Kalp Cerrahisi Geçiren Kronik Böbrek Hastalığı Hastalarında Levosimendan ve Milrinon Kombinasyonunun Etkisi

Year 2022, Issue: 34, 805 - 811, 31.03.2022

Gökhan Keskin Ahmet Feyzi Abacılar

https://doi.org/10.31590/ejosat.1083467

Abstract

Amaç: Levosimendan kullanımının etkisi kalp ameliyatı geçirmiş kronik böbrek hastalığı (KBH) hastalarında az sayıda denekte araştırılmıştır. Bu çalışmanın amacı, kalp cerrahisi geçirmiş ve sol ventrikülü zayıf olan KBH hastalarında milrinon uygulaması ile kombinasyon halinde perioperatif levosimendan'ın hemodinamik etkilerini araştırmaktı.
Method: Bu çalışmaya, sol ventrikülü zayıf ve pulmoner arter hipertansiyonu yüksek olan 164 KBH hastası (ortalama yaş = 56 yıl) dahil edildi. Ortalama kreatinin klerensi 30-59 mL/dak/1,73 m²'den düşüktü (orta ila şiddetli böbrek yetmezliği). 84 hastaya (çalışma grubu; SG) levosimendan ve milrinon uygulandı. Kalan 80 hasta plasebo ile tedavi edildi (plasebo grubu; PG). Kardiyak output (CO), kardiyak indeks (CI), sistemik vasküler direnc (SVRI), pulmoner vasküler direnç (PVR), miyokardiyal enzimler ve tümör nekroz faktörü alfa (TNF-alfa) ameliyattan hemen sonra ve 2. , 6. , 12. ve 24. saatte karşılaştırdık.
Bulgular: Gruplar arasında operatif mortalite açısından anlamlı bir fark gözlenmedi (%6.3'e karşı %7.7, P=0.76). SG, daha düşük postoperatif düşük kalp debisi sendromu (LCOS) (%29.3'e karşı %41.6, P=0.001) ve aritmi (%26.8'e karşı %44.6) (P=0.01) gösterdi. CO ve CI değerleri 6 saatin sonunda SG'de anlamlı olarak daha yüksekti. SG'de PVR değerleri anlamlı derecede düşüktü (P=0.034). SG'de inotropik gereksinim miktarı düşüktü (P= 0.002). Laboratuvar analizleri SG'de c-TnI ve TNF-alfa düzeylerinin düşük olduğunu gösterdi (P= 0.0001). Ameliyat öncesi dönem ile karşılaştırıldığında, ameliyat sonrası dönemde her iki grupta da ortalama LVEF daha yüksek bulundu, ancak SG'de LVEF'deki ortalama artış PG'den daha yüksekti (11.70±2.39'a karşı 6.2±1.30) (P<0.001).
Sonuç: Kalp cerrahisi geçiren sol ventrikülü zayıf olan KBH hastalarında levosimendan ve milrinon kullanımı hemodinamiyi önemli ölçüde iyileştirdiği saptandı. İnodilatör tedavi ile yoğun bakım ve hastanede kalış süresi önemli ölçüde azaldı. Bu nedenle KBH ve ejeksiyon fraksiyonu düşük sol ventrikülü olan kalp cerrahisi hastalarında postoperatif ve peroperatif dönemde levosimendan ve milrinon kombinasyonunun kullanılmasının gerekliliği görüldü.

Keywords

Düşük ejeksiyon fraksiyonlu sol ventrikül, Kronik böbrek hastaliğı, Levosimendan, Milrinone, Kalp Cerrahisi

Supporting Institution

Destekleyen kurum yoktur.

Project Number

Yoktur.

Thanks

editöre teşekkürlerimizi bildiririz

Effect of Levosimendan and Milrinone Combination in Chronic Kidney Disease Patients Who Underwent Cardiac Surgery

Abstract

Background: The effect of levosimendan use in chronic kidney disease (CKD) patients who underwent cardiac surgery has been investigated in a small number of subjects. Our purpose of this study was to investigate the hemodynamic effects of perioperative levosimendan in combination with milrinone administration in CKD patients underwent cardiac surgery and with poor left ventricle.
Methods: 164 CKD patients (the mean age = 56 yrs) with poor left ventricle and a high pulmonary artery hypertension were included in this study. Mean creatinine clearance was lower than 30-59 mL/min/1,73 m² (moderate to severe renal impairment). Levosimendan and milrinone were administered to 84 patients (study group; SG). The remaining 80 patients treated with placebo (placebo group; PG). We compared cardiac output (CO), cardiac index (CI), systemic vascular resistance (SVRI), pulmonary vascular resistance (PVR), myocardial enzymes, and tumor necrosis factor alpha (TNF-alpha) immediately after surgery and at 2 h, 6 h, 12 h, and 24 h after operation.
Results: No significant difference in operative mortality between groups was observed (6.3% vs. 7.7%, P=0.76). The SG showed lower rates of postoperative low-cardiac output syndrome (LCOS) (29.3% vs. 41.6%, P=0.001), and arrhytmia (26.8% vs. 44.6%) (P=0.01). CO and CI values were significantly higher in SG after the end of 6 h. PVR values were significantly low in SG (P=0.034). The amount of inotropic requirement was low in SG (P= 0.002). The laboratory analyses showed that c-TnI and TNF-alpha levels were low in SG (P= 0.0001). Compared to preoperative period, higher mean LVEF was found in both groups in the postoperative period, but the mean increase in LVEF in SG was higher than in the PG (11.70±2.39 vs. 6.2±1.30) (P<0.001).
Conclusion: The use of levosimendan plus milrinone significantly improved hemodynamics in CKD patients with poor left ventricle who underwent cardiac surgery. Duration of ICU and hospitalization were decreased significantly with inodilators treatment. Therefore, we suggest the use of levosimendan and milrinone combination in per- and postoperative period in cardiac surgery patients with CKD and poor left ventricle.

Keywords

Poor left ventricle, Chronic kidney disease, Levosimendan, Milrinone, Cardiac surgery

Project Number

Yoktur.

References

• Álvarez, J., Bouzada, M., Fernández, Á. L., Caruezo, V., Taboada, M., Rodríguez, J., ... & González-Juanatey, J. R. (2006). Hemodynamic effects of levosimendan compared with dobutamine in patients with low cardiac output after cardiac surgery. Revista Española de Cardiología (English Edition), 59(4), 338-345.
• Atalay, H., Temizturk, Z., Altinsoy, H. B., Azboy, D., Colak, S., Atalay, A., & Dogan, O. F. (2016, October). Levosimendan Use Increases Cardiac Performance after Coronary Artery Bypass Grafting in End-Stage Renal Disease Patients. In The Heart Surgery Forum (Vol. 19, No. 5, pp. E230-E236).
• Bersin, R. M., Wolfe, C., Kwasman, M., Lau, D., Klinski, C., Tanaka, K., ... & Chatterjee, K. (1994). Improved hemodynamic function and mechanical efficiency in congestive heart failure with sodium dichloroacetate. Journal of the American College of Cardiology, 23(7), 1617-1624.
• Breisblatt, W. M., Stein, K. L., Wolfe, C. J., Follansbee, W. P., Capozzi, J., Armitage, J. M., & Hardesty, R. L. (1990). Acute myocardial dysfunction and recovery: a common occurrence after coronary bypass surgery. Journal of the American College of Cardiology, 15(6), 1261-1269.
• Cavusoglu, Y., Beyaztas, A., Birdane, A., & Ata, N. (2009). Levosimendan is not effective in reducing pulmonary pressures in patients with idiopathic pulmonary arterial hypertension: report of two cases. Journal of Cardiovascular Medicine, 10(6), 503-507.
• Cohen-Solal, A., Logeart, D., Huang, B., Cai, D., Nieminen, M. S., & Mebazaa, A. (2009). Lowered B-type natriuretic peptide in response to levosimendan or dobutamine treatment is associated with improved survival in patients with severe acutely decompensated heart failure. Journal of the American College of Cardiology, 53(25), 2343-2348.
• De Hert, S. G., Lorsomradee, S., Cromheecke, S., & Van der Linden, P. J. (2007). The effects of levosimendan in cardiac surgery patients with poor left ventricular function. Anesthesia & Analgesia, 104(4), 766-773.
• Du Toit, E., Hofmann, D., McCarthy, J., & Pineda, C. (2001). Effect of levosimendan on myocardial contractility, coronary and peripheral blood flow, and arrhythmias during coronary artery ligation and reperfusion in the in vivo pig model. Heart, 86(1), 81-87.
• Eichhorn, E. J., Heesch, C. M., Barnett, J. H., Alvarez, L. G., Fass, S. M., Grayburn, P. A., ... & Malloy, C. R. (1994). Effect of metoprolol on myocardial function and energetics in patients with nonischemic dilated cardiomyopathy: a randomized, double-blind, placebo-controlled study. Journal of the American College of Cardiology, 24(5), 1310-1320.
• Eriksson, H. I., Jalonen, J. R., Heikkinen, L. O., Kivikko, M., Laine, M., Leino, K. A., ... & Salmenperä, M. T. (2009). Levosimendan facilitates weaning from cardiopulmonary bypass in patients undergoing coronary artery bypass grafting with impaired left ventricular function. The Annals of thoracic surgery, 87(2), 448-454.
• Feneck, R. O., Sherry, K. M., Withington, P. S., Oduro-Dominah, A., & European Milrinone Multicenter Trial Group. (2001). Comparison of the hemodynamic effects of milrinone with dobutamine in patients after cardiac surgery. Journal of cardiothoracic and vascular anesthesia, 15(3), 306-315.
• Hadadzadeh, M., Hosseini, S. H., Mostafavi-Pour-Manshadi, S. M. Y., Naderi, N., & Emami-Meybodi, M. (2013). Effect of milrinone on short term outcome of patients with myocardial dysfunction undergoing off-pump coronary artery bypass graft: a randomized clinical trial. Acta Medica Iranica. Haikala, H., Kaivola, J., Nissinen, E., Wall, P., Levijoki, J., & Lindén, I. B. (1995). Cardiac troponin C as a target protein for a novel calcium sensitizing drug, levosimendan. Journal of molecular and cellular cardiology, 27(9), 1859-1866.
• Hasenfuss, G., Holubarsch, C. H., Just, H., Blanchard, E., Mulieri, L. A., & Alpert, N. R. (1987). Energetic aspects of inotropic interventions in rat myocardium. In Cardiac Energetics (pp. 251-259). Steinkopff, Heidelberg.
• Hasenfuss, G., Pieske, B., Kretschmann, B., Holubarsch, C., Alpert, N. R., & Just, H. (1995). Effects of calcium sensitizers on intracellular calcium handling and myocardial energetics. Journal of cardiovascular pharmacology, 26, S45-51.
• Hein, M., Roehl, A. B., Baumert, J. H., Scherer, K., Steendijk, P., & Rossaint, R. (2009). Anti‐ischemic effects of inotropic agents in experimental right ventricular infarction. Acta anaesthesiologica scandinavica, 53(7), 941-948.
• Heringlake, M., Wernerus, M., Grünefeld, J., Klaus, S., Heinze, H., Bechtel, M., ... & Schön, J. (2007). The metabolic and renal effects of adrenaline and milrinone in patients with myocardial dysfunction after coronary artery bypass grafting. Critical Care, 11(2), 1-10.
• Hernandez, A. F., Li, S., Dokholyan, R. S., O'Brien, S. M., Ferguson, T. B., & Peterson, E. D. (2009). Variation in perioperative vasoactive therapy in cardiovascular surgical care: data from the Society of Thoracic Surgeons. American heart journal, 158(1), 47-52.
• Jörgensen, K., Bech-Hanssen, O., Houltz, E., & Ricksten, S. E. (2008). Effects of levosimendan on left ventricular relaxation and early filling at maintained preload and afterload conditions after aortic valve replacement for aortic stenosis. Circulation, 117(8), 1075-1081.
• Karlsberg, R. P., DeWood, M. A., DeMaria, A. N., Berk, M. R., Lasher, K. P., & Milrinone‐Dobutamine Study Group. (1996). Comparative efficacy of short‐term intravenous infusions of milrinone and dobutamine in acute congestive heart failure following acute myocardial infarction. Clinical cardiology, 19(1), 21-30.
• Kikura, M., & Sato, S. (2003). Effects of preemptive therapy with milrinone or amrinone on perioperative platelet function and haemostasis in patients undergoing coronary bypass grafting. Platelets, 14(5), 277-282.
• Kikura, M., Levy, J. H., Michelsen, L. G., Shanewise, J. S., Bailey, J. M., Sadel, S. M., & Szlam, F. (1997). The effect of milrinone on hemodynamics and left ventricular function after emergence from cardiopulmonary bypass. Anesthesia & Analgesia, 85(1), 16-22.
• Labriola, C., Siro-Brigiani, M., Carrata, F., Santangelo, E., & Amantea, B. (2004). Hemodynamic effects of levosimendan in patients with low-output heart failure after cardiac surgery. International journal of clinical pharmacology and therapeutics, 42(4), 204-211.
• Lilleberg, J., Sundberg, S., & Nieminen, M. S. (1995). Dose-range study of a new calcium sensitizer, levosimendan, in patients with left ventricular dysfunction. Journal of cardiovascular pharmacology, 26, S63-9.
• Lobato, E. B., Gravenstein, N., & Martin, T. D. (2000). Milrinone, not epinephrine, improves left ventricular compliance after cardiopulmonary bypass. Journal of cardiothoracic and vascular anesthesia, 14(4), 374-377.
• Lobo Martínez, P., Oulego Erroz, I., Gautreux Minaya, S., & Rodríguez Fernández, L. M. (2011). Treatment of acute heart failure using levosimendan for a patient with dilated cardiomyopathy, chronic renal failure, and hypertension. Pediatric cardiology, 32(7), 1012-1016.
• Malliotakis, P. O. L. Y. C. H. R. O. N. I. S., Xenikakis, T. H. E. O. P. H. I. L. O. S., Linardakis, M., & Hassoulas, J. (2007). Haemodynamic effects of levosimendan for low cardiac output after cardiac surgery: a case series. Hellenic J Cardiol, 48(2), 80-88.
• Missant, C., Rex, S., Segers, P., & Wouters, P. F. (2007). Levosimendan improves right ventriculovascular coupling in a porcine model of right ventricular dysfunction. Critical care medicine, 35(3), 707-715.
• Nijhawan, N., Nicolosi, A. C., Montgomery, M. W., Aggarwal, A., Pagel, P. S., & Warltier, D. C. (1999). Levosimendan enhances cardiac performance after cardiopulmonary bypass: a prospective, randomized placebo-controlled trial. Journal of cardiovascular pharmacology, 34(2), 219-228.
• Opie LH. Fuels: Carbohydrates and lipids. In: Opie LH. The Heart, Physiology and Metabolism. (1991). New York: Raven Press, 208–44.
• OZTEKIN, I., Yazici, S., ÖZTEKIN, D. S., Goksel, O., Issever, H., & Canik, S. (2007). Effects of low dose milrinone on weaning from cardiopulmonary bypass and after in patients with mitral stenosis and pulmonary hypertension. Yakugaku Zasshi, 127(2), 375-383.
• Papadopoulos, G., Baikoussis, N. G., Tzimas, P., Siminelakis, S. N., & Karanikolas, M. (2010). Intravenous levosimendan-norepinephrine combination during off-pump coronary artery bypass grafting in a hemodialysis patient with severe myocardial dysfunction. Journal of Cardiothoracic Surgery, 5(1), 1-4.
• Parissis, J. T., Farmakis, D., & Nieminen, M. (2007). Classical inotropes and new cardiac enhancers. Heart failure reviews, 12(2), 149-156.
• Puttonen, J., Kantete, S., Kivikko, M., Häkkinen, S., Harjola, V. P., Koskinen, P., & Pentikäinen, P. J. (2007). Effect of severe renal failure and haemodialysis on the pharmacokinetics of levosimendan and its metabolites. Clinical pharmacokinetics, 46(3), 235-246. Végh, A., Papp, J. G., Udvary, E., & Kaszala, K. (1995). Hemodynamic effects of calcium-sensitizing agents. Journal of cardiovascular pharmacology, 26, S20-31