Levosimendan Use Increases Cardiac Performance after Coronary Artery Bypass Grafting in End-Stage Renal Disease Patients
DOI:
https://doi.org/10.1532/hsf.1426Abstract
Background: The effect of levosimendan on myocardial performance has not been studied in dialysis-dependent end-stage renal disease patients who have undergone coronary artery bypass grafting (CABG) surgery. Our aim was to investigate the effect of levosimendan on postoperative hemodynamic effects in end-stage renal disease patients undergoing CABG operation.Methods: We performed 58 elective isolated CABG operations in end-stage renal disease patients. The study group received levosimendan at a slow bolus dose of 3 µg/kg, followed by a 24-hour infusion of 0.03-0.05 µg/kg/kg/min. (study group [SG]: n = 25). The remaining patients received a placebo (control group [CG]: n = 33). The mean left ventricular ejection fraction of both groups was similar (44.6 ± 55.4% versus 42.8 ± 53.9%). Hemodynamic data were collected at the end, at 1 hour after CPB, and thereafter at 6, 12, and 24 hours in the ICU. Preoperatively, at the end of the operation, at 1 hour after CPB, and thereafter at 6, 12, and 24 hours in the ICU, blood samples from the peripheral vein were collected for cardiac troponin-I (c-TnI) and lactate levels. Norepinephrine if needed started during the rewarming period in both groups.
Results: One patient in SG (4%) and 4 patients (12.1%) in CG died postoperatively (P < .01). Cardiac output and cardiac index values did not change early after weaning from extracorporeal circulation, and they were nearly similar during the next 6 hours in both groups. In SG, cardiac output and cardiac index significantly improved at 6 hours, and were stable at the end of 24 hours (P < .001). Hemodynamic parameters were nearly similar after the operation, and did not change significantly at the end of 24 hours in CG. Hemodynamic improvement caused a significant reduction in systemic and pulmonary artery vascular resistance index in SG (P < .002). Pulmonary capillary wedge pressure decreased significantly in SG (P < .034). Cumulative inotrope dose requirement and intraaortic balloon pump use were significantly lower in SG. In addition, blood lactate and cTnI levels were significanly lower in SG (P < .044).
Conclusion: No important adverse effect was detected during levosimendan infusion. Because levosimendan at a dose of 0.03-0.05 μg/kg/min increased myocardial performance significantly in the postoperative period, it can be used safely in end-stage renal disease patients undergoing isolated CABG. The requirement of vasopressors were lower in SG.
References
Abacilar AF, Dogan OF. 2013. Levosimendan use decreases atrial fibrillation in patients after coronary artery bypass grafting: a pilot study. Heart Surg Forum 16:287-94.
Ahmed I, House CM, Nelson WB. 2009. Predictors of inotrope use in patients undergoing concomitant coronary artery bypass graft (CABG) and aortic valve replacement (AVR) surgeries at separation from cardiopulmonary bypass (CPB). J Cardiothorac Surg 12:24-5.
Cummins P, Young A, Auckland ML, Michie AC, Stone PC. 1987. Comparison of serum cardiac specific troponin I, creatine kinase, creative kinase-MB isoenzyme, tropomyosin, myoglobin and C-reactive protein release in marathon runners: Cardiac or skeletal muscle trauma? Eur J Clin Invest 17:317-24.
Deutsch O, Spiliopoulos K, Kiask T, et al. 2013. Cardiac surgery in dialysis-dependent patients: impact of gender on early outcome in single-center experience with 204 consecutive cases. Thorac Cardiovasc Surg 61:22-8.
Dimmitt DC, Shah AK, Arumugham T, et al. 1998. Pharmacokinetics of oral and intravenous dolasetron mesylate in patients with renal impairment. J Clin Pharmacol 38:798-806.
Eris C, Yavuz S, Toktas F, et al. 2014. Preoperative usages of levosimendan in patients undergoing coronary artery bypass grafting. Int J Clin Exp Med 7:219-29.
Etienvent JP, Chocron S, Toubin G, et al. 1995. Use of cardiac troponin-I as a marker of perioperative myocardial ischemia. Ann Thorac Surg 59:1192-4.
Follath F, Cleland JG, Just H, et al. 2002. Steering Committee and Investigators of the Levosimendan Infusion versus Dobutamine (LIDO) Study. Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised double-blind trial. Lancet 20:196-202.
Johnson MA, Verpooten GA, Daniel MJ, et al. 1998. Single dose of pharmacokinetics of lamivudine in subjects with impaired renal function and the effect of haemodialysis. Br J Clin Pharmacol 46:21-7.
Karara AH, Frye RF, Hayes PE, et al. 1996. Pharmacokinetics of abecarnil in patients with renal insufficiency. Clin Pharmacol Ther 59:520-8.
Kivikko M, Lehtonen L. 2005. Levosimendan: a new inodilatory drug for the treatment of decompensated heart failure. Curr Pharm Des 11:435-55.
Lam YW, Banerji S, Hatfield C, et al. 1997. Principles of drug administration in renal insufficiency. Clin Pharmacokinet 32:30-57.
Lehtonen L. 2004. Levosimendan: a calcium-sensitizing agent for the treatment of patients with decompensated heart failure. Curr Heart Fail Rep 1:136-44.
Lim JY, Deo SV, Jung SH, et al. 2015. Does off-pump coronary artery bypass confer any advantage in patients with end-stage renal failure? A systematic review and meta-analysis. Heart Lung Circ 24:55-61.
Lobo Martínez P, Oulego Erroz I, Gautreux Minaya S, Rodríguez Fernández LM. 2011. Treatment of acute heart failure using levosimendan for a patient with dilated cardiomyopathy, chronic renal failure, and hypertension. Pediatr Cardiol 32:1012-6.
Martin DE, Chapelevosimendanky MC, Ilevosimendanon B, et al. 1998. Pharmacokinetics and protein binding of eprosartan in healthy volunteers and in patients with varying degrees of renal impairment. J Clin Pharmacol 38:129-37.
Pagel PS, Harkin CP, Hettrick DA, et al. 1994. Levosimendan (OR-1259), a myofilament calcium sensitizer, enhances myocardial contractility but does not alter isovolumic relaxation in con scious and anesthetized dogs. Anesthesiology 81:974-7.
Papadopoulos G, Baikoussis NG, Tzimas P, Siminelakis SN, Karanikolas M. 2010. Intravenous levosimendan-norepinephrine combination during off-pump coronary artery bypass grafting in a hemodialysis patient with severe myocardial dysfunction. J Cardiothorac Surg 2:5-9.
Puttonen J, Kantele S, Kivikko M, et al. 2007. Effect of severe renal failure and haemodialysis on the pharmacokinetics of levosimendan and its metabolites. Clin Pharmacokinet 46:235-46.
Rajek AM, Koinig H, Jelen M, Schiferer A, Hutschala D. 2003. Levosimendan, a new Ca-sensitizer, in patients with poor left ventricular function undergoing cardiac surgery. Anesthesiol 99:A133.
Sahin V, Uyar IS, Gul I, et al. 2014. Evaluation of myocardial contractility determination with tissue tracking echocardiography after levosimendan infusion in patients with poor left ventricular function and hemodynamics. Heart Surg Forum 17:313-8.
Smith SC, Ladenson JH, Mason JW, Jaffe AS. 1997. Elevations of cardiac troponin I associated with myocarditis. Exp Clin Correl Circ 95:163-8.
Vohra HA, Armstrong LA, Modi A, Barlow CW. 2014. Outcomes following cardiac surgery in patients with preoperative renal dialysis. Interact Cardiovasc Thorac Surg 18:103-11.