Levosimendan does not improve resuscitation success after hypovolemic cardiac arrest

Introduction

Resuscitation from hemorrhagic shock and subsequent cardiac arrest (CA) is a major clinical challenge in the care of trauma patients. Levosimendan, a new calcium sensitizer, exerts positive inotropic and lusitropic effects in failing human myocardium without increase in energy expenditure [1]. The aim of this study was to evaluate possible beneficial effects of levosimendan in combination with vasopressin in hypovolemic CA and subsequent cardiopulmonary resuscitation.

Methods

Five anesthetized male piglets (26.5 ± 1.1 kg) were bled (25.1 ± 3.4% of calculated total blood volume) to a mean arterial blood pressure of 35 mmHg during 12.9 ± 0.2 minutes. Afterwards the piglets were subject to 4 minutes untreated ventricular fibrillation followed by 12 minutes open-chest cardiopulmonary resuscitation (CPR). At 5 minutes of CA, 0.4 U/kg vasopressin and 12 μg/kg levosimendan were given intravenously and an infusion of 3 ml/kg hypertonic saline and dextran (7.5% saline, 6% dextran 70) was given in 20 minutes. Internal defibrillation was attempted from 7 minutes of CA to achieve restoration of spontaneous circulation (ROSC). If necessary, at 8 minutes of CA, 0.4 U/kg vasopressin was repeated intravenously. Hemodynamic variables, continuous cerebral cortical blood flow and blood gas parameters were measured during CPR and up to 180 minutes after ROSC. Blood samples for 8-iso-PGF_2α, 15-keto-dihydro-PGF_2α, protein S-100β and troponin I were taken.

Results

ROSC was achieved in two out of five piglets. Only one of these piglets survived the whole experiment. Another piglet died 60 minutes after ROSC due to a new episode of ventricular fibrillation. It was difficult to achieve ROSC due to persistent ventricular fibrillation during CPR. The mean number of defibrillation attempts was 14.2 (range: 8–21). The mean coronary perfusion pressure was 19–21 mmHg during CPR. Piglets that achieved ROSC needed a constant dobutamine infusion for hemodynamic stability. Concentrations of troponin I continuously increased after ROSC, reaching maximum levels at the end of the study. During the very early reperfusion phase (5–15 min after ROSC) the cerebral cortical blood flow was 18–47% greater than baseline values. Thereafter, it remained elevated about 18% at 30 minutes, and was decreased to baseline level during the remainder of the experiment.

Conclusion

A combination of levosimendan and vasopressin did not improve resuscitation success. A combination of levosimendan and vasopressin produced ventricular fibrillation resistant to defibrillation attempts in a hypovolemic cardiac arrest model. Further studies are necessary in order to evaluate effects of vasopressin and other inotropic agents in hypovolemic animal models.