Levosimendan versus dobutamine in septic shock

Introduction

Levosimendan is a calcium sensitizer that increases cardiac contractility without increasing intracellular calcium levels. Its efficacy has been demonstrated in acute decompensated heart failure but has not been evaluated in severe sepsis/septic shock. We hypothesized that levosimendan increases the cardiac index similar to dobutamine in patients with severe sepsis/septic shock.

Methods

In a randomized, open-label trial, 42 patients admitted to the ICU with severe sepsis/septic shock were randomized to receive either levosimendan (group L) or dobutamine (group D) as part of an early-goal directed therapy protocol [1]. Study drugs were titrated incrementally to an ScvO₂ ≥ 70% or to a maximum dose, whichever was achieved first, and were continued for a total of 24 hours only. Group L received levosimendan 0.05 μg/kg/minute intravenously that was increased by 0.05 μg/kg/minute every 30 minutes (maximum 0.2 μg/kg/min). Group D received dobutamine 5 μg/kg/minute intravenously which was increased by 5 μg/kg/minute every 30 minutes (maximum 20 μg/kg/min). Rescue therapy consisted of dobutamine 10 μg/kg/minute intravenously titrated to ScvO₂ ≥ 70% or a maximum of 20 μg/kg/minute, which-ever was achieved first. Hypotension (mean arterial pressure (MAP) <65 mmHg) was treated with norepinephrine infusion, titrated to a MAP ≥ 65 mmHg. ScvO₂ was recorded hourly. Cardiac output was measured continuously using the FloTrac™ device (Edwards Lifesciences, Irvine, CA, USA). Continuous data were analyzed using repeated-measures ANOVA, and proportions were compared using Fisher's exact test. Results are presented as the mean ± SD unless otherwise indicated. Significance was defined as P < 0.05.

Results

APACHE II scores were 21 ± 7 versus 27 ± 7 (P = 0.02), and the ICU mortality was 10 (48%) versus 13 (62%) (P = 0.35) for groups L and D, respectively. The cardiac index was lower in group L compared with group D (estimated marginal mean ± SEM: 2.8 ± 0.1 vs. 3.2 ± 0.1, respectively, P < 0.01) but the ScvO₂ changes over time did not differ between groups (P > 0.5). Norepinephrine was administered to 17 (81%) patients in group L and 21 (100%) in group D (P = 0.04).

Conclusion

Dobutamine increased the cardiac index more than did levosimendan, although there was no difference between the two drugs with regard to their effects on ScvO₂.