Nutritional Deficiencies Contribute to Anemia in the ICU
Nutritional Deficiencies Contribute to Anemia in the ICU
Abstract & Commentary
Synopsis: Anemia is a common, often unexplained problem in critically ill and injured patients. Many factors (including occult bleeding, shortened red cell life span, DIC, and excessive diagnostic blood examinations [often associated with indwelling arterial lines]) have been identified as contributors in some anemic ICU patients. The incidence of iron and vitamin deficiency at baseline was 13% in a group of selected ICU patients.
Source: Rodriguez RM, et al. Nutritional deficiencies and blunted erythropoietin response as causes of the anemia of critical illness. J Crit Care. 2001;16(1):36-41.
Many factors have been identified that may contribute to the high incidence of anemia and need for blood transfusion in the critically ill. The identification of depressed erythropoiesis or low effective erythropoietin (EP) levels has led to the development and use of recombinant EP in managing critically ill patients. Even with this intervention, many patients fail to mount a response to administered EP. Supplying additional iron and vitamins to patients receiving EP is commonly practiced to eliminate deficiencies of these nutrients as a cause for failure of EP. The role of vitamin deficiency as a contributor to the anemia observed in ICU patients has not been carefully studied. The role of deficiencies and ineffective erythropoiesis is also poorly understood. Recognized factors explain only a minority of the cases of anemia, which are observed in ICU patients.
Rodriguez and colleagues measured iron; total iron biding capacity, ferritin, reticulocyte count, vitamin B12, folate, and EP levels in a group of anemic ICU patients (mean hemoglobin concentration, 10.3 g/dL) with no identified cause of anemia. Exclusion criteria were broad and included most severe acute and chronic diseases, prior treatment with EP, active bleeding, cancer or cancer treatment, expected death within 3 days, and known prior deficiencies of iron, B12, or folate. In this relatively healthy group of 184 patients (mostly uncomplicated respiratory failure patients or those with trauma), iron deficiency was found in 9%, B12 deficiency in 2%, and folate deficiency in 2% (levels measured on the second or third ICU day). Mortality in this group was 28%. In the nondeficient patients, EP levels were not elevated (which would be appropriate in anemia) in 30% of patients at baseline, and remained low and normal in subsequent weekly measurements in 30-40% of the patients remaining in the hospital. Reticulocyte counts averaged only 1.3% at the initial determination and never exceeded 6% in any patient.
As this was an observation study,1 no interventions based on these measurements were made. The high incidence of vitamin and iron deficiency at baseline suggests screening for levels of these necessary nutrients in anemic ICU patients with no obvious cause of deficiency or anemia.
Comment by Charles G. Durbin, Jr., MD
While this is not a perfect study, it adds to the understanding of the anemia commonly seen in ICU patients. It suggests that a substantial percentage of anemic ICU patients will have reduced iron, B12, or folate levels, and many of these will not have an appropriately elevated EP level. What was not studied is the question of whether vitamin and iron supplementation will improve hematopoiesis and anemia in ICU patients. In the non-deficient patients, hematopoiesis was not normal. Most of these patients had normal or low levels of EP, despite significant anemia. Even in patients with high levels of EP, reticulocyte responses were reduced. This anemia is very much like the anemia of chronic disease, the cause of which is not well understood but includes reduced red cell life span and decreased EP responsiveness. In some studies, therapeutically administered exogenous EP has improved reticulocytosis and reduced transfusion requirements in populations of ICU patients.
Although not the focus of this report, it is interesting to note that of the large number of ICU patients screened who remained in an ICU at least 3 days (1778), 1594 were eliminated due to confounding issues that could explain or interfere with evaluation of anemia. This left only 184 patients with unexplained, uncomplicated anemia who made up the study population reported in this paper. Another interesting observation was that of the nearly 2000 patients screened, only 1% had a hematocrit level above the 38% criterion used. Anemia in the larger ICU population is the rule rather than the exception.
The current push by manufacturers, including television-based, patient-directed advertisements, to use recombinant EP therapeutically is fueled by studies such as this. However, the number of patients who might actually benefit is apparently small. The actual optimal hemoglobin level has not been determined and the actual level for which intervention is appropriate is not known. It is important to understand the etiology of the anemias seen in the ICU. What is less clear is when and how to treat it. A simple and inexpensive approach to at least some of these patients could simply be replacement of vitamin deficiencies.
Dr. Durbin, Jr., MD, Professor of Anesthesiology, Medical Director of Respiratory Care, University of Virginia, is Associate Editor of Critical Care Alert.
Reference
1. Corwin HL, et al. Efficacy of recombinant human erythropoietin in the critically ill patient: A randomized, double-blind, placebo-controlled trial. Crit Care Med. 1999;27:2346-2350.
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