Impact of treating iron deficiency, diagnosed according to hepcidin quantification, on outcomes after a prolonged ICU stay compared to standard care: a multicenter, randomized, single-blinded trial

Département Anesthésie Réanimation, CHU Angers, Université D'Angers, 4 rue Larrey, 49933, Angers Cedex 9, France. sigismond@lasocki.com. Département Médecine Intensive Réanimation, CHU Angers, Université D'Angers, Angers, France. Département Anesthésie Réanimation, Université de Montpellier, Montpellier, France. Département Anesthésie Réanimation, CHU de Tours, Université de Tours, Tours, France. Service D'anesthésie-réanimation, CHU de Poitiers, Université de Poitiers, Poitiers, France. Département Anesthésie Réanimation, CHU de Nantes, Université de Nantes, Nantes, France. Département Anesthésie Réanimation, APHP, HUPNSV, CHU Bichat, Université Paris Diderot Sorbonne, Paris, France. Département Anesthésie Réanimation, CHU de Rennes, Université de Rennes, Rennes, France. INSERM U1149, UFR de Médecine Bichat, Centre de Recherche Sur L'Inflammation, Université de Paris, Paris, France. APHP Nord Hôpital Universitaire Louis Mourier, Assistance Publique des Hôpitaux de Paris, Colombes, France. Laboratoire D'Excellence GR-Ex Ou Laboratory of Excellence GR-Ex, Paris, France. Département Anesthésie Réanimation, CHU Angers, Université D'Angers, 4 rue Larrey, 49933, Angers Cedex 9, France. Département D'information médicale, CHU Montpellier, Université de Montpellier, Montpellier, France. Laboratoire de Biochimie Protéomique Clinique Et IRMB INSERM, CHU de Montpellier, Université de Montpellier, Montpellier, France.

Critical care (London, England). 2021;25(1):62
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PICO Summary

Population

Critically ill patients with a prolonged ICU stay (n= 399).

Intervention

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, (n= 201).

Comparison

Standard care (n= 198).

Outcome

A total of 220 patients (55%) had iron deficiency at discharge (i.e., a hepcidin < 41 μg/l). The number of days spent in hospital 90 days after ICU discharge was not different (medians: 33 vs. 33) days for intervention and control, respectively. Day 90 mortality was significantly lower in intervention arm (16 (8%) vs. 33 (16.6%) deaths, and one-year survival was improved.
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).
Study details
Language : eng
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