Sigismond Lasocki1, Pierre Asfar2, Samir Jaber3, Martine Ferrandiere4, Thomas Kerforne5, Karim Asehnoune6, Philippe Montravers7, Philippe Seguin8, Katell Peoc'h9,10,11, Soizic Gergaud12, Nicolas Nagot13, Thibaud Lefebvre9, Sylvain Lehmann14. 1. Département Anesthésie Réanimation, CHU Angers, Université D'Angers, 4 rue Larrey, 49933, Angers Cedex 9, France. sigismond@lasocki.com. 2. Département Médecine Intensive Réanimation, CHU Angers, Université D'Angers, Angers, France. 3. Département Anesthésie Réanimation, Université de Montpellier, Montpellier, France. 4. Département Anesthésie Réanimation, CHU de Tours, Université de Tours, Tours, France. 5. Service D'anesthésie-réanimation, CHU de Poitiers, Université de Poitiers, Poitiers, France. 6. Département Anesthésie Réanimation, CHU de Nantes, Université de Nantes, Nantes, France. 7. Département Anesthésie Réanimation, APHP, HUPNSV, CHU Bichat, Université Paris Diderot Sorbonne, Paris, France. 8. Département Anesthésie Réanimation, CHU de Rennes, Université de Rennes, Rennes, France. 9. INSERM U1149, UFR de Médecine Bichat, Centre de Recherche Sur L'Inflammation, Université de Paris, Paris, France. 10. APHP Nord Hôpital Universitaire Louis Mourier, Assistance Publique des Hôpitaux de Paris, Colombes, France. 11. Laboratoire D'Excellence GR-Ex Ou Laboratory of Excellence GR-Ex, Paris, France. 12. Département Anesthésie Réanimation, CHU Angers, Université D'Angers, 4 rue Larrey, 49933, Angers Cedex 9, France. 13. Département D'information médicale, CHU Montpellier, Université de Montpellier, Montpellier, France. 14. Laboratoire de Biochimie Protéomique Clinique Et IRMB INSERM, CHU de Montpellier, Université de Montpellier, Montpellier, France.
Abstract
BACKGROUND: Anemia is a significant problem in patients on ICU. Its commonest cause, iron deficiency (ID), is difficult to diagnose in the context of inflammation. Hepcidin is a new marker of ID. We aimed to assess whether hepcidin levels would accurately guide treatment of ID in critically ill anemic patients after a prolonged ICU stay and affect the post-ICU outcomes. METHODS: In a controlled, single-blinded, multicenter study, anemic (WHO definition) critically ill patients with an ICU stay ≥ 5 days were randomized when discharge was expected to either intervention by hepcidin treatment protocol or control. In the intervention arm, patients were treated with intravenous iron (1 g of ferric carboxymaltose) when hepcidin was < 20 μg/l and with intravenous iron and erythropoietin for 20 ≤ hepcidin < 41 μg/l. Control patients were treated according to standard care (hepcidin quantification remained blinded). Primary endpoint was the number of days spent in hospital 90 days after ICU discharge (post-ICU LOS). Secondary endpoints were day 15 anemia, day 30 fatigue, day 90 mortality and 1-year survival. RESULTS:Of 405 randomized patients, 399 were analyzed (201 in intervention and 198 in control arm). A total of 220 patients (55%) had ID at discharge (i.e., a hepcidin < 41 μg/l). Primary endpoint was not different (medians (IQR) post-ICU LOS 33(13;90) vs. 33(11;90) days for intervention and control, respectively, median difference - 1(- 3;1) days, p = 0.78). D90 mortality was significantly lower in intervention arm (16(8%) vs 33(16.6%) deaths, absolute risk difference - 8.7 (- 15.1 to - 2.3)%, p = 0.008, OR 95% IC, 0.46, 0.22-0.94, p = 0.035), and one-year survival was improved (p = 0.04). CONCLUSION: Treatment of ID diagnosed according to hepcidin levels did not reduce the post-ICU LOS, but was associated with a significant reduction in D90 mortality and with improved 1-year survival in critically ill patients about to be discharged after a prolonged stay. TRIAL REGISTRATION: www.clinicaltrial.gov NCT02276690 (October 28, 2014; retrospectively registered).
RCT Entities:
BACKGROUND:Anemia is a significant problem in patients on ICU. Its commonest cause, iron deficiency (ID), is difficult to diagnose in the context of inflammation. Hepcidin is a new marker of ID. We aimed to assess whether hepcidin levels would accurately guide treatment of ID in critically ill anemicpatients after a prolonged ICU stay and affect the post-ICU outcomes. METHODS: In a controlled, single-blinded, multicenter study, anemic (WHO definition) critically illpatients with an ICU stay ≥ 5 days were randomized when discharge was expected to either intervention by hepcidin treatment protocol or control. In the intervention arm, patients were treated with intravenous iron (1 g of ferric carboxymaltose) when hepcidin was < 20 μg/l and with intravenous iron and erythropoietin for 20 ≤ hepcidin < 41 μg/l. Control patients were treated according to standard care (hepcidin quantification remained blinded). Primary endpoint was the number of days spent in hospital 90 days after ICU discharge (post-ICU LOS). Secondary endpoints were day 15 anemia, day 30 fatigue, day 90 mortality and 1-year survival. RESULTS: Of 405 randomized patients, 399 were analyzed (201 in intervention and 198 in control arm). A total of 220 patients (55%) had ID at discharge (i.e., a hepcidin < 41 μg/l). Primary endpoint was not different (medians (IQR) post-ICU LOS 33(13;90) vs. 33(11;90) days for intervention and control, respectively, median difference - 1(- 3;1) days, p = 0.78). D90 mortality was significantly lower in intervention arm (16(8%) vs 33(16.6%) deaths, absolute risk difference - 8.7 (- 15.1 to - 2.3)%, p = 0.008, OR 95% IC, 0.46, 0.22-0.94, p = 0.035), and one-year survival was improved (p = 0.04). CONCLUSION: Treatment of ID diagnosed according to hepcidin levels did not reduce the post-ICU LOS, but was associated with a significant reduction in D90 mortality and with improved 1-year survival in critically illpatients about to be discharged after a prolonged stay. TRIAL REGISTRATION: www.clinicaltrial.gov NCT02276690 (October 28, 2014; retrospectively registered).
Entities:
Keywords:
Anemia; Critically ill; Erythropoietin; Hepcidin; Iron (treatment); Iron deficiency; Length of stay; Mortality
Authors: Matthew A Warner; Andrew C Hanson; Phillip J Schulte; Nareg H Roubinian; Curt Storlie; Gabriel Demuth; Ognjen Gajic; Daryl J Kor Journal: J Intensive Care Med Date: 2022-02-01 Impact factor: 2.889