Effects of Dexmedetomidine on Endogenous Antioxidant Levels and Clinical Outcomes Among Patients Undergoing Coronary Artery Bypass Grafting: A Randomized Clinical Trial

Document Type : Original Article

Authors

1 Department of Cardiac Surgery, Imam Hossein Educational Hospital, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.

2 Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, IR Iran.

3 Pharmacology and Toxicology Department, Faculty of Pharmacy and Pharmaceutical Sciences, Tehran Medical Sciences, Islamic Azad University, IR Iran.

4 Mazandaran University of Medical Sciences, Tehran, IR Iran.

5 AJA University of Medical Sciences Tehran IR Iran.

Abstract

Background: Dexmedetomidine reduces perioperative catecholamine concentrations and confers hemodynamic and sympathetic stability. It adjusts coronary blood flow and is known as one of the ideal anesthetic drugs, especially for patients undergoing coronary artery bypass graft surgery (CABG). The present study was performed to evaluate the potential of dexmedetomidine to protect against oxidative stress during CABG.
 
Methods: The present double-blinded randomized clinical trial was performed on 58 patients undergoing CABG at Rajaie Cardiovascular Medical and Research Center. After anesthesia induction, the patients were allocated to the trial (dexmedetomidine) and control (normal saline solution) groups. Total antioxidant capacity and malondialdehyde were measured in samples obtained from arterial catheters before the intervention, after pump weaning, and 24 hours after intensive care unit (ICU) admission.
 
Results: Only total antioxidant capacity and malondialdehyde at the third measurement point at the ICU were lower in the trial group than in the control group. The levels of circulatory antioxidants were higher in the trial group than in the control group before the intervention and after pump weaning. No significant differences were observed regarding circulatory antioxidant levels between the trial and control groups.
 
Conclusions: Dexmedetomidine infusion before and during CABG might improve endocardial blood flow and hemodynamic stability among patients undergoing CABG. (Iranian Heart Journal 2023; 24(3): 24-31)

Keywords


  1. Sadeghpour Tabaei A, Mortazian M, Yaghoubi A, Gorjipour F, Arasteh Manesh S, Totonchi Z, et al. Modified Ultrafiltration in Coronary Artery Bypass Grafting: A Randomized, Double-Blinded, Controlled Clinical Trial. Iran Red Crescent Med J. 2018; 20(5):e6
  2. Gorjipour F, Dehaki MG, Totonchi Z, Hajimiresmaiel SJ, Azarfarin R, Pazoki-Toroudi H, et al. Inflammatory cytokine response and cardiac troponin I changes in cardiopulmonary bypass using two cardioplegia solutions; del Nido and modified St. Thomas': a randomized controlled trial. Perfusion. 2017; 32(5):394-402.
  3. Gorjipour F, Totonchi Z, Gholampour Dehaki M, Hosseini S, Tirgarfakheri K, Mehrabanian M, et al. Serum levels of interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-α, renal function biochemical parameters and clinical outcomes in pediatric cardiopulmonary bypass surgery. Perfusion. 2019; 34(8):651-9.
  4. Gorjipour F, Saeedzadeh T, Toloueitabar Y, Kachoueian N, Bahlouli Ghashghaei S, Mortazian M, et al. Remote ischemic preconditioning effects on inflammatory markers and myocardial protection in coronary artery bypass graft surgery. Perfusion. 2020:0267659120979293.
  5. Adamik B, Kübler A, Gozdzik A, Gozdzik W. Prolonged cardiopulmonary bypass is a risk factor for intestinal ischaemic damage and endotoxaemia. Heart, Lung and Circulation. 2017; 26(7):717-23.
  6. Doğan A, Türker FS. The Effect of On-Pump and Off-Pump Bypass Surgery on Arginase Activity and Nitric Oxide Level.
  7. Ebert TJ, Hall JE, Barney JA, Uhrich TD, Colinco MD. The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology. 2000; 93(2):382-94.
  8. Gellai M, Ruffolo RR, Jr. Renal effects of selective alpha-1 and alpha-2 adrenoceptor agonists in conscious, normotensive rats. J Pharmacol Exp Ther. 1987; 240(3):723-8.
  9. Biccard BM, Goga S, de Beurs J. Dexmedetomidine and cardiac protection for non-cardiac surgery: a meta-analysis of randomised controlled trials. Anaesthesia. 2008; 63(1):4-14.
  10. Devereaux PJ, Investigators P-. Rationale and design of the PeriOperative ISchemic Evaluation-2 (POISE-2) trial: an international 2 x 2 factorial randomized controlled trial of acetyl-salicylic acid vs placebo and clonidine vs placebo in patients undergoing noncardiac surgery. Am Heart J. 2014;167(6):804-9 e4.
  11. Frumento RJ, Logginidou HG, Wahlander S, Wagener G, Playford HR, Sladen RN. RETRACTED: Dexmedetomidine infusion is associated with enhanced renal function after thoracic surgery. Elsevier; 2006.
  12. Mehrabanian MJ, Dehghani Firoozabadi M, Ahmadi Tafti SH, Forouzan Nia SK, Najafi A, Mortazian M, et al. Clinical Outcomes and Electrolyte Balance Factors in Complex Cardiac Operations in Adults; Del Nido® Versus Custodiol® Cardioplegia Solutions: A Randomized Controlled Clinical Trial. Iran Red Crescent Med J. 2018; 20(4):e64648.
  13. Mehrabanian MJ, Firoozabadi MD, Tafti SHA, Nia SKF, Najafi A, Mortazian M, et al. Clinical outcomes and electrolyte balance factors in complex cardiac operations in adults; del nido versus custodiol cardioplegia solutions: a randomized controlled clinical trial. Iranian Red Crescent Medical Journal. 2018; 20(4).
  14. Bloor BC, Ward DS, Belleville JP, Maze M. Effects of intravenous dexmedetomidine in humans. II. Hemodynamic changes. Anesthesiology. 1992; 77(61134-42.)
  15. Chiu TH, Chen MJ, Yang YR, Yang JJ, Tang FI. Action of dexmedetomidine on rat locus coeruleus neurones: intracellular recording in vitro. Eur J Pharmacol. 1995; 285(3):261-8.
  16. Farsad BF, Janipour M, Totonchi Z, Gorjipour F, Oroji Omid S. Effects of dexmedetomidine on surgical stress responses at patients under CABG. Biosciences Biotechnology Research Asia. 2016; 13(3):1537-45.
  17. Ammar AS, Mahmoud KM, Kasemy ZA, Helwa MA. Cardiac and renal protective effects of dexmedetomidine in cardiac surgeries: A randomized controlled trial. Saudi J Anaesth. 2016; 10(4):395-401.
  18. Hall JE, Uhrich TD, Barney JA, Arain SR, Ebert TJ. Sedative, amnestic, and analgesic properties of small-dose dexmedetomidine infusions. Anesth Analg. 2000; 90(3):699-705.
  19. Gao JM, Meng XW, Zhang J, Chen WR, Xia F, Peng K, et al. Dexmedetomidine Protects Cardiomyocytes against Hypoxia/Reoxygenation Injury by Suppressing TLR4-MyD88-NF-kappaB Signaling. Biomed Res Int. 2017; 2017:1674613.
  20. Ibacache M, Sanchez G, Pedrozo Z, Galvez F, Humeres C, Echevarria G, et al. Dexmedetomidine preconditioning activates pro-survival kinases and attenuates regional ischemia/reperfusion injury in rat heart. Biochim Biophys Acta. 2012; 1822(4):537-45.
  21. Cui J, Zhao H, Yi B, Zeng J, Lu K, Ma D. Dexmedetomidine Attenuates Bilirubin-Induced Lung Alveolar Epithelial Cell Death In Vitro and In Vivo. Crit Care Med. 2015; 43(9):e356-68.
  22. Shen J, Fu G, Jiang L, Xu J, Li L, Fu G. Effect of dexmedetomidine pretreatment on lung injury following intestinal ischemia-reperfusion. Exp Ther Med. 2013; 6(6):1359-64.
  23. Si Y, Bao H, Han L, Shi H, Zhang Y, Xu L, et al. Dexmedetomidine protects against renal ischemia and reperfusion injury by inhibiting the JAK/STAT signaling activation. J Transl Med. 2013;11:141.
  24. Zhang XY, Liu ZM, Wen SH, Li YS, Li Y, Yao X, et al. Dexmedetomidine administration before, but not after, ischemia attenuates intestinal injury induced by intestinal ischemia-reperfusion in rats. Anesthesiology. 2012; 116(5):1035-46.
  25. Okada H, Kurita T, Mochizuki T, Morita K, Sato S. The cardioprotective effect of dexmedetomidine on global ischaemia in isolated rat hearts. Resuscitation. 2007; 74(3):538-45.
  26. Devasagayam TP, Tilak JC, Boloor KK, Sane KS, Ghaskadbi SS, Lele RD. Free radicals and antioxidants in human health: current status and future prospects. J Assoc Physicians India. 2004; 52:794-804.
  27. Desborough JP. The stress response to trauma and surgery. Br J Anaesth. 2000; 85(1):109-17.
  28. Tsukada K, Katoh H, Shiojima M, Suzuki T, Takenoshita S, Nagamachi Y. Concentrations of cytokines in peritoneal fluid after abdominal surgery. Eur J Surg. 1993; 159(9):475-9.
  29. Vertanen R, Savola J, Sano V, Nyman L. Characterization of selectivity, specificity and potency of medetomidine as alpha-2 adrenoreceptor agonists. Eur J Pharmacol. 1988; 150:9-14.
  30. Venn R, Bradshaw C, Spencer R, Brealey D, Caudwell E, Naughton C, et al. Preliminary UK experience of dexmedetomidine, a novel agent for postoperative sedation in the intensive care unit. 1999; 54(12):1136-42.
  31. Virtanen R, Savola J-M, Saano V, Nyman L. Characterization of the selectivity, specificity and potency of medetomidine as an α2-adrenoceptor agonist. European journal of pharmacology. 1988; 150(1-2):9-14.
  32. McDonald T, Hoffman WE, Berkowitz R, Cunningham F, Cooke B. Heart rate variability and plasma catecholamines in patients during opioid detoxification. Journal of neurosurgical anesthesiology. 1999; 11(3):195-9.
  33. Kallio A, Scheinin M, Koulu M, Ponkilainen R, Ruskoaho H, Viinamäki O, et al. Effects of dexmedetomidine, a selective α2‐adrenoceptor agonist, on hemodynamic control mechanisms. Clinical Pharmacology & Therapeutics. 1989; 46(1):33-42.
  34. Scheinin M, Kallio A, Koulu M, Viikari J, Scheinin H. Sedative and cardiovascular effects of medetomidine, a novel selective alpha 2‐adrenoceptor agonist, in healthy volunteers. British journal of clinical pharmacology. 1987; 24(4):443-51.