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Published in: Critical Care 1/2019

Open Access 01-12-2019 | Anemia | Review

Iron Metabolism: An Emerging Therapeutic Target in Critical Illness

Authors: Edward Litton, Jolene Lim

Published in: Critical Care | Issue 1/2019

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Abstract

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2019. Other selected articles can be found online at https://​www.​biomedcentral.​com/​collections/​annualupdate2019​. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://​www.​springer.​com/​series/​8901.
Literature
1.
go back to reference Bellamy MC, Gedney JA. Unrecognised iron deficiency in critical illness. Lancet. 1998;352:1903.CrossRef Bellamy MC, Gedney JA. Unrecognised iron deficiency in critical illness. Lancet. 1998;352:1903.CrossRef
2.
go back to reference Tacke F, Nuraldeen R, Koch A, et al. Iron parameters determine the prognosis of critically ill patients. Crit Care Med. 2016;44:1049–58.CrossRef Tacke F, Nuraldeen R, Koch A, et al. Iron parameters determine the prognosis of critically ill patients. Crit Care Med. 2016;44:1049–58.CrossRef
3.
go back to reference Bazuave GN, Buser A, Gerull S, Tichelli A, Stern M. Prognostic impact of iron parameters in patients undergoing Allo-SCT. Bone Marrow Transplant. 2011;47:60.CrossRef Bazuave GN, Buser A, Gerull S, Tichelli A, Stern M. Prognostic impact of iron parameters in patients undergoing Allo-SCT. Bone Marrow Transplant. 2011;47:60.CrossRef
4.
go back to reference Fernández-Ruiz M, López-Medrano F, Andrés A, et al. Serum iron parameters in the early post-transplant period and infection risk in kidney transplant recipients. Transpl Infect Dis. 2013;15:600–11.CrossRef Fernández-Ruiz M, López-Medrano F, Andrés A, et al. Serum iron parameters in the early post-transplant period and infection risk in kidney transplant recipients. Transpl Infect Dis. 2013;15:600–11.CrossRef
5.
go back to reference Mohus RM, Paulsen J, Gustad L, et al. Association of iron status with the risk of bloodstream infections: results from the prospective population-based HUNT study in Norway. Intensive Care Med. 2018;44:1276–83.CrossRef Mohus RM, Paulsen J, Gustad L, et al. Association of iron status with the risk of bloodstream infections: results from the prospective population-based HUNT study in Norway. Intensive Care Med. 2018;44:1276–83.CrossRef
6.
go back to reference Litton E, Xiao J, Ho KM. Safety and efficacy of intravenous iron therapy in reducing requirement for allogeneic blood transfusion: systematic review and meta-analysis of randomised clinical trials. BMJ. 2013;347:f4822.CrossRef Litton E, Xiao J, Ho KM. Safety and efficacy of intravenous iron therapy in reducing requirement for allogeneic blood transfusion: systematic review and meta-analysis of randomised clinical trials. BMJ. 2013;347:f4822.CrossRef
7.
go back to reference Litton E, Baker S, Erber WN, et al. Intravenous iron or placebo for anaemia in intensive care: the IRONMAN multicentre randomized blinded trial: a randomized trial of IV iron in critical illness. Intensive Care Med. 2016;42:1715–22.CrossRef Litton E, Baker S, Erber WN, et al. Intravenous iron or placebo for anaemia in intensive care: the IRONMAN multicentre randomized blinded trial: a randomized trial of IV iron in critical illness. Intensive Care Med. 2016;42:1715–22.CrossRef
8.
go back to reference Abbaspour N, Hurrell R, Kelishadi R. Review on iron and its importance for human health. J Res Med Sci. 2014;19:164–74.PubMedPubMedCentral Abbaspour N, Hurrell R, Kelishadi R. Review on iron and its importance for human health. J Res Med Sci. 2014;19:164–74.PubMedPubMedCentral
9.
go back to reference Bruner AB, Joffe A, Duggan AK, Casella JF, Brandt J. Randomised study of cognitive effects of iron supplementation in non-anaemic iron-deficient adolescent girls. Lancet. 1996;348:992–6.CrossRef Bruner AB, Joffe A, Duggan AK, Casella JF, Brandt J. Randomised study of cognitive effects of iron supplementation in non-anaemic iron-deficient adolescent girls. Lancet. 1996;348:992–6.CrossRef
10.
go back to reference Brutsaert TD, Hernandez-Cordero S, Rivera J, Viola T, Hughes G, Haas JD. Iron supplementation improves progressive fatigue resistance during dynamic knee extensor exercise in iron-depleted, nonanemic women. Am J Clin Nutr. 2003;77:441–8.CrossRef Brutsaert TD, Hernandez-Cordero S, Rivera J, Viola T, Hughes G, Haas JD. Iron supplementation improves progressive fatigue resistance during dynamic knee extensor exercise in iron-depleted, nonanemic women. Am J Clin Nutr. 2003;77:441–8.CrossRef
11.
go back to reference Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005;352:1011–23.CrossRef Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005;352:1011–23.CrossRef
12.
go back to reference Bobbio-Pallavicini F, Verde G, Spriano P, et al. Body iron status in critically ill patients: significance of serum ferritin. Intensive Care Med. 1989;15:171–8.CrossRef Bobbio-Pallavicini F, Verde G, Spriano P, et al. Body iron status in critically ill patients: significance of serum ferritin. Intensive Care Med. 1989;15:171–8.CrossRef
13.
go back to reference Hobisch-Hagen P, Wiedermann F, Mayr A, et al. Blunted erythropoietic response to anemia in multiply traumatized patients. Crit Care Med. 2001;29:743–7.CrossRef Hobisch-Hagen P, Wiedermann F, Mayr A, et al. Blunted erythropoietic response to anemia in multiply traumatized patients. Crit Care Med. 2001;29:743–7.CrossRef
14.
go back to reference Ganz T. Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood. 2003;102:783–8.CrossRef Ganz T. Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood. 2003;102:783–8.CrossRef
15.
go back to reference Thomas DW, Hinchliffe RF, Briggs C, et al. Guideline for the laboratory diagnosis of functional iron deficiency. Br J Haematol. 2013;161:639–48.CrossRef Thomas DW, Hinchliffe RF, Briggs C, et al. Guideline for the laboratory diagnosis of functional iron deficiency. Br J Haematol. 2013;161:639–48.CrossRef
16.
go back to reference Litton E, Xiao J, Allen CT, Ho KM. Iron-restricted erythropoiesis and risk of red blood cell transfusion in the intensive care unit: a prospective observational study. Anaesth Intensive Care. 2015;43:612–6.PubMed Litton E, Xiao J, Allen CT, Ho KM. Iron-restricted erythropoiesis and risk of red blood cell transfusion in the intensive care unit: a prospective observational study. Anaesth Intensive Care. 2015;43:612–6.PubMed
17.
go back to reference Lasocki S, Baron G, Driss F, et al. Diagnostic accuracy of serum hepcidin for iron deficiency in critically ill patients with anemia. Intensive Care Med. 2010;36:1044–8.CrossRef Lasocki S, Baron G, Driss F, et al. Diagnostic accuracy of serum hepcidin for iron deficiency in critically ill patients with anemia. Intensive Care Med. 2010;36:1044–8.CrossRef
18.
go back to reference Litton E, Baker S, Erber WN, et al. Hepcidin predicts response to IV iron therapy in patients admitted to the intensive care unit: a nested cohort study. J Intensive Care. 2018;6:60.CrossRef Litton E, Baker S, Erber WN, et al. Hepcidin predicts response to IV iron therapy in patients admitted to the intensive care unit: a nested cohort study. J Intensive Care. 2018;6:60.CrossRef
19.
go back to reference Steensma DP, Sasu BJ, Sloan JA, Tomita DK, Loprinzi CL. Serum hepcidin levels predict response to intravenous iron and darbepoetin in chemotherapy-associated anemia. Blood. 2015;125:3669–71.CrossRef Steensma DP, Sasu BJ, Sloan JA, Tomita DK, Loprinzi CL. Serum hepcidin levels predict response to intravenous iron and darbepoetin in chemotherapy-associated anemia. Blood. 2015;125:3669–71.CrossRef
20.
go back to reference Westbrook A, Pettila V, Nichol A, et al. Transfusion practice and guidelines in Australian and New Zealand ICUs. Intensive Care Med. 2010;36:1138–46.CrossRef Westbrook A, Pettila V, Nichol A, et al. Transfusion practice and guidelines in Australian and New Zealand ICUs. Intensive Care Med. 2010;36:1138–46.CrossRef
21.
go back to reference Lim J, Miles L, Litton E. Intravenous iron therapy in patients undergoing cardiovascular surgery: a narrative review. J Cardiothorac Vasc Anesth. 2018;32:1439–51.CrossRef Lim J, Miles L, Litton E. Intravenous iron therapy in patients undergoing cardiovascular surgery: a narrative review. J Cardiothorac Vasc Anesth. 2018;32:1439–51.CrossRef
22.
go back to reference Klein AA, Collier T, Yeates J, et al. The ACTA PORT-score for predicting perioperative risk of blood transfusion for adult cardiac surgery. Br J Anaesth. 2017;119:394–401.CrossRef Klein AA, Collier T, Yeates J, et al. The ACTA PORT-score for predicting perioperative risk of blood transfusion for adult cardiac surgery. Br J Anaesth. 2017;119:394–401.CrossRef
23.
go back to reference Munoz M, Acheson AG, Auerbach M, et al. International consensus statement on the perioperative management of anaemia and iron deficiency. Anaesthesia. 2017;72:233–47.CrossRef Munoz M, Acheson AG, Auerbach M, et al. International consensus statement on the perioperative management of anaemia and iron deficiency. Anaesthesia. 2017;72:233–47.CrossRef
24.
go back to reference Ng O, Keeler BD, Mishra A, Simpson A, Neal K, Brookes MJ, Acheson AG. Iron therapy for pre-operative anaemia. Cochrane Database Syst Rev. 2015:CD011588. Ng O, Keeler BD, Mishra A, Simpson A, Neal K, Brookes MJ, Acheson AG. Iron therapy for pre-operative anaemia. Cochrane Database Syst Rev. 2015:CD011588.
25.
go back to reference Shah A, Roy NB, McKechnie S, Doree C, Fisher SA, Stanworth SJ. Iron supplementation to treat anaemia in adult critical care patients: a systematic review and meta-analysis. Crit Care. 2016;20:306.CrossRef Shah A, Roy NB, McKechnie S, Doree C, Fisher SA, Stanworth SJ. Iron supplementation to treat anaemia in adult critical care patients: a systematic review and meta-analysis. Crit Care. 2016;20:306.CrossRef
26.
go back to reference Connor JR, Zhang X, Nixon AM, Webb B, Perno JR. Comparative evaluation of nephrotoxicity and management by macrophages of intravenous pharmaceutical iron formulations. PLoS One. 2015;10:e0125272.CrossRef Connor JR, Zhang X, Nixon AM, Webb B, Perno JR. Comparative evaluation of nephrotoxicity and management by macrophages of intravenous pharmaceutical iron formulations. PLoS One. 2015;10:e0125272.CrossRef
27.
go back to reference Pandharipande PP, Girard TD, Jackson JC, et al. Long-term cognitive impairment after critical illness. N Engl J Med. 2013;369:1306–16.CrossRef Pandharipande PP, Girard TD, Jackson JC, et al. Long-term cognitive impairment after critical illness. N Engl J Med. 2013;369:1306–16.CrossRef
28.
go back to reference Youdim MB, Yehuda S. The neurochemical basis of cognitive deficits induced by brain iron deficiency: involvement of dopamine-opiate system. Cell Mol Biol. 2000;46:491–500.PubMed Youdim MB, Yehuda S. The neurochemical basis of cognitive deficits induced by brain iron deficiency: involvement of dopamine-opiate system. Cell Mol Biol. 2000;46:491–500.PubMed
29.
go back to reference Lozoff B. Early iron deficiency has brain and behavior effects consistent with dopaminergic dysfunction. J Nutr. 2011;141:740S–6S.CrossRef Lozoff B. Early iron deficiency has brain and behavior effects consistent with dopaminergic dysfunction. J Nutr. 2011;141:740S–6S.CrossRef
30.
go back to reference Favrat B, Balck K, Breymann C, et al. Evaluation of a single dose of ferric carboxymaltose in fatigued, iron-deficient women—PREFER a randomized, placebo-controlled study. PLoS One. 2014;9:e94217.CrossRef Favrat B, Balck K, Breymann C, et al. Evaluation of a single dose of ferric carboxymaltose in fatigued, iron-deficient women—PREFER a randomized, placebo-controlled study. PLoS One. 2014;9:e94217.CrossRef
31.
go back to reference Guarneri B, Bertolini G, Latronico N. Long-term outcome in patients with critical illness myopathy or neuropathy: the Italian multicentre CRIMYNE study. J Neurol Neurosurg Psychiatry. 2008;79:838–41.CrossRef Guarneri B, Bertolini G, Latronico N. Long-term outcome in patients with critical illness myopathy or neuropathy: the Italian multicentre CRIMYNE study. J Neurol Neurosurg Psychiatry. 2008;79:838–41.CrossRef
32.
go back to reference Lasocki S, Chudeau N, Papet T, et al. Prevalence of iron deficiency on ICU discharge and its relation with fatigue: a multicenter prospective study. Crit Care. 2014;18:542.CrossRef Lasocki S, Chudeau N, Papet T, et al. Prevalence of iron deficiency on ICU discharge and its relation with fatigue: a multicenter prospective study. Crit Care. 2014;18:542.CrossRef
33.
go back to reference Jankowska EA, Kasztura M, Sokolski M, et al. Iron deficiency defined as depleted iron stores accompanied by unmet cellular iron requirements identifies patients at the highest risk of death after an episode of acute heart failure. Eur Heart J. 2014;35:2468–76.CrossRef Jankowska EA, Kasztura M, Sokolski M, et al. Iron deficiency defined as depleted iron stores accompanied by unmet cellular iron requirements identifies patients at the highest risk of death after an episode of acute heart failure. Eur Heart J. 2014;35:2468–76.CrossRef
34.
go back to reference Jankowska EA, Tkaczyszyn M, Suchocki T, et al. Effects of intravenous iron therapy in iron-deficient patients with systolic heart failure: a meta-analysis of randomized controlled trials. Eur J Heart Fail. 2016;18:786–95.CrossRef Jankowska EA, Tkaczyszyn M, Suchocki T, et al. Effects of intravenous iron therapy in iron-deficient patients with systolic heart failure: a meta-analysis of randomized controlled trials. Eur J Heart Fail. 2016;18:786–95.CrossRef
35.
go back to reference Maeder MT, Khammy O. dos Remedios C, Kaye DM. Myocardial and systemic iron depletion in heart failure: implications for anemia accompanying heart failure. J Am Coll Cardiol. 2011;58:474–80.CrossRef Maeder MT, Khammy O. dos Remedios C, Kaye DM. Myocardial and systemic iron depletion in heart failure: implications for anemia accompanying heart failure. J Am Coll Cardiol. 2011;58:474–80.CrossRef
36.
go back to reference Ramakrishnan L, Pedersen SL, Toe QK, Quinlan GJ, Wort SJ. Pulmonary arterial hypertension: iron matters. Front Physiol. 2018;9:641.CrossRef Ramakrishnan L, Pedersen SL, Toe QK, Quinlan GJ, Wort SJ. Pulmonary arterial hypertension: iron matters. Front Physiol. 2018;9:641.CrossRef
37.
go back to reference Zochios V, Parhar K, Tunnicliffe W, Roscoe A, Gao F. The right ventricle in ARDS. Chest. 2017;152:181–93.CrossRef Zochios V, Parhar K, Tunnicliffe W, Roscoe A, Gao F. The right ventricle in ARDS. Chest. 2017;152:181–93.CrossRef
38.
go back to reference Cassat JE, Skaar EP. Iron in infection and immunity. Cell Host Microbe. 2013;13:509–19.CrossRef Cassat JE, Skaar EP. Iron in infection and immunity. Cell Host Microbe. 2013;13:509–19.CrossRef
40.
go back to reference Puntarulo S. Iron, oxidative stress and human health. Mol Asp Med. 2005;26:299–312.CrossRef Puntarulo S. Iron, oxidative stress and human health. Mol Asp Med. 2005;26:299–312.CrossRef
41.
go back to reference Neuberger A, Okebe J, Yahav D, Paul M. Oral iron supplements for children in malaria-endemic areas. Cochrane Database Syst Rev. 2016:CD006589. Neuberger A, Okebe J, Yahav D, Paul M. Oral iron supplements for children in malaria-endemic areas. Cochrane Database Syst Rev. 2016:CD006589.
42.
go back to reference Agarwal R, Kusek JW, Pappas MK. A randomized trial of intravenous and oral iron in chronic kidney disease. Kidney Int. 2015;88:905–14.CrossRef Agarwal R, Kusek JW, Pappas MK. A randomized trial of intravenous and oral iron in chronic kidney disease. Kidney Int. 2015;88:905–14.CrossRef
43.
go back to reference Anker SD, Comin Colet J, Filippatos G, et al. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med. 2009;361:2436–48.CrossRef Anker SD, Comin Colet J, Filippatos G, et al. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med. 2009;361:2436–48.CrossRef
44.
go back to reference Pammi M, Suresh G. Enteral lactoferrin supplementation for prevention of sepsis and necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev. 2017:CD007137. Pammi M, Suresh G. Enteral lactoferrin supplementation for prevention of sepsis and necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev. 2017:CD007137.
45.
go back to reference Muscedere J, Maslove DM, Boyd JG, et al. Prevention of nosocomial infections in critically ill patients with lactoferrin: a randomized, double-blind, placebo-controlled study. Crit Care Med. 2018;46:1450–6.CrossRef Muscedere J, Maslove DM, Boyd JG, et al. Prevention of nosocomial infections in critically ill patients with lactoferrin: a randomized, double-blind, placebo-controlled study. Crit Care Med. 2018;46:1450–6.CrossRef
46.
go back to reference Sebastiani G, Wilkinson N, Pantopoulos K. Pharmacological targeting of the hepcidin/ferroportin axis. Front Pharmacol. 2016;7:160.CrossRef Sebastiani G, Wilkinson N, Pantopoulos K. Pharmacological targeting of the hepcidin/ferroportin axis. Front Pharmacol. 2016;7:160.CrossRef
47.
go back to reference Balhara M, Chaudhary R, Ruhil S, et al. Siderophores; iron scavengers: the novel & promising targets for pathogen specific antifungal therapy. Expert Opin Ther Targets. 2016;20:1477–89.CrossRef Balhara M, Chaudhary R, Ruhil S, et al. Siderophores; iron scavengers: the novel & promising targets for pathogen specific antifungal therapy. Expert Opin Ther Targets. 2016;20:1477–89.CrossRef
48.
go back to reference Kim YW, Bae JM, Park YK, et al. Effect of intravenous ferric carboxymaltose on hemoglobin response among patients with acute isovolemic anemia following gastrectomy: the FAIRY randomized clinical trial. JAMA. 2017;317:2097–104.CrossRef Kim YW, Bae JM, Park YK, et al. Effect of intravenous ferric carboxymaltose on hemoglobin response among patients with acute isovolemic anemia following gastrectomy: the FAIRY randomized clinical trial. JAMA. 2017;317:2097–104.CrossRef
49.
go back to reference Johansson PI, Rasmussen AS, Thomsen LL. Intravenous iron isomaltoside 1000 (Monofer®) reduces postoperative anaemia in preoperatively non-anaemic patients undergoing elective or subacute coronary artery bypass graft, valve replacement or a combination thereof: a randomized double-blind placebo-controlled clinical trial (the PROTECT trial). Vox Sang. 2015;109:257–66.CrossRef Johansson PI, Rasmussen AS, Thomsen LL. Intravenous iron isomaltoside 1000 (Monofer®) reduces postoperative anaemia in preoperatively non-anaemic patients undergoing elective or subacute coronary artery bypass graft, valve replacement or a combination thereof: a randomized double-blind placebo-controlled clinical trial (the PROTECT trial). Vox Sang. 2015;109:257–66.CrossRef
50.
go back to reference Bernabeu-Wittel M, Romero M, Ollero-Baturone M, et al. Ferric carboxymaltose with or without erythropoietin in anemic patients with hip fracture: a randomized clinical trial. Transfusion. 2016;56:2199–211.CrossRef Bernabeu-Wittel M, Romero M, Ollero-Baturone M, et al. Ferric carboxymaltose with or without erythropoietin in anemic patients with hip fracture: a randomized clinical trial. Transfusion. 2016;56:2199–211.CrossRef
51.
go back to reference Froessler B, Palm P, Weber I, Hodyl NA, Singh R, Murphy EM. The important role for intravenous iron in perioperative patient blood management in major abdominal surgery: a randomized controlled trial. Ann Surg. 2016;264:41–6.CrossRef Froessler B, Palm P, Weber I, Hodyl NA, Singh R, Murphy EM. The important role for intravenous iron in perioperative patient blood management in major abdominal surgery: a randomized controlled trial. Ann Surg. 2016;264:41–6.CrossRef
Metadata
Title
Iron Metabolism: An Emerging Therapeutic Target in Critical Illness
Authors
Edward Litton
Jolene Lim
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2019
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-019-2373-1

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