Levosimendan improves central haemodynamic status and gas exchange in a model of ischaemic cardiac arrest: A large animal study.

Abstract

Background: Ischaemic cardiac arrest has poor survival. In an earlier animal study, we have shown that levosimendan increases the return of spontaneous circulation and survival compared with placebo. However, the impact of levosimendan on central cardiovascular variables and gas exchange during resuscitation in ischaemic cardiac arrest is unknown.

Objective: To evaluate levosimendan's dose-response effect on central cardiovascular variables and gas exchange in an established swine cardiac arrest model.

Design: A large animal study.

Setting: Animal study with Swedish landrace pigs at Karolinska Institutet, Sweden.

Intervention: Ten swine underwent induced acute myocardial infarction and ventricular fibrillation. Levosimendan (62.5 μg kg-1) was administered during resuscitation, and immediate outcomes were compared with low dose levosimendan (12 μg kg-1, n  = 12) or placebo (n  = 12) from earlier experiments using the same model.

Main outcome measures: Haemodynamic and gas exchange variables during resuscitation. Time to and proportion of return to spontaneous circulation.

Results: High-dose levosimendan improved gas exchange, with better arterial O2 and CO2 levels (P < 0.01), reduced systolic pulmonary arterial pressure, central venous pressure and vasopressor support with adrenaline after return to spontaneous circulation compared with low dose and placebo (P = 0.01). All animals in both levosimendan groups achieved return to spontaneous circulation compared with 67% in the placebo group (P = 0.02). Median [IQR] time to return of spontaneous circulation was 15 min [12 to 18] for high dose 17 min [15 to 26] for low dose compared with 23 min [15 to 60] for placebo (P = 0.08).

Conclusions: Levosimendan enhances key resuscitation outcomes in the immediate period of ischaemic cardiac arrest, promoting its potential as an effective pharmacological intervention. With an apparent dose-dependent reduction in right ventricular afterload and subsequent improvement in gas exchange, we cautiously propose that levosimendan-induced pulmonary vasodilation alleviates right heart strain and improves interventricular dependency, thereby enhancing the likelihood of return of spontaneous circulation.