Sigismond Lasocki1, Pascale Piednoir, Camille Couffignal, Emmanuel Rineau, Guillaume Dufour, Thibaud Lefebvre, Herve Puy, Xavier Duval, Fathi Driss, Clementine Schilte. 1. 1Département Anesthésie Réanimation, CHU Angers, LUNAM Université d'Angers, Angers, France.2Service d'Anesthésie-Réanimation, AP-HP, Groupe Hospitalier Paris Nord Val de Seine, Paris, France.3INSERM, IAME, UMR 1137, Paris, France.4Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, Paris, France.5Service de Biostatistique, AP-HP, Groupe Hospitalier Paris Nord Val de Seine, Paris, France.6INSERM U1149, Centre de Recherche sur l'inflammation, Paris, France.7Laboratory of Excellence, GR-Ex, Paris, France.8INSERM CIC 1425, AP-HP, Groupe Hospitalier Paris Nord Val de Seine, Paris, France.9INSERM, UMR1152, Paris, France.
Abstract
OBJECTIVE: To compare the oxidative stress induced by IV iron infusion in critically ill patients and in healthy volunteers. DESIGN: Multicenter, interventional study. SETTING: Two ICUs and one clinical research center. SUBJECTS: Anemic critically ill patients treated with IV iron and healthy volunteers. INTERVENTIONS: IV infusion of 100 mg of iron sucrose. MEASUREMENTS AND MAIN RESULTS: Thirty-eight anemic patients (hemoglobin, median [interquartile range] = 8.4 g/dL [7.7-9.2]) (men, 25 [66%]; aged 68 yr [48-77]; Simplified Acute Physiology Score II, 48.5 [39-59]) and 39 healthy volunteers (men, 18 [46%]; aged 42.1 yr [29-50]) were included. Blood samples were drawn before (H0) and 2, 6, and 24 hours (H2, H6, and H24) after a 60-minute iron infusion for the determination of nontransferrin bound iron, markers of lipid peroxidation-8α-isoprostanes, protein oxidation-advanced oxidized protein product, and glutathione reduced/oxidized. Iron infusion had no effect on hemodynamic parameter in patients and volunteers. At baseline, patients had much higher interleukin-6, C-reactive protein, and hepcidin levels. 8α-isoprostanes was also higher in patients at baseline (8.5 pmol/L [6.5-12.9] vs 4.6 pmol/L [3.5-5.5]), but the area under the curve above baseline from H0 to H6 was not different (p = 0.38). Neither was it for advanced oxidized protein product and nontransferrin bound iron. The area under the curve above baseline from H0 to H6 (glutathione reduced/oxidized) was lower in volunteers (p = 0.009). Eight patients had a second set of dosages (after the fourth iron infusion), showing higher increase in 8α-isoprostanes. CONCLUSIONS: In our observation, IV iron infusion does not induce more nontransferrin bound iron, lipid, or protein oxidation in patients compared with volunteers, despite higher inflammation, oxidative stress, and hepcidin levels and lower antioxidant at baseline. In contrary, iron induces a greater decrease in antioxidant, compatible with higher oxidative stress in volunteers than in critically ill patients.
OBJECTIVE: To compare the oxidative stress induced by IV iron infusion in critically illpatients and in healthy volunteers. DESIGN: Multicenter, interventional study. SETTING: Two ICUs and one clinical research center. SUBJECTS:Anemic critically illpatients treated with IV iron and healthy volunteers. INTERVENTIONS: IV infusion of 100 mg of iron sucrose. MEASUREMENTS AND MAIN RESULTS: Thirty-eight anemicpatients (hemoglobin, median [interquartile range] = 8.4 g/dL [7.7-9.2]) (men, 25 [66%]; aged 68 yr [48-77]; Simplified Acute Physiology Score II, 48.5 [39-59]) and 39 healthy volunteers (men, 18 [46%]; aged 42.1 yr [29-50]) were included. Blood samples were drawn before (H0) and 2, 6, and 24 hours (H2, H6, and H24) after a 60-minute iron infusion for the determination of nontransferrin bound iron, markers of lipid peroxidation-8α-isoprostanes, protein oxidation-advanced oxidized protein product, and glutathione reduced/oxidized. Iron infusion had no effect on hemodynamic parameter in patients and volunteers. At baseline, patients had much higher interleukin-6, C-reactive protein, and hepcidin levels. 8α-isoprostanes was also higher in patients at baseline (8.5 pmol/L [6.5-12.9] vs 4.6 pmol/L [3.5-5.5]), but the area under the curve above baseline from H0 to H6 was not different (p = 0.38). Neither was it for advanced oxidized protein product and nontransferrin bound iron. The area under the curve above baseline from H0 to H6 (glutathione reduced/oxidized) was lower in volunteers (p = 0.009). Eight patients had a second set of dosages (after the fourth iron infusion), showing higher increase in 8α-isoprostanes. CONCLUSIONS: In our observation, IV iron infusion does not induce more nontransferrin bound iron, lipid, or protein oxidation in patients compared with volunteers, despite higher inflammation, oxidative stress, and hepcidin levels and lower antioxidant at baseline. In contrary, iron induces a greater decrease in antioxidant, compatible with higher oxidative stress in volunteers than in critically illpatients.