The project produced a comprehensive Cochrane systematic review on the prophylactic use of inotropic agents to prevent low‑cardiac‑output syndrome (LCOS) and mortality in adults undergoing cardiac surgery. A total of 29 eligible studies comprising 3,307 participants were identified, together with four ongoing trials. All studies were published in peer‑reviewed journals and followed an intention‑to‑treat design. In 19 of the 29 studies, funding from the pharmaceutical industry or undisclosed conflicts of interest were reported, raising concerns about potential bias. The overall quality of evidence was limited by small sample sizes, inadequate random‑sequence generation, and lack of blinding, which contributed to selection, performance, and detection bias. Heterogeneity was generally low for mortality (I² = 11 %) but moderate for LCOS (I² = 66 %).
Meta‑analyses revealed that levosimendan reduced the risk of overall mortality (relative risk = 0.65, 95 % confidence interval = 0.43 to 0.97, 14 studies, 2,347 participants, GRADE moderate). For LCOS, levosimendan lowered the risk (RR = 0.43, 95 % CI = 0.25 to 0.74, 6 studies, 1,724 participants, GRADE low). No significant mortality benefit was seen when levosimendan was compared with standard cardiac therapy or milrinone. Subgroup analyses indicated that the greatest benefit occurred when levosimendan was administered pre‑operatively. Additional analyses suggested a possible reduction in intensive‑care unit length of stay and duration of mechanical ventilation, although the certainty of these findings ranged from moderate to very low. The review employed a random‑effects model, assessed heterogeneity and publication bias, and performed sensitivity and subgroup analyses, with results presented both textually and graphically. The manuscript underwent external peer review by the Cochrane Heart Group and was revised accordingly before submission to the Cochrane Database of Systematic Reviews, where it will be made freely available through Cochrane Gold Access.
The collaboration involved the University Medicine Halle (Saale), the Institute for Medical Epidemiology, Biostatistics and Informatics, the University Clinic and Polyclinic for Internal Medicine III, and the Cochrane Society’s Cochrane Heart thematic group. The project was funded by the German Federal Ministry of Education and Research under grant number 01KG2101 and ran from 1 July 2021 to 31 December 2022. The protocol was registered in PROSPERO (CRD42021260551) and published in the Cochrane Database of Systematic Reviews (DOI 10.1002/14651858.CD013781). Throughout the project, staff received training in Cochrane methodology, and a sustainable study group was established to support ongoing evidence synthesis. Findings were presented at national conferences, including the DGK Herztage 2022, the DGAI congress 2022, and the 2023 “Modifying Cardiovascular Ageing” symposium. The University Medicine Halle formally recognized the scientific contribution with a Letter of Merit. This coordinated effort has produced a high‑quality evidence synthesis that will inform clinical decision‑making and guide future research on prophylactic inotropic therapy in cardiac surgery.
