An estimated 310 million patients undergo surgery worldwide each year.¹ The International Surgical Outcomes Study reported that, globally, 26.8% of patients who underwent major surgery had postoperative complications, and 24.3% of those who underwent low abdominal surgery developed complications.² These findings are similar to those of a previous study.³ Postoperative complications after major surgery have been shown to increase the length of stay (LOS), cost, and mortality.^4-6 Moreover, the presence of postoperative complications after colorectal surgery was associated with decreased long-term survival, independent of patient, disease, and treatment factors.³

Iron is an essential micronutrient, as it is required for adequate erythropoietic function, oxidative metabolism and cellular immune responses. Although the absorption of dietary iron (1-2 mg/d) is regulated tightly, it is just balanced with losses. Therefore, internal turnover of iron is essential to meet the requirements for erythropoiesis (20-30 mg/d). Increased iron requirements, limited external supply, and increased blood loss may lead to iron deficiency (ID) and iron-deficiency anemia. Hepcidin, which is made primarily in hepatocytes in response to liver iron levels, inflammation, hypoxia and anemia, is the main iron regulatory hormone. Once secreted into the circulation, hepcidin binds ferroportin on enterocytes and macrophages, which triggers its internalization and lysosomal degradation. Thus, in chronic inflammation, the excess of hepcidin decreases iron absorption and prevents iron recycling, which results in hypoferremia and iron-restricted erythropoiesis, despite normal iron stores (functional ID), and anemia of chronic disease (ACD), which can evolve to ACD plus true ID (ACD + ID). In contrast, low hepcidin expression may lead to iron overload, and vice versa. Laboratory tests provide evidence of iron depletion in the body, or reflect iron-deficient red cell production. The appropriate combination of these laboratory tests help to establish a correct diagnosis of ID status and anemia.

Main disorders of iron metabolism Increased iron requirements, limited external supply, and increased blood loss may lead to iron deficiency (ID) and iron deficiency anaemia. In chronic inflammation, the excess of hepcidin decreases iron absorption and prevents iron recycling, resulting in hypoferraemia and iron restricted erythropoiesis, despite normal iron stores (functional iron deficiency), and finally anaemia of chronic disease (ACD), which can evolve to ACD plus true ID (ACD+ID). In contrast, low hepcidin expression may lead to hereditary haemochromatosis (HH type I, mutations of the HFE gene) and type II (mutations of the hemojuvelin and hepcidin genes). Mutations of transferrin receptor 2 lead to HH type III, whereas those of the ferroportin gene lead to HH type IV. All these syndromes are characterised by iron overload. As transferrin becomes saturated in iron overload states, non-transferrin bound iron appears. Part of this iron is highly reactive (labile plasma iron), inducing free radical formation. Free radicals are responsible for the parenchymal cell injury associated with iron overload syndromes. Role of laboratory testing in diagnosis In iron deficiency status, laboratory tests may provide evidence of iron depletion in the body or reflect iron deficient red cell production. Increased transferrin saturation and/or ferritin levels are the main cues for further investigation of iron overload. The appropriate combination of different laboratory tests with an integrated algorithm will help to establish a correct diagnosis of iron overload, iron deficiency and anaemia. Review of treatment options Indications, advantages and side effects of the different options for treating iron overload (phlebotomy and iron chelators) and iron deficiency (oral or intravenous iron formulations) will be discussed.

Summary: Pre‐operative anaemia in patients undergoing major surgical procedures has been linked to poor outcomes. Therefore, early detection and treatment of pre‐operative anaemia is recommended. However, to effectively implement a pre‐operative anaemia management protocol, an estimation of its prevalence and main causes is needed. We analysed data from 3342 patients (44.5% female) scheduled for either: elective orthopaedic surgery (n = 1286); cardiac surgery (n = 691); colorectal cancer resection (n = 735); radical prostatectomy (n = 362); gynaecological surgery (n = 203) or resection of liver metastases (n = 122). For both sexes, anaemia was defined by a haemoglobin level < 130 g.l ⁻¹ ; absolute iron deficiency by ferritin < 30 ng.ml ⁻¹ (< 100 ng.ml ⁻¹ , if transferrin saturation < 20% or C‐reactive protein > 5 mg.l ⁻¹ ); iron sequestration by transferrin saturation < 20% and ferritin > 100 ng.ml ⁻¹ ; and low iron stores by transferrin saturation > 20% and ferritin 30–100 ng.ml ⁻¹ . The overall prevalence of anaemia was 36%, with differences according to the type of surgery. Laboratory parameters allowing classification of iron status were available for 2884 patients. Among those with anaemia (n = 986), 677 (69%) were women, 608 (62%) presented with absolute iron deficiency, 101 (10%) with iron sequestration; and 150 (5%) with low iron stores. Iron status alterations were similar in women with haemoglobin < 130 g.l ⁻¹ or < 120 g.l ⁻¹ . For those who were not anaemic (n = 1898), corresponding figures were 656 (35%), 621 (33%), 165 (9%) and 518 (27%), respectively. Anaemia was present in one‐third of patients undergoing major elective procedures. Over two‐thirds of anaemic patients presented with absolute iron deficiency or iron sequestration. Over half of non‐anaemic patients presented with absolute iron deficiency or low iron stores. We consider these data useful for planning pre‐operative management of patients scheduled for major elective surgery.

A multidisciplinary panel of physicians was convened by Network for Advancement of Transfusion Alternatives to review the evidence on the efficacy and safety of i.v. iron administration to increase haemoglobin levels and reduce blood transfusion in patients undergoing surgery, and to develop a consensus statement on perioperative use of i.v. iron as a transfusion alternative. After conducting a systematic literature search to identify the relevant studies, critical evaluation of the evidence was performed and recommendations formulated using the Grades of Recommendation Assessment, Development and Evaluation Working Group methodology. Two randomized controlled trials (RCTs) and six observational studies in orthopaedic and cardiac surgery were evaluated. Overall, there was little benefit found for the use of i.v. iron. At best, i.v. iron supplementation was found to reduce the proportion of patients requiring transfusions and the number of transfused units in observational studies in orthopaedic surgery but not in cardiac surgery. The two RCTs had serious limitations and the six observational limited by the selection of the control groups. Thus, the quality of the available evidence is considered moderate to very low. For patients undergoing orthopaedic surgery and expected to develop severe postoperative anaemia, the panel suggests i.v. iron administration during the perioperative period (weak recommendation based on moderate/low-quality evidence). For all other types of surgery, no evidence-based recommendation can be made. The panel recommends that large, prospective, RCTs be undertaken to evaluate the efficacy and safety of i.v. iron administration in surgical patients. The implementation of some general good practice points is suggested.