The important role for intravenous iron in perioperative patient blood management in major abdominal surgery: a randomized controlled trial

Objective: To determine if preoperative intravenous (IV) iron improves outcomes in abdominal surgery patients. Summary Background Data: Preoperative iron deficiency anemia (IDA) occurs frequently; however if left untreated, increases the risk of blood transfusion allogeneic blood transfusion (ABT). Limited evidence supports IDA treatment with preoperative IV iron. This randomized controlled trial aimed to determine whether perioperative IV iron reduced the need for ABT. Methods: Between August 2011 and November 2014, 72 patients with IDA were assigned to receive either IV iron or usual care. The primary endpoint was incidence of ABT. Secondary endpoints were various hemoglobin (Hb) levels, change in Hb between time points, length of stay, iron status, morbidity, mortality, and quality of life 4 weeks postsurgery. Results: A 60% reduction in ABT was observed in the IV iron group compared with the usual care group (31.25% vs 12.5%). Hb values, although similar at randomization, improved by 0.8 g/dL with IV iron compared with 0.1 g/dL with usual care (P = 0.01) by the day of admission. The IV iron group had higher Hb 4 weeks after discharge compared with the usual care group (1.9 vs 0.9 g/dL, P = 0.01), and a shorter length of stay (7.0 vs 9.7 d, P = 0.026). There was no difference in discharge Hb levels, morbidity, mortality, or quality of life. Conclusions: Administration of perioperative IV iron reduces the need for blood transfusion, and is associated with a shorter hospital stay, enhanced restoration of iron stores, and a higher mean Hb concentration 4 weeks after surgery.Bernd Froessler, Peter Palm, Ingo Weber, Nicolette A. Hodyl, Rajvinder Singh and Elizabeth M. Murph

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.Bernd Froessler, Catalin Tufanaru, Allan Cyna, Alan Pearso

Getting patient blood management Pillar 1 right in the Asia-Pacific: a call for action

Preoperative anaemia is common in the Asia-Pacific. Iron-deficiency anaemia (IDA) is a risk factor that can be addressed under patient blood management (PBM) Pillar 1, leading to reduced morbidity and mortality. We examined PBM implementation under four different healthcare systems, identified challenges and proposed several measures. (a) Test for anaemia once patients are scheduled for surgery. (b) Inform patients about risks of preoperative anaemia and benefits of treatment. (c) Treat IDA and replenish iron stores before surgery, using intravenous iron when oral treatment is ineffective, not tolerated or rapid iron replenishment is needed; transfusion should not be the default management. (d) Harness support from multiple medical disciplines and relevant bodies to promote PBM implementation. (e) Demonstrate better outcomes and cost savings from reduced mortality and morbidity. Although PBM implementation may seem complex and daunting, it is feasible to start small. Implementing PBM Pillar 1, particularly in preoperative patients, is a sensible first step regardless of the healthcare setting

Risk Factors Associated with Adverse Fetal Outcomes in Pregnancies Affected by Coronavirus Disease 2019 (COVID-19): A Secondary Analysis of the WAPM study on COVID-19

To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Mean gestational age at diagnosis was 30.6\ub19.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; p<0.001), birthweight (OR: 1.17, 95% CI 1.09-1.12.7 per 100 g decrease; p=0.012) and maternal ventilatory support, including either need for oxygen or CPAP (OR: 4.12, 95% CI 2.3-7.9; p=0.001) were independently associated with composite adverse fetal outcome. Early gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible

Intravenous iron sucrose - an effective and attractive modality for perioperative anaemia management

B. Froessler and D. Papendor

Assessing the costs and benefits of perioperative iron deficiency anemia management with ferric carboxymaltose in Germany

Bernd Froessler,1,2 Alexandra M Rueger,3,4 Mark P Connolly5,6 1Department of Anesthesia, Lyell McEwin Hospital, Elizabeth Vale, SA, Australia; 2Discipline of Acute Care Medicine, University of Adelaide, Adelaide, SA, Australia; 3Vifor Pharma, Munich, Germany; 4Charit&eacute; Universit&auml;tsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Kardiologie Campus Virchow-Klinikum, Berlin, Germany; 5Unit of PharmacoEpidemiology and PharmacoEconomics, Department of Pharmacy, University of Groningen, Groningen, the Netherlands; 6Global Market Access Solutions S&agrave;rl, St-Prex, Switzerland Background: Perioperative administration of ferric carboxymaltose (FCM) was previously shown to reduce both the need for transfusions and the hospital length of stay in patients with preoperative iron deficiency anemia (IDA). In this study, we estimated the economic consequences of perioperative administration using FCM vs usual care in patients with IDA from the perspective of a German hospital using decision-analytic modeling.Materials and methods: The model was populated with clinical inputs (transfusion rates, blood units transfused, hospital length of stay) from a previously reported randomized trial comparing FCM vs usual care for managing IDA patients undergoing elective abdominal surgery. We applied a hospital perspective to all costs, excluding surgery-related costs in both treatment arms. One-way sensitivity analyses were undertaken to evaluate key drivers of cost analysis.Results: The average costs per case treated using FCM compared to usual care were &euro;2,461 and &euro;3,246, respectively, for resource expenses paid by hospital per case. This would suggest potential savings achieved with preoperative intravenous iron treatment per patient of &euro;786 per case. A sensitivity analysis varying the key input parameters indicated the cost analysis is most sensitive to changes in the length of stay and the cost of hospitalization per day.Conclusion: Perioperative administration of FCM results in cost savings to hospitals based on reduced blood transfusions and length of stay following elective abdominal surgery. Keywords: intravenous iron, economic evaluation, anemia, iron deficiency, blood transfusion, patient blood managemen

Are intravenous fluid boluses beneficial in late preterm or term infants with suspected haemodynamic compromise?

Amy Keir, Bernd Froessler, Simon Stanwort

Effectiveness and efficiency of pre-operative anaemia management with intravenous iron: a systematic review

Review objectives The quantitative objective is to identify the effectiveness of intravenous iron administration on the correction of iron deficiency anaemia in the perioperative setting. More specifically, the objectives are to identify the effectiveness of iron infusion on the rate of red blood cell (RBC) transfusion and incidence of transfusion related co morbidities such as postoperative infection, immunological morbidity and mortality. In addition changes in functional capacity that could impact on quality of life. The economic objective of this review is to identify the cost aspects of anaemia management. More specifically, the objectives are to identify the evidence of cost benefits on pre-operative anaemia correction and the potential for cost savings on blood products and the indirect cost savings on transfusion related adverse effects. Inclusion criteria Types of participants Both the quantitative component and the economic component of the review will consider studies that include adult patients presenting for major surgery, regardless of gender, ethnicity, diagnosis and co-morbidities with pre-operative anaemia. Types of intervention(s)/phenomena of interest The quantitative component of the review will consider studies that evaluate the management of anaemia with iron infusions compared to oral iron treatment alone, oral iron in combination with erythropoietin, erythropoietin alone or haemoglobin correction with blood transfusion. This will include the dosage of iron, the frequency of its administration and the time frame of treatment prior to surgery. In addition it is of interest to assess how the intervention was employed, the personnel involved and the time spent to complete management. The economic component of this review will consider studies that evaluate the costs and benefits (cost- effectiveness, cost-utility, or cost-benefit) of iron infusions compared to oral iron treatment or haemoglobin correction with blood transfusion for the treatment of pre-operative anaemia. Types of outcomes The quantitative component of this review will consider studies that include (but not limited to) the following outcome measures: • The effect of iron administration on haemoglobin levels • The rate of red blood cell (RBC) transfusion measured as proportion of patients transfused with allogeneic RBC and the average number of units transfused. • The length of stay in hospital • Rate of readmission within 30 days of discharge • The incidence of transfusion related co- morbidities measured as infection rates, the occurrence of transfusion related lung injury (TRALI), transfusion related circulatory overload (TACO) and the number of deaths. • The imReview objectives The quantitative objective is to identify the effectiveness of intravenous iron administration on the correction of iron deficiency anaemia in the perioperative setting. More specifically, the objectives are to identify the effectiveness of iron infusion on the rate of red blood cell (RBC) transfusion and incidence of transfusion related co morbidities such as postoperative infection, immunological morbidity and mortality. In addition changes in functional capacity that could impact on quality of life. The economic objective of this review is to identify the cost aspects of anaemia management. More specifically, the objectives are to identify the evidence of cost benefits on pre-operative anaemia correction and the potential for cost savings on blood products and the indirect cost savings on transfusion related adverse effects. Inclusion criteria Types of participants Both the quantitative component and the economic component of the review will consider studies that include adult patients presenting for major surgery, regardless of gender, ethnicity, diagnosis and co-morbidities with pre-operative anaemia. Types of intervention(s)/phenomena of interest The quantitative component of the review will consider studies that evaluate the management of anaemia with iron infusions compared to oral iron treatment alone, oral iron in combination with erythropoietin, erythropoietin alone or haemoglobin correction with blood transfusion. This will include the dosage of iron, the frequency of its administration and the time frame of treatment prior to surgery. In addition it is of interest to assess how the intervention was employed, the personnel involved and the time spent to complete management. The economic component of this review will consider studies that evaluate the costs and benefits (cost- effectiveness, cost-utility, or cost-benefit) of iron infusions compared to oral iron treatment or haemoglobin correction with blood transfusion for the treatment of pre-operative anaemia. Types of outcomes The quantitative component of this review will consider studies that include (but not limited to) the following outcome measures: • The effect of iron administration on haemoglobin levels • The rate of red blood cell (RBC) transfusion measured as proportion of patients transfused with allogeneic RBC and the average number of units transfused. pact of intravenous iron administration on functional outcomes The economic component of the review will consider (but not limited to) the following outcome measures: • the reduction in costs for units of allogeneic blood avoided • the reduction in cost associated with a reduction in length of stay in hospital LOS • the reduction in transfusion laboratory cost and nursing time • The increase in cost for iron administered and nursing time Types of studies The quantitative component of the review will consider any experimental study design including randomised controlled trials, non-randomised controlled trials, quasi-experimental, before and after studies for inclusion. The economic component of the review will consider cost effectiveness, cost-utility, and cost-benefit studies for inclusion.Bernd Froessler, Catalin Tufanaru, Alan Pearson, Allan Cyn

Intravenous ferric carboxymaltose for anaemia in pregnancy

Background: Iron deficiency is a common nutritional deficiency amongst women of childbearing age. Peri-partum iron deficiency anaemia (IDA) is associated with significant maternal, fetal and infant morbidity. Current options for treatment are limited: these include oral iron supplementation, which can be ineffective and poorly tolerated, and red blood cell transfusions, which carry an inherent risk and should be avoided. Ferric carboxymaltose is a new treatment option that may be better tolerated. The study was designed to assess the safety and efficacy of iron deficiency anaemia (IDA) correction with intravenous ferric carboxymaltose in pregnant women with mild, moderate and severe anaemia in the second and third trimester. Methods: Prospective observational study; 65 anaemic pregnant women received ferric carboxymaltose up to 15 mg/kg between 24 and 40 weeks of pregnancy (median 35 weeks gestational age, SD 3.6). Treatment effectiveness was assessed by repeat haemoglobin (Hb) measurements and patient report of well-being in the postpartum period. Safety was assessed by analysis of adverse drug reactions and fetal heart rate monitoring during the infusion. Results: Intravenous ferric carboxymaltose infusion significantly increased Hb values (p < 0.01) above baseline levels in all women. Increased Hb values were observed at 3 and 6 weeks post infusion and up to 8 weeks post-infusion. Ferritin values increased significantly after the infusion. Only 4 women had repeat ferritin values post-partum which remained above baseline levels. Fetal heart rate monitoring did not indicate a drug related negative impact on the fetus. Of the 29 (44.6%) women interviewed, 19 (65.5%) women reported an improvement in their well-being and 9 (31%) felt no different after the infusion. None of the women felt worse. No serious adverse effects were found and minor side effects occurred in 13 (20%) patients. Conclusions: Our prospective data is consistent with existing observational reports of the safe and effective use of ferric carboxymaltose in the treatment of iron deficiency anaemia in pregnancy.Bernd Froessler, Joshua Collingwood, Nicolette A Hodyl, and Gustaaf Dekke