IRON supplementation in ICU patients: The IRONMAN Trial

ARTICLE REVIEW

Achieving the optimal balance between permissive anemia and excessive Red Blood Cell (RBC) transfusions is a well known issue for ICU physicians. Intravenous (IV) iron supplementation has been suggested as viable strategic option to decrease the severity of anemia and the incidence of RBC transfusion in non-critically ill patients.

In this randomised, placebo-controlled trial, the authors investigated the therapeutic effect of IV iron in an ICU anemic population, enrolling adult ICU patients admitted with Hb levels lower than 100 g/L. Patients were randomised in two groups: IV iron (receiving 500 mg of ferric carboxymaltose in saline solution) or placebo (receiving normal saline). In both groups re-dosing was administered every four days, until inclusion criteria were matched and for a maximum of four doses. The primary study outcome was the reduction of RBC units transfused. Secondary outcomes included Hb value at hospital discharge, total length of stay (LOS), adverse events rate and mortality. Of the 330 screened patients, 140 were randomised: 70 to IV iron, and 70 to placebo. As for the primary outcome, no significant difference in the total number of RBC units transfused was detected: 97 in the IV iron group vs 136 in the placebo group (p= 0.19), with a median of 2 units for patient. However, Hb level at hospital discharge was significantly higher in the IV iron group (107 g/l vs 100 g/l, p = 0.02), without any difference in terms of LOS and safety outcomes.

The results should be interpreted in light of important limitations: no Hb level threshold was planned as a trigger for transfusion and the study population was not completely homogeneous in terms of severity of illness and admission category.

This study does not support the use of IV iron as a strategy to reduce anemia and RBC transfusion among ICU patients, even though it resulted in higher Hb levels at hospital discharge. The physio-pathologycal erythropoietic response to IV iron supplementation in critical patients proved to be more complex than expected and requires further evaluation before being widely implemented in daily clinical practice.

Article review submitted by Gennaro De Pascale and Simone Carelli on behalf of NEXT.

REFERENCE

The IRONMAN Investigators, Edward Litton, Stuart Baker, Wendy N. Erber, Shannon Farmer, Janet Ferrier, Craig French, Joel Gummer, David Hawkins, Alisa Higgins, Axel Hofmann, Bart De Keulenaer, Julie McMorrow, John K. Olynyk, Toby Richards, Simon Towler, Robert Trengove, Steve Webb and The Australian and New Zealand Intensive Care Society Clinical Trials Group. Intravenous iron or placebo for anaemia in intensive care: the IRONMAN multicentre randomised blinded trial.  Intensive Care Med 42, 1715–1722 (2016). https://doi.org/10.1007/s00134-016-4465-6