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Intravenous iron in the perioperative setting

To the Editor: In an attempt to provide a short term, practical, and effective regimen for perioperative anemia therapy as an alternative to autologous blood transfusion, Rutherford et al., evaluated three different regimens of recombinant human erythropoietin and concluded that irrespective of dose, “normal” iron stores for basal erythropoiesis may not always be sufficient to supply optimal amounts of iron for the accelerated erythropoiesis associated with acute recombinant erythropoietin administration, even with oral iron supplementation [1]. The comorbidity burden of surgical complications of perioperative anemia, present in one-third to one-half of all surgical patients remains clinically and economically formidable. Perioperative allogeneic blood transfusion is associated with an increased postoperative infection rate, longer hospital stays, poorer outcomes, and increased cost. Much of the data on the use of erythropoietic therapy in the perioperative setting is observational. Garcia Erce et al., randomized patients undergoing elective knee arthroplasty who had preoperative hemoglobin levels of <13.0 g/dl to one dose of 40,000 units of erythropoietin plus two 200 mg doses of intravenous iron sucrose plus or minus red cell salvage. Both arms were compared to intrainstitutional historic controls. The observed transfusion reduction was nearly 90% with no significant difference in the two treatment arms [2]. In a prospective, randomized controlled study Serrano et al. studied 200 patients with hip fractures and hemoglobin levels <12 g/dl randomized to the standard no treatment of 600 mg of intravenous iron sucrose without erythropoiesis stimulating agents, preoperatively [3]. Perioperative transfusions overall were reduced from 41 to 33% and with subcapital fractures, more likely to be transfused, from 46 to 14% with intravenous iron. No quantitatively significant toxicity was observed with intravenous iron in either study. Despite such a formidable benefit, regulatory bodies do not recommend the routine use of intravenous iron in anemic subjects undergoing elective surgery. Shander et al. described a multidisciplinary, multimodal, individualized strategy collectively termed Patient Blood Management with the aim to reduce allogeneic blood transfusion [4]. Perioperative anemia is detected and treated along with a higher transfusion threshold if or when transfusion is indicated. In an amalgam of published evidence (see Fig. 1, presented by Shander at the 2014 Annual Meeting of the European Society of Anaesthesiology) the use of allogeneic red blood cell transfusion provides the lowest benefit, highest risk, and sadly, has the highest use The Spanish consensus statement recommends routine, proactive diagnostic, and interventional anemia management [5]. In line with these conclusions, the clinical practice guidelines published by the American Association of Blood Banks [6] recommend adhering to a restrictive transfusion strategy (7–8 g/dl) in hospitalized stable patients as well as those with preexisting cardiovascular disease and limit transfusion to those with symptoms. In a pooled analysis of 2,547 perioperative patients who underwent either hip fracture repair or lower limb arthroplasty, Munoz et al. reported a decrement in transfusion rate from 48.8 to 32.4% in those who received perioperative intravenous iron versus those who did not [7]. Postoperative infections were reduced from 26.9 to 10.7%, length of stay from 13.4 to 11.9 days and remarkably thirty day mortality from 9.4 to 4.8% in the IV iron group. Nonetheless, perioperative anemia management is not a priority for most surgeons. A simple therapeutic paradigm directing the administration of intravenous iron 2–4 weeks preoperatively would now be nearly seamless with the availability of four new intravenous iron whose carbohydrate cores bind the elemental iron much more tightly, allowing full replacement dosing in a single 15–60 min visit. The cost/benefit would be substantial. In my community, the actual Committee for Medicare and Medicaid Services payment for two units of blood, administered in the ambulatory setting is greater than $5,200 based on Explanation of Benefit receipts mailed to patients. In contradistinction, the administration of a complete replacement dose of intravenous iron ranges from $290– $1,000 and avoids all of the morbidity of allogeneic blood transfusion. While this therapy has been proven to be safe and effective it remains underutilized. At a time when resources are scarce the adoption of intravenous iron as a standard for preoperative anemia is likely to be clinically and economically important as well as prognosis changing.