Levosimendan in patients undergoing extracorporeal membrane oxygenation after cardiac surgery: an emulated target trial using observational data

Background Retrospective cohorts have suggested that levosimendan may facilitate the weaning of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). We therefore studied this clinical question by emulating a rand-omized trial with observational data. Methods All patients with refractory postcardiotomy cardiogenic shock and assisted with VA-ECMO, admitted to a surgical intensive care unit at La Pitie-Salpetri & egrave;re Hospital between 2016 and 2019, were eligible. To avoid immortal-time bias, we emulated a target trial sequentially comparing levosimendan administration versus no levosimendan administration in patients treated with VA-ECMO. The primary outcome was time to successful ECMO weaning. The secondary outcomes were 30-day and 1-year mortality. We performed a multivariable analysis to adjust for confound-ing at baseline. Results Two hundred and thirty-nine patients were included in the study allowing building a nested trials cohort of 1434 copies of patients. No association of levosimendan treatment and VA-ECMO weaning was found (HR =0.91, [0.57; 1.45], p =0.659 in multivariable analysis), or 30-day mortality (OR =1.03, [0.52; 2.03], p= 0.940) and 1-year mor-tality (OR =1.00, [0.53; 1.89], p = 0.999). Conclusions Using the emulated target trial framework, this study did not find any association of levosimendan treatment and ECMO weaning success after postcardiotomy cardiogenic shock. However, the population of interest remains heterogeneous and subgroups might benefit from levosimendan.

Automated summary

This study emulated a randomized trial using observational data to investigate the effect of levosimendan on weaning from VA-ECMO. No association was found between levosimendan treatment and successful ECMO weaning or mortality rates. However, the researchers suggest that subgroups within the population of interest may still benefit from levosimendan.