Efficacy of using dexmedetomidine as an adjuvant to bupivacaine

Author(s):

Alireza Abdullahi Baghaee, Hashem Jarineshin, Nasim Abdi, Fereydoon Fekrat

Abstract

Dexmedetomidine is a member of the alpha-2 agonist family which is highly specific and has highly selective properties. When used as an adjuvant to Bupivacaine, it has been reported to have positive effects. In this review article, the most important efficacies of Dexmedetomidine as an adjuvant to Bupivacaine including prolonging the analgesic and anesthetic effects of bupivacaine, improving post-operative analgesia, improving analgesic effects of bupivacaine, providing better sedation, shortening the onset of block, improving local anesthesia, providing better hemodynamic stability, and reducing the consumption of analgesic substances are discussed.

Keywords

Dexmedetomidine, Bupivacaine, Adjuvant

References
  1. Savola JM, Ruskoaho H, Puurunen J, Salonen JS, Karki NT. Evidence for medetomidine as a selective and potent agonist at alpha 2-adrenoreceptors. J Auton Pharmacol. 1986 Dec;6(4):275-84. PubMed PMID: 2880852.

  2. Virtanen R, Savola JM, Saano V, Nyman L. Characterization of the selectivity, specificity and potency of medetomidine as an alpha 2-adrenoceptor agonist. Eur J Pharmacol. 1988 May 20;150(1-2):9-14. PubMed PMID: 2900154.

  3. Wewers ME, Lowe NK. A critical review of visual analogue scales in the measurement of clinical phenomena. Research in nursing & health. 1990 Aug;13(4):227-36. PubMed PMID: 2197679. Epub 1990/08/01. eng.

  4. Grewal A. Dexmedetomidine: New avenues. Journal of Anaesthesiology, Clinical Pharmacology. 2011 Jul-Sep;27(3):297-302. PubMed PMID: PMC3161450.

  5. Arain SR, Ebert TJ. The Efficacy, Side Effects, and Recovery Characteristics of Dexmedetomidine Versus Propofol When Used for Intraoperative Sedation. Anesthesia & Analgesia. 2002;95(2):461-6. PubMed PMID: 00000539-200208000-00042.

  6. Singh PM, Panwar R, Borle A, Mulier JP, Sinha A, Goudra B. Perioperative analgesic profile of dexmedetomidine infusions in morbidly obese undergoing bariatric surgery: a meta-analysis and trial sequential analysis. Surg Obes Relat Dis. 2017 Mar 10. PubMed PMID: 28396128.

  7. Panchgar V, Shetti AN, Sunitha HB, Dhulkhed VK, Nadkarni AV. The Effectiveness of Intravenous Dexmedetomidine on Perioperative Hemodynamics, Analgesic Requirement, and Side Effects Profile in Patients Undergoing Laparoscopic Surgery Under General Anesthesia. Anesth Essays Res. 2017 Jan-Mar;11(1):72- PubMed PMID: 28298760. PMCID: PMC5341677.

  8. Gupta S, Sharma R. Comparison of analgesic efficacy of caudal dexmedetomidine versus caudal tramadol with ropivacaine in paediatric infraumbilical surgeries: A prospective, randomised, double-blinded clinical study. Indian J Anaesth. 2017 Jun;61(6):499-504. PubMed PMID: 28655957. PMCID: PMC5474920.

  9. Gupta B, Verma RK, Kumar S, Chaudhary G. Comparison of Analgesic Efficacy of Dexmedetomidine and Midazolam as Adjuncts to Lignocaine for Intravenous Regional Anesthesia. Anesth Essays Res. 2017 Jan-Mar;11(1):62-6. PubMed PMID: 28298758. PMCID: PMC5341646.

  10. 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. J Neurosurg Anesthesiol. 2017 Jul;29(3):258-63. PubMed PMID: 27035842.

  11. Rajan S, Hutcherson MT, Sessler DI, Kurz A, Yang D, Ghobrial M, et al. The Effects of Dexmedetomidine and Remifentanil on Hemodynamic Stability and Analgesic Requirement After Craniotomy: A Randomized Controlled Trial. J Neurosurg Anesthesiol. 2016 Oct;28(4):282-90. PubMed PMID: 26325514.

  12. Oza VP, Parmar V, Badheka J, Nanavati DS, Taur P, Rajyaguru AM. Comparative study of postoperative analgesic effect of intraperitoneal instillation of dexmedetomidine with bupivacaine and bupivacaine alone after laparoscopic surgery. J Minim Access Surg. 2016 Jul-Sep;12(3):260-4. PubMed PMID: 27279399. PMCID: PMC4916754.

  13. Sheehy KA, Finkel JC, Darbari DS, Guerrera MF, Quezado ZM. Dexmedetomidine as an Adjuvant to Analgesic Strategy During Vaso-Occlusive Episodes in Adolescents with Sickle-Cell Disease. Pain Pract. 2015 Nov;15(8):E90-7. PubMed PMID: 26205912. PMCID: PMC4670780.

  14. She YJ, Xie GT, Tan YH, Kuang XH, Yu GF, Lian GH, et al. A prospective study comparing the onset and analgesic efficacy of different concentrations of levobupivacaine with/without dexmedetomidine in young children undergoing caudal blockade. J Clin Anesth. 2015 Feb;27(1):17-22. PubMed PMID: 25468576.

  15. Kundu R, Dehran M, Chandralekha, Trikha A, Nag HL. Safety and analgesic efficacy of intravenous dexmedetomidine in arthroscopic knee surgery. Anesth Essays Res. 2015 Sep-Dec;9(3):391-6. PubMed PMID: 26712980. PMCID: PMC4683487.

  16. Bharti N, Sardana DK, Bala I. The Analgesic Efficacy of Dexmedetomidine as an Adjunct to Local Anesthetics in Supraclavicular Brachial Plexus Block: A Randomized Controlled Trial. Anesth Analg. 2015 Dec;121(6):1655-60. PubMed PMID: 26496366.

  17. Yang YC, Meng QT, Pan X, Xia ZY, Chen XD. Dexmedetomidine produced analgesic effect via inhibition of HCN currents. Eur J Pharmacol. 2014 Oct 05;740:560-4. PubMed PMID: 24998873.

  18. Tong Y, Ren H, Ding X, Jin S, Chen Z, Li Q. Analgesic effect and adverse events of dexmedetomidine as additive for pediatric caudal anesthesia: a meta-analysis. Paediatr Anaesth. 2014 Dec;24(12):1224-30. PubMed PMID: 25203847.

  19. Surendar MN, Pandey RK, Saksena AK, Kumar R, Chandra G. A comparative evaluation of intranasal dexmedetomidine, midazolam and ketamine for their sedative and analgesic properties: a triple blind randomized study. J Clin Pediatr Dent. 2014 Spring;38(3):255-61. PubMed PMID: 25095322.

  20. Mohamed SA, Fares KM, Mohamed AA, Alieldin NH. Dexmedetomidine as an adjunctive analgesic with bupivacaine in paravertebral analgesia for breast cancer surgery. Pain Physician. 2014 Sep-Oct;17(5):E589-98. PubMed PMID: 25247908.

  21. Ter Bruggen FF, Eralp I, Leliveld L, Jansen C, Stronks DL, Huygen FJ. Dexmedetomidine as a Sedative in the Awake Implantation of a Neuromodulative System. Pain Pract. 2017 Feb;17(2):208-13. PubMed PMID: 26914618.

  22. Ter Bruggen F, Eralp I, Jansen CK, Stronks DL, Huygen F. Efficacy of Dexmedetomidine as a Sole Sedative Agent in Small Diagnostic and Therapeutic Procedures: A Systematic Review. Pain Pract. 2017 Jul;17(6):829-40. PubMed PMID: 27862903.

  23. Kumar A, Sinha C, Kumar A, Kumari P. The Effect of Intravenous Dexmedetomidine Compared to Propofol on Patients Hemodynamics as a Sedative in Brachial Plexus Block: A Comparative Study. Anesth Essays Res. 2017 Jan-Mar;11(1):201-5. PubMed PMID: 28298785. PMCID: PMC5341667.

  24. Kim HJ, Shin WJ, Park S, Ahn HS, Oh JH. The sedative effects of the intranasal administration of dexmedetomidine in children undergoing surgeries compared to other sedation methods: A systematic review and meta-analysis. J Clin Anesth. 2017 May;38:33-9. PubMed PMID: 28372674.

  25. Behrle N, Birisci E, Anderson J, Schroeder S, Dalabih A. Intranasal Dexmedetomidine as a Sedative for Pediatric Procedural Sedation. J Pediatr Pharmacol Ther. 2017 Jan-Feb;22(1):4-8. PubMed PMID: 28337075. PMCID: PMC5341530.

  26. Zhou LJ, Fang XZ, Gao J, Zhangm Y, Tao LJ. Safety and Efficacy of Dexmedetomidine as a Sedative Agent for Performing Awake Intubation: A Meta-analysis. Am J Ther. 2016 Nov/Dec;23(6):e1788-e800. PubMed PMID: 26196522.

  27. Malhotra PU, Thakur S, Singhal P, Chauhan D, Jayam C, Sood R, et al. Comparative evaluation of dexmedetomidine and midazolam-ketamine combination as sedative agents in pediatric dentistry: A double-blinded randomized controlled trial. Contemp Clin Dent. 2016 Apr-Jun;7(2):186-92. PubMed PMID: 27307665. PMCID: PMC4906861.

  28. Lu C, Zhang LM, Zhang Y, Ying Y, Li L, Xu L, et al. Intranasal Dexmedetomidine as a Sedative Premedication for Patients Undergoing Suspension Laryngoscopy: A Randomized Double-Blind Study. PLoS One. 2016;11(5):e0154192. PubMed PMID: 27196121. PMCID: PMC4873234.

  29. Baier NM, Mendez SS, Kimm D, Velazquez AE, Schroeder AR. Intranasal dexmedetomidine: an effective sedative agent for electroencephalogram and auditory brain response testing. Paediatr Anaesth. 2016 Mar;26(3):280-5. PubMed PMID: 26814037.

  30. Sriganesh K, Reddy M, Jena S, Mittal M, Umamaheswara Rao GS. A comparative study of dexmedetomidine and propofol as sole sedative agents for patients with aneurysmal subarachnoid hemorrhage undergoing diagnostic cerebral angiography. J Anesth. 2015 Jun;29(3):409-15. PubMed PMID: 25424589.

  31. Devasya A, Sarpangala M. Dexmedetomidine: A Review of a Newer Sedative in Dentistry. J Clin Pediatr Dent. 2015 Fall;39(5):401-9. PubMed PMID: 26551360.

  32. Wang SS, Zhang MZ, Sun Y, Wu C, Xu WY, Bai J, et al. The sedative effects and the attenuation of cardiovascular and arousal responses during anesthesia induction and intubation in pediatric patients: a randomized comparison between two different doses of preoperative intranasal dexmedetomidine. Paediatr Anaesth. 2014 Mar;24(3):275-81. PubMed PMID: 24224515.

  33. Singh C, Pandey RK, Saksena AK, Chandra G. A comparative evaluation of analgo-sedative effects of oral dexmedetomidine and ketamine: a triple-blind, randomized study. Paediatr Anaesth. 2014 Dec;24(12):1252-9. PubMed PMID: 25065424.

  34. Arcangeli A, D'Alo C, Gaspari R. Dexmedetomidine use in general anaesthesia. Curr Drug Targets. 2009 Aug;10(8):687-95. PubMed PMID: 19702517.

  35. Das BP, Singh AP, Singh RB. Emergency Corrective Surgery of Congenital Diaphragmatic Hernia With Pulmonary Hypertension: Prolonged Use of Dexmedetomidine as a Pharmacologic Adjunct. Anesth Pain Med. 2016 Jun;6(3):e31880. PubMed PMID: 27635388. PMCID: PMC5013697.

  36. Yang L, Tang J, Dong J, Zheng J. Alpha2-adrenoceptor-independent inhibition of acetylcholine receptor channel and sodium channel by dexmedetomidine in rat superior cervical ganglion neurons. Neuroscience. 2015 Mar 19;289:9-18. PubMed PMID: 255836

  37. Gulabani M, Gurha P, Dass P, Kulshreshtha N. Comparative analysis of efficacy of lignocaine 1.5 mg/kg and two different doses of dexmedetomidine (0.5 mug/kg and 1 mug/kg) in attenuating the hemodynamic pressure response to laryngoscopy and intubation. Anesth Essays Res. 2015 Jan-Apr;9(1):5-14. PubMed PMID: 25886414. PMCID: PMC4383101.

  38. Ebert TJ, Hall JE, Barney JA, Uhrich TD, Colinco MD. The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology. 2000 Aug;93(2):382-94. PubMed PMID: 10910487.

  39. Venn RM, Hell J, Grounds RM. Respiratory effects of dexmedetomidine in the surgical patient requiring intensive care. Crit Care. 2000;4(5):302-8. PubMed PMID: 11056756. PMCID: PMC29047.

  40. Keniya VM, Ladi S, Naphade R. Dexmedetomidine attenuates sympathoadrenal response to tracheal intubation and reduces perioperative anaesthetic requirement. Indian Journal of Anaesthesia. 2011 Jul-Aug;55(4):352-7. PubMed PMID: PMC3190508.

  41. Bhagat N, Yunus M, Karim HM, Hajong R, Bhattacharyya P, Singh M. Dexmedetomidine in Attenuation of Haemodynamic Response and Dose Sparing Effect on Opioid and Anaesthetic Agents in Patients undergoing Laparoscopic Cholecystectomy- A Randomized Study. J Clin Diagn Res. 2016 Nov;10(11):UC01-UC5. PubMed PMID: 28050479. PMCID: PMC5198432.

  42. Song J, Ji Q, Sun Q, Gao T, Liu K, Li L. The Opioid-sparing Effect of Intraoperative Dexmedetomidine Infusion After Craniotomy. J Neurosurg Anesthesiol. 2016 Jan;28(1):14-20. PubMed PMID: 25955866.

  43. Song Y, Shim JK, Song JW, Kim EK, Kwak YL. Dexmedetomidine added to an opioid-based analgesic regimen for the prevention of postoperative nausea and vomiting in highly susceptible patients: A randomised controlled trial. Eur J Anaesthesiol. 2016 Feb;33(2):75-83. PubMed PMID: 26258655.

  44. Su S, Ren C, Zhang H, Liu Z, Zhang Z. The Opioid-Sparing Effect of Perioperative Dexmedetomidine Plus Sufentanil Infusion during Neurosurgery: A Retrospective Study. Front Pharmacol. 2016;7:407. PubMed PMID: 27833559. PMCID: PMC5080288.

  45. Agarwal S, Aggarwal R, Gupta P. Dexmedetomidine prolongs the effect of bupivacaine in supraclavicular brachial plexus block. J Anaesthesiol Clin Pharmacol. 2014 Jan;30(1):36-40. PubMed PMID: 24574591. PMCID: PMC3927290.

  46. Tripathi A, Sharma K, Somvanshi M, Samal RL. A comparative study of clonidine and dexmedetomidine as an adjunct to bupivacaine in supraclavicular brachial plexus block. J Anaesthesiol Clin Pharmacol. 2016 Jul-Sep;32(3):344-8. PubMed PMID: 27625483. PMCID: PMC5009841.

  47. Shukla U, Prabhakar T, Malhotra K, Srivastava D. Dexmedetomidine versus midazolam as adjuvants to intrathecal bupivacaine: A clinical comparison. J Anaesthesiol Clin Pharmacol. 2016 Apr-Jun;32(2):214-9. PubMed PMID: 27275052. PMCID: PMC4874077.

  48. Sathyanarayana LA, Heggeri VM, Simha PP, Narasimaiah S, Narasimaiah M, Subbarao BK. Comparison of Epidural Bupivacaine, Levobupivacaine and Dexmedetomidine in Patients Undergoing Vascular Surgery. J Clin Diagn Res. 2016 Jan;10(1):UC13-7. PubMed PMID: 26894153. PMCID: PMC4740681.

  49. Santpur MU, Kahalekar GM, Saraf N, Losari A. Effect of intravenous dexmedetomidine on spinal anaesthesia with 0.5% hyperbaric bupivacaine in lower abdominal surgeries: A prospective randomized control study. Anesth Essays Res. 2016 Sep-Dec;10(3):497-501. PubMed PMID: 27746540. PMCID: PMC5062200.

  50. Safari F, Aminnejad R, Mohajerani SA, Farivar F, Mottaghi K, Safdari H. Intrathecal Dexmedetomidine and Fentanyl as Adjuvant to Bupivacaine on Duration of Spinal Block in Addicted Patients. Anesth Pain Med. 2016 Feb;6(1):e26714. PubMed PMID: 27110524. PMCID: PMC4837787.

  51. Patro SS, Deshmukh H, Ramani YR, Das G. Evaluation of Dexmedetomidine as an Adjuvant to Intrathecal Bupivacaine in Infraumbilical Surgeries. J Clin Diagn Res. 2016 Mar;10(3):UC13-6. PubMed PMID: 27134975. PMCID: PMC4843360.

  52. Nazir N, Jain S. A Randomized Controlled Trial Study on the Effect of Adding Dexmedetomidine to Bupivacaine in Supraclavicular Block Using Ultrasound Guidance. Ethiopian Journal of Health Sciences. 2016;26(6):561-6. PubMed PMID: PMC5389076.

  53. Mohamed SA, El-Rahman AM, Fares KM. Intrathecal Dexmedetomidine, Ketamine, and their Combination Added to Bupivacaine for Postoperative Analgesia in Major Abdominal Cancer Surgery. Pain Physician. 2016 Jul;19(6):E829-39. PubMed PMID: 27454273.

  54. Kubre J, Sethi A, Mahobia M, Bindal D, Narang N, Saxena A. Single dose intravenous dexmedetomidine prolongs spinal anesthesia with hyperbaric bupivacaine. Anesth Essays Res. 2016 May-Aug;10(2):273-7. PubMed PMID: 27212760. PMCID: PMC4864683.

  55. Sudheesh K, Rao RR, Kavya M, Aarthi J, Rani DD, Nethra SS. Comparative study of two doses of intrathecal dexmedetomidine as adjuvant with low dose hyperbaric bupivacaine in ambulatory perianal surgeries: A prospective randomised controlled study. Indian J Anaesth. 2015 Oct;59(10):648-52. PubMed PMID: 26644612. PMCID: PMC4645353.

  56. Goyal V, Kubre J, Radhakrishnan K. Dexmedetomidine as an adjuvant to bupivacaine in caudal analgesia in children. Anesth Essays Res. 2016 May-Aug;10(2):227-32. PubMed PMID: 27212752. PMCID: PMC4864692.

  57. Sarma J, Narayana PS, Ganapathi P, Shivakumar MC. A comparative study of intrathecal clonidine and dexmedetomidine on characteristics of bupivacaine spinal block for lower limb surgeries. Anesth Essays Res. 2015 May-Aug;9(2):195-207. PubMed PMID: 26417127. PMCID: PMC4563966.

  58. Samantaray A, Hemanth N, Gunnampati K, Pasupuleti H, Mukkara M, Rao MH. Comparison of the effects of adding dexmedetomidine versus midazolam to intrathecal bupivacaine on postoperative analgesia. Pain Physician. 2015 Jan-Feb;18(1):71-7. PubMed PMID: 25675061.

  59. Salem RA, Darweesh EI, Wanis MA, Mohamed AA. Evaluation of the effects of intrathecal bupivacaine-dexmedetomidine for lumbar spine fusion: a double blinded randomized controlled study. Eur Rev Med Pharmacol Sci. 2015 Dec;19(23):4542-8. PubMed PMID: 26698250.

  60. Khan AL, Singh RB, Tripathi RK, Choubey S. A comparative study between intrathecal dexmedetomidine and fentanyl as adjuvant to intrathecal bupivacaine in lower abdominal surgeries: A randomized trial. Anesth Essays Res. 2015 May-Aug;9(2):139-48. PubMed PMID: 26417118. PMCID: PMC45639

  61. Das A, Halder S, Chattopadhyay S, Mandal P, Chhaule S, Banu R. Effect of Two Different Doses of Dexmedetomidine as Adjuvant in Bupivacaine Induced Subarachnoid Block for Elective Abdominal Hysterectomy Operations: A Prospective, Double-blind, Randomized Controlled Study. Oman Med J. 2015 Jul;30(4):257-63. PubMed PMID: 26366259. PMCID: PMC4561636.

  62. Yektas A, Belli E. The effects of 2 microg and 4 microg doses of dexmedetomidine in combination with intrathecal hyperbaric bupivacaine on spinal anesthesia and its postoperative analgesic characteristics. Pain Res Manag. 2014 Mar-Apr;19(2):75-81. PubMed PMID: 24527467. PMCID: PMC4028656.

  63. Shahi V, Verma AK, Agarwal A, Singh CS. A comparative study of magnesium sulfate vs dexmedetomidine as an adjunct to epidural bupivacaine. J Anaesthesiol Clin Pharmacol. 2014 Oct;30(4):538-42. PubMed PMID: 25425781. PMCID: PMC4234792.

  64. Halder S, Das A, Mandal D, Chandra M, Ray S, Biswas MR, et al. Effect of different doses of dexmedetomidine as adjuvant in bupivacaine -induced subarachnoid block for traumatized lower limb orthopaedic surgery: a prospective, double-blinded and randomized controlled study. J Clin Diagn Res. 2014 Nov;8(11):GC01-6. PubMed PMID: 25584237. PMCID: PMC4290256.

  65. Gupta M, Shailaja S, Hegde KS. Comparison of intrathecal dexmedetomidine with buprenorphine as adjuvant to bupivacaine in spinal asnaesthesia. J Clin Diagn Res. 2014 Feb;8(2):114-7. PubMed PMID: 24701498. PMCID: PMC3972523.

  66. Dinesh CN, Sai Tej NA, Yatish B, Pujari VS, Mohan Kumar RM, Mohan CV. Effects of intravenous dexmedetomidine on hyperbaric bupivacaine spinal anesthesia: A randomized study. Saudi J Anaesth. 2014 Apr;8(2):202-8. PubMed PMID: 24843333. PMCID: PMC4024677.

  67. 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. J Anaesthesiol Clin Pharmacol. 2013 Oct;29(4):496-502. PubMed PMID: 24249987. PMCID: PMC3819844.

  68. Kim JE, Kim NY, Lee HS, Kil HK. Effects of intrathecal dexmedetomidine on low-dose bupivacaine spinal anesthesia in elderly patients undergoing transurethral prostatectomy. Biol Pharm Bull. 2013;36(6):959-65. PubMed PMID: 23727917.

  69. Jung SH, Lee SK, Lim KJ, Park EY, Kang MH, Lee JM, et al. The effects of single-dose intravenous dexmedetomidine on hyperbaric bupivacaine spinal anesthesia. J Anesth. 2013 Jun;27(3):380-4. PubMed PMID: 23307164.

  70. Harsoor S, Rani DD, Yalamuru B, Sudheesh K, Nethra S. Effect of supplementation of low dose intravenous dexmedetomidine on characteristics of spinal anaesthesia with hyperbaric bupivacaine. Indian J Anaesth. 2013 May;57(3):265-9. PubMed PMID: 23983285. PMCID: PMC3748681.

  71. Erdivanli B, Altun M, Sezen OK, Colakoglu SA. Anti-nociceptive, analgesic and pathohistological effects of intrathecal dexmedetomidine and bupivacaine in rats. Braz J Anesthesiol. 2013 Mar-Apr;63(2):183-7. PubMed PMID: 23601258.

  72. Hong JY, Kim WO, Yoon Y, Choi Y, Kim SH, Kil HK. Effects of intravenous dexmedetomidine on low-dose bupivacaine spinal anaesthesia in elderly patients. Acta Anaesthesiol Scand. 2012 Mar;56(3):382-7. PubMed PMID: 22220945.

  73. Ammar AS, Mahmoud KM. Ultrasound-guided single injection infraclavicular brachial plexus block using bupivacaine alone or combined with dexmedetomidine for pain control in upper limb surgery: A prospective randomized controlled trial. Saudi J Anaesth. 2012 Apr;6(2):109-14. PubMed PMID: 22754434. PMCID: PMC3385250.

  74. Shukla D, Verma A, Agarwal A, Pandey HD, Tyagi C. Comparative study of intrathecal dexmedetomidine with intrathecal magnesium sulfate used as adjuvants to bupivacaine. J Anaesthesiol Clin Pharmacol. 2011 Oct;27(4):495-9. PubMed PMID: 22096283. PMCID: PMC3214555.

  75. Gupta R, Verma R, Bogra J, Kohli M, Raman R, Kushwaha JK. A Comparative study of intrathecal dexmedetomidine and fentanyl as adjuvants to Bupivacaine. J Anaesthesiol Clin Pharmacol. 2011 Jul;27(3):339-43. PubMed PMID: 21897504. PMCID: PMC3161458.

  76. Obayah GM, Refaie A, Aboushanab O, Ibraheem N, Abdelazees M. Addition of dexmedetomidine to bupivacaine for greater palatine nerve block prolongs postoperative analgesia after cleft palate repair. Eur J Anaesthesiol. 2010 Mar;27(3):280-4. PubMed PMID: 19935071.

  77. Kaya FN, Yavascaoglu B, Turker G, Yildirim A, Gurbet A, Mogol EB, et al. Intravenous dexmedetomidine, but not midazolam, prolongs bupivacaine spinal anesthesia. Can J Anaesth. 2010 Jan;57(1):39-45. PubMed PMID: 20039221.

  78. Saadawy I, Boker A, Elshahawy MA, Almazrooa A, Melibary S, Abdellatif AA, et al. Effect of dexmedetomidine on the characteristics of bupivacaine in a caudal block in pediatrics. Acta Anaesthesiol Scand. 2009 Feb;53(2):251-6. PubMed PMID: 19076110.

  79. Al-Mustafa MM, Badran IZ, Abu-Ali HM, Al-Barazangi BA, Massad IM, Al-Ghanem SM. Intravenous dexmedetomidine prolongs bupivacaine spinal analgesia. Middle East J Anaesthesiol. 2009 Jun;20(2):225-31. PubMed PMID: 19583070.

  80. Brummett CM, Norat MA, Palmisano JM, Lydic R. Perineural administration of dexmedetomidine in combination with bupivacaine enhances sensory and motor blockade in sciatic nerve block without inducing neurotoxicity in rat. Anesthesiology. 2008 Sep;109(3):502-11. PubMed PMID: 18719449. PMCID: PMC2709835.

  81. Coskuner I, Tekin M, Kati I, Yagmur C, Elcicek K. Effects of dexmedetomidine on the duration of anaesthesia and wakefulness in bupivacaine epidural block. Eur J Anaesthesiol. 2007 Jun;24(6):535-40. PubMed PMID: 17241499.

  82. Kanazi 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 Feb;50(2):222-7. PubMed PMID: 16430546.

  83. Raof RA, El Metainy SA, Alia DA, Wahab MA. Dexmedetomidine decreases the required amount of bupivacaine for ultrasound-guided transversus abdominis plane block in pediatrics patients: a randomized study. J Clin Anesth. 2017 Feb;37:55-60. PubMed PMID: 28235529.

  84. Zhang H, Li M, Zhang SY, Fu M, Zhang SY. Intravenous Dexmedetomidine Promotes Spinal Bupivacaine Anesthesia and Postoperative Analgesia in Lower Limb Surgery: A Double-Blind, Randomized Clinical CONSORT Study. Medicine (Baltimore). 2016 Feb;95(8):e2880. PubMed PMID: 26937924. PMCID: PMC4779021.

  85. Sharma A, Kumar NJ, Azharuddin M, Mohan LC, Ramachandran G. Evaluation of low-dose dexmedetomidine and neostigmine with bupivacaine for postoperative analgesia in orthopedic surgeries: A prospective randomized double-blind study. J Anaesthesiol Clin Pharmacol. 2016 Apr-Jun;32(2):187-91. PubMed PMID: 27275047. PMCID: PMC4874072.

  86. Shaikh SI, Mahesh SB. The efficacy and safety of epidural dexmedetomidine and clonidine with bupivacaine in patients undergoing lower limb orthopedic surgeries. J Anaesthesiol Clin Pharmacol. 2016 Apr-Jun;32(2):203-9. PubMed PMID: 27275050. PMCID: PMC4874075.

  87. Meenakshi Karuppiah NP, Shetty SR, Patla KP. Comparison between two doses of dexmedetomidine added to bupivacaine for caudal analgesia in paediatric infraumbilical surgeries. Indian J Anaesth. 2016 Jun;60(6):409-14. PubMed PMID: 27330203. PMCID: PMC4910481.

  88. Helal SM, Eskandr AM, Gaballah KM, Gaarour IS. Effects of perineural administration of dexmedetomidine in combination with bupivacaine in a femoral-sciatic nerve block. Saudi J Anaesth. 2016 Jan-Mar;10(1):18-24. PubMed PMID: 26955305. PMCID: PMC4760035.

  89. Al-Zaben KR, Qudaisat IY, Alja'bari AN, Ababneh OA, Yousef AM, Al-Shudifat AM. The effects of caudal or intravenous dexmedetomidine on postoperative analgesia produced by caudal bupivacaine in children: a randomized controlled double-blinded study. J Clin Anesth. 2016 Sep;33:386-94. PubMed PMID: 27555197.

  90. Sun Y, Xu Y, Wang GN. Comparative Evaluation of Intrathecal Bupivacaine Alone, Bupivacaine-fentanyl, and Bupivacaine-dexmedetomidine in Caesarean Section. Drug Res (Stuttg). 2015 Sep;65(9):468-72. PubMed PMID: 25207707.

  91. Li Z, Tian M, Zhang CY, Li AZ, Huang AJ, Shi CX, et al. A Randomised Controlled Trial to Evaluate the Effectiveness of Intrathecal Bupivacaine Combined with Different Adjuvants (Fentanyl, Clonidine and Dexmedetomidine) in Caesarean Section. Drug Res (Stuttg). 2015 Nov;65(11):581-6. PubMed PMID: 25504002.

  92. Karhade SS, Acharya SA, Harnagale K. Comparative analysis of epidural bupivacaine versus bupivacaine with dexmedetomidine for vaginal hysterectomy. Anesth Essays Res. 2015 Sep-Dec;9(3):310-3. PubMed PMID: 26712965. PMCID: PMC4683497.

  93. Fares KM, Mohamed SA, Abd El-Rahman AM, Mohamed AA, Amin AT. Efficacy and safety of intraperitoneal dexmedetomidine with bupivacaine in laparoscopic colorectal cancer surgery, a randomized trial. Pain Med. 2015 Jun;16(6):1186-94. PubMed PMID: 25585502.

  94. Al-Zaben KR, Qudaisat IY, Abu-Halaweh SA, Al-Ghanem SM, Al-Mustafa MM, Alja'bari AN, et al. Comparison of caudal bupivacaine alone with bupivacaine plus two doses of dexmedetomidine for postoperative analgesia in pediatric patients undergoing infra-umbilical surgery: a randomized controlled double-blinded study. Paediatr Anaesth. 2015 Sep;25(9):883-90. PubMed PMID: 26033312.

  95. Nayagam HA, Singh NR, Singh HS. A prospective randomised double blind study of intrathecal fentanyl and dexmedetomidine added to low dose bupivacaine for spinal anesthesia for lower abdominal surgeries. Indian J Anaesth. 2014 Jul;58(4):430-5. PubMed PMID: 25197111. PMCID: PMC4155288.

  96. Fares KM, Othman AH, Alieldin NH. Efficacy and safety of dexmedetomidine added to caudal bupivacaine in pediatric major abdominal cancer surgery. Pain Physician. 2014 Sep-Oct;17(5):393-400. PubMed PMID: 25247897.

  97. El Shamaa HA, Ibrahim M. A comparative study of the effect of caudal dexmedetomidine versus morphine added to bupivacaine in pediatric infra-umbilical surgery. Saudi J Anaesth. 2014 Apr;8(2):155-60. PubMed PMID: 24843324. PMCID: PMC4024668.

  98. Almarakbi WA, Kaki AM. Addition of dexmedetomidine to bupivacaine in transversus abdominis plane block potentiates post-operative pain relief among abdominal hysterectomy patients: A prospective randomized controlled trial. Saudi J Anaesth. 2014 Apr;8(2):161-6. PubMed PMID: 24843325. PMCID: PMC4024669.

  99. Xiang Q, Huang DY, Zhao YL, Wang GH, Liu YX, Zhong L, et al. Caudal dexmedetomidine combined with bupivacaine inhibit the response to hernial sac traction in children undergoing inguinal hernia repair. Br J Anaesth. 2013 Mar;110(3):420-4. PubMed PMID: 23161357.

  100. Solanki SL, Bharti N, Batra YK, Jain A, Kumar P, Nikhar SA. The analgesic effect of intrathecal dexmedetomidine or clonidine, with bupivacaine, in trauma patients undergoing lower limb surgery: a randomised, double-blind study. Anaesth Intensive Care. 2013 Jan;41(1):51-6. PubMed PMID: 23362890.

  101. Reddy VS, Shaik NA, Donthu B, Reddy Sannala VK, Jangam V. Intravenous dexmedetomidine versus clonidine for prolongation of bupivacaine spinal anesthesia and analgesia: A randomized double-blind study. J Anaesthesiol Clin Pharmacol. 2013 Jul;29(3):342-7. PubMed PMID: 24106359. PMCID: PMC3788233.

  102. Hanoura SE, Hassanin R, Singh R. Intraoperative conditions and quality of postoperative analgesia after adding dexmedetomidine to epidural bupivacaine and fentanyl in elective cesarean section using combined spinal-epidural anesthesia. Anesth Essays Res. 2013 May-Aug;7(2):168-72. PubMed PMID: 25885827. PMCID: PMC4173533.

  103. Singh S, Prasad C. Post-operative analgesic effect of dexmedetomidine administration in wound infiltration for abdominal hysterectomy: A randomised control study. Indian J Anaesth. 2017 Jun;61(6):494-8. PubMed PMID: 28655956. PMCID: PMC5474919.

  104. Jarineshin H, Fekrat F, Kargar Kermanshah A. Treatment of Postoperative Pain in Pediatric Operations: Comparing the Efficiency of Bupivacaine, Bupivacaine-Dexmedetomidine and Bupivacaine-Fentanyl for Caudal Block. Anesth Pain Med. 2016 Oct;6(5):e39495. PubMed PMID: 27847704. PMCID: PMC5101645.

  105. Selim MF, Elnabtity AM, Hasan AM. Comparative evaluation of epidural bupivacaine - dexmedetomidine and bupivacaine -fentanyl on Doppler velocimetry of uterine and umbilical arteries during labor. J Prenat Med. 2012 Jul;6(3):47-54. PubMed PMID: 23181173. PMCID: PMC3503522.

  106. El-Hennawy AM, Abd-Elwahab AM, Abd-Elmaksoud AM, El-Ozairy HS, Boulis SR. Addition of clonidine or dexmedetomidine to bupivacaine prolongs caudal analgesia in children. Br J Anaesth. 2009 Aug;103(2):268-74. PubMed PMID: 19541679.

  107. Al-Mustafa MM, Abu-Halaweh SA, Aloweidi AS, Murshidi MM, Ammari BA, Awwad ZM, et al. Effect of dexmedetomidine added to spinal bupivacaine for urological procedures. Saudi Med J. 2009 Mar;30(3):365-70. PubMed PMID: 19271064.

  108. Tufek A, Kaya S, Tokgoz O, Firat U, Evliyaoglu O, Celik F, et al. The protective effect of dexmedetomidine on bupivacaine-induced sciatic nerve inflammation is mediated by mast cells. Clin Invest Med. 2013 Apr 01;36(2):E95-102. PubMed PMID: 23544611.

  109. Hanci V, Karakaya K, Yurtlu S, Hakimoglu S, Can M, Ayoglu H, et al. Effects of dexmedetomidine pretreatment on bupivacaine cardiotoxicity in rats. Reg Anesth Pain Med. 2009 Nov-Dec;34(6):565-8. PubMed PMID: 19916248.