Nutrition Support Blog: Iron Supplements in Critical Illness
December 1, 2012
Iron – just say the word and you instantly conjure up images of strength and power: Iron Man, The Iron Curtain, Pump some Iron, and let’s not forget Popeye. All Popeye needed to vanquish someone far above his weight class was the iron from a single can of spinach (oxalates notwithstanding). The images that we have built around iron in our culture and language have created the ultimate marketing tool for iron supplements as a ‘good thing’ regardless of circumstances.
However, we need to consider nature and how the human system has adapted to manage iron within the body. Iron is one of the most important rate-limiting nutrients for the well being of micro-organisms that could cause harm in the human body. Free iron in the body is also a pro-oxidant nutrient that can promote tissue and enzyme damage through free radicals if left unbound.
A complex set of proteins strictly regulates and safeguards iron so that it is not available to pathogens in our body. Hemoglobin and heme are tightly bound by transferrin, lactoferrin, ferritin and haptoglobin in the body. In the event of any illness, injury or infection, the acute phase response rapidly increases our iron binding proteins such as ferritin, to protect the body by denying iron to pathogens. An article in the November 9th issue of Science describes the role of hepcidin and other “chaperone proteins” in producing the decreased serum iron seen in infection that are part of our innate defenses against illness, injury and infection (Hepcidin and the Iron-Infection Axis http://www.sciencemag.org/content/338/6108.toc).
Considering that our natural response to critical illness is to sequester iron, it would appear counterintuitive to give iron supplements in the ICU. Nevertheless, I have observed increased enteral iron supplements ordered in some ICU patients in recent years. Studies have found that a restrictive transfusion policy (waiting until hemoglobin drops below 7 before transfusing patients) improves outcomes for some types of ICU patients.1,2 Iron supplements are sometimes ordered in an attempt to limit the need for transfusions.
There is only one randomized, double-blind study of enteral iron supplements in critically ill surgical, burn and neurosurgical patients.3 The study reported that only those patients that were admitted with preexisting iron deficiency anemia had a trend towards improved hematocrit (after 28 days). There were significantly less transfusions provided to the iron supplemented group, but the subgroup analysis showed that only those patients with a preexisting iron deficiency had a significantly decreased need for transfusions. There were no significant differences in infection rates between the iron and placebo groups. However, considering the group that received iron supplements also received less transfusions, the results can also be restated in a less flattering way as, “iron supplements are just as bad as increased transfusions regarding infection risk.” If we remember that red cells turn over every 3 months it is not surprising that starting iron supplements in the ICU did not seem to benefit most patients.
Intravenous iron may have more potential to reverse anemia from critical illness, but also more potential risk from infections. There are no published studies of the effects of intravenous iron in critical illness, but there is an active multicenter randomized study of IV iron in critically ill trauma patients (http://clinicaltrials.gov/show/NCT01180894) currently in progress.
In the meantime, given the lack of apparent benefits of iron supplementation in the ICU population, my bias is that unless your patient’s name is Popeye, we should probably be avoiding iron supplements in patients with active infections, and until further information is available, consider holding iron supplements in ICU patients until they are less critically ill.
“It ain't so much what you don't know that gets you into trouble, it's what you know for sure that just ain't so.”
“Remember that the goal is not to make the labs normal, the goal is to help the patient”
1) Hebert PC, et al. N Engl J Med.1999;340:409–417
2) Vincent JL, et al: JAMA 2002; 288:1499–1507
3) Pieracci FM, et al. Surg Infect (Larchmt). 2009;10(1):9-19.