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

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

Öz

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.

Anahtar Kelimeler

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

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