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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.

References

  1. 1.

    Rivers E, et al.: N Engl J Med. 2001, 345: 1368-1377. 10.1056/NEJMoa010307

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Alhashemi, J., Alotaibi, Q. Levosimendan versus dobutamine in septic shock. Crit Care 13, P171 (2009). https://doi.org/10.1186/cc7335

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Keywords

  • Norepinephrine
  • Septic Shock
  • Mean Arterial Pressure
  • Intracellular Calcium
  • Cardiac Index