler RN. Clonidine suppresses plasma and cerebrospinal fluid concentrations of TNF‐alpha during the perioperative period. Anesthesia and Analgesia 2001;93(2):363‐9. [PUBMED: 11473862] - PubMed
Nader 2009 {published data only}
    1. Nader ND, Li CM, Dosluoglu HH, Ignatowski TA, Spengler RN. Adjuvant therapy with intrathecal clonidine improves postoperative pain in patients undergoing coronary artery bypass graft. Clinical Journal of Pain 2009;25(2):101‐6. [EMBASE: 2009320482; PUBMED: 19333153] - PubMed
Nakagawa 2001 {published data only}
    1. Nakagawa M, Mammoto T, Sakai T, Kishi Y, Mashimoto T. Premedication modifies the quality of sedation with propofol during regional anesthesia. Canadian Journal of Anaesthesia 2001;48(3):284‐7. [PUBMED: 11305831] - PubMed
Nitta 2013 {published data only}
    1. Nitta R, Goyagi T, Nishikawa T. Combination of oral clonidine and intravenous low‐dose ketamine reduces the consumption of postoperative patient‐controlled analgesia morphine after spine surgery. Acta Anaesthesiologica Taiwanica 2013;51(1):14‐7. [EMBASE: 2013334847; PUBMED: 23711600] - PubMed
Nour El‐Din 2004 {published data only}
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Nunez‐Bacarreza 2006 {published data only}
    1. Nunez‐Bacarreza JJ, Portela‐Ortiz JM, Magro‐Ibanez E, Garcia‐Hernandez L, Cabrera‐Jardines R, Alarcon‐Rodriguez J. Hypertension induced by pneumoperitoneum and its treatment with dexmedetomidine. Revista Mexicana de Anestesiologia 2006;29(2):70‐3. [EMBASE: 2006386472]
Oddby‐Muhrbeck 2002 {published data only}
    1. Oddby‐Muhrbeck E, Eksborg S, Bergendahl HTG, Muhrbeck O, Lonnqvist PA. Effects of clonidine on postoperative nausea and vomiting in breast cancer surgery. Anesthesiology 2002;96(5):1109‐14. [PUBMED: 11981150] - PubMed
Ohata 1999 {published data only}
    1. Ohata H, Iida H, Watanabe Y, Dohi S. Hemodynamic responses induced by dopamine and dobutamine in anesthetized patients premedicated with clonidine. Anesthesia and Analgesia 1999;89(4):843‐8. [PUBMED: 10512253] - PubMed
Ohtani 2008 {published data only}
    1. 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. Anesthesia and Analgesia 2008;107(6):1871‐4. [EMBASE: 2009307257; PUBMED: 19020132] - PubMed
Ohtani 2011 {published data only}
    1. Ohtani N, Yasui Y, Watanabe D, Kitamura M, Shoji K, Masaki E. Perioperative infusion of dexmedetomidine at a high dose reduces postoperative analgesic requirements: a randomized control trial. Journal of Anesthesia 2011;25(6):872‐8. [EMBASE: 2011705273; PUBMED: 21953329] - PubMed
Okuyama 2005 {published data only}
    1. Okuyama K, Inomata S, Toyooka H. The effects of prostaglandin E1 or oral clonidine premedication on blood loss during paranasal sinus surgery. Canadian Journal of Anaesthesia 2005;52(5):546‐7. [PUBMED: 15872138] - PubMed
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Onodera 2011 {published data only}
    1. Onodera Y, Yamagishi A, Kunisawa T, Kurosawa A, Takahata O, Iwasaki H. Postoperative analgesia by continuous intravenous fentanyl or dexmedetomidine in patients receiving anticoagulant therapy. [Japanese]. Japanese Journal of Anesthesiology 2011;60(8):936‐40. [EMBASE: 2011473798; PUBMED: 21861419] - PubMed
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Ozbakis 2008 {published data only}
    1. Ozbakis Akkurt BC, Inanoglu K, Turhanoglu S, Asfuroglu Z. Effects of dexmedetomidine and tramadol administered before induction of anesthesia on postoperative pain. [Turkish]. Anestezi Dergisi 2008;16(4):183‐7. [EMBASE: 2009075183]
Ozkose 2006 {published data only}
    1. Ozkose Z, Demir FS, Pampal K, Yardim S. Hemodynamic and anesthetic advantages of dexmedetomidine, an a2‐agonist, for surgery in prone position. Tohoku Journal of Experimental Medicine 2006;210(2):153‐60. [PUBMED: 17023769] - PubMed
Panda 2012a {published data only}
    1. Panda BK, Singh P, Marne S, Pawar A, Keniya V, Ladi S, et al. A comparison study of dexmedetomidine vs clonidine for sympathoadrenal response, perioperative drug requirements and cost analysis. Asian Pacific Journal of Tropical Disease 2012;2(SUPPL2):S815‐21. [EMBASE: 2013011143]
Panda 2012b {published data only}
    1. Panda NB, Amutha V. Dexmedetomidine‐an ideal anesthetic adjuvant in cervical spine surgery. European Journal of Anaesthesiology 2012;29:S18‐9. [EMBASE: 71077477]
Pandazi 2011 {published data only}
    1. Pandazi A, Karamanis P, Sidiropoulou T, Matsota P, Papasideris C, Niokou D, et al. Low‐dose (1 mug/kg) clonidine premedication and hypotension after carotid artery surgery. Vascular and Endovascular Surgery 2011;45(7):614‐8. [EMBASE: 2011577079; PUBMED: 21984028] - PubMed
Pant 2012 {published data only}
    1. Pant KC, Gandhi S. Intravenous clonidine improves glycemic control in type‐2 diabetic patients undergoing laparoscopic cholecystectomy. British Journal of Anaesthesia 2012;108:ii350‐1. [EMBASE: 70719541]
Parameswara 2012 {published data only}
    1. Parameswara G, Badgandi A, Murthy HK. Clonidine vs dexmeditomidine in intracranial tumor surgeries: comparison of haemodynamic stability, brain relaxation and emergence. British Journal of Anaesthesia 2012;108:ii74. [EMBASE: 70719073]
Paris 2009 {published data only}
    1. Paris A, Kaufmann M, Tonner PH, Renz P, Lemke T, Ledowski T, et al. Effects of clonidine and midazolam premedication on bispectral index and recovery after elective surgery. European Journal of Anaesthesiology 2009;26(7):603‐10. [EMBASE: 2010242180; PUBMED: 19367170] - PubMed
Park 1996 {published data only}
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Park 2012 {published data only}
    1. Park JK, Cheong SH, Lee KM, Lim SH, Lee JH, Cho K, et al. Does dexmedetomidine reduce postoperative pain after laparoscopic cholecystectomy with multimodal analgesia?. Korean Journal of Anesthesiology 2012;63(5):436‐40. [EMBASE: 2012714558] - PMC - PubMed
Parlow 1999 {published data only}
    1. Parlow JL, Begou G, Sagnard P, Cottet‐Emard JM, Levron JC, Annat G, et al. Cardiac baroreflex during the postoperative period in patients with hypertension: effect of clonidine. Anesthesiology 1999;90(3):681‐92. [PUBMED: 10078667] - PubMed
Patel 2012 {published data only}
    1. Patel CR, Engineer SR, Shah BJ, Madhu S. Effect of intravenous infusion of dexmedetomidine on perioperative haemodynamic changes and postoperative recovery: a study with entropy analysis. Indian Journal of Anaesthesia 2012;56(6):542‐6. [EMBASE: 2012747718; PUBMED: 23325938] - PMC - PubMed
Patil 2012 {published data only}
    1. Patil PM, Patil SP. Is clonidine an adequate alternative to epinephrine as a vasoconstrictor in patients with hypertension?. Journal of Oral and Maxillofacial Surgery 2012;70(2):257‐62. [EMBASE: 2012038438; PUBMED: 21940091] - PubMed
Pestilci 2015 {published data only}
    1. Pestilci Z, Sergin D, Alper I, Kocabas S, Ulukaya S, Askar FZ. Propofol versus dexmedetomidine for postoperative sedation in fast‐track cardiac anesthesia. [Turkish]. Gogus‐Kalp‐Damar Anestezi ve Yogun Bakim Dernegi Dergisi 2015;21(1):8‐15. [EMBASE: 2015077461]
Piper 1999 {published data only}
    1. Piper SN, Suttner SW, Schmidt CC, Maleck WH, Kumle B, Boldt J. Nefopam and clonidine in the prevention of postanaesthetic shivering. Anaesthesia 1999;54:695‐9. [PUBMED: 10417466] - PubMed
Piper 2004 {published data only}
    1. Piper SN, Rohm KD, Suttner SW, Maleck WH, Kranke P, Boldt J. A comparison of nefopam and clonidine for the prevention of postanaesthetic shivering: a comparative, double‐blind and placebo‐controlled dose‐ranging study. Anaesthesia 2004;59:559‐64. [PUBMED: 15144295] - PubMed
Porkkala 1998 {published data only}
    1. Porkkala T, Jantti V, Hakkinen V, Kaukinen S. Colonidine does not attenuate median nerve somatosensory evoked potentials during isoflurane anesthesia. Journal of Clinical Monitoring and Computing 1998;14:165‐70. [PUBMED: 9676863] - PubMed
Pouttu 1987 {published data only}
    1. Pouttu J, Scheinin B, Rosenberg PH, Viinamaki O, Scheinin M. Oral premedication with clonidine: effects on stress responses during general anaesthesia. Acta Anaesthesiologica Scandinavica 1987;31(8):730‐4. [PUBMED: 3434164] - PubMed
Procaccini 1993 {published data only}
    1. Procaccini B, Clementi G, Varrassi G. Effects of clonidine vs trinitroglycerin on myocardial oxygen balance and on pulmonary gas exchange after myocardial revascularization. Minerva Anestesiologica 1993;59(5):235‐45. [PUBMED: 8355864] - PubMed
Quintin 1990 {published data only}
    1. Quintin L, Bonnet F, Macquin I, Szekely B, Becquemin JP, Ghignone M. Aortic surgery: effect of clonidine on intraoperative catecholaminergic and circulatory stability. Acta Anaesthesiologica Scandinavica 1990;34(2):132‐7. [PUBMED: 2407044] - PubMed
Quintin 1991a {published data only}
    1. Quintin L, Roudot F, Roux C, Macquin I, Basmaciogullari A, Guyene T, et al. Effect of clonidine on the circulation and vasoactive hormones after aortic surgery. British Journal of Anaesthesia 1991;66(1):108‐15. [PUBMED: 1997045] - PubMed
Quintin 1991b {published data only}
    1. Quintin L, Viale JP, Annat G, Hoen JP, Butin E, Cottet‐Emard JM, et al. Oxygen uptake after major abdominal surgery: effect of clonidine. Anesthesiology 1991;74(2):236‐41. [PUBMED: 1990899] - PubMed
Raouf 2004 {published data only}
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Ray 2010 {published data only}
    1. Ray M, Bhattacharjee DP, Hajra B, Pal R, Chatterjee N. Effect of clonidine and magnesium sulphate on anaesthetic consumption, haemodynamics and postoperative recovery: a comparative study. Indian Journal of Anaesthesia 2010;54(2):137‐41. [EMBASE: 2011051651; PUBMED: 20661352] - PMC - PubMed
Reddy 2013 {published data only}
    1. Reddy VS, Shaik NA, Donthu B, Sannala VKR, Jangam V. Intravenous dexmedetomidine versus clonidine for prolongation of bupivacaine spinal anesthesia and analgesia: a randomized double‐blind study. Journal of Anaesthesiology Clinical Pharmacology 2013;29(3):342‐7. [EMBASE: 2013584803; PUBMED: 24106359] - PMC - PubMed
Richa 2008 {published data only}
    1. Richa F, Yazigi A, Sleilaty G, Yazbeck P. Comparison between dexmedetomidine and remifentanil for controlled hypotension during tympanoplasty. European Journal of Anaesthesiology 2008;25(5):369‐74. [PUBMED: 18294411] - PubMed
Rohrbach 1999 {published data only}
    1. Rohrbach A, Jage J, Olthoff D. Intraoperative clonidine modulates sympathetic tone in the early postoperative period after remifentanil. A double blind, placebo‐controlled study. Acute Pain 1999;2(3):129‐38. [EMBASE: 1999373401]
Rosenfeld 1993 {published data only}
    1. Rosenfeld BA, Faraday N, Campbell D, Dorman T, Clarkson K, Siedler A, et al. Perioperative platelet reactivity and the effects of clonidine. Anesthesiology 1993;79(2):255‐61. [PUBMED: 8342838] - PubMed
Ruan 2011 {published data only}
    1. Ruan XC, Ruan X, He L, She S. Dexthomedine does not increase risk of trigemino‐Cardiac reflex during microvascular trigeminal decompression in cases of trigeminal neuralgia. Journal of Neurosurgical Anesthesiology 2011;23(4):423. [EMBASE: 70538809] - PubMed
Rubino 2010 {published data only}
    1. Rubino AS, Onorati F, Caroleo S, Galato E, Nucera S, Amantea B, et al. Impact of clonidine administration on delirium and related respiratory weaning after surgical correction of acute type‐A aortic dissection: results of a pilot study. Interactive Cardiovascular and Thoracic Surgery 2010;10(1):58‐62. [EMBASE: 2010057909; PUBMED: 19854793] - PubMed
Salgado 2008 {published data only}
    1. Salgado PFS, Sabbag AT, Silva PC, Brienze SLA, Dalto HP, Modolo NSP, et al. Synergistic effect between dexmedetomidine and 0.75% ropivacaine in epidural anesthesia. [Portuguese]. Revista da Associacao Medica Brasileira 2008;54(2):110‐5. [PUBMED: 18506317] - PubMed
Salgado Filho 2013 {published data only}
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Samantaray 2012 {published data only}
    1. Samantaray A, Rao M, Chandra A. The effect on post‐operative pain of intravenous clonidine given before induction of anaesthesia. Indian Journal of Anaesthesia 2012;56(4):359‐64. [EMBASE: 2012539842; PUBMED: 23087458] - PMC - PubMed
Sassi 2013 {published data only}
    1. Sassi M, Zekaj E, Grotta A, Pollini A, Pellanda A, Borroni M, et al. Safety in the use of dexmedetomidine (Precedex) for deep brain stimulation surgery: our experience in 23 randomized patients. Neuromodulation 2013;16(5):401‐6. [EMBASE: 2013695343; PUBMED: 22780449] - PubMed
Scheinin 1992 {published data only}
    1. Scheinin 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. British Journal of Anaesthesia 1992;68(2):126‐31. [PUBMED: 1347229] - PubMed
Schlimp 2011 {published data only}
    1. Schlimp CJ, Pipam W, Wolrab C, Ohner C, Kager HI, Likar R. Clonidine for remifentanil‐induced hyperalgesia: a double‐blind randomized, placebo‐controlled study of clonidine under intra‐operative use of remifentanil in elective surgery of the shoulder. [German]. Schmerz 2011;25(3):290‐5. [EMBASE: 2011388625; PUBMED: 21594659] - PubMed
Schreiberova 2008 {published data only}
    1. Schreiberova J, Hess L, Krajina A, Lojik M. Dexmedetomidine‐ketamine‐midazolam combination for sedation in endovascular treatment of cerebral arterio‐venousmalformations and carotid artery stenosis. [Czech]. Ceska a Slovenska Neurologie a Neurochirurgie 2008;71(4):446‐52. [EMBASE: 2008446158]
Segal 1991 {published data only}
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Selina 2011 {published data only}
    1. Selina F, Akhtaruzzaman KM, Talha KA, Hossain MM, Iqbal KM. Role of oral clonidine on intraoperative haemodynamic stability for craniotomies of intracranial space occupying lesion. Mymensingh medical journal : MMJ 2011;20(2):257‐63. [PUBMED: 21522097] - PubMed
Senses 2013 {published data only}
    1. Senses E, Apan A, Arzu Kouml, se E, Oz G, Rezak H. The effects of midazolam and dexmedetomidine infusion on peri‐operative anxiety in regional anesthesia. Middle East Journal of Anesthesiology 2013;22(1):35‐40. [EMBASE: 23833848] - PubMed
Shams 2013 {published data only}
    1. Shams T, Bahnasawe NS, Abu‐Samra M, El‐Masry R. Induced hypotension for functional endoscopic sinus surgery: a comparative study of dexmedetomidine versus esmolol. Saudi Journal of Anaesthesia 2013;7(2):175‐80. [EMBASE: 2013447907; PUBMED: 23956719] - PMC - PubMed
Shin 2012 {published data only}
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Shin 2013 {published data only}
    1. Shin HW, Yoo HN, Kim DH, Lee H, Shin HJ, Lee HW. Preanesthetic dexmedetomidine 1 mug/kg single infusion is a simple, easy, and economic adjuvant for general anesthesia. Korean Journal of Anesthesiology 2013;65(2):114‐20. [EMBASE: 2013571775] - PMC - PubMed
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Si 2011 {published data only}
    1. Si YN, Zhang Y, Lu YL, Chen H, Bao HG. Influences of dexmedetomidine in doses of propofol and fentanyl and recovery from anesthesia. [Chinese]. Journal of Jilin University Medicine Edition 2011;37(1):135‐8. [EMBASE: 2013739730]
Simoni 2009 {published data only}
    1. Simoni RF, Cangiani LM, Pereira AMSA, Abreu MP, Cangiani LH, Zemi G. Efficacy of intraoperative methadone and clonidine in pain control in the immediate postoperative period after the use of remifentanil. [Portuguese, English]. Revista Brasileira de Anestesiologia 2009;59(4):421‐30. [EMBASE: 2009503681; PUBMED: 19669016] - PubMed
Singh 2011 {published data only}
    1. Singh S, Arora K. Effect of oral clonidine premedication on perioperative haemodynamic response and postoperative analgesic requirement for patients undergoing laparoscopic cholecystectomy. Indian Journal of Anaesthesia 2011;55(1):26‐30. [EMBASE: 2011246356; PUBMED: 21431049] - PMC - PubMed
Singh 2013 {published data only}
    1. Singh M, Choudhury A, Kaur M, Liddle D, Verghese M, Balakrishnan I. The comparative evaluation of intravenous with intramuscular clonidine for suppression of hemodynamic changes in laparoscopic cholecystectomy. Saudi Journal of Anaesthesia 2013;7(2):181‐6. [EMBASE: 2013447905; PUBMED: 23956720] - PMC - PubMed
Singh Bajwa 2012 {published data only}
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