Use of levosimendan in myocardial dysfunction due to sepsis

Introduction

Myocardial dysfunction observed within the context of sepsis is partially due to desensitization of the cardiac muscle to vasoactive agents. Levosimendan, a calcium sensitizer and a K⁺-ATP channel opener, plays a significant role in the treatment of myocardial depression although its use in sepsis has not yet been established.

Methods

We studied 42 patients (66.1 ± 7.54 years, 24 male) who met the criteria for sepsis (infection by Gram-negative bacteria and at least two SIRS criteria) and displayed severe heart dysfunction (cardiac index (CI) ≤ 2.2, ejection fraction (EF) ≤ 35%). The APACHE II score was 21.2 ± 4.9. Patients were randomized to receive additionally to their standard treatment levosimendan (0.1 μg/kg/minute 24-hour infusion) (group A, n = 23) without loading dose or dobutamine (5 to 10 μg/kg/minute 24-hour infusion) (group B, n = 19). Noradrenaline was used to preserve the mean arterial pressure above 65 mmHg. The primary goal was mortality at 7 and 30 days.

Results

Mortality at 7 and 30 days was 30% and 60% in group A versus 36% and 68% in group B (P = 0.05, P = 0.03, respectively). The CI and EF significantly increased in group A (ΔCI: 1.79 ± 0.16 vs. 1.4 ± 0.12, P = 0.027; ΔEF: 4.8 ± 0.2% vs. 3.5 ± 0.7%, P = 0.04), and also SvO₂ (P = 0.012) and mean arterial pressure (P = 0.035) were significantly increased.

Conclusion

Levosimendan compared with dobutamine improves the hemodynamic profile of septic patients with myocardial dysfunction; and while there is evidence that it reduces mortality, further studies are needed to verify this.