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Levosimendan for the Prevention of Acute Organ Dysfunction in Sepsis
Levosimendan for the Prevention of Acute Organ Dysfunction in Sepsis
Gordon AC, Perkins GD, Singer M, et al. N Engl J Med. 2016; 375: 1638-1648.
Study Question: Does administration of levosimendan to patients with septic shock prevent acute organ dysfunction over the ICU stay?
Study Description: This multicenter, randomized, double-blind, placebo-controlled trial included adult patients with septic shock receiving vasopressors ≥4 hours. Patients were randomized to receive either placebo or levosimendan IV infusion at a rate of 0.1 mcg/kg/min for 2-4 hours and then increased to 0.2 mcg/kg/min if tolerated for a total of 24 hours of therapy. The primary outcome was the mean daily Sequential Organ Failure Assessment (SOFA) score while in the ICU up to 28 days.
Results: A total of 516 patients were included, with 259 receiving levosimendan. There was no difference in the unadjusted primary outcome (mean SOFA 6.68 ± 3.96 levosimendan group vs. 6.06 ± 3.89 placebo, p = 0.053) or adjusted for ICU, age and APACHE II scores. Mortality at 28-days was not statistically different and numerically higher in the levosimendan group (34.5% vs. 30.9%, p = 0.43). Patients in the levosimendan group were less likely to be weaned from the ventilator and more likely to have supraventricular tachyarrhythmias in the first four days and a lower MAP in the first 24 hours.
Conclusion(s): Levosimendan was not associated with a reduction in acute organ dysfunction as quantified by mean SOFA scores or reduction in mortality in patients with septic shock.
Perspective: Given the lack of demonstrated improvement in organ dysfunction along with the increased adverse events encountered, this study suggests that levosimendan is not useful in this adult patients with septic shock.