Is there a role for iron supplementation in critically ill patients? / Suplementos de hierro: ¿son útiles en el paciente crítico?

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An international consensus statement on the management of postoperative anaemia after major surgical procedures.

Despite numerous guidelines on the management of anaemia in surgical patients, there is no pragmatic guidance for the diagnosis and management of anaemia and iron deficiency in the postoperative period. A number of experienced researchers and clinicians took part in a two-day expert workshop and developed the following consensus statement. After presentation of our own research data and local policies and procedures, appropriate relevant literature was reviewed and discussed. We developed a series of best-practice and evidence-based statements to advise on patient care with respect to anaemia and iron deficiency in the postoperative period. These statements include: a diagnostic approach to iron deficiency and anaemia in surgical patients; identification of patients appropriate for treatment; and advice on practical management and follow-up that is easy to implement. Available data allow the fulfilment of the requirements of Pillar 1 of Patient Blood Management. We urge national and international research funding bodies to take note of these recommendations, particularly in terms of funding large-scale prospective, randomised clinical trials that can most effectively address the important clinical questions and this clearly unmet medical need.

Pre-operative haemoglobin levels and iron status in a large multicentre cohort of patients undergoing major elective surgery.

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.

Pre-operative haematological assessment in patients scheduled for major surgery.

Peri-operative anaemia, blood loss and allogeneic blood transfusion are associated with increased postoperative morbidity and mortality, and prolonged hospital stay. A multidisciplinary, multimodal, individualised strategy, collectively termed 'patient blood management', may reduce or eliminate allogeneic blood transfusion and improve outcomes. This approach has three objectives: the detection and treatment of peri-operative anaemia; the reduction of peri-operative bleeding and coagulopathy; and harnessing and optimising the physiological tolerance of anaemia. This review focuses on the pre-operative evaluation of erythropoiesis, coagulation status and platelet function. Where possible, evidence is graded systematically and recommended therapies follow recently published consensus guidance.

'Fit to fly': overcoming barriers to preoperative haemoglobin optimization in surgical patients.

In major surgery, the implementation of multidisciplinary, multimodal and individualized strategies, collectively termed Patient Blood Management, aims to identify modifiable risks and optimise patients' own physiology with the ultimate goal of improving outcomes. Among the various strategies utilized in Patient Blood Management, timely detection and management of preoperative anaemia is most important, as it is in itself a risk factor for worse clinical outcome, but also one of the strongest predisposing factors for perioperative allogeneic blood transfusion, which in turn increases postoperative morbidity, mortality and costs. However, preoperative anaemia is still frequently ignored, with indiscriminate allogeneic blood transfusion used as a 'quick fix'. Consistent with reported evidence from other medical specialties, this imprudent practice continues to be endorsed by non-evidence based misconceptions, which constitute serious barriers for a wider implementation of preoperative haemoglobin optimisation. We have reviewed a number of these misconceptions, which we unanimously consider should be promptly abandoned by health care providers and replaced by evidence-based strategies such as detection, diagnosis and proper treatment of preoperative anaemia. We believe that this approach to preoperative anaemia management may be a viable, cost-effective strategy that is beneficial both for patients, with improved clinical outcomes, and for health systems, with more efficient use of finite health care resources.

Perioperative intravenous iron; an upfront therapy for treating anaemia and reducing transfusion requirements / Hierro intravenoso perioperatorio; una opción terapéutica para el tratamiento de la anemia y la reducción de los requerimientos de transfusión

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 (AU)

La anemia perioperatoria, cuya principal causa es la deficiencia de hierro, es frecuente entre pacientes quirúrgicos y se asocia a un aumento de la morbimortalidad postoperatoria y a una disminución de la calidad de vida. La anemia postoperatoria es aún más frecuente y está causada principalmente por la pérdida perioperatoria de sangre, agravada por la reducción de la actividad eritropóyetica inducida por la inflamación. La transfusión alogénica es el tratamiento habitual de la anemia aguda perioperatoria, pero también aumenta la tasas de morbimortalidad en pacientes quirúrgicos y críticos. La preocupación por los efectos adversos de la anemia preoperatoria y la transfusión alogénica han impulsado la revisión de la práctica transfusional y la búsqueda de opciones de tratamiento más seguras y biológicamente más racionales. En este artículo se revisa el papel de la terapia con hierro intravenoso (mayoritariamente hierro sacarosa y carboxymaltosa de hierro), como herramienta segura y eficaz para el tratamiento de la anemia y la reducción de los requerimientos transfusionales en el paciente quirúrgico, así como en otras áreas médicas. Del análisis de los datos publicados y a pesar de la falta de evidencia de alta calidad en algunas áreas, parece razonable concluir que la administración perioperatoria de hierro intravenoso, con o sin agentes estimuladores de la eritropoyesis, es segura, reduce las necesidades de transfusión y acelera la recuperación de la anemia postoperatoria. Además, algunos estudios han encontrado una reducción de las tasas de infección postoperatoria y de mortalidad, así como de la duración de la estancia hospitalaria, en pacientes quirúrgicos tratados con hierro intravenoso (AU)

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.

Iron deficiency and anaemia in bariatric surgical patients: causes, diagnosis and proper management / Deficiencia de hierro y anemia en pacientes de cirugía bariátrica: causas, diagnóstico y tratamiento adecuado

Obesity-induced chronic inflammation leads to activation of the immune system that causes alterations of iron homeostasis including hypoferraemia, iron-restricted erythropoiesis, and finally mild-to-moderate anaemia. Thus, preoperative anaemia and iron deficiency are common among obese patients scheduled for bariatric surgery (BS). Assessment of patients should include a complete haematological and biochemical laboratory work-up, including measurement of iron stores, vitamin B12 and folate. In addition, gastrointestinal evaluation is recommended for most patients with iron-deficiency anaemia. On the other hand, BS is a long-lasting inflammatory stimulus in itself and entails a reduction of the gastric capacity and/or exclusion from the gastrointestinal tract which impair nutrients absorption, including dietary iron. Chronic gastrointestinal blood loss and iron-losingenteropathy may also contribute to iron deficiency after BS. Perioperative anaemia has been linked to increased postoperative morbidity and mortality and decreased quality of life after major surgery, whereas treatment of perioperative anaemia, and even haematinic deficiency without anaemia, has been shown to improve patient outcomes and quality of life. However, long-term follow-up data in regard to prevalence, severity, and causes of anaemia after BS are mostly absent. Iron supplements should be administered to patients after BS, but compliance with oral iron is no good. In addition, once iron deficiency has developed, it may prove refractory to oral treatment. In these situations, IV iron (which can circumvent the iron blockade at enterocytes and macrophages) has emerged as a safe and effective alternative for perioperative anaemia management. Monitoring should continue indefinitely even after the initial iron repletion and anaemia resolution, and maintenance IV iron treatment should be provided as required. New IV preparations, such ferric carboxymaltose, are safe, easy to use and up to 1000 mg can be given in a single session, thus providing an excellent tool to avoid or treat iron deficiency in this patient population (AU)

La inflamación crónica inducida por la obesidad provoca alteraciones en la homeostasis del hierro, incluyendo hiposideremia, restricción del hierro para la eritropoyesis y anemia leve o moderada. Consecuentemente, la anemia y la deficiencia de hierro son frecuentes entre los pacientes candidatos a cirugía bariátrica (CB). El estudio preoperatorio debe incluir un hemograma completo y la evaluación del status férrico, vitamina B12 y ácido fólico. Se recomienda realizar un estudio gastrointestinal en la mayoría paciente con anemia ferropénica. Ante una anemia inexplicada, debería postergarse la cirugía hasta que se haya realizado un diagnóstico apropiado. La anemia perioperatoria se ha relacionado con aumento de morbi-mortalidad postoperatoria y disminución de la calidad de vida después de una cirugía mayor, mientras que la corrección de la anemia y la deficiencia de micronutrientes (hierro, vitamina B12, folato) mejoran el pronóstico y la calidad de vida. Sin embargo, no existen estudios de seguimiento a largo plazo en lo que respecta a la prevalencia, gravedad y causas de la anemia en pacientes CB. Tras la CB, los pacientes deben recibir suplementos de hierro, pero la tolerancia al hierro oral no es buena; una vez instaurada la situación de ferropenia, ésta podría ser refractaria al tratamiento oral. En estas situaciones, el uso de preparados IV (que evitan el bloqueo del hierro en enterocitos y macrófagos) ha surgido como una alternativa segura y efectiva en el tratamiento de la anemia perioperatoria. Los nuevos preparados de hierro IV, como la carboximaltosa férrica, son seguros, fáciles de utilizar y permiten administrar hasta 1.000 mg en una sola sesión, proporcionando así una excelente herramienta para tratar o prevenir el déficit de hierro en estos pacientes. Después de la repleción de hierro y la resolución de la anemia, deben realizarse controles periódicos de forma indefinida para realizar nuevos tratamientos de mantenimiento si fueran necesarios (AU)

Iron deficiency and anaemia in bariatric surgical patients: causes, diagnosis and proper management.

Obesity-induced chronic inflammation leads to activation of the immune system that causes alterations of iron homeostasis including hypoferraemia, iron-restricted erythropoiesis, and finally mild-to-moderate anaemia. Thus, preoperative anaemia and iron deficiency are common among obese patients scheduled for bariatric surgery (BS). Assessment of patients should include a complete haematological and biochemical laboratory work-up, including measurement of iron stores, vitamin B12 and folate. In addition, gastrointestinal evaluation is recommended for most patients with iron-deficiency anaemia. On the other hand, BS is a long-lasting inflammatory stimulus in itself and entails a reduction of the gastric capacity and/or exclusion from the gastrointestinal tract which impair nutrients absorption, including dietary iron. Chronic gastrointestinal blood loss and iron-losingenteropathy may also contribute to iron deficiency after BS. Perioperative anaemia has been linked to increased postoperative morbidity and mortality and decreased quality of life after major surgery, whereas treatment of perioperative anaemia, and even haematinic deficiency without anaemia, has been shown to improve patient outcomes and quality of life. However, long-term follow-up data in regard to prevalence, severity, and causes of anaemia after BS are mostly absent. Iron supplements should be administered to patients after BS, but compliance with oral iron is no good. In addition, once iron deficiency has developed, it may prove refractory to oral treatment. In these situations, IV iron (which can circumvent the iron blockade at enterocytes and macrophages) has emerged as a safe and effective alternative for perioperative anaemia management. Monitoring should continue indefinitely even after the initial iron repletion and anaemia resolution, and maintenance IV iron treatment should be provided as required. New IV preparations, such ferric carboxymaltose, are safe, easy to use and up to 1000 mg can be given in a single session, thus providing an excellent tool to avoid or treat iron deficiency in this patient population.

Efficacy and safety of intravenous iron therapy as an alternative/adjunct to allogeneic blood transfusion.

Anaemia is a common condition among patients admitted to hospital medicosurgical departments, as well as in critically ill patients. Anaemia is more frequently due to absolute iron deficiency (e.g. chronic blood loss) or functional iron deficiency (e.g. chronic inflammatory states), with other causes being less frequent. In addition, preoperative anaemia is one of the major predictive factors for perioperative blood transfusion. In surgical patients, postoperative anaemia is mainly caused by perioperative blood loss, and it might be aggravated by inflammation-induced inhibition of erythropoietin and functional iron deficiency (a condition that cannot be corrected by the administration of oral iron). All these mechanisms may be involved in the anaemia of the critically ill. Intravenous iron administration seems to be safe, as very few severe side-effects were observed, and may result in hastened recovery from anaemia and lower transfusion requirements. However, it is noteworthy that many of the recommendations given for intravenous iron treatment are not supported by a high level of evidence and this must be borne in mind when making decisions regarding its application to a particular patient. Nonetheless, this also indicates the need for further large, randomized controlled trials on the safety and efficacy of intravenous iron for the treatment of anaemia in different clinical settings.