Is it time for a new standard?

As recently as March 23, 2013, at the annual meeting of the American Academy of Orthopedic Surgeons, a significant increase in infection rates was reported after total hip and knee arthroplasty in those who received allogeneic transfusion compared to autologous or no blood. In this issue of TRANSFUSION, Munoz and colleagues1 report the results of a pooled observational trial of 2547 perioperative patients who underwent elective lower limb arthroplasty or hip fracture repair who received intravenous (IV) iron with or without erythropoiesis-stimulating agents versus standard therapy consisting of oral or no iron. Transfusion rates in patients with hip fracture who received IV iron were 32.4% versus 48.8% in the non-IV iron therapy group. Postoperative nosocomial infection rates were 10.7% with IV iron versus 26.9% in non-IV iron therapy patients. Thirty-day mortality was 4.8% versus 9.4% and hospital stay of 11.9 days versus 13.4 days in iron versus non-IV iron groups. After elective arthroplasty, IV iron reduced transfusion rates and length of hospital stay (p = 0.001), with no difference in infection rates. The use of pooled data in an observational analysis could be a source of criticism but these significant improvements are consistent with the preponderance of published data demonstrating decreased morbidity with the use of IV iron. In a recent review by Shander and coworkers,2 a multidisciplinary, multimodal, individualized strategy, collectively termed patient blood management (PBM) used to minimize allogeneic blood transfusion, with the ultimate goal of improving patient outcomes was recommended. PBM detects and treats perioperative anemia, reduces blood loss and perioperative coagulopathy, and adopts a higher transfusion threshold if and when transfusion is needed. In the same journal, Goodnough and colleagues3 recommend a 30-day window to allow implementation of appropriate anemia therapy. These data are supported by a new published consensus statement from Spain recommending routine proactive interventional preoperative anemia management for elective surgery.4 Cuenca and colleagues5 in a retrospective study reported a decrement in allogeneic transfusions in patients who received IV iron undergoing surgery for hip fracture from 49% to 37%. In the subgroup sustaining subcapital fractures the observed reduction was from 37% to 15% or a greater than 59% decrement in transfusion rate. In dozens of studies extant, encompassing thousands of patients, no quantitatively significant toxicity was observed. In the experience of one author of this editorial (MA), at those institutions where a proactive anemia management protocol is in place, allogeneic blood transfusions are becoming uncommon.6 IV iron before spinal surgery has not been prospectively studied. Blood loss leading to anemia is considered a complication of spinal surgery if it leads directly or indirectly to an adverse event such as myocardial infarction or allogeneic transfusion. Other softer complications related to postoperative anemia include poorer rehab potential, extended hospital stay, and increased risk for surgical site infection. In major reconstructive spinal surgery, these associated factors are not trivial as extended in-hospital recovery and need for revision surgery may have potentially negative impact on outcomes. In a so-called back-of-the-envelope analysis at one of our institutions (JT) over the past 2 years, we have instituted several measures to reduce the need for allogeneic blood in the perioperative period. These include routine use of cell saver for multilevel spinal fusion procedures, thrombin-soaked gel foam in the surgical wound for hemostasis and perioperative administration of the antifibrinolytic tranexamic acid. Despite these measures, the transfusion rate for all spinal surgery patients over a 2-year period (2010-2012) was 16.7% (169 transfused/1008 cases). A total of 354 units of blood were transfused. Although further analysis of this preliminary data has not been performed (surgical or patient-specific risk factors for transfusion), we were surprised to discover a transfusion rate this high. If this experience is generalizable to other institutions, considerable room for improvements remain. To enhance the cost-effectiveness of spinal surgery we must either reduce the costs associated with any given surgical procedure or improve our surgical outcomes. Given the recently published evidence demonstrating that some of the most common spinal procedures are approaching the effectiveness of total hip replacement (long considered the gold standard surgical procedure in terms of quality of life improvement), the cost side of the cost-effectiveness equation is gaining much more attention.7 If IV iron administered proactively can substantially cut costs by decreasing allogeneic blood transfusion and at the same time reduce transfusion-related complications for spinal procedures, then widespread adoption in appropriately selected individuals should become the standard of care. Despite the known risks of anemia in cardiac and noncardiac surgical patients, perioperative anemia management is not a priority for most surgeons who are unlikely to administer iron 2 to 4 weeks preoperatively in divided doses before surgery. The availability of four formulations whose carbohydrate cores bind elemental iron tightly and release iron slowly allows complete replacement dosing in 1 hour or less, so that these patients can now be treated in a single visit. One barrier to promoting iron therapy for preoperative anemia as a routine measure has been the history of overstated safety concerns fueled by misinterpretation of the incidence and the clinical nature of adverse events.8 Inappropriate use of antihistamines as preinfusion medication may cause somnolence, diaphoresis, hypotension, and tachycardia attributed to the IV iron. In one series, the majority of perceived adverse events was due to the antihistamines.9 Minor and self-limited arthralgias and myalgias or flushing uncommonly occur with the test dose or early after the start of the infusion. These reactions usually require no intervention and resolve leaving no residua.10 Unfortunately, IV iron has been painted as “dangerous” and these minor reactions deemed as needing intervention, often with antihistamines and vasopressors; overtreatment of these minor reactions can convert them to serious hemodynamic events ostensibly attributed to the IV iron thus fueling the erroneous perception of danger. Such perception is further exacerbated by earlier reports of infrequent serious adverse events with high-molecular-weight iron dextran (now infrequently used), which included anaphylaxis and, rarely, death, discouraging physicians from thinking about IV iron as a credible tool in otherwise healthy patients. More recent data suggest that low-molecular-weight (LMW) iron dextran, ferumoxytol, ferric carboxymaltose, and iron isomaltoside (latter not approved in United States) have a much more favorable safety profile and in all prospective and intrainstitutional retrospective studies have been shown to be of equal efficacy and safety when compared to iron sucrose.11-15 A gram of LMW iron dextran can be safety administered in 1 hour16 and the other three formulations in 15 minutes.17 Given the growing litany of studies in orthopedic surgery, comprising thousands of patients, demonstrating decreased allogeneic blood transfusion, shorter hospital stays, decreased infections, and decreased perioperative morbidity with marginal to no toxicity, perhaps it is time to adopt IV iron as standard for perioperative anemic elective orthopedic surgical cases likely to require transfusion. Implementation of PBM includes detection, diagnosis, and treatment of anemia and when adhered to results in improved patient outcome and lower costs (ONTRAC–Canada). The adoption of IV iron with or without an erythropoiesis-stimulating agent 2 to 4 weeks before surgery has been demonstrated to be safe and effective in this population yet remains significantly underutilized. Overall benefits are likely to be clinically and economically important, changing the prognosis for treated patients. Neither author has any relevant financial disclosures.

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