Intravenous Iron Administration Research Articles

Preoperative anemia management with intravenous iron: a systematic review

Background Iron deficiency anemia is a common condition in patients presenting for surgery, but despite its negative health impacts, the condition remains frequently unmanaged. Optimizing the patient’s own red cell mass should be addressed in the preoperative period. Intravenous iron has been advocated as an effective treatment modality. Objectives The objective of this systematic review was to critically appraise and synthesize the best available evidence related to the effectiveness and economic aspects of intravenous iron administration on the correction of iron deficiency anemia in the preoperative period. Inclusion criteria Types of participants Adult patients 18 years of age and older receiving intravenous iron compared with those taking iron orally, and those who were not on iron or were transfused with red blood cells for the correction of anemia. Studies assessing the economic aspects of anemia management were also considered. Types of intervention(s)/phenomena of interest The quantitative component of the review considered studies that evaluated the management of anemia with iron infusions compared to oral iron treatment alone, oral iron in combination with erythropoietin, erythropoietin alone or hemoglobin correction with blood transfusion. The economic component of this review considered studies that evaluated the costs and benefits of iron infusions compared to oral iron treatment or hemoglobin correction with blood transfusion for the treatment of preoperative anemia. Types of studies The quantitative component of the review considered any experimental study design including randomized controlled trials (RCTs), non-RCTs and quasi-experimental studies for inclusion. The economic component of the review considered cost effectiveness, cost utility and cost benefit studies for inclusion. Types of outcomes The quantitative component of this review considered studies that reported on the impact of intravenous iron administration on: hemoglobin levels, red blood cell transfusion, length of stay in hospital, rate of readmission within 30 days of discharge, incidence of transfusion-related complications and changes in functional outcomes. The economic component of the review focused on cost benefits resulting from intravenous iron administration. Search strategy The search strategy aimed to find both published and unpublished studies. A three-step search strategy was utilized in this review. Studies published in English, German, Italian and Dutch from 2001 until December 2012 were considered for inclusion in this review. Methodological quality The studies were independently assessed by two reviewers using standardized critical appraisal instruments from the Joanna Briggs Institute. Data collection Quantitative data was extracted from papers included in the review using the standardized data extraction tool from the Joanna Briggs Institute, specifically the Meta Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI). Economic data was extracted from papers included in the review using the standardized data extraction tool from the Joanna Briggs Institute Analysis of Cost, Technology and Utilisation Assessment and Review Instrument (JBI-ACTUARI). Data synthesis This review set out to conduct both meta-analyses of the findings of effectiveness studies using JBI-MAStARI and pooling of economic findings using JBI-ACTUARI. Because of the number of studies found, this was not possible and the findings are therefore presented in tabular or narrative form. Results The quantitative component of the review identified two RCTs for inclusion with one of the trials favoring intravenous iron over oral iron for anemia correction. Only a subgroup could be included from the second trial and the results were inconclusive. Data was heterogeneous and did not allow a meta-analysis. The search for the economic component of the review revealed no examination of the cost effectiveness of preoperative correction of iron deficiency anemia with intravenous iron. Conclusions The review found insufficient data to make firm conclusions about the effectiveness of preoperative intravenous iron administration for the correction of anemia. Neither could we establish firm conclusions on the potential cost savings due to intravenous iron supplementation.

Darbepoetin‐alfa and intravenous iron administration after autologous hematopoietic stem cell transplantation: A prospective multicenter randomized trial

We conducted a randomized study analyzing the impact of darbepoetin alfa (DA) administration with or without intravenous (i.v.) iron on erythroid recovery after autologous hematopoietic cell transplantation (HCT). Patients were randomized between no DA (Arm 1), DA 300 μg every 2 weeks starting on Day 28 after HCT (Arm 2), or DA plus i.v. iron 200 mg on Days 28, 42, and 56 (Arm 3). The proportion achieving complete hemoglobin (Hb) response within 18 weeks (primary end point) was 21% in Arm 1 (n = 24), 79% in Arm 2 (n = 25), and 100% in Arm 3 (n = 23; P < 0.0001). Erythropoietic response was shown to be significantly higher in Arm 3 (n = 46) than in Arm 2 (n = 50; P = 0.008), resulting in lower DA use, reduced drug costs, and improved quality of life scores, but the effect on transfusions was not significant. In multivariate analysis, DA administration (P < 0.0001), i.v. iron administration (P = 0.0010), high baseline Hb (P < 0.0001), and low baseline creatinine (P = 0.0458) were independently associated with faster achievement of complete Hb response. In conclusion, DA is highly effective to ensure full erythroid reconstitution after autologous HCT when started on Day 28 post-transplant. I.v. iron sucrose further improves erythroid recovery.

Effect of intravenous iron on exercise capacity and quality of life in iron deficient pulmonary arterial hypertension patients

Background: Pulmonary arterial hypertension (PAH) is a gradually worsening disease with an unfavourable outcome. Iron deficiency seemingly has an essential part in the progress of the disease, as its relationship with disease severity and mortality from any cause has been demonstrated. While suitable substitution therapy may be advantageous (analogous to patients with left heart failure), iron absorption from the gut is suppressed in PAH by hepcidin, the master regulator of iron metabolism. We therefore examined the potential benefit of intravenous iron administration in iron deficient PAH patients. Methods: A single infusion of ≤ 1000 mg ferric carboxymaltose was administered to 20 iron deficient patients with PAH (NYHA-FC II/III) on stable background PAH treatment. These patients were assessed at baseline and two months after intervention. The 6-minute-walking distance (6MWD) was measured to assess exercise capacity and the SF-36 questionnaire (100 point scale) was used to evaluate quality of life. The results were compared with 20 matched patients with stable disease who were not given iron infusions. Results: In patients with iron deficiency, iron infusion led to a markedly enhanced iron status (serum iron 5.7±2.0 to 11.1±5.0 μmol/l, ferritin 29.3±28.2 to 145.2±113.7 μg/dl, transferrin saturation 7.5±3.1 to 19.3±10.2%, all p<0.001), whereas no differences in iron status were seen in the control group. Ferric carboxymaltose lead to a mean increase in the 6MWD of 37.8 m in patients with iron deficiency compared with controls (95% CL -40.8, 116.4 m; mean increase from 346.5±126.4 to 374.0±113.9 m; p=0.003), and quality of life improved, too (raise of the SF-36 score from 44.3±16.5 to 50.6±15.9; p=0.01). There were only slight adverse effects. Expectedly, no significant differences in exercise capacity were found in the control group not receiving iron infusions (6MWD 389.9±113.1 vs. 379.6±117.3 m; n.s.). Conclusions: Our study shows that intravenous iron loading with ferric carboxymaltose is well tolerated in iron deficienct PAH patients and has significant benefit on exercise capacity and quality of life in addition to background PAH therapies. These benefits warrant additional studies to assess the value of iron as supplementary therapy for an extended population of PAH patients.

Spanish Consensus Statement on alternatives to allogeneic blood transfusion: the 2013 update of the "Seville Document".

Grade 1A recommendations We recommend: The use of restrictive transfusion strategies in nonbleeding, euvolaemic anaemic patients. Perioperative administration of tranexamic acid to patients undergoing cardiac surgery. The administration of intravenous iron to cancer patients, as an adjuvant to erythropoiesis-stimulating agents, for correcting chemotherapy-induced anaemia. Preoperative administration of erythropoiesisstimulating agents to anaemic, orthopaedic surgical patients expected to have moderate blood losses. We do not recommend: The administration of desmopressin to patients undergoing elective surgery. The administration of erythropoiesis-stimulating agents to critically ill patients who do not have a previous indication for this therapy.

Administration of intravenous iron complexes on implantable central venous access port in cancer patients in France: the FERPAC survey

Implantable central venous access port (portacath) is used to provide long-term venous access and to deliver chemotherapy in cancer patients. Intravenous iron complexes are frequently prescribed in this setting, and some physicians use a portacath for their administration. The aim of this survey was to assess the frequency of this practice and the reasons supporting it. This declarative survey was conducted in France; 497 oncologists/hematologists were contacted to answer a survey on their practices regarding the administration of intravenous iron via a portacath. A total of 141 recipients (29.5 %) completed the questionnaire. The intravenous iron complexes most frequently used were iron sucrose and ferric carboxymaltose, and 55.2 % of the responders reported using a portacath to administer intravenous iron complexes. The main reasons mentioned for this practice were ease of administration (27.9 %) and preservation of venous capital (27.6 %). The main reasons reported for not using a portacath to administer intravenous iron were a history of thrombosis (45.1 %) or potential drug interactions (17.7 %). Efficacy and safety were expected to be similar to those observed with peripheral administration. A 47.6 % of physicians declared that they usually did not observe adverse reactions after use of a portacath for iron administration. Intravenous iron administration was always planned after chemotherapy for 46.6 % of the responders and before chemotherapy for 38.2 %, whereas 15.3 % did not have any preference for either option. Intravenous iron complexes (mainly iron sucrose and ferric carboxymaltose) are commonly administered through a portacath in cancer patients in France. The choice for this route of administration is supported by clinical considerations, but further studies are needed to confirm the efficacy and safety of this practice.

Severe and prolonged hypophosphatemia after intravenous iron administration in a malnourished patient

Effects of a Protein Optimized Diet Combined with Moderate Resistance Training on the Postoperative Course in Older Patients with Hip Fracture

Pomegranate juice intake attenuates the increase in oxidative stress induced by intravenous iron during hemodialysis

The hemodialysis (HD) procedure induces oxidative stress (OS), which is further aggravated by intravenous (IV) iron administration, aimed at correcting anemia of patients with HD. We have recently shown that 1 year of pomegranate juice (PJ) intake attenuated OS and inflammation in patients with HD. In the current study, we hypothesized that a single dose of PJ can attenuate the enhanced OS and inflammation induced by both the dialysis procedure and IV iron administration during HD session. Twenty-seven patients with HD were randomized to receive PJ or placebo during 1 dialysis session with IV iron. Blood samples were drawn before and after the session to asses OS biomarkers such as advanced oxidation protein products and myeloperoxidase (MPO), whereas polymorphonuclear leukocyte (PMNL) counts served as an indirect measure of inflammation. At the end of the dialysis session, an increase in advanced oxidation protein products and MPO levels as well as a decrease in PMNLs counts were observed in the placebo group, whereas no significant changes occurred in the PJ group. The postdialysis increase in MPO levels in the placebo group is a direct result of PMNL degranulation, associated with postdialysis decrease in PMNL counts. Degranulation of PMNLs leads to the release of other cell moieties, such as inflammatory mediators and proteases that enhance inflammation. We conclude that PJ intake attenuated the increase in systemic OS and inflammation induced by IV iron administration during the dialysis session. These beneficial effects illuminate the previously observed attenuation in OS and inflammation in patients with HD on prolonged PJ intake.

931Beneficial effect of intravenous iron administration on left ventricular remodelling in patients with acute ST-elevation myocardial infarction – a cardiovascular magnetic resonance (CMR) study

Background: The infusion of iron has been associated with improved symptoms, functional capacity, and quality of life in patients with heart failure and chronic myocardial infarction – even in the absence of anemia. Objectives: We aimed to investigate the safety profile and effect of intravenous iron administration on short-term ventricular remodeling in patients with myocardial infarction in the acute setting. Material and methods: Seventeen study patients (IRON, 54 ± 9 yrs, 88% male) and 22 matched controls (CONTROL, 57 ± 9 yrs, 77% male) both with primary reperfused ST-elevation myocardial infarctions (STEMI) underwent cine and late gadolinium enhancement cardiovascular magnetic resonance (CMR) imaging in the first week and three months after the acute event. IRON patients received a unique intravenous bolus of 510 mg elemental iron as ferumoxytol (Feraheme®) in the 24 hours following the first CMR exam. Results: Ferumoxytol administration was well tolerated by all patients, with no adverse events. No significant differences regarding baseline infarct characteristics or ventricular function were present between groups. At 3 months follow-up, all patients were alive, with no new adverse cardiac events. In both groups significant changes in left ventricular ejection fraction (IRON: 53 ± 10 to 59 ± 9%, p = 0.002; CONTROL: 54 ± 6 to 57 ± 10, p = 0.005), LV mass index (IRON: 65, 59-76 gr/m2 to 54, 38-114 gr/m2, p = 0.0006; CONTROL: 65, 58-92 gr/m2 to 62, 49-74 gr/m2, p<0.0001) and infarct size (IRON: 27 ± 8 to 17 ± 9%, p<0.0001; CONTROL: 27 ± 12 to 20 ± 11, p<0.0001) were seen at follow-up with a clear (but non-significant) trend towards a higher increase in ejection fraction and smaller scars in the IRON group. In addition, in IRON but not in CONTROL patients, significant decreases in LV end systolic volume (71 ± 25 to 59 ± 25 mL, p = 0.002) and transmural infarctions (17, 100% to 7, 41%, p = 0.0003) were encountered. Conclusion: Intravenous iron administration in acute STEMI patients is associated with both improved infarct healing and beneficial global left ventricular remodeling compared to controls. Moreover, a good safety profile for iron administration was observed.

Very‐short‐term perioperative intravenous iron administration and postoperative outcome in major orthopedic surgery: a pooled analysis of observational data from 2547 patients

Postoperative nosocomial infection (PNI) is a severe complication in surgical patients. Known risk factors of PNI such as allogeneic blood transfusions (ABTs), anemia, and iron deficiency are manageable with perioperative intravenous (IV) iron therapy. To address potential concerns about IV iron and the risk of PNI, we studied a large series of orthopedic surgical patients for possible relations between IV iron, ABT, and PNI. Pooled data on ABT, PNI, 30-day mortality, and length of hospital stay (LHS) from 2547 patients undergoing elective lower-limb arthroplasty (n = 1186) or hip fracture repair (n = 1361) were compared between patients who received either very-short-term perioperative IV iron (200-600 mg; n = 1538), with or without recombinant human erythropoietin (rHuEPO; 40,000 IU), or standard treatment (n = 1009). Compared to standard therapy, perioperative IV iron reduced rates of ABT (32.4% vs. 48.8%; p = 0.001), PNI (10.7% vs. 26.9%; p = 0.001), and 30-day mortality (4.8% vs. 9.4%; p = 0.003) and the LHS (11.9 days vs. 13.4 days; p = 0.001) in hip fracture patients. These benefits were observed in both transfused and nontransfused patients. Also in elective arthroplasty, IV iron reduced ABT rates (8.9% vs. 30.1%; p = 0.001) and LHS (8.4 days vs.10.7 days; p = 0.001), without differences in PNI rates (2.8% vs. 3.7%; p = 0.417), and there was no 30-day mortality. Despite known limitations of pooled observational analyses, these results suggest that very-short-term perioperative administration of IV iron, with or without rHuEPO, in major lower limb orthopedic procedures is associated with reduced ABT rates and LHS, without increasing postoperative morbidity or mortality.

High-risk anaemic Jehovah's Witness patients should be managed in the intensive care unit.

Severely anaemic Jehovah’s Witness (JW) patients who refuse blood transfusion on religious grounds have high mortality and morbidity1,2. Carson et al. have shown that the odds of death increase 2.5 times for every 10 g/L postoperative haemoglobin (Hb) decrease below 70 g/L3. The latest study4 demonstrated that an unadjusted nadir Hb concentration is a poor predictor of mortality of anaemic JW patients (Figure 1). Early risk factors including age ≥45 years of age, weight ≥90 kg, hypertension, cardiac arrhythmia, angina, previous myocardial infarction, valvular heart disease, heart failure, being on haemodialysis, acute admission and Hb ≤80 g/L on admission to hospital are associated with mortality of anaemic JW patients5. It was shown that an Auckland Anaemia Mortality Risk Score (Auckland AMRS), which is a composite score of the number of early risk factors each anaemic JW patient had, was associated with mortality. JW patients with Auckland AMRS of 0 to 3 had 4% mortality, Auckland AMRS 4 to 5, 32%, Auckland AMRS 6 to 7, 50% and Auckland AMRS ≥8, 83%5. During their hospital stay JW patients can develop anaemia-related (late) mortality risk factors including shock, acute gastro-intestinal bleeding, pneumonia, nadir Hb concentration ≤70 g/L, septicaemia, worsened congestive heart failure and neurologic complications4. Among these late risk factors, shock was the strongest predictor of mortality followed by acute gastro-intestinal bleeding and pneumonia. Figure 1 ROC curve: Nadir haemoglobin concentration as a predictor of Jehovah’s Witness patients mortality. When weights of individual statistically significant anaemia-related risk factors of mortality were combined and a composite mortality risk score, the Hamilton Anaemia Mortality Risk Score (Hamilton AMRS), was calculated, it was shown that JW patients with Hamilton AMRS of 0 to 2 had 4% mortality, Hamilton AMRS of 3 to 4, 29%, Hamilton AMRS of 5, 40%, and Hamilton AMRS of ≥6, 67%. On admission to hospital the trauma patient described by Lorentzen et al.6 had an Auckland AMRS of 3 (age, acute admission and Hb ≤80 g/L on admission to hospital) and a Hamilton AMRS of 6 (shock, ischaemic bowel perforation and the nadir Hb concentration ≤70 g/L) that estimated the patient’s mortality risk exceeding 70%. The patient underwent an open bowel resection and was managed in an intensive care unit (ICU) with physiologic parameters monitoring, ventilatory support, fluid resuscitation and an administration of vasopressors. The patient’s infective complications were treated with broad spectrum intravenous antibiotics, collection drainage, and wounds debridement and washout. Also the patient was treated with intravenous iron, B12 supplementation and subcutaneous administration of erythropoetin (EPO) in the dose of 10,000 units every second day. JW patients accept EPO, which is an erythropoiesis stimulating agent, as an alternative to blood transfusion. EPO is a 165 amino-acid glycoprotein, which is mainly produced by renal peritubular capillary endothelial cells in response to hypoxia7. As a haematopoietic cytokine, EPO promotes proliferation, differentiation and survival of erythroid progenitor cells8. In addition, EPO exerts a potent protective effect against hypoxia through its anti-apoptotic action9. After binding to its receptor on the cell surface, EPO initiates a JAK2 signalling cascade leading to NF-kB- and STAT5-dependent transcription of anti-apoptotic genes, including Bcl-xL, Bcl-210. Furthermore, EPO exerts a potent vascular protection and induces neoangiogenesis11–13.

Management of iron deficiency and anemia after Roux-en-Y gastric bypass surgery: An observational study

BackgroundIron deficiency (ID) is common after Roux-en-Y gastric bypass surgery (RYGB). Optimal iron management in this population is unclear. The objective of this study was to assess our management of RYGB patients with ID and anemia. MethodsClinic visit records of RYGB patients with ID or anemia from January 1, 2008, to February 1, 2010 were evaluated. Demographic characteristics, postsurgery iron and anemia indices, and prescribed treatments were recorded. Three separate definitions for ID and anemia were used (standard textbook, ASBMS, and recent literature). An intravenous iron protocol was later implemented, and follow-up laboratory values were obtained. ResultsA total of 125 with ID or anemia (89% female, 86% Caucasian), mean (SD) age 44.7 (8.6) years, and BMI 47.3 (10.8) kg/m2 at time of RYGB, were included. Proportion of values meeting criteria for ID or anemia at first follow-up: standard textbook, hemoglobin (Hb, 35%), transferrin saturation (Tsat, 48%), ferritin (28%); ASBMS, ferritin (43%); recent literature, ferritin (58%), serum iron (21%). At mean follow-up of 45.7 (43) months, oral iron (n = 49) or intravenous iron (n = 4) had been prescribed for 53 (42.4%) patients, and 32 (25.6%) patients received multiple blood transfusions. Nine patients received intravenous iron using the new protocol (400–1400 mg), resulting in increases in Hb (1.8 g/dL; P<.05) and ferritin (31.8 ng/mL; P< .002). ConclusionIron management was inadequate. Hematologic values often were deficient for sustained periods. Initially, few patients received intravenous iron after oral iron failure, many received no iron supplementation, and there was high use of blood transfusions. Subsequently, administration of intravenous iron was beneficial.

P123 Use of soluble transferrin receptor/log10 ferritin index as a predictor of response to intravenous iron administration in patients with inflammatory bowel disease and anemia

P123 Use of soluble transferrin receptor/log10 ferritin index as a predictor of response to intravenous iron administration in patients with inflammatory bowel disease and anemia

Anemia of Inflammation (AI) Elevated Serum Hepcidin Level and Therapeutic Intravenous Administration of Iron

An 81-year-old female complained of anorexia and puffy face. Complete blood cell counts (CBC) demonstrated normocytic normochromic anemia. Serum iron and total iron binding capacity (TIBC) were decreased, and ferritin was increased. CRP and acute phase proteins were elevated. Serum levels of interleukin (IL)-6 and hepcidin-25 were elevated. The patient was diagnosed as having anemia of inflammation (AI), although the cause was unknown. The oral administration of iron was ineffective, whereas intravenous administration was effective for the amelioration of anemia. The levels of ferritin and hepcidin increased, whereas those of CRP and IL-6 decreased without specific treatment. J Med Cases. 2013;4(6):411-415 doi: https://doi.org/10.4021/jmc1272w

Hierro intravenoso preoperatorio como estrategia de ahorro de sangre en cirugía de fractura de cadera

Background and objectiveTo determine whether administration of intravenous iron in a patient diagnosed with hip fracture reduces the need for blood transfusion. Patients and methodsA retrospective observational case-control study was performed comparing a control group of 63 patients diagnosed with hip fracture with another group of 57 patients treated with parenteral iron. Demographic, clinical condition/clinical record and hematometric differences of the case-control patients were described. We analyzed the morbidity (post-surgical infection) and mortality rate. SPSS® was used for statistical studies. ResultsBeing statistically significant, after the administration of intravenous iron sucrose, the need of blood transfusion was reduced in the case group, as well as the quantity of concentrates required (1.37 vs 0.6). In the case group, there was a statistically significant decreasing trend in hospital mortality rate (case group: 0.8%/control group: 8.3%). It was not been proven the relation between the decrease in nosocomial infection and the administration of intravenous iron ConclusionsThe administration of intravenous iron sucrose in patients diagnosed with hip fracture before surgery could be effective blood saving measure in this type of trauma surgery. Furthermore, its use has been reliable without causing any side effects.

Intravenous iron sucrose versus oral iron ferrous sulfate for antenatal and postpartum iron deficiency anemia: a randomized trial

Objective: To compare oral iron to intravenous iron administration to women in late pregnancy and/or after labor to correct iron deficiency.Methods: 271 anemic women (148 pregnant women and 123 women post lower segment caesarean section) with hemoglobin (Hb) levels below 110 g/L were enrolled over a two-year period and randomized to receive either two tablets FGF (ferrous sulfate with folic acid) or 400 mg of intravenous iron sucrose plus folic acid 600 µg. Treatment effectiveness was assessed by measuring Hb and ferritin postpartum on day 1, day 14 and day 42. Transfusions of red blood cells and adverse drug reactions were recorded.Results: Data of 214 women were available for analysis. Both forms of iron replacement therapy led to increased hemoglobin and ferritin levels over the testing period. Ferritin was significantly higher in the i.v. iron treatment group compared to the oral iron treatment group (p = 0.004) two weeks after delivery, while Hb values did not differ between the groups. No serious adverse drug reactions were observed. Red blood cell transfusion rate was low (1.9%), with equal rates observed in both treatment groups.Conclusion: Intravenous and oral irons were both effective in correcting peripartum anemia, although intravenous iron restored stores faster than oral iron.

Intravenous Ferric Chloride Hexahydrate Supplementation Induced Endothelial Dysfunction and Increased Cardiovascular Risk among Hemodialysis Patients

BackgroundThe association between intravenous (IV) iron administration and outcomes in hemodialysis (HD) patients is still debated. Therefore, this study was aimed to assess the relationship between the IV administration of ferric chloride hexahydrate (Atofen®) and cardiovascular (CV) outcome and the interaction between iron-induced oxidative stress and endothelial dysfunction in chronic HD patients.Methodology/Principal FindingsA cohort of 1239 chronic HD patients was recruited. In a follow-up of 12 months, Kaplan-Meier survival curves showed that higher doses of IV Atofen associated with higher risks for CV events and deaths in HD patients. In multivariate Cox models, compared to no iron supplementation, IV Atofen administration was an independent predictor for CV events and overall mortality. However, the nature of the observational cohort study possibly bears selection bias. We further found that IV Atofen enhanced the superoxide production of mononuclear cells (MNCs), the levels of circulating soluble adhesion molecules, and the adhesion of MNCs to human aortic endothelial cells (HAECs). In vitro experiments showed that Atofen increased the expression of intracellular cell adhesion molecule-1 and vascular cell adhesion molecule-1 in HAECs and aggravated the endothelial adhesiveness in a dose-dependent manner. These iron-induced changes were significantly attenuated by the co-treatment of HAECs with N-acetylcysteine and inhibitors of NADPH oxidase, nuclear factor κB, and activator protein-1.ConclusionA cumulative dose of IV Atofen >800 mg within 6 months was associated with an adverse CV outcome and a higher mortality among chronic HD patients. The detrimental effects of IV iron supplementation were partly due to the increased oxidative stress and induction of MNC adhesion to endothelial cells, a pivotal index of early atherogenesis.

Perioperative intravenous iron: an upfront therapy for treating anaemia and reducing transfusion requirements.

Perioperative anaemia, with iron deficiency being its leading cause, is a frequent condition among surgical patients, and has been linked to increased postoperative morbidity and mortality, and decreased quality of life. Postoperative anaemia is even more frequent and is mainly caused by perioperative blood loss, aggravated by inflammation-induced blunting of erythropoiesis. Allogenic transfusion is commonly used for treating acute perioperative anaemia, but it also increases the rate of morbidity and mortality in surgical and critically ill patients. Thus, overall concerns about adverse effects of both preoperative anaemia and allogeneic transfusion have prompted the review of transfusion practice and the search for safer and more biologically rational treatment options. In this paper, the role of intravenous iron therapy (mostly with iron sucrose and ferric carboxymaltose), as a safe and efficacious tool for treating anaemia and reducing transfusion requirements in surgical patients, as well as in other medical areas, has been reviewed. From the analysis of published data and despite the lack of high quality evidence in some areas, it seems fair to conclude that perioperative intravenous iron administration, with or without erythropoiesis stimulating agents, is safe, results in lower transfusion requirements and hastens recovery from postoperative anaemia. In addition, some studies have reported decreased rates of postoperative infection and mortality, and shorter length of hospital stay in surgical patients receiving intravenous iron.

Should we reconsider iron administration based on prevailing ferritin and hepcidin concentrations?

The results of recent randomized, controlled trials in patients with chronic kidney disease and anemia have suggested that hyporesponsiveness to erythropoiesis stimulating agents (ESA) is a significant predictor of poor patient outcomes. Functional iron deficiency (FID) is the most common cause of suboptimal ESA response, and intravenous iron administration (IVFe) efficiently raises hemoglobin (Hb) concentrations even under the condition of FID. Consequently, renal anemia correction has conceptually shifted from ‘higher Hb values with high ESA doses’ to ‘prevention of ESA hyporesponsiveness with IVFe’. The discovery of hepcidin has profoundly changed our understanding of the place of FID in renal anemia therapy. Hepcidin reduces the abundance of iron transport proteins which facilitate iron absorption from the gut and iron mobilization from macrophages. Serum hepcidin is mainly modulated by iron stores, as is serum ferritin. High hepcidin or ferritin levels block intestinal iron absorption and iron recycling in macrophages and decrease iron availability for erythropoiesis, leading to FID. Iron administration, especially IVFe, increases hepcidin levels and concomitantly inhibits iron supply to erythroid cells. This in turn could lead to a vicious circle, exacerbating FID and increasing iron demand. Therefore, physicians should be cautious with unrestricted IVFe to chronic kidney disease patients with FID.

The effect of intravenous and oral iron administration on perioperative anaemia and transfusion requirements in patients undergoing elective cardiac surgery: a randomized clinical trial

Anaemia is a frequent complication after cardiopulmonary bypass surgery. Iron therapy has been variably employed by medical centres over the years. In our study we test the clinical effectiveness of intravenous and oral iron supplementation in correcting anaemia, and its impact on blood transfusion requirements, in patients undergoing cardiopulmonary bypass surgery. A double-blind, randomized, placebo-controlled clinical trial with three parallel groups of patients. Group I (n = 54): intravenous iron(III)-hydroxide sucrose complex, three doses of 100 mg/24 h during pre- and postoperative hospitalization and 1 pill/24 h of oral placebo in the same period and during 1 month after discharge. Group II (n = 53): oral ferrous fumarate iron 1 pill/24 h pre- and postoperatively and during 1 month after discharge, and intravenous placebo while hospitalized. Group III (n = 52): oral and intravenous placebo pre- and postoperatively, following the same protocol. Data were collected preoperatively, at theatre, at intensive care unit admission, before hospital discharge and 1 month later. (1) Baseline clinical and demographic characteristics and surgical procedures were similar in the three groups; (2) no inter-group differences were found in haemoglobin and haematocrit during the postoperative period; (3) the intravenous iron group showed higher serum ferritin levels at hospital discharge (1321 ± 495 ng/ml; P < 0.001) and 1 month later (610 ± 387; P < 0.001) compared with the other groups and (4) we did not observe statistical differences in blood transfusion requirements between the three groups. The use of intravenous or oral iron supplementation proved ineffective in correcting anaemia after cardiopulmonary bypass and did not reduce blood transfusion requirements. [Current Controlled Trials number: NCT01078818 (oral and intravenous iron in patients postoperative cardiovascular surgery under EC)].

Effects of Preoperative Intravenous Erythropoietin Plus Iron on Outcome in Anemic Patients After Cardiac Valve Replacement

Preoperative anemia is a risk factor for postoperative morbidity and in-hospital mortality in cardiac surgery. However, it is not known whether treatment of anemia before cardiac surgery by administering recombinant human erythropoietin (rhEPO) plus iron improves postoperative outcomes and decreases red blood cell transfusions in these patients. In 1998 a collection of consecutive data for patients who underwent valve replacement was initiated and the inclusion criterion was anemia. Treatment with rhEPO was given at a dose of 500 IU/kg/day every week for 4 weeks and the fifth dose 48 hours before valve replacement. During each rhEPO session, patients received intravenous iron sucrose supplementation. The intervention cohort (2006 to 2011) included 75 patients and the observation cohort was composed of 59 patients who did not receive any treatment (1998 to 2005). Multivariable logistic regression analysis showed that administration of combined therapy was independently associated with decreased postoperative morbidity (odds ratio [OR] 0.13, 95% confidence interval [CI] 0.03 to 0.59 p = 0.008) and in-hospital mortality (OR 0.16, 95% CI 0.28 to 0.95 p = 0.04) after adjusting for logistic European System for Cardiac Operative Risk Evaluation score, type of intervention, time of cardiopulmonary bypass, and year of surgery. Individually, this treatment also decreased postoperative renal failure (OR 0.23, 95% CI 0.06 to 0.88, p = 0.03). Rate of red blood cell transfusion decreased from 93% in the observation cohort to 67% in the intervention cohort as did days of hospitalization (median, 15 days, 10 to 27, versus 10 days, 8 to 14, respectively, p = 0.01 for all comparisons). In conclusion, administration of intravenous rhEPO plus iron in anemic patients before valve replacement improves postoperative survival, decreases blood transfusions, and shortens hospitalization.