Timing of intravenous iron for treatment of anaemia in surgical patients: a systematic review and network meta-analysis

Authors: Liu C, Han J, Fu R, Li T, Margonis GA, Wang JJ, Ma K, Wang W, Lin C

Affiliation: Peking Union Medical College Hospital (CAMS/PUMC) + collaborators (MSKCC, UCSF, etc.)

Journal: eClinicalMedicine (The Lancet group), July 2025

PMID: 40727015

Key takeaways

• Postop IV iron reduced transfusion versus control (RR 0.80, 95% CI 0.68–0.94; I²=0%).

• Preop IV iron did not reduce transfusion versus control (RR 0.91, 0.72–1.15; I²=0%).

• Hemoglobin (Hb) recovery: no clear benefit by POD7; by POD30 both strategies improved Hb versus control, with preop > postop (preop vs postop MD 6.67, 1.61–11.72).

• Postop IV iron increased early iron indices (POD7 ferritin/TSAT), but this did not translate into earlier Hb rise at POD7.

• No signal that IV iron timing changes length of stay, complications, mortality, or drug-related adverse events in pooled analyses.

Background

Perioperative anemia is common and is associated with worse surgical recovery and higher transfusion exposure. Intravenous (IV) iron is widely used in patient blood management, but the optimal timing, preoperative “prehabilitation” versus postoperative “rescue”, remains uncertain.

Objective

Compare preoperative (7–30 days before) versus postoperative (0–30 days after) IV iron in surgical patients for transfusion, Hb recovery, safety, and related outcomes.

Methods

• Design: Systematic review + meta-analysis of randomized controlled trials (RCTs) of patients receiving IV iron

• Search: PubMed/EMBASE/Cochrane/Web of Science through May 1, 2025; English only.

• Included studies/patients: 22 RCTs; 3026 patients; mean age 65.8; ~54% women; cardiac, abdominal, orthopedic and other surgeries.

• Interventions: IV iron (various dosages from 300 mg–3 g); multiple formulations (iron sucrose, ferric carboxymaltose, ferric derisomaltose, iron polymaltose).

• Comparators: placebo/standard care/oral iron (varied across trials).

• Primary endpoints: (1) proportion transfused; (2) Hb change from baseline to POD7 and POD30.

• Secondary endpoints: POD7 ferritin/TSAT; length of stay; complications; adverse events; mortality; quality of life.

Results

• Transfusion (19 studies; n=2847):

  • Postop IV iron vs control: RR 0.80 (0.68–0.94), I²=0%.

  • Preop IV iron vs control: RR 0.91 (0.72–1.15), I²=0%.

  • Indirect preop vs postop: RR 0.88 (0.66–1.17) (no significant difference).

  • Subgroup signal: postop transfusion reduction was largely driven by cardiac surgery trials*.

• Hb change POD7 (6 studies; n=586):

  • Preop vs control: MD 4.64 (−4.49 to 13.78) (not significant).

  • Postop vs control: MD −4.51 (−9.75 to 0.72) (not significant; high heterogeneity).

• Hb change POD30 (7 studies; n=905):

  • Preop vs control: MD 12.11 (7.88–16.35).

  • Postop vs control: MD 5.45 (2.70–8.20).

  • Preop vs postop: MD 6.67 (1.61–11.72) (preop better at ~1 month).

• Iron indices POD7:

  • Ferritin: postop vs control increased (large MD); preop vs control not significant.

  • TSAT: postop vs control increased; preop vs control not significant.

• LOS/complications/adverse events/mortality: no significant differences across strategies.

Conclusion

Postoperative IV iron is associated with lower transfusion rates, while preoperative IV iron yields better hemoglobin recovery by POD30; either approach can be selected based on patient goals and context, recognizing heterogeneity and lack of direct head-to-head trials.

Strengths

• Clinically meaningful timing windows (preop 7–30 days; postop 0–30 days).

• RCT-only inclusion with formal risk-of-bias assessment.

• Network meta-analysis enables an indirect timing comparison despite absent head-to-head trials.

Limitations

• No direct preop vs postop RCTs; indirect comparisons are vulnerable to differences in surgery type, transfusion protocols, and trial era.

• “Timing” may be confounded by phenotype: preop trials often enroll preop anemia (often iron deficiency anemia), whereas postop trials often enroll postoperative anemia/functional iron deficiency.

• Control arms vary (placebo vs oral iron vs usual care); transfusion triggers are inconsistent across trials.

• Early Hb (POD7) is biologically and clinically noisy; heterogeneity is high in postop POD7 Hb.

Clinical relevance

Early postoperative IV iron shows the clearest signal for reducing transfusion exposure (notably in cardiac surgery–heavy datasets), whereas IV iron given 1–4 weeks preop is associated with a better hemoglobin trajectory by ~1 month. In practical terms, preop iron “optimizes the runway,” postop iron “rescues the crash,” and neither strategy should be expected to meaningfully raise Hb by POD7.