General Characteristics of the Included Studies.

BackgroundHigh-dose intravenous iron supplementation offers substantial hematologic protective benefits in clinical practice; however, its efficacy in enhancing blood protection during cardiac surgery remains uncertain. The present study aimed to investigate the effects and safety of high-dose intravenous iron as an optimal blood management strategy for patients undergoing cardiac procedures.MethodsMajor databases, including PubMed, Embase, and Cochrane, were searched on June 20, 2025, for randomized controlled trials (RCTs) comparing red blood cell transfusion rates in adult patients undergoing high-dose intravenous iron supplementation versus those receiving control therapy (placebo) following cardiac surgery. The secondary outcome measures included postoperative hemoglobin levels, length of hospital stay, and incidence of adverse events.ResultsSeven RCTs involving 975 subjects were identified in the database search. Compared with the control group (placebo), high-dose intravenous iron significantly decreased the rate of postoperative red blood cell transfusion among patients undergoing cardiac surgery (risk ratio 0.69, 95% confidence interval [CI] 0.52–0.91, P = 0.009, I2 = 61%, n = 975, certainty of evidence: moderate). Furthermore, one week or more following surgery, administration of high-dose intravenous iron resulted in a significant increase in postoperative hemoglobin levels (mean difference 0.71, 95% CI 0.41 to 1.01, P 2 = 63%, certainty of evidence: moderate). Significant differences between the groups were not observed for the other outcome measures, including mortality, infection rates, and cardiovascular events.ConclusionsHigh-dose intravenous iron supplementation during the perioperative period of cardiac surgery significantly reduces the risk of red blood cell transfusion and enhances postoperative hemoglobin levels. Although the present study demonstrated a favorable safety profile for intravenous iron administration, the limitations of the present meta-analysis necessitate continued vigilance regarding potential drug-related risks associated with intravenous iron therapy. Systematic review protocol: CRD420251069827 (PROSPERO).