Iron deficiency diagnosed using hepcidin on critical care discharge is an independent risk factor for death and poor quality of life at one year: an observational prospective study on 1161 patients

Sigismond Lasocki,Thibaud Lefebvre,Alexandre Mebazaa,Etienne Gayat,Claire Mayeur,Hervé Puy

doi:10.1186/s13054-018-2253-0

Abstract

BackgroundIron deficiency is difficult to diagnose in critically ill patients, but may be frequent and may impair recovery. Measurement of hepcidin could help in the diagnosis of iron deficiency. We aim to assess if iron deficiency diagnosed using hepcidin is associated with poorer outcome one year after an intensive care unit stay.MethodsWe used the prospective FROG-ICU, multicentre (n = 28 ICUs), observational cohort study of critically ill survivors followed up one year after intensive care unit discharge. Iron deficiency was defined as hepcidin < 20 ng/l, ferritin < 100 ng/l or soluble transferrin receptor (sTfR)/log(ferritin) > 0.8, measured in blood drawn at intensive care unit discharge. Main outcomes were one-year all-cause mortality and poor quality of life (defined as a Short Form 36 (SF-36) score below the median).ResultsAmong the 2087 patients in the FROG-ICU cohort, 1570 were discharged alive and 1161 had a blood sample available at intensive care unit discharge and were included in the analysis. Using hepcidin, 429 (37%) patients had iron deficiency, compared to 72 (6%) using ferritin alone and 151 (13%) using the sTfR/log(ferritin) ratio. Iron deficiency diagnosed according to low hepcidin was an independent predictor of one-year mortality (OR 1.51 (1.10–2.08)) as was high sTfR/log ferritin ratio (OR = 1.95 (1.27–3.00)), but low ferritin was not. Severe ID, defined as hepcidin < 10 ng/l, was also an independent predictor of poor one-year physical recovery (1.58 (1.01–2.49)).ConclusionsIron deficiency, diagnosed using hepcidin, is very frequent at intensive care unit discharge and is associated with increased one-year mortality and poorer physical recovery. Whether iron treatment may improve these outcomes remains to be investigated.

Highlights

Iron deficiency is difficult to diagnose in critically ill patients, but may be frequent and may impair recovery
Because the diagnosis of Iron deficiency (ID) may be modified in the presence of inflammation, we modelled the probability of one-year mortality according to the ID markers (i.e. hepcidin and soluble transferrin receptor (sTfR)/log(ferritin)) and the level of inflammation, by separating the population according to the different tertiles of interleukin-6 levels at discharge
ID diagnosis Hepcidin measurements were available for 1161 patients, ferritin for 1157 patients and sTfR/ferritin for 1146 patients

Summary

Introduction

Iron deficiency is difficult to diagnose in critically ill patients, but may be frequent and may impair recovery. We aim to assess if iron deficiency diagnosed using hepcidin is associated with poorer outcome one year after an intensive care unit stay. ID is responsible for anaemia, it causes fatigue and muscle weakness, independently of anaemia [3] This has been notably described in patients with heart failure, for whom ID is associated with impaired cardiac function and increased mortality [4, 5]. Because critically ill patients are exposed to frequent blood sampling and other causes of blood loss (including surgery, extracorporeal circuit, invasive procedures, etc.) [9, 10], they are exposed to high iron losses. The remaining proposed marker in this context is the ratio between soluble transferrin receptor and the log (ferritin) (sTfR/log ferritin) [15]

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