Effects of levosimendan on the outcome of veno-arterial extracorporeal membrane oxygenation: a systematic review and meta-analysis

Abstract

Objectives: For patients with severe cardiopulmonary failure, such as cardiogenic shock, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is primarily utilized to preserve their life by providing continuous extracorporeal respiration and circulation. However, because of the complexity of patients' underlying diseases and serious complications, successful weaning from ECMO is often difficult. At present, there have been limited studies on ECMO weaning strategies, so the principal purpose of this meta-analysis is to examine how levosimendan contributes to the weaning of extracorporeal membrane oxygenation.

Methods: The Cochrane Library, Embase, Web of Science, and PubMed were browsed for all potentially related research about clinical benefits of levosimendan in weaning patients receiving VA-ECMO and included 15 of them. The main outcome is success of weaning from extracorporeal membrane oxygenation, with the secondary outcomes of 1-month mortality (28 or 30 days), ECMO duration, hospital or intensive care unit (ICU) length of stay, and use of vasoactive drugs.

Results: 1772 patients altogether from 15 publications were incorporated in our meta-analysis. We used fixed and random-effect models to combine odds ratio (OR) and 95% confidence interval (CI) for dichotomous outcomes and standardized mean difference (SMD) for continuous outcomes. The weaning success rate in the levosimendan group was considerably higher in contrast to the comparison (OR = 2.78, 95% CI 1.80-4.30; P < 0.00001; I² = 65%), and subgroup analysis showed that there was less heterogeneity in patients after cardiac surgery (OR = 2.06, 95% CI, 1.35-3.12; P = 0.0007; I² = 17%). In addition, the effect of levosimendan on improving weaning success rate was statistically significant only at 0.2 mcg/kg/min (OR = 2.45, 95% CI, 1.11-5.40; P = 0.03; I² = 38%). At the same time, the 28-day or 30-day proportion of deaths in the sample receiving levosimendan also decreased (OR = 0.47, 95% CI, 0.28-0.79; P = 0.004; I² = 73%), and the difference was statistically significant. In terms of secondary outcomes, we found that individuals undergoing levosimendan treatment had a longer duration of VA-ECMO support.

Conclusions: In patients receiving VA-ECMO, levosimendan treatment considerably raised the weaning success rate and helped lower mortality. Since most of the evidence comes from retrospective studies, more randomized multicenter trials are required to verify the conclusion.

Keywords: Cardiogenic shock; Cardiopulmonary support; Extracorporeal membrane oxygenation; Levosimendan; Mortality; Weaning.