Hemodynamic effects of levosimendan in cardiac surgery patients: a systemic review and meta-analysis

Introduction Levosimendan is a potent inodilator agent. The net effect of haemodynamic changes may result in a hyperdynamic state with low systemic vascular resistance. To assess the haemodynamic effects in cardiac surgery patients treated with levosimendan we conducted a systemic review. Our hypothesis was that levosimendan improves cardiac function, but also triggers a systemic vasodilatation. Methods Systematic review with meta-analysis. English-language literature with access to full texts and supplements in US National Library of Medicine (PUBMED), MEDLINE, EMBASE, and CENTRAL was searched systematically from 2006 until July 2018. Included randomized controlled trials, case-matched or retrospective studies providing at least two sequentially measured haemodynamic variables in adult patients undergoing cardiac surgery with cardio pulmonary bypass and treated with levosimendan in comparison to alternative drugs or devices. Results Cardiac index significantly increased in the levosimendan group by 0.74 (0.24 to 1.23) [standardised mean difference (95% CI); p = 0.003] from baseline to postoperative day (POD) 1, and by 0.75 (0.25 to 1.25; p = 0.003) from baseline to POD 7, when corrected for the standardized mean difference (SMD) at baseline by a multivariate mixed effects meta-analysis model. With the correction for baseline differences, other haemodynamic variables, especially the systemic vascular resistance did not significantly differ until POD 1 [-0.17 (-0.64 to 0.30), p=0.48] and POD 7 [-0.13 (-0.61 to 0.34), p=0.58] between the levosimendan and the comparator group. Discussion Levosimendan increased cardiac index in patients undergoing cardiac surgery. Although levosimendan has inodilator properties, this meta-analysis finds no clinical evidence that levosimendan produces vasopressor-resistant vasoplegic syndrome. Hypotension seems not to be statistically relevant.