CHAPTER 89

#### KEY POINTS

• Anemia is common in the critically ill and often results in a large number of red blood cell transfusions.

• Anemia can be tolerated in many critically ill patients.

• The risks of red blood cell transfusions have expanded and are well documented.

• Little data support efficacy of red blood cell transfusions in many clinical situations in which they are given.

• Avoiding red blood cell transfusion is a positive outcome.

Historically, red blood cell (RBC) transfusions have been viewed as a safe and effective means of improving oxygen delivery to tissues. Beginning in the early 1980s, transfusion practice began to come under scrutiny. Initially, this was primarily driven by concerns related to the risks of transfusion-related infection. However, today other concerns have continued to drive the debate over transfusion practice. What started as a concern for RBC transfusion risks over the last two decades has shifted to include a more critical examination of RBC transfusion benefits. These issues are particularly important in the critically ill patient population.

#### PATHOPHYSIOLOGY OF ANEMIA IN CRITICAL ILLNESS

Anemia is best defined as a reduction in RBC mass. As RBC mass measurement is not practical in day-to-day clinical practice, hemoglobin (Hb) concentration and/or hematocrit (HCT) are the common surrogates used for RBC mass. While this works well in the steady state, it may present problems in nonsteady states such as resuscitation where Hb and HCT might not accurately reflect RBC mass. The definition of “normal” Hb currently is defined using standardized values referent to the Scripps-Kaiser database from 1998 to 2002.1 Anemia is of particular importance in the critically ill; 95% of critically ill patients are anemic by the third hospital day and the presence of this anemia results in a large number of RBC transfusions.2

Critically ill patients have an underproduction anemia, which combined with blood loss, most commonly from phlebotomy, explains the high prevalence of anemia seen in critically ill patients.3 Over 90% of ICU patients have low serum iron (Fe), total iron binding capacity (TIBC), and Fe/TIBC ratio, but have a normal or, more usually, an elevated serum ferritin level. On the other hand, nutritional deficiencies are uncommon.4 At the same time, serum erythropoietin (EPO) levels are only mildly elevated, with little evidence of reticulocyte response to endogenous EPO. The blunted EPO response observed in the critically ill appears to result from inhibition of the EPO gene by inflammatory mediators. These same inflammatory cytokines directly inhibit RBC production by the bone marrow and may produce the distinct abnormalities of iron metabolism. Anemia of critical illness therefore is a distinct clinical entity characterized by blunted EPO production and abnormalities in iron metabolism similar to what is commonly referred to as the anemia of chronic disease.

Hemoglobin is a complex molecule to which oxygen binds. The O2-carrying capacity of hemoglobin, or binding affinity to O...

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