Introduction: Mechanical circulatory support (MCS) of venoarterial extracorporeal membrane oxygenation (VA ECMO) leads to specific hemodynamic changes. Due to its retrograde circulatory support, it inherently leads to increased left ventricular (LV) afterload and LV enddiastolic pressure with increasing mechanical cardiac stress and impairment of cardiac recovery whenever intrinsic cardiac output is reduced. Inodilative calcium sensitizer levosimendan increases cardiac inotropy via cardiac troponin C and has vasodilative effects on adenosin triphosphate (ATP) dependent potassium channels, shown as cardioprotective. However, its implications on outcome of patients (pts) following remains elusive.
We thus aimed to determine the effects of early levosimendan therapy on survival and weaning failure in pts presenting with in- or out of hospital cardiac arrest (IHCA/OHCA) and therapy-refractory cardiogenic shock (CS) treated with VA-ECMO.

Methods: We retrospectively analysed 352 pts treated with VA-ECMO at our institution from 2016 to 2022 stratified according to early levosimendan therapy following VA-ECMO implantation. Survival was determined as survival at day 14 and weaning failure was defined as ECMO therapy longer than 7 days, or death within 7 days after ECMO weaning. Statistical analyses were performed using baseline comparison, survival analysis, and logrank tests.

Results: Of the 357 pts 87% (311 pts) underwent extracorporal cardiopulmonary resuscitation (eCPR) (60% OHCA, 27% IHCA), 13% (46 pts) had CS. 175 pts (49%) underwent standard VA-ECMO care, 182 pts (51%) received additional levosimendan on the first day of ECMO therapy via continuous infusion (0.1 – 0.2 µg/kg/min) for 24 hours, without prior loading dose. The average age was 59 years (y), standard deviation (SD) 13, no-levosimendan (no-levo) 60y (SD 13), levosimendan (levo) 59y (SD 13)], 20% female [no-levo 25% (44pts), levo 16% (29pts)]. The cause of cardiac failure was in 63% (174 pts) [no-levo 52% (64 pts), levo 72% (110 pts)] coronary occlusion, 9.5% (26 pts) [no-levo 17% (21 pts), levo 3.3% (5 pts)] pulmonary embolism, 7.6 % (21 pts) [no-levo 8.9% (11 pts), levo 6.6% (10 pts)] pulseless arrythmia and in 15% (41 pts) [no-levo 12% (15 pts), levo 17% (26 pts)] CS.

The survival rate at day 14 in pts treated additionally with Levosimendan [levo: 39.2% (SD-error 3.7%), p<0.0001] was significantly higher compared with standard VA-ECMO care [27.2% (SD-error 3.6%)] Tab.1. The risk of ECMO weaning failure was reduced by 14.7% [SD-error 3.8%)] in the levosimendan group.

Conclusion: Our analysis suggests for the first time in eCPR a significant survival benefit for pts treated with VA-ECMO and additional levosimendan in cardiac arrest and CS compared with pts undergoing standard VA-ECMO care. The administration of levosimendan showed a positive effect as well on ECMO weaning and reduces VA-ECMO weaning failure significantly. Further studies regarding mechanism and subgroups are necessary to identify the underlying effect more precisely.