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Question 3#

Which of the following statements regarding red blood cell transfusion in critically ill patients is MOST correct?

A. Transfusion of leukoreduced red blood cells (RBCs) is associated with decreased risk of ARDS in trauma patients
B. Transfusion of RBCs that have been stored for a longer period of time is associated with increased infection, organ dysfunction, and mortality
C. A liberal transfusion goal may be associated with an increased risk of nosocomial infections
D. Patients with coronary artery disease should have a transfusion threshold of hemoglobin 10 g/dL

Correct Answer is C


Correct Answer: C

The primary goal of red blood cell transfusion is to improve oxygen delivery. However, potential adverse effects include transfusion reactions, infection, transfusion-related acute lung injury (TRALI), transfusionrelated circulatory overload (TRCO), and transfusion-related immunomodulation (TRIM).

Transfusions are associated with immunosuppression (TRIM) and may result in an increased risk of nosocomial infections in hospitalized patients. One small, retrospective study found a dose-related response between the number of transfusions, and the risk for infection showed a dose-response relation such that the risk of infection increased by a factor of 1.5 for each unit transfused. A meta-analysis of 17 randomized trials comparing restrictive versus liberal RBC transfusion strategies involving 7456 patients found an increased risk of serious infections among patients treated with a liberal transfusion strategy with a number needed to treat (NNT) of 48 with a restrictive strategy in order to prevent serious infections. 

Leukoreduction not only removes donor leukocytes from packed RBCs but also filters inflammatory mediators (eg, tumor necrosis factor [TNF-α], interleukin-1 [IL-1]) and viruses transmitted via leukocytes (eg, EpsteinBarr virus [EBV], cytomegalovirus [CMV]), and reduces human leukocyte antigen (HLA) alloimmunization. Multiple studies have been performed looking at the effect of transfusion leukoreduced RBCs on infection, organ dysfunction scores, mortality, and risk of ARDS. Many of these studies are limited by size and study design but show no advantage to using leukoreduced RBCs.

The maximum storage period for RBC units is 42 days as mandated by the US Food and Drug Administration. However, the storage of blood for longer periods results in changes in the RBC membrane, which can impede microvascular flow and trigger inflammation, decreased 2,3-DPG concentrations, which can make red cells ineffective as oxygen carriers, and increased concentrations of proinflammatory cytokines. Two recent studies have looked at the effect of age of transfused blood in critically ill patients. The Age of Blood Evaluation (ABLE) trial was a multicenter trial that randomized 2430 critically ill patients (mean APACHE score 21.8 ± 7.6) to receive either fresh red cells (stored a mean of 6.1 ± 4.9 days) or standardissue red cells (stored a mean of 22 ± 8.4 days). There was no difference in 90-day mortality (primary outcome) or duration of respiratory, hemodynamic, or renal support, hospital length of stay, and transfusion reactions (secondary outcomes) between the two groups. The Standard Issue Transfusion versus Fresher Red-Cell Use in Intensive Care (TRANSFUSE) trial randomized 4994 critically ill patients (mean APACHE III score 72.9 ± 29.4, median APACHE III risk of death of 21.5%) to receive either blood that was stored for a mean of 11.8 days or blood that was stored for a mean of 22.4 days. There was no difference between the two groups in the primary outcome of 90-day mortality and secondary outcomes of organ dysfunction, need of mechanical ventilation and renal replacement therapy, blood stream infection, transfusion reactions, and ICU and hospital length of stay. 

The Transfusion Requirements in Critical Care (TRICC) trial found no difference in 30-day mortality in 838 euvolemic patients with normal baseline hemoglobin and no active ischemia or bleeding randomized to either a restrictive or liberal transfusion strategy (threshold hemoglobin, 7 vs 10 g/dL). However, there was a higher mortality that was not statistically significant in patients with coronary artery disease receiving a restrictive transfusion strategy. Although not done in critically ill patients, two studies suggest that a transfusion threshold of a hemoglobin of 8 is safe in patients with cardiovascular disease. The Transfusion Requirements after Cardiac Surgery (TRACS) showed that a restrictive transfusion strategy (maintain hematocrit ≥24%) was noninferior to a liberal transfusion strategy (maintain hematocrit ≥30%) in terms of a composite end-point consisting of 30-day all-cause mortality and severe morbidity (cardiogenic shock, ARDS, or acute renal injury requiring dialysis or hemofiltration). A second study randomized 2016 patients with either a history of or risk factors for cardiovascular disease undergoing hip fracture surgery, either a liberal transfusion strategy (if hemoglobin <10 g/dL) or a restrictive transfusion strategy (symptoms of anemia with a hemoglobin <8 g/dL). There was no difference between the groups in the primary outcome of death or functional disability on 60-day follow-up. Furthermore, there was no difference between the groups in the rates of in-hospital acute myocardial infarction, unstable angina, or death.


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