The effect of levosimendan on survival and cardiac performance in an ischemic cardiac arrest model - A blinded randomized placebo-controlled study in swine

Resuscitation. 2020 May:150:113-120. doi: 10.1016/j.resuscitation.2020.02.032. Epub 2020 Mar 28.

Abstract

Background: Survival after out-of-hospital cardiac arrest remains poor. Levosimendan could be a new intervention in this setting. Therefore, we conducted a blinded, placebo controlled randomized study investigating the effects of levosimendan on survival and cardiac performance in an ischemic cardiac arrest model in swine.

Methods: Twenty-four anesthetised swines underwent experimentally-induced acute myocardial infarction and ventricular fibrillation. At the start of CPR, a bolus dose of levosimendan (12 μg kg-1) or placebo was given followed by a 24-h infusion (0.2 μg kg-1 min-1) after return of spontaneously circulation. Animals were evaluated by risk of death, post-resuscitation hemodynamics and infarction size by magnetic resonance imaging (MRI) up to 32 h post arrest.

Results: Spontaneous circulation was restored in all (12/12) animals in the levosimendan group compared to two thirds (8/12) in the placebo group (P = 0.09). Protocol survival was higher for the levosimendan group (P = 0.02) with an estimated 88% lower risk of death compared to placebo (hazard ratio [95% confidence interval] 0.12 [0.01-0.96], P = 0.046). Cardiac output (CO) recovered 40% faster during the first hour of the intensive care period for the levosimendan group (difference 0.13 [0.01-0.26] L min-1P = 0.04). The placebo group required higher inotropic support during the intensive care period which masked an even bigger recovery in CO in the levosimendan group (58%). The MRI showed no difference in myocardial scar size or in myocardial area at risk.

Conclusions: Levosimendan given intra-arrest and during the first 24-h of post-resuscitation care improved survival and cardiac performance in this ischemic cardiac arrest model. Institutional Protocol Number; KERIC 5.2.18-14933.

Keywords: CPR; Cardiac MRI; Cardiac arrest; Levosimendan; Myocardial infarction; OHCA; Out-of-hospital cardiac arrest; Resuscitation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiopulmonary Resuscitation*
  • Cardiotonic Agents / therapeutic use
  • Disease Models, Animal
  • Hemodynamics
  • Hydrazones / pharmacology
  • Pyridazines* / pharmacology
  • Simendan / pharmacology
  • Swine

Substances

  • Cardiotonic Agents
  • Hydrazones
  • Pyridazines
  • Simendan