J Cardiothorac Surg. 2026 Jun 6. doi: 10.1186/s13019-026-04309-0. Online ahead of print.
ABSTRACT
BACKGROUND: Preoperative intravenous iron has become increasingly popular as a strategy to optimize hemoglobin before major surgery. However, its potential benefit in non-anaemic patients undergoing cardiac surgery remains unclear. To address this uncertainty, we conducted a systematic review and meta-analysis to investigate whether preoperative IV iron reduces red blood cell transfusion requirements and improves hematologic and clinical outcomes in adults with normal baseline hemoglobin undergoing cardiac surgery.
METHODS: We conducted a systematic review and meta-analysis following PRISMA 2020 guidelines. We searched PubMed, Embase, Scopus, Web of Science, and the Cochrane Library until October 2025 for randomized controlled trials. Eligible studies compared preoperative IV iron to a control (placebo, saline, or standard care) in non-anaemic (per WHO definition) adult patients (≥ 18 years) undergoing cardiac surgery. The primary outcomes were the incidence of postoperative RBC transfusion and the number of units transfused. Secondary outcomes included postoperative hemoglobin level, Postoperative iron indices, length of ICU stay, length of hospital stay (LOS), overall postoperative infection, All-cause mortality, and adverse events possibly related to IV iron (hypersensitivity, anaphylaxis). We used the Cochrane ROB 2 tool for bias assessment and for evidence certainty. Pooled Risk ratios, odds ratios, mean difference, and standardized mean difference with 95% confidence intervals were calculated using random-effects models, with the fixed-effects model applied when heterogeneity was absent or low (I² < 10%).
RESULTS: From 529 initial records, 3 RCTs met the inclusion criteria, encompassing 338 patients. The overall risk of bias was low to moderate. Preoperative IV iron significantly reduced the incidence of postoperative RBC transfusion compared to the control group (Risk Ratio [RR] = 0.62; 95% CI 0.43-0.88; p = 0.008; I² = 0%), representing a 38% relative risk reduction. Furthermore, IV iron significantly decreased the mean number of RBC units transfused (Mean Difference [MD] = – 1.08 units; 95% CI – 1.61 to – 0.54; I² = 0%). While no significant difference was observed in hemoglobin levels at 48 h or one week postoperatively, the IV iron group showed significantly higher hemoglobin at 4-6 weeks (MD = 0.84 g/dL; 95% CI 0.41-1.26; p = 0.0001). IV iron also significantly increased postoperative serum ferritin and transferrin saturation. There were no statistically significant differences in overall postoperative infection rates (RR = 1.16; 95% CI 0.64-2.08) or all-cause mortality (Risk Difference = – 0.00; 95% CI – 0.03 to 0.03). The GRADE certainty of evidence for the primary outcome was moderate.
CONCLUSION: In non-anaemic adult patients undergoing cardiac surgery, preoperative IV iron administration significantly reduces the incidence of postoperative RBC transfusion and the total volume of blood transfused. This intervention also improves hemoglobin levels during the 4-6 week recovery period without an increased risk of infection or mortality. The moderate-certainty evidence suggests this is a beneficial strategy, though further adequately powered RCTs are warranted to strengthen these findings.
PROSPERO REGISTRY REFERENCE: CRD420251161421.
PMID:42251415 | DOI:10.1186/s13019-026-04309-0
