Levosimendan confers perioperative renoprotection in severe patients undergoing cardiac surgery: A systematic review and meta-analysis_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

ZHOU Chenghui ¹ , GONG Junsong ¹ ,  LIU Bin ²

1. Department of Anesthesiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, P.R.China;
2. Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, 610041, P.R.China;

Corresponding author：

LIU Bin, Email: liubin_hx@126.com

Keywords：

Levosimendan; left ventricular dysfunction; cardiac surgery; acute kidney injury; systematic review and meta-analysis

DOI：

10.7507/1007-4848.201803013

Video：

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Objective To evaluate the effect of levosimendan on acute kidney injury (AKI) in patients with left ventricular dysfunction (preoperative left ventricular ejection fraction≤40.0%) undergoing cardiac surgery.Methods A systematic review and meta-analysis was conducted based on a comprehensive search of the randomized controlled trial (RCT) from PubMed, EMbase and The Cochrane Library (up to Jan 2018). The clinical endpoints included the incidence of AKI and need for renal replacement therapy (RRT), mortality, mechanic ventilation (MV) duration and intensive care unit (ICU) stay. Random-effect model was used for the potential clinical inconsistency. All analyses were performed by RevMan 5.3 and Stata 12.0.Results Thirteen trials with a total of 2 046 patients were selected. Compared with controls, levosimendan significantly reduced the incidence of postoperative AKI (OR=0.44, P=0.000 1, I²=0%), the risk of RRT (OR=0.63, P=0.02, I²=0%) and the mortality (OR=0.49, P<0.000 1, I²=0%). Levosimendan also shortened the postoperative MV duration (WMD=–5.62, P=0.07, I²=93%) and ICU stay (WMD=–1.50, P=0.005, I²=98%).Conclusion The present meta-analysis suggests that perioperative levosimendan for patients with left ventricular ejection fraction≤40.0% undergoing cardiac surgery reduces the incidence of AKI, RRT and death, as well as shortens MV duration and ICU stay.

Citation： ZHOU Chenghui, GONG Junsong, LIU Bin. Levosimendan confers perioperative renoprotection in severe patients undergoing cardiac surgery: A systematic review and meta-analysis. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2019, 26(5): 470-479. doi: 10.7507/1007-4848.201803013 Copy

1.	Ryckwaert F, Boccara G, Frappier JM, et al. Incidence, risk factors, and prognosis of a moderate increase in plasma creatinine early after cardiac surgery. Crit Care Med, 2002, 30(7): 1495-1498.
2.	Stafford-Smith M, Podgoreanu M, Swaminathan M, et al. Association of genetic polymorphisms with risk of renal injury after coronary bypass graft surgery. Am J Kidney Dis, 2005, 45(3): 519-530.
3.	Brown JR, Cochran RP, Dacey LJ, et al. Perioperative increases in serum creatinine are predictive of increased 90-day mortality after coronary artery bypass graft surgery. Circulation, 2006, 114(1 Suppl): I409-I413.
4.	Koyner JL, Bennett MR, Worcester EM, et al. Urinary cystatin C as an early biomarker of acute kidney injury following adult cardiothoracic surgery. Kidney Int, 2008, 74(8): 1059-1069.
5.	Hobson CE, Yavas S, Segal MS, et al. Acute kidney injury is associated with increased long-term mortality after cardiothoracic surgery. Circulation, 2009, 119(18): 2444-2453.
6.	Zimmerman RF, Ezeanuna PU, Kane JC, et al. Ischemic preconditioning at a remote site prevents acute kidney injury in patients following cardiac surgery. Kidney Int, 2011, 80(8): 861-867.
7.	Lassnigg A, Schmidlin D, Mouhieddine M, et al. Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study. J Am Soc Nephrol, 2004, 15(6): 1597-1605.
8.	Lassnigg A, Schmid ER, Hiesmayr M, et al. Impact of minimal increases in serum creatinine on outcome in patients after cardiothoracic surgery: do we have to revise current definitions of acute renal failure? Crit Care Med, 2008, 36(4): 1129-1137.
9.	Pickering JW, James MT, Palmer SC. Acute kidney injury and prognosis after cardiopulmonary bypass: a meta-analysis of cohort studies. Am J Kidney Dis, 2015, 65(2): 283-293.
10.	Ferguson TB Jr, Hammill BG, Peterson ED, et al. A decade of change--risk profiles and outcomes for isolated coronary artery bypass grafting procedures, 1990-1999: a report from the STS National Database Committee and the Duke Clinical Research Institute. Society of Thoracic Surgeons. Ann Thorac Surg, 2002, 73(2): 480-489.
11.	Gaffney AM, Sladen RN. Acute kidney injury in cardiac surgery. Curr Opin Anaesthesiol, 2015, 28(1): 50-59.
12.	Burns KE, Chu MW, Novick RJ, et al. Perioperative N-acetylcysteine to prevent renal dysfunction in high-risk patients undergoing CABG surgery: a randomized controlled trial. JAMA, 2005, 294(3): 342-350.
13.	Bove T, Zangrillo A, Guarracino F, et al. Effect of fenoldopam on use of renal replacement therapy among patients with acute kidney injury after cardiac surgery: a randomized clinical trial. JAMA, 2014, 312(21): 2244-2253.
14.	Haase M, Haase-Fielitz A, Plass M, et al. Prophylactic perioperative sodium bicarbonate to prevent acute kidney injury following open heart surgery: a multicenter double-blinded randomized controlled trial. PLoS Med, 2013, 10(4): e1001426.
15.	Follath F, Cleland JG, Just H, et al. Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised double-blind trial. Lancet, 2002, 360(9328): 196-202.
16.	Moiseyev VS, Põder P, Andrejevs N, et al. Safety and efficacy of a novel calcium sensitizer, levosimendan, in patients with left ventricular failure due to an acute myocardial infarction. A randomized, placebo-controlled, double-blind study (RUSSLAN). Eur Heart J, 2002, 23(18): 1422-1432.
17.	Zager RA, Johnson AC, Lund S, et al. Levosimendan protects against experimental endotoxemic acute renal failure. Am J Physiol Renal Physiol, 2006, 290(6): F1453-F1462.
18.	Yakut N, Yasa H, Bahriye Lafci B, et al. The influence of levosimendan and iloprost on renal ischemia-reperfusion: an experimental study. Interact Cardiovasc Thorac Surg, 2008, 7(2): 235-239.
19.	Grossini E, Molinari C, Pollesello P, et al. Levosimendan protection against kidney ischemia/reperfusion injuries in anesthetized pigs. J Pharmacol Exp Ther, 2012, 342(2): 376-388.
20.	Al-Shawaf E, Ayed A, Vislocky I, et al. Levosimendan or milrinone in the type 2 diabetic patient with low ejection fraction undergoing elective coronary artery surgery. J Cardiothorac Vasc Anesth, 2006, 20(3): 353-357.
21.	De Hert SG, Lorsomradee S, Cromheecke S, et al. The effects of levosimendan in cardiac surgery patients with poor left ventricular function. Anesth Analg, 2007, 104(4): 766-773.
22.	Tritapepe L, De Santis V, Vitale D, et al. Levosimendan pre-treatment improves outcomes in patients undergoing coronary artery bypass graft surgery. Br J Anaesth, 2009, 102(2): 198-204.
23.	Mehta RH, Leimberger JD, van Diepen S, et al. Levosimendan in patients with left ventricular dysfunction undergoing cardiac surgery. N Engl J Med, 2017, 376(21): 2032-2042.
24.	Cholley B, Caruba T, Grosjean S, et al. Effect of levosimendan on low cardiac output syndrome in patients with low ejection fraction undergoing coronary artery bypass grafting with cardiopulmonary bypass: The LICORN randomized clinical trial. JAMA, 2017, 318(6): 548-556.
25.	Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med, 2009, 6(7): e1000097.
26.	Jadad AR, Moore RA RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials, 1996, 17(1): 1-12.
27.	Levin RL, Degrange MA, Porcile R, et al. The calcium sensitizer levosimendan gives superior results to dobutamine in postoperative low cardiac output syndrome. Rev Esp Cardiol, 2008, 61(5): 471-479.
28.	Lomivorotov VV, Cherniavskiy AM, Boboshko VA, et al. Levosimendan vs. intra-aortic balloon pump in high-risk cardiac surgery. Asian Cardiovasc Thorac Ann, 2011, 19(2): 154-159.
29.	Levin R, Degrange M, Del Mazo C, et al. Preoperative levosimendan decreases mortality and the development of low cardiac output in high-risk patients with severe left ventricular dysfunction undergoing coronary artery bypass grafting with cardiopulmonary bypass. Exp Clin Cardiol, 2012, 17(3): 125-130.
30.	Lomivorotov VV, Boboshko VA, Efremov SM, et al. Levosimendan versus an intra-aortic balloon pump in high-risk cardiac patients. J Cardiothorac Vasc Anesth, 2012, 26(4): 596-603.
31.	Ristikankare A, Pöyhiä R, Eriksson H, et al. Effects of levosimendan on renal function in patients undergoing coronary artery surgery. J Cardiothorac Vasc Anesth, 2012, 26(4): 591-595.
32.	Sharma P, Malhotra A, Gandhi S, et al. Preoperative levosimendan in ischemic mitral valve repair. Asian Cardiovasc Thorac Ann, 2014, 22(5): 539-545.
33.	Erb J, Beutlhauser T, Feldheiser A, et al. Influence of levosimendan on organ dysfunction in patients with severely reduced left ventricular function undergoing cardiac surgery. J Int Med Res, 2014, 42(3): 750-764.
34.	Shah B, Sharma P, Brahmbhatt A, et al. Study of levosimendan during off-pump coronary artery bypass grafting in patients with LV dysfunction: a double-blind randomized study. Indian J Pharmacol, 2014, 46(1): 29-34.
35.	Anastasiadis K, Antonitsis P, Vranis K, et al. Effectiveness of prophylactic levosimendan in patients with impaired left ventricular function undergoing coronary artery bypass grafting: a randomized pilot study. Interact Cardiovasc Thorac Surg, 2016, 23(5): 740-747.
36.	Baysal A, Yanartas M, Dogukan M, et al. Levosimendan improves renal outcome in cardiac surgery: a randomized trial. J Cardiothorac Vasc Anesth, 2014, 28(3): 586-594.
37.	Metnitz PG, Krenn CG, Steltzer H, et al. Effect of acute renal failure requiring renal replacement therapy on outcome in critically ill patients. Crit Care Med, 2002, 30(9): 2051-2058.
38.	Che M, Li Y, Liang X, et al. Prevalence of acute kidney injury following cardiac surgery and related risk factors in Chinese patients. Nephron Clin Pract, 2011, 117(4): c305-c311.
39.	Schetz M, Bove T, Morelli A, et al. Prevention of cardiac surgery-associated acute kidney injury. Int J Artif Organs, 2008, 31(2): 179-189.
40.	Lahtinen P, Pitkänen O, Pölönen P, et al. Levosimendan reduces heart failure after cardiac surgery: a prospective, randomized, placebo-controlled trial. Crit Care Med, 2011, 39(10): 2263-2270.
41.	Dickstein K, Cohen-Solal A, Filippatos G, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J, 2008, 29(19): 2388-2442.
42.	Landoni G, Biondi-Zoccai G, Greco M, et al. Effects of levosimendan on mortality and hospitalization. A meta-analysis of randomized controlled studies. Crit Care Med, 2012, 40(2): 634-646.
43.	Toller W, Algotsson L, Guarracino F, et al. Perioperative use of levosimendan: best practice in operative settings. J Cardiothorac Vasc Anesth, 2013, 27(2): 361-366.
44.	Papp Z, Édes I, Fruhwald S, et al. Levosimendan: molecular mechanisms and clinical implications: consensus of experts on the mechanisms of action of levosimendan. Int J Cardiol, 2012, 159(2): 82-87.
45.	Faivre V, Kaskos H, Callebert J, et al. Cardiac and renal effects of levosimendan, arginine vasopressin, and norepinephrine in lipopolysaccharide-treated rabbits. Anesthesiology, 2005, 103(3): 514-521.
46.	Gecit I, Kavak S, Yüksel MB, et al. Effect of short-term treatment with levosimendan on oxidative stress in renal tissues of rats. Toxicol Ind Health, 2014, 30(1): 47-51.
47.	Abelha FJ, Botelho M, Fernandes V, et al. Determinants of postoperative acute kidney injury. Crit Care, 2009, 13(3): R79.
48.	Hu Y, Li Z, Chen J, et al. Risk factors for acute kidney injury in patients undergoing same admission coronary angiography and valve replacement. J Card Surg, 2013, 28(6): 627-631.
49.	Kim WH, Park MH, Kim HJ, et al. Potentially modifiable risk factors for acute kidney injury after surgery on the thoracic aorta: a propensity score matched case-control study. Medicine (Baltimore), 2015, 94(2): e273.
50.	Cai J, Xu R, Yu X, et al. Volatile anesthetics in preventing acute kidney injury after cardiac surgery: a systematic review and meta-analysis. J Thorac Cardiovasc Surg, 2014, 148(6): 3127-3136.
51.	Singh I, Rajagopalan S, Srinivasan A, et al. Preoperative statin therapy is associated with lower requirement of renal replacement therapy in patients undergoing cardiac surgery: a meta-analysis of observational studies. Interact Cardiovasc Thorac Surg, 2013, 17(2): 345-352.

1. Ryckwaert F, Boccara G, Frappier JM, et al. Incidence, risk factors, and prognosis of a moderate increase in plasma creatinine early after cardiac surgery. Crit Care Med, 2002, 30(7): 1495-1498.
2. Stafford-Smith M, Podgoreanu M, Swaminathan M, et al. Association of genetic polymorphisms with risk of renal injury after coronary bypass graft surgery. Am J Kidney Dis, 2005, 45(3): 519-530.
3. Brown JR, Cochran RP, Dacey LJ, et al. Perioperative increases in serum creatinine are predictive of increased 90-day mortality after coronary artery bypass graft surgery. Circulation, 2006, 114(1 Suppl): I409-I413.
4. Koyner JL, Bennett MR, Worcester EM, et al. Urinary cystatin C as an early biomarker of acute kidney injury following adult cardiothoracic surgery. Kidney Int, 2008, 74(8): 1059-1069.
5. Hobson CE, Yavas S, Segal MS, et al. Acute kidney injury is associated with increased long-term mortality after cardiothoracic surgery. Circulation, 2009, 119(18): 2444-2453.
6. Zimmerman RF, Ezeanuna PU, Kane JC, et al. Ischemic preconditioning at a remote site prevents acute kidney injury in patients following cardiac surgery. Kidney Int, 2011, 80(8): 861-867.
7. Lassnigg A, Schmidlin D, Mouhieddine M, et al. Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study. J Am Soc Nephrol, 2004, 15(6): 1597-1605.
8. Lassnigg A, Schmid ER, Hiesmayr M, et al. Impact of minimal increases in serum creatinine on outcome in patients after cardiothoracic surgery: do we have to revise current definitions of acute renal failure? Crit Care Med, 2008, 36(4): 1129-1137.
9. Pickering JW, James MT, Palmer SC. Acute kidney injury and prognosis after cardiopulmonary bypass: a meta-analysis of cohort studies. Am J Kidney Dis, 2015, 65(2): 283-293.
10. Ferguson TB Jr, Hammill BG, Peterson ED, et al. A decade of change--risk profiles and outcomes for isolated coronary artery bypass grafting procedures, 1990-1999: a report from the STS National Database Committee and the Duke Clinical Research Institute. Society of Thoracic Surgeons. Ann Thorac Surg, 2002, 73(2): 480-489.
11. Gaffney AM, Sladen RN. Acute kidney injury in cardiac surgery. Curr Opin Anaesthesiol, 2015, 28(1): 50-59.
12. Burns KE, Chu MW, Novick RJ, et al. Perioperative N-acetylcysteine to prevent renal dysfunction in high-risk patients undergoing CABG surgery: a randomized controlled trial. JAMA, 2005, 294(3): 342-350.
13. Bove T, Zangrillo A, Guarracino F, et al. Effect of fenoldopam on use of renal replacement therapy among patients with acute kidney injury after cardiac surgery: a randomized clinical trial. JAMA, 2014, 312(21): 2244-2253.
14. Haase M, Haase-Fielitz A, Plass M, et al. Prophylactic perioperative sodium bicarbonate to prevent acute kidney injury following open heart surgery: a multicenter double-blinded randomized controlled trial. PLoS Med, 2013, 10(4): e1001426.
15. Follath F, Cleland JG, Just H, et al. Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised double-blind trial. Lancet, 2002, 360(9328): 196-202.
16. Moiseyev VS, Põder P, Andrejevs N, et al. Safety and efficacy of a novel calcium sensitizer, levosimendan, in patients with left ventricular failure due to an acute myocardial infarction. A randomized, placebo-controlled, double-blind study (RUSSLAN). Eur Heart J, 2002, 23(18): 1422-1432.
17. Zager RA, Johnson AC, Lund S, et al. Levosimendan protects against experimental endotoxemic acute renal failure. Am J Physiol Renal Physiol, 2006, 290(6): F1453-F1462.
18. Yakut N, Yasa H, Bahriye Lafci B, et al. The influence of levosimendan and iloprost on renal ischemia-reperfusion: an experimental study. Interact Cardiovasc Thorac Surg, 2008, 7(2): 235-239.
19. Grossini E, Molinari C, Pollesello P, et al. Levosimendan protection against kidney ischemia/reperfusion injuries in anesthetized pigs. J Pharmacol Exp Ther, 2012, 342(2): 376-388.
20. Al-Shawaf E, Ayed A, Vislocky I, et al. Levosimendan or milrinone in the type 2 diabetic patient with low ejection fraction undergoing elective coronary artery surgery. J Cardiothorac Vasc Anesth, 2006, 20(3): 353-357.
21. De Hert SG, Lorsomradee S, Cromheecke S, et al. The effects of levosimendan in cardiac surgery patients with poor left ventricular function. Anesth Analg, 2007, 104(4): 766-773.
22. Tritapepe L, De Santis V, Vitale D, et al. Levosimendan pre-treatment improves outcomes in patients undergoing coronary artery bypass graft surgery. Br J Anaesth, 2009, 102(2): 198-204.
23. Mehta RH, Leimberger JD, van Diepen S, et al. Levosimendan in patients with left ventricular dysfunction undergoing cardiac surgery. N Engl J Med, 2017, 376(21): 2032-2042.
24. Cholley B, Caruba T, Grosjean S, et al. Effect of levosimendan on low cardiac output syndrome in patients with low ejection fraction undergoing coronary artery bypass grafting with cardiopulmonary bypass: The LICORN randomized clinical trial. JAMA, 2017, 318(6): 548-556.
25. Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med, 2009, 6(7): e1000097.
26. Jadad AR, Moore RA RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials, 1996, 17(1): 1-12.
27. Levin RL, Degrange MA, Porcile R, et al. The calcium sensitizer levosimendan gives superior results to dobutamine in postoperative low cardiac output syndrome. Rev Esp Cardiol, 2008, 61(5): 471-479.
28. Lomivorotov VV, Cherniavskiy AM, Boboshko VA, et al. Levosimendan vs. intra-aortic balloon pump in high-risk cardiac surgery. Asian Cardiovasc Thorac Ann, 2011, 19(2): 154-159.
29. Levin R, Degrange M, Del Mazo C, et al. Preoperative levosimendan decreases mortality and the development of low cardiac output in high-risk patients with severe left ventricular dysfunction undergoing coronary artery bypass grafting with cardiopulmonary bypass. Exp Clin Cardiol, 2012, 17(3): 125-130.
30. Lomivorotov VV, Boboshko VA, Efremov SM, et al. Levosimendan versus an intra-aortic balloon pump in high-risk cardiac patients. J Cardiothorac Vasc Anesth, 2012, 26(4): 596-603.
31. Ristikankare A, Pöyhiä R, Eriksson H, et al. Effects of levosimendan on renal function in patients undergoing coronary artery surgery. J Cardiothorac Vasc Anesth, 2012, 26(4): 591-595.
32. Sharma P, Malhotra A, Gandhi S, et al. Preoperative levosimendan in ischemic mitral valve repair. Asian Cardiovasc Thorac Ann, 2014, 22(5): 539-545.
33. Erb J, Beutlhauser T, Feldheiser A, et al. Influence of levosimendan on organ dysfunction in patients with severely reduced left ventricular function undergoing cardiac surgery. J Int Med Res, 2014, 42(3): 750-764.
34. Shah B, Sharma P, Brahmbhatt A, et al. Study of levosimendan during off-pump coronary artery bypass grafting in patients with LV dysfunction: a double-blind randomized study. Indian J Pharmacol, 2014, 46(1): 29-34.
35. Anastasiadis K, Antonitsis P, Vranis K, et al. Effectiveness of prophylactic levosimendan in patients with impaired left ventricular function undergoing coronary artery bypass grafting: a randomized pilot study. Interact Cardiovasc Thorac Surg, 2016, 23(5): 740-747.
36. Baysal A, Yanartas M, Dogukan M, et al. Levosimendan improves renal outcome in cardiac surgery: a randomized trial. J Cardiothorac Vasc Anesth, 2014, 28(3): 586-594.
37. Metnitz PG, Krenn CG, Steltzer H, et al. Effect of acute renal failure requiring renal replacement therapy on outcome in critically ill patients. Crit Care Med, 2002, 30(9): 2051-2058.
38. Che M, Li Y, Liang X, et al. Prevalence of acute kidney injury following cardiac surgery and related risk factors in Chinese patients. Nephron Clin Pract, 2011, 117(4): c305-c311.
39. Schetz M, Bove T, Morelli A, et al. Prevention of cardiac surgery-associated acute kidney injury. Int J Artif Organs, 2008, 31(2): 179-189.
40. Lahtinen P, Pitkänen O, Pölönen P, et al. Levosimendan reduces heart failure after cardiac surgery: a prospective, randomized, placebo-controlled trial. Crit Care Med, 2011, 39(10): 2263-2270.
41. Dickstein K, Cohen-Solal A, Filippatos G, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J, 2008, 29(19): 2388-2442.
42. Landoni G, Biondi-Zoccai G, Greco M, et al. Effects of levosimendan on mortality and hospitalization. A meta-analysis of randomized controlled studies. Crit Care Med, 2012, 40(2): 634-646.
43. Toller W, Algotsson L, Guarracino F, et al. Perioperative use of levosimendan: best practice in operative settings. J Cardiothorac Vasc Anesth, 2013, 27(2): 361-366.
44. Papp Z, Édes I, Fruhwald S, et al. Levosimendan: molecular mechanisms and clinical implications: consensus of experts on the mechanisms of action of levosimendan. Int J Cardiol, 2012, 159(2): 82-87.
45. Faivre V, Kaskos H, Callebert J, et al. Cardiac and renal effects of levosimendan, arginine vasopressin, and norepinephrine in lipopolysaccharide-treated rabbits. Anesthesiology, 2005, 103(3): 514-521.
46. Gecit I, Kavak S, Yüksel MB, et al. Effect of short-term treatment with levosimendan on oxidative stress in renal tissues of rats. Toxicol Ind Health, 2014, 30(1): 47-51.
47. Abelha FJ, Botelho M, Fernandes V, et al. Determinants of postoperative acute kidney injury. Crit Care, 2009, 13(3): R79.
48. Hu Y, Li Z, Chen J, et al. Risk factors for acute kidney injury in patients undergoing same admission coronary angiography and valve replacement. J Card Surg, 2013, 28(6): 627-631.
49. Kim WH, Park MH, Kim HJ, et al. Potentially modifiable risk factors for acute kidney injury after surgery on the thoracic aorta: a propensity score matched case-control study. Medicine (Baltimore), 2015, 94(2): e273.
50. Cai J, Xu R, Yu X, et al. Volatile anesthetics in preventing acute kidney injury after cardiac surgery: a systematic review and meta-analysis. J Thorac Cardiovasc Surg, 2014, 148(6): 3127-3136.
51. Singh I, Rajagopalan S, Srinivasan A, et al. Preoperative statin therapy is associated with lower requirement of renal replacement therapy in patients undergoing cardiac surgery: a meta-analysis of observational studies. Interact Cardiovasc Thorac Surg, 2013, 17(2): 345-352.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Levosimendan confers perioperative renoprotection in severe patients undergoing cardiac surgery: A systematic review and meta-analysis

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