Anemia

Introduction

Anemia is defined as a reduction in the circulating red cell mass, the hemoglobin concentration, or both with an associated decrease in the oxygen-carrying capacity of blood. It is among the most common clinical problems encountered among critically ill patients in the intensive care unit (ICU). Although a proportion are anemic on admission, the majority of the remainder become anemic during their ICU stay, and over 90% of ICU patients are anemic by day 3. The likelihood of becoming anemic increases with each additional day in the ICU. Because of the association of anemia with worse clinical outcomes, the traditional approach had been to transfuse packed red blood cells (PRBCs) in response to low hemoglobin (Hb) levels, with a Hb level of <10 g/dL being the most commonly used trigger for transfusion. As a result, 30%–50% of ICU patients were transfused an average of 5 units of PRBCs in response to a mean Hb concentration of 8.5 g/dL. The Transfusion Requirements in Critical Care (TRICC) study was seminal in establishing the safety of a restrictive transfusion strategy. Additionally, the increased recognition of transfusion-related complications, growing concerns about the scarcity of blood, and the economic impact of transfusion (approximately $270 per unit transfused in the United States) have prompted a major paradigm shift in the approach to the management of anemia in the ICU. ^, Current approaches include preventing blood loss, conserving blood, minimizing hemodilution resulting from the use of excess volumes of crystalloid for resuscitation, avoiding transfusions based on “transfusion triggers” alone, and accepting a lower Hb threshold in the majority of critically ill patients. Future efforts focus on improved conservation of blood, transfusion alternatives, and further advancements in blood substitutes.

Epidemiology

Clinically, anemia is defined by the hemoglobin concentration of blood. The World Health Organization defined anemia as a hemoglobin concentration of <14 g/dL for men and <12 g/dL for nonpregnant adult females. Others have described the limits of a normal hemoglobin to range from 13.0 to 14.2 g/dL for men and from 11.6 to 12.3 g/dL for nonpregnant adult females. Using these definitions, more than 60% of all critically ill patients are anemic at admission, and the majority of those with normal hemoglobin levels at admission will become anemic while in the ICU. ^, Over 90% will be anemic within 72 hours of ICU admission, and up to 25% of critically ill patients will have a hemoglobin concentration of <9 g/dL at some point in their ICU stay, especially when the ICU length of stay exceeds 7 days. Among patients who are not admitted for bleeding, have not been transfused, and do not have acute or chronic renal failure, there is an initial rapid decline in hemoglobin levels over the first 3 days by about 5 g/dL, followed by a slower rate of subsequent decline in hemoglobin concentration. ^, Each day spent in the ICU increases the chance of receiving a transfusion by 7%, and 25%–53% of ICU patients will be transfused an average of 5 units of PRBCs per patient. ^, ^, ^, Among subgroups, patients admitted to the ICU for emergency surgery and trauma are transfused more often than medical ICU patients (57% and 48% vs. 32%). Patients with malignancies also have a higher prevalence of anemia at admission (68%), develop it during the ICU stay (47%), and have a need for transfusions.

Etiology

The cause of anemia in critically ill ICU patients is often multifactorial. The relative contribution of a particular etiologic factor varies from patient to patient and in the same patient from one time point to another. Key among these are (1) hemodilution, (2) blood loss, (3) impaired erythropoiesis, and (4) altered iron metabolism. Together the impairment in the development of mature red blood cells and alteration in metabolism of iron contribute to the development of the anemia of critical illness. Other concurrent derangements secondary to sepsis, hemolysis, use of antibiotics and chemotherapeutic agents, underlying hepatic or renal dysfunction, bone marrow suppression, and nutritional deficiencies further exacerbate anemia in the critically ill ( Fig. 21.1 ).

Fig. 21.1, Physiologic classification of anemia.

Hemodilution

In the absence of bleeding, hemodilution is mostly responsible for the initial decrease in hemoglobin levels observed in the first 72 hours after admission to the ICU and results from the liberal use of crystalloids and, on occasion, colloids for the initial resuscitation of critically ill patients. ^, Limiting crystalloid use, earlier use of vasopressor therapy in patients who fail to respond to fluid resuscitation, and close monitoring of volume status are key to prevention of anemia caused by hemodilution.

Blood loss

Blood loss can occur as a consequence of pathologic bleeding caused by the underlying disease process necessitating admission to the ICU, especially trauma and gastrointestinal (GI) hemorrhage, or from surgical interventions to treat the underlying or associated disorders. Stress gastritis, although rare since the advent of effective acid suppression therapy, remains a serious problem. The overwhelming majority of critically ill patients demonstrate some evidence of mucosal damage within the first 24 hours of admission. Overt anemia occurs in 5% of patients with stress-related GI bleeding, and clinically important bleeding necessitating transfusion is observed in 1%–4% of critically ill patients. The risk for bleeding secondary to erosive gastritis is greatest in those on mechanical ventilation, those with coagulopathy, those with head injury, and those receiving corticosteroids. Phlebotomy is an often unrecognized yet significant cause of hospital-acquired anemia in the ICU. Patients are on average phlebotomized 4.6 times a day with the removal of 40–60 mL of blood daily. ^, For every 50 mL of blood drawn, the risk of moderate to severe anemia increases by up to 18%. The volume of blood required to be drawn varies with the test being ordered, but typical volumes required for the various common tests are presented in Table 21.1 . Increasing severity of illness correlates with an increased number of laboratory studies ordered and thereby the blood volume drawn. The presence of an arterial line further increases the phlebotomized blood volume because of the need to “waste” before an appropriate sample can be obtained. Approximately half of all patients are transfused as a direct result of phlebotomy.

TABLE 21.1

Average Volumes of Blood Drawn for Diagnostic Testing

Arterial blood gas	2 mL
Chemistry	5 mL
Coagulation studies	4.5 mL
Complete blood counts	5 mL
Blood culture	10 mL
Drug levels	5 mL
Standard discard amount	2 mL

Impaired erythropoiesis

Under normal circumstances, in response to low arterial oxygen tension, the peritubular capillary endothelium of the kidney produces a glycoprotein hormone erythropoietin (EPO), which acts on bone marrow to stimulate the production of red blood cells. In critically ill patients, this erythropoietic response is blunted. It is believed to result from inappropriately low EPO levels compared with the degree of anemia. ^, EPO levels were reduced by up to 75% when compared with patients with iron-deficiency anemia not related to critical illness. The blunted EPO production is likely mediated by proinflammatory cytokines such as interleukin (IL)-1, and IL-6, which downregulate the expression of the gene encoding EPO. IL-6 also inhibits the renal production of EPO. Subsequent studies, however, have questioned reduced EPO levels as the basis for impaired erythropoiesis. A resistance to the effects of EPO, rather than its absolute level, may be the dominant mechanism behind the impaired erythropoiesis.

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