MPA | Pharmacy News

By Jennifer Gregory, Pharm.D., PGY1 pharmacy resident, St. Joseph Mercy, Ann Arbor

Anemia 
Anemia is defined as a hemoglobin (Hg) concentration of less than 13 g/dl or less than 12 g/dl for adult males and females, respectively.1 Less than optimal Hg levels can result in insufficient tissue oxygenation.2 Blood transfusion remains the main stay of treatment for anemic patients, although there are risks. For example, transfusion has been shown to increase nosocomial infection risk, trigger an allergic reaction and even cause immunosuppression.3 In addition, transfusion-related circulatory overload may occur when patients are over transfused.2 This can cause an increase in blood viscosity, impeding blood flow and hindering tissue oxygen delivery.2  

Anemia and Critically Ill Patients
The incidence of anemia in the critical care setting is quite common. Approximately 40 to 60 percent of critically ill patients become anemic during their intensive care unit (ICU) stay.3,4 Various contributors of anemia exist in the ICU setting. Blood loss is one main etiology, and may be attributed to trauma, surgery or injury sites.5 Furthermore, critically ill patients tend to require more frequent lab monitoring and therefore end up with a higher amount of blood draws per day as compared to general medicine patients.4 This extensive lab testing can correlate to an estimated average daily blood loss of up to 70 mL from phlebotomy alone.4 Of note, blood loss may additionally be associated with considerable iron depletion.6 Iron is a necessary component for proper Hg production, and a potential iron deficit could further exacerbate the development of anemia.1 Since iron is mostly obtained via dietary sources, critical care patients are at even greater risk, as it is more difficult for them to meet the daily recommended nutritional requirements.7 Acute inflammation may also contribute to anemia and in critical illness inflammation is common.8 Inflammatory processes induce the amino acid hepcidin.4 Hepcidin degrades ferroportin, a transporter protein responsible for the exportation of iron from intracellular stores.6 Increases in hepcidin ultimately decrease cell iron liberalization. Additionally, inflammatory cytokines have been shown to suppress red blood cell formation via another mechanism involving interactions with erythroid progenitor cells.

Transfusion Thresholds 
The 2017 Society of Critical Care Medicine Surviving Sepsis Guidelines strongly recommend a transfusion threshold of 7 g/dl in most critically ill patients.9 Higher Hg targets of 8-10 g/dl have been suggested for certain subsets of critically ill patients, such as those diagnosed with coronary disease.2,3 

Consider the following equation:

Oxygen Delivery [DO2] = Cardiac Output [Q'] x Arterial Oxygen Content [CaO2]*

*Arterial Oxygen Content= Amount of Oxygen Dissolved in Blood + Amount of Oxygen Bound to Hg 

Arterial oxygen content decreases with declining Hg.2 Tissue oxygen delivery becomes deficient if cardiac output fails to adequately compensate for a loss in arterial oxygen content.2  Higher Hg transfusion thresholds have been hypothesized to be beneficial in patients with cardiac disease, such as heart failure or acute myocardial infarction, as damaged myocardium may prevent adequate compensatory cardiac output. It should be noted, however, that data is currently limited to suggest the safety and efficacy of this practice.2,3,6,10  

Summary 
Anemia is commonly associated with critical illness. The general accepted threshold for transfusion is an Hg concentration less than 7 g/dl. More research is needed to define the optimal transfusion Hg ‘threshold’ in critically ill patients with greater risk factors for hypoxia, especially considering the complex pathophysiologic mechanisms and disease state concerns that exist within this population. It is important to weigh the risks and benefits of red blood cell transfusions, as well as specific patient characteristics and disease state concerns, when making these treatment decisions.   

References 
1. Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group. KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease. Kidney inter., Suppl. 2012;2:279-335.
2. Du Pont-Thibodeau G, Harrington K, Lacroix J. Anemia and red blood cell transfusion in critically ill cardiac patients. Ann Intensive Care. 2014;4(16).
3. Napolitano LM, Kurek S, Luchette FA, et al. Clinical practice guideline: Red blood cell transfusion in adult trauma and critical care. J Trauma. 2009;67(6):1439-1441.
4. Hayden SJ,  Albert TJ, Watkins TR, et al. Anemia in critical illness: Insights into etiology, consequences, and management. Am J Respir Crit Care Med. 2012;185(10):1049-1057. 
5. Debellis RJ. Anemia in critical care patients: Incidence, etiology, impact, management, and use of treatment guidelines and protocols. Am J Health Syst Pharm. 2007;64:S14-S21. 
6. Prakash D. Anemia in the ICU: Anemia of chronic disease versus anemia of acute illness. Crit Care Clin. 2012;28:333-343.
7. McClave SA, Taylor BE, Martindale RG, et al. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). J Parenter Enteral Nutr. 2016;40(2):159-211.
8. Preiser JC, Ichai C, Orban JC, et al. Metabolic response to the stress of critical illness. British J Anaesthesia. 2014;113(6):945-954.
9. Rhodes A, Evans LE, Waleed A, et al. Surviving sepsis campaign: International guidelines for management of sepsis and septic shock: 2016. Crit Care Med. 2017;45(3):486-552.
10. Retter A, Wyncoll D, Pearse R, et al. Guidelines on the management of anemia and red cell transfusion in adult critically ill patients. Br J Haematol. 2013;160:445-464.

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