Intravenous Iron Successfully Treats Postoperative Anemia, Oral Ineffective

A recent meta-analysis of post-surgery iron therapy revealed that intravenous iron had a substantial effect on raising hemoglobin levels and preventing anemia, while oral iron therapy exhibited no benefit.1

Investigators at the University of Western Australia examined fifteen randomized controlled trials highlighting 1865 adults with postoperative anemia, with a mean age ranging from 46 to 75 years, and more than half (50.8%) of the patients were female. The team identified an increase in hemoglobin levels in the intravenous group compared to the control group, while the oral iron group exhibited no significant difference.

“The aim of our review was to assess the efficacy of intravenous iron and oral iron administered after major surgery in improving postoperative haemoglobin levels and to identify which surgical population may have the greatest benefit from iron therapy,” wrote the investigative team, led by Jayne Lim, school of medicine, The University of Western Australia.1

Anemia is a significant risk to surgical patients, leading to increased chances of allogeneic red blood cell transfusion, delayed recovery, and potential mortality. Studies have indicated that patients with postoperative anemia have an 18% risk of disability or death up to three months after an operation, while those without had a 9% risk.2

The search identified 379 records: after removing duplicate studies and excluding others due to risks of bias, the results were narrowed to 15 for the meta-analysis. Among these, six investigated oral iron therapy, seven intravenous iron therapy, and two compared both methods.

Upon analysis, Lim and colleagues found intravenous or oral iron increased hemoglobin levels compared with placebo or no intervention (P <.01). Further analysis showed intravenous iron significantly boosted hemoglobin levels (mean difference [MD], 4.51 g.l-1, 95%CI 2.63–6.38, I2 = 0%, P < 0.01), while oral iron showed no significant benefit after surgery (MD, 0.61 g.l-1, 95%CI -2.79–4.01, I2 = 23%, P = 0.66).1

After excluding four studies with high risk of bias, Lim and colleagues identified an increase in hemoglobin levels in the intravenous group (MD 4.53 g.l-1, 95%CI, 2.28-6.78, I2 = 0%, P <0.01) and no significant difference in the oral iron group (MD 1.93 g.l-1, 95%CI, -3.74-7.61, I2 = 0%, P = 0.19), compared with control.1

Subgroup analysis based on surgical operations–including cardiac, orthopedic, and gastrectomy–indicated that the greatest benefit was the treatment of anemic patients after orthopedic surgery (MD 3.63 g.l-1, 95% CI, 0.78-6.47, I2 = 20%, P = 0.02). Neither method of treatment resulted in higher hemoglobin levels after cardiac surgery (MD1.61 g.l-1, 95%CI, -2.21-5.44, I2 = 36%, P = 0.33).1

Lim and colleagues suggest the inflammatory response to surgery causes a surge in hepcidin, and prevents iron transport and tissue storage. Although there is no clear answer on how long the surge remains in the system, they noted it is likely to last at least one month.1

The other potential explanation lies in iron’s already low absorption rate, with Lim and colleagues indicating a healthy individual can only absorb approximately 200 mg every month on an iron supplementation course.

To alleviate anemic symptoms, an oral iron supplementation course could last 4-6 months, with no guarantee of tolerance. Intravenous iron, however, can be injected 30-45 minutes after an operation, circumventing both the malabsorption period and negative digestive effects linked to oral iron.

Intravenous iron has long been used to treat preoperative anemia; However, Lim and colleagues noted an issue in consistently identifying and responding to preoperative anemia. Intravenous administration can avoid these challenges, as the patient will already have venous access and monitoring in place.1

“A broader challenge remains in the lack of consensus on how to measure recovery after surgery,” writes Lim and colleagues. “While immediate postoperative adverse events can be monitored using tools such as the Clavien-Dindo classification, there is no standardised assessment to evaluate ‘recovery’ comprehensively.”1

References

1. Lim J, Joo J, MacLean B, Richards T. The use of iron after surgery: A systematic review and meta‐analysis. Anaesthesia. Published online March 24, 2025. doi:10.1111/anae.16605

2. Myles PS, Richards T, Klein A, et al. Postoperative anaemia and patient-centred outcomes after major abdominal surgery: A retrospective cohort study. British Journal of Anaesthesia. 2022;129(3):346-354. doi:10.1016/j.bja.2022.06.014