Severe anemia is common in critically ill patients. Severe anemia is usually diagnosed early during their stay in the intensive care unit (ICU). After three days in the ICU, up to 95% of patients are anemic.

Chapter 8: Iron Therapy in the Critically Ill

Introduction

Anemia is common in critically ill patients and is usually diagnosed early during their stay in the intensive care unit (ICU). After three days in the ICU, up to 95% of patients are anemic. ¹

1. Mechanisms of Anemia in Critical Illness

Anemia in critically ill patients is multifactorial. EPO resistance ² associated or not with anemia of chronic disease, ³ overt or occult blood loss as well as deficiencies in iron, vitamin B12 or folate are possible causes. ⁴ Moreover, phlebotomy has emerged as an important factor contributing to the development of anemia in this population. In a study by Smoller and Kruskall on 50 ICU patients, the authors found that patients were phlebotomized, on average, 3.4 times a day, for a total volume of 41.5 mL of blood drawn a day. ⁵ This amount accounted for an average total volume of 762.2 mL of blood withdrawn during the ICU stay.

2. Transfusion Needs in the ICU

Transfusion continues to play a major role in anemia management in the ICU. In a 1995 study, 50% of all patients admitted to the ICU received transfusions during their stay. ⁶ Prolonged ICU stay was associated with an increased likelihood of blood transfusion. In fact, 85% of patients staying in the ICU for more than one week received, on average, 9.5 red blood cell units during their stay. These numbers have changed little over the last 10 years. In a study conducted from 2000 to 2001 in 284 ICUs at 213 hospitals in the United States, 44% of 4892 ICU patients received at least one transfusion during their ICU stay.105 The mean pre-transfusion hemoglobin value was 8.6 ? 1.7 g/dL, and mean time to first ICU transfusion was 2.3 ? 3.7 days. ⁷ Blood transfusion, however, is accompanied by serious adverse events, including mismatch errors, infection, ⁸ immunosuppression, ⁹ transfusion-related acute lung injury (TRALI), ¹⁰ and microcirculation disturbances owing to prolonged blood storage. ¹¹ Consequently, alternative approaches to anemia have been explored recently, including erythropoiesis-stimulating agents (ESAs) and iron therapy.

3. The Role of Iron in Critical Illness

Often, the development and the persistence of anemia in critically ill patients are caused by an impairment in erythropoiesis. In this setting, anemia is probably fundamentally related to mechanisms of ACD. ³ More important, EPO levels in critically ill patients fail to increase in response to physiological stimuli. ¹² It has been estimated that over 90% of critically ill patients in the ICU have low serum iron, total iron binding capacity, and iron/total iron binding capacity ratio but normal or, more commonly, elevated serum ferritin levels. ⁷ Elevated SF levels likely reflect the ongoing acute-phase response.

4. Iron Therapy in Critical Illness

In a prospective, randomized, double-blind, placebo-controlled, multicenter trial at 65 centers in the United States, a total of 1302 critically ill patients who had been in the ICU for two days were randomized to SC rHuEPO 40,000 U (treatment group) or placebo. ¹³ The regimen was repeated weekly for three weeks in patients who remained in hospital. A fourth dose was given to those who stayed in the ICU for more than 21 days. All patients received at least 150 mg oral iron daily.

Main results:

• Patients in the treatment group were less likely to receive blood transfusions than those on placebo (relative risk 0.67, 95% confidence interval 0.54 to 0.83, p < 0.001).
• The increase in Hb from baseline to study end was greater in the treatment than in the placebo group (+1.32 ? 2.0 vs. +0.04 ? 1.9 g/dL, p < 0.001).

A prospective, randomized, multicenter study ¹⁴ from 13 Greek ICUs studied 148 critically ill patients with Hb < 12 g/dL and no signs of iron deficiency (defined as transferrin saturation < 10% and ferritin < 50 ?g/L) who were administered three treatment regimens: 1) IV iron sucrose 100 mg three times weekly; 2) SC rHuEPO 40,000 U once weekly plus IV iron sucrose 100 mg three times weekly; or 3) SC rHuEPO 40,000 U three times weekly plus IV iron sucrose 100 mg three times weekly.

Main results:

• Only SC EPO three times weekly plus IV intravenous iron sucrose led to a significant increase in Hb from 9.2 ? 0.9 to 11.6 ? 1.9 g/dL within 28 days.
• The total number of blood units transfused was significantly smaller in the once- and three times-weekly EPO groups compared with IV iron sucrose alone (33, 23 and 138, respectively; p < 0.05 vs. IV iron sucrose alone for both comparisons). The number of units transfused/ patient was 0.64 ? 1.0, 0.47 ? 0.9 and 2.83 ? 3.9, respectively(p < 0.05 vs. IV iron sucrose alone for both comparisons).

Conclusion

Anemia occurs in up to 95% of patients in the ICU. EPO, in conjunction with iron therapy, significantly reduces the number of blood transfusions in anemic patients even without signs of iron deficiency. The efficacy and safety of intravenous iron therapy deserve further evaluation in controlled trials.




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