Packed Red Blood Cell Transfusions. Tara Ann Collins, CRNP

Cover Article Packed Red Blood Cell Transfusions in Critically Ill Patients Tara Ann Collins, CRNP Anemia, which is prevalent in critically ill patients, often requires frequent blood transfusions. These blood transfusions are not without risks. A critical review of 6 studies shows an association between red blood cell transfusion and increased mortality. However, when disease state was adjusted for in 2 studies, researchers found that red blood cell transfusion correlated with decreased mortality. Thus further research, particularly on leukoreduction and age of stored blood, must be done before a change in practice can be implemented. It is vital that nurses stay current on this research in order to improve patients outcomes. (Critical Care Nurse. 2011; 31[1]:25-34) Anemia is a prevailing problem in critically ill patients that often results in frequent red blood cell (RBC) transfusions. Approximately 95% of patients who have been in the intensive care unit (ICU) for 3 days or CEContinuing Education This article has been designated for CE credit. A closed-book, multiple-choice examination follows this article, which tests your knowledge of the following objectives: 1. Describe the cause of anemia in critical illness 2. Describe the effects of storage on red blood cells 3. Review the current literature on blood transfusions in critically ill patients 2011 American Association of Critical- Care Nurses doi: 10.4037/ccn2011200 longer are anemic, with almost 50% of these patients receiving a mean of 5 units of RBCs while in the ICU. 1-3 Anemia results in a reduction in the oxygen-carrying capacity of the blood, which can increase morbidity, mortality, organ failure, and length of stay in the hospital. Although treating anemic patients with RBC transfusions appears logical, some research studies suggest that transfusions may not increase oxygen-carrying capacity and may actually be more harmful to patients than anemia itself. 4-6 This article describes the effects of RBC transfusions on critically ill patients by highlighting ICU patients susceptibility to anemia as well as the risks associated with blood transfusions. Six studies conducted to examine the relationship between blood transfusions and outcomes in ICU patients are critically reviewed. The role of health care providers in making decisions about blood transfusion also is discussed and future research is proposed. Background Anemia in Critically Ill Patients Normally, RBCs are continually replaced via erythropoiesis every 120 days or so and in response to decreased oxygen levels in the blood detected by the kidneys. 7 In critically ill patients, however, RBCs may be destroyed before the normal 120 days because of hemolysis or splenic sequestration. 8,9 Often these patients have microorganisms, cancer, and/or inflammation that activates T cells and monocytes, leading to increased levels of cytokines, interferons, tumor necrosis factor, interleukin 1, interleukin 6, and interleukin 10. 10 These inflammatory markers lead to decreased iron absorption, iron retention in macrophages, bone marrow suppression, and decreased erythropoiesis, leaving the patient unable to www.ccnonline.org CriticalCareNurse Vol 31, No. 1, FEBRUARY 2011 25

secrete the level of erythropoietin necessary to increase RBC production. 7 Even if erythropoietin is secreted, tumor necrosis factor, interferon gamma, and interleukin 1 inhibit erythrocyte proliferation, causing these patients to become anemic without a history of bleeding. 7,10 In patients who become anemic because of blood loss, these inflammatory markers increase vasodilatation and vascular permeability, which worsens bleeding. 7 Phlebotomy practices also contribute to anemia, with ICU patients having a mean of 41 ml of blood samples withdrawn per day. 3 Surgery, stress-related gastrointestinal bleeding, myelosuppressive drugs, malnutrition, renal insufficiency, and endocrine disorders also contribute to anemia in the critically ill. 9 Healthy patients are able to compensate for anemia. Anemia is compensated for by a shift in the hemoglobin oxygen dissociation curve to the right, usually caused by an increase in the level of 2,3- diphosphoglycerate (2,3-DPG). 7,11 This shift allows more oxygen to leave hemoglobin and reach the tissue despite the decrease in oxygencarrying capacity due to the anemia. 11 Acute anemia is compensated for by an increase in cardiac output, an increase in vascular tone, and a decrease in blood viscosity. 7,11 Critically ill patients have a difficult time adjusting to the effects of anemia because they are already compensating for their disease states and increased metabolic demands. Therefore, critically ill patients are more likely to receive a blood transfusion, which would be expected to increase the amount of oxygen-carrying capacity and diminish the effects of anemia. The compensatory mechanisms related to anemia can be reversed as long as the transfused blood was not altered during storage. 11 Packed RBC Storage and Leukoreduction Depending on the storage solutions used, RBCs may be stored for 35 to 42 days before being transfused, according to the United States Food and Drug Administration and the AABB, formerly known as the American Association of Blood Banks. 12,13 Blood banks use the oldest blood in the bank for transfusion on the basis of this expiration policy. 14 However, the storage of RBCs causes changes in the structure and function of RBCs, termed the RBC storage lesion. 4 Stored erythrocytes lack adenosine 5'-triphosphate (ATP), which leads to significant changes in the shape and function of the erythrocyte due to the lack of energy. 4,5,15 The change in shape results in a loss of volume in the cell and a lack of deformability, leaving the cell unable to change shape when placed in solutions of differing tonicity. 4,5 The change in structure when the blood is transfused leads to a decrease in function and an increase in RBC adhesion, which may result in Author Tara Ann Collins is a surgical critical care nurse practitioner at the Hospital of the University of Pennsylvania in Philadelphia. Corresponding author: Tara Collins, CRNP, Hospital of the University of Pennsylvania, Rhoads 5 SICU, 3400 Spruce Street, Philadelphia, PA 19104 (e-mail: tara.collins@uphs.upenn.edu). To purchase electronic or print reprints, contact The InnoVision Group, 101 Columbia, Aliso Viejo, CA 92656. Phone, (800) 899-1712 or (949) 362-2050 (ext 532); fax, (949) 362-2049; e-mail, reprints@aacn.org. occlusions in the microcirculation that lead to organ failure. 4,5,15 When blood is stored, the level of antioxidants decreases, resulting in oxidative damage that converts hemoglobin to methemoglobin, which cannot bind to oxygen. If blood is stored for more than 7 days, it loses 2,3-DPG. 4,5 Without 2,3-DPG, the hemoglobin-oxygen dissociation curve shifts to the left and less oxygen moves into the tissues (Table 1). 11 Storage also promotes hemolysis and acidosis. 4,5,15 Researchers have found that transfused blood is an independent predictor of multisystem organ failure and death. 16,17 Transfusion-related immunomodulation, also termed immune down-regulation, is a suppression of the immune system related to stored blood. This down-regulation has been noted in a decrease in rejection rates of transplanted renal grafts and an increase in relapse rates of resected cancer. 7 If the immune system were functioning properly, increased rejection rates and decreased relapse rates would be expected. Immune down-regulation is most likely related to the transfused white blood cells; however, the exact mechanism is not clear. 7 White blood cells, when stored, increase hemolysis and potassium leakage from RBCs, which is thought to result from free radicals released during apoptosis of white blood cells. 4 After transfusion, the immune system is affected, as manifested by a decrease in interleukin 2 and an increase in T helper cells, killer T cells, B cells, and prostaglandins. 8,18,19 Leukoreduction is the removal of white blood cells from stored blood. More than 99% of leukocytes 26 CriticalCareNurse Vol 31, No. 1, FEBRUARY 2011 www.ccnonline.org

Table 1 Effects of storage of packed red blood cells a Effect of storage Lack of adenosine 5 -triphosphate Decrease in antioxidants Decrease in 2,3-diphosphoglycerate Apoptosis of white blood cells Mechanism Change in shape and function of red blood cells Oxidative damage converts hemoglobin to methemoglobin Hemoglobin-oxygen dissociation curve shifts to the left Hemolysis and potassium leakage Result Microvascular occlusion and possible organ failure A decrease in the amount of oxygen available to the tissues Less oxygen moves into the tissues Possible immunomodulation and increased risk of infection a Based on data from Hebert et al. 11 in stored blood are removed by centrifugation or filtration before the blood is stored. 15 The benefits of leukoreduction include decreased hemolysis, decreased potassium leakage, and decreased RBC adhesion due to storage. 4,15 In addition, inflammatory mediators present in stored blood, such as cytokines, histamines, lipids, antigens, interleukin 7, interleukin 8, and tumor necrosis factor are removed by leukoreduction. 4 Leukoreduction also decreases the risk of febrile nonhemolytic reactions, HLA alloimmunizations, and transmission of cytomegalovirus, herpes simplex, and Epstein-Barr virus (Table 2). 15,20 Risks of Transfusions Transfusions can be lifesaving in critically ill patients but are not without risks (Table 3). 21 In consideration of the risks involved with RBC transfusions and the risks of anemia, Herbert et al 6 conducted a now classic clinical trial known as the Transfusion Requirements in Critical Care (TRICC) Study. This multicenter, randomized, controlled clinical trial showed that a restrictive transfusion strategy, defined as transfusion when the hemoglobin level is less than 7 g/dl, decreased rates of mortality, cardiac complications, Table 2 Benefits of leukroreduction a Proven benefits Reduction in risk of febrile nonhemolytic reactions risk of transmission of cytomegalovirus risk of transmission of HLA alloimmunization a Based on data from Vincent et al 15 and Cervia et al. 18 Table 3 Risks associated with blood transfusions a Coagulopathy Iron overload Hemolytic transfusion reaction Febrile nonhemolytic reactions Allergic reactions Anaphylaxis Pulmonary edema Transfusion-associated acute lung injury Transfusion-related immunomodulation Graft versus host disease a Based on data from Kuiryan and Carson. 21 and organ dysfunction as compared with the liberal transfusion strategy, defined as transfusion when the hemoglobin level is less than 10 g/dl. On the basis of this landmark study, Proposed benefits Reduction in transfusion-related immunomodulation transfusion-transmitted bacteria transfusion-associated acute lung injury mortality postoperative infection transfusion-associated infections, including infection with Epstein Barr virus, human herpesvirus 8, and human immunodeficiency virus Bacterial contamination Thrombocytopenia Infection with human immunodeficiency virus Hepatitis Cytomegalovirus infection Parasitic infection Transfusion-associated circulatory overload HLA alloimmunization Platelet alloimmunization Posttransfusion purpura the Surviving Sepsis Campaign and many institutions recommend using a hemoglobin level of 7 g/dl as a transfusion trigger in ICU patients. 22-24 Since the publication of this landmark www.ccnonline.org CriticalCareNurse Vol 31, No. 1, FEBRUARY 2011 27

Table 4 Mortality and complications in studies of blood transfusions in critically ill patients Reference, year Sample Study design Outcome measures % getting transfusion Mortality definition Taylor et al, 25 2006 2085 patients admitted to medical and surgical ICUs Prospective observational study Mortality, LOS, and rate of infections 21.5 Death occurring while in the hospital Croce et al, 29 2005 5260 patients admitted to a trauma ICU Retrospective study Mortality, VAP, and ARDS 15 Death occurring while in the hospital Corwin et al, 2 2004 4892 patients admitted to medical or surgical ICUs Prospective observational study Mortality and LOS 44.1 Death occurring either within 30 days from enrollment or before discharge Vincent et al, 26 2006; Vincent et al, 27 2008 3147 patients admitted to participating ICUs Prospective observational study Rate of sepsis, mortality, and LOS 33 Death occurring while in the hospital or within 60 days after enrollment Ruttinger et al, 30 2007 3037 patients admitted to a surgical ICU Retrospective study Mortality 59 Death occurring while in the ICU Netzer et al, 28 2007 262 patients with acute lung injury admitted to medical or surgical ICUs Prospective observational study Mortality Not disclosed Death occurring while in the hospital Abbreviations: ARDS, acute respiratory distress syndrome; ICU, intensive care unit; LOS, length of stay; RBC, red blood cell; VAP, ventilator-associated pneumonia. study, a number of other studies have been done to examine the relationship between blood transfusions and patients outcomes. Literature Review A literature search was conducted via PubMed and MEDLINE by using the key search terms blood transfusions, mortality, and critically ill. In addition, articles identified from reference lists also were evaluated. Research studies found were narrowed by using the following inclusion criteria: published within the past 5 years, written in English, studies used adult subjects, defined as age greater than 17 years, studies involved more than 200 patients, and studies had primary or secondary outcomes focused on comparing mortality rates in patients who received blood transfusions with rates in patients who did not receive blood transfusions. Six studies met these criteria and were analyzed. Comparison of the Studies Study Design Each of the analyzed studies compared the mortality rates of ICU patients who received a blood transfusion with the mortality rates of ICU patients who did not receive a transfusion. All study designs were descriptive and observational; 4 of the studies 2,25-28 were prospective and 2 of the studies 29,30 were retrospective. Table 4 provides more detail on each of the 6 studies. Variables Although each study was focused on mortality related to blood transfusions as an end point, in some of the studies, researchers looked at other variables associated 28 CriticalCareNurse Vol 31, No. 1, FEBRUARY 2011 www.ccnonline.org

Mortality data Mortality rate was 21.8% for patients receiving a transfusion vs 10.2% for patients who did not receive a transfusion (P <.001) Mortality rate for patients who received a transfusion was 5.5% vs 0.7% for patients who did not receive a transfusion (P <.001) Mortality rate for patients who received a transfusion of 6 or more units of RBCs was 25% vs 10% for patients who did not receive a transfusion Patients receiving a transfusion of 3-4 units (P <.001) and more than 4 units (P <.001) of packed RBCs had higher mortality rates than patients not receiving a transfusion Mortality rate was 23% for patients who received a transfusion vs 16.3% for patients who did not receive a transfusion (P <.001) In univariate analysis, significant association found between the maximum units of RBCs transfused in 1 day and mortality (P <.001) and between total number of units transfused during ICU stay and mortality (P <.001) 92% of patients who died had received a transfusion vs 78% of patients who did not die Transfusion correlated with odds ratio for mortality of 2.90 Other findings 14.3% of patients receiving a transfusion acquired an infection vs 5.8% of patients who did not receive a transfusion (P <.001) Mean LOS in the ICU for patients who received a transfusion was 8.2 (SD, 11.7) days vs 3.3 (SD, 5.1) days for patients who did not receive a transfusion (P <.001); when adjusted for probability of survival, patients in 3 quartiles who had received a transfusion had increased mortality rates (P =.01, P <.001, and P =.01, respectively) 19.4% of patients who received a transfusion had VAP diagnosed vs 2.2% of the patients who did not receive a transfusion (P <.001) 2.8% of patients who received a transfusion had ARDS diagnosed vs 0.2% of patients who did not receive a transfusion (P <.001) Patients who received a transfusion had significantly longer LOS in the ICU and hospital (P <.001, P <.001); after propensity score matching, transfusion was still associated with increased mortality (P <.001) LOS in the ICU was 5.9 days and LOS in the hospital was 23 days for patients who received a transfusion vs 2.5 days and 13 days, respectively, for patients who did not receive a transfusion (P <.001 for ICU LOS, P <.001 for hospital LOS) When adjusted for disease severity, 30-day risk of death was lower in the patients who received a transfusion than in the patients who did not (P =.004); the same result was apparent in the groups matched by propensity scores (P =.02) When adjusted for disease state, mortality rates did not differ significantly between patients who received a transfusion and patients who did not Mortality rates differed significantly between patients who received a transfusion and patients who did not, even when adjusted for severity of disease (P =.01) with blood transfusions as well. Other variables examined included nosocomial infections, acute respiratory distress syndrome (ARDS), ventilator-associated pneumonia (VAP), and length of stay. The study by Vincent et al 26,27 was focused on the rate of sepsis in ICUs; however, a subset of this study was focused on mortality and length of stay in relation to blood transfusions. The primary end point of the study by Corwin et al 2 was to determine current transfusion practices; the impact of RBC transfusions on outcome was a secondary end point. Population of Patients All patients were admitted to ICUs; however, the population of patients varied among the studies. Most of the studies included patients admitted to general surgical or medical ICUs; however, Croce et al 29 focused only on patients admitted to a trauma ICU. Corwin et al 2 excluded patients admitted to pediatric, cardiothoracic, cardiac, neurologic, or burn ICUs. Four of the studies 25,28-30 were single-center studies, whereas Corwin et al 2 included patients admitted to 284 general medical or surgical ICUs across the United States and Vincent et al 26,27 included patients admitted to numerous ICUs throughout Europe. Taylor et al 25 included a random sample of half the patients admitted to medical or surgical ICUs at a single center during a 2-year period. Croce et al 29 tried to reduce the confounding effects of shock and injury on outcome by including trauma patients with a blunt mechanism of injury, an Injury Severity Score of less than 25, and patients who did not receive a blood transfusion within the first 48 hours of admission. Ruttinger et al 30 included patients who had undergone surgery and were admitted to a surgical ICU www.ccnonline.org CriticalCareNurse Vol 31, No. 1, FEBRUARY 2011 29

in Germany for more than 1 day. Netzer et al 28 studied patients with acute lung injury (as defined by the American European Consensus Criteria) who were admitted to a medical or surgical ICU. Results First, general findings are presented, followed by findings related to blood transfusions and associated complications. Last, findings related to blood transfusions and mortality rates are discussed. General Findings The number of patients receiving a blood transfusion differed significantly among the studies, ranging from 15% to 59%. Ruttinger et al 30 reported that the mean age of the transfused blood was 30 days. Taylor et al 25 also reported that the mean age of the oldest RBC unit each patient received was 32 days; with 92.7% receiving at least 1 unit of RBCs that was more than 2 weeks old and 65.3% receiving at least 1 unit that was more than 4 weeks old. In the studies by Taylor et al, 25 Croce et al, 29 and Vincent et al, 26,27 patients who received transfusions were significantly older than patients who did not (P<.001, P=.001, P=.03, respectively). Patients in the study by Taylor et al 25 who received transfusions had a lower probability of survival on ICU admission according to the Mortality Prediction Models score than did patients who did not receive transfusions; however, only 94% of the patients had Mortality Prediction Model scores. Additionally, Croce et al 29 found that patients who received transfusions had more significant injuries; the Injury Severity Score was lower in the group that did not receive transfusions than in the group that did (P=.001). Vincent et al 26,27 also reported that patients who received transfusions were more critically ill as evidenced by higher Sequential Organ Failure Assessment scores (P <.001) and higher Simplified Acute Physiology Scores II (P<.001). Transfusions and Complications In some of the studies, researchers examined the relationship between RBC transfusions and complications. Corwin et al 2 reported that 67.6% of patients who received a transfusion experienced at least 1 complication versus 31.7% of the patients who did not receive a transfusion. Complications included transfusion reactions, ARDS, pulmonary edema, sepsis, infection, pneumonia, deep venous thrombosis, pulmonary embolus, and significant bleeding. Taylor et al 25 reported that RBC transfusion correlated significantly with increased rates of nosocomial infections (P<.001). Pneumonia and sepsis were the most frequently acquired nosocomial infections. Additionally, multivariate logistic regression analysis indicated that the number of units of blood transfused was the only independent risk factor for nosocomial infections. Every unit of blood transfused increased the risk of nosocomial infection by 9.7%. 25 No association was found between the age of stored blood and the occurrence of nosocomial infections; however, a negative association was found between leukoreduced blood and nosocomial infections, but the association was not significant. 25 Croce et al 29 also reported a significant increase in complications of ARDS and VAP. Netzer et al 28 found in multivariate analysis that the administration of blood before the development of acute lung injury was not a risk factor for mortality (P =.62), whereas administration of blood after the development of acute lung injury was a risk factor for mortality (P<.001). Transfusions and Mortality Rates Although mortality rates varied among the studies, results of all studies indicated that patients receiving blood transfusions also had a higher rate of mortality. Additionally, Taylor et al, 25 Corwin et al, 2 and Vincent et al 26,27 all reported that patients who received blood transfusions had a significantly longer stay in both the ICU and the hospital. Corwin et al 2 reported that patients with a transfusion amount of 1 to 2, 3 to 4, and more than 4 units of RBCs had ICU stays that were 2.1, 3.8, and 10.1 days longer, respectively, as well as hospital stays that were 3.5, 6.7, and 16.6 days longer, respectively, than the median ICU stay of 4.6 days and the median hospital stay of 11 days in patients who did not receive transfusions. It can be argued that patients who require blood transfusions are more critically ill and therefore have a higher risk of mortality because of their injuries or disease state rather than because of any negative effects of transfused blood products. 28 However, Taylor et al, 25 Corwin et al, 2 and Netzer et al 28 adjusted for probability of survival or severity of disease and still found a significant difference in the rate of mortality related to blood transfusions. Taylor et al 25 grouped patients in quartiles by probability of survival based on Mortality Prediction Model score at 30 CriticalCareNurse Vol 31, No. 1, FEBRUARY 2011 www.ccnonline.org

admission and found a significant increase in mortality for patients who received transfusions compared with patients who did not receive a transfusion in all but the lowest quartile. Corwin et al 2 performed propensity score matching and still found blood transfusion was significantly associated with increased mortality (P<.001). Netzer et al 28 reported that transfusion was associated with an unadjusted odds ratio for mortality of 2.9 (P=.008). When disease severity, including age, sex, APACHE III score, and precipitating event, was adjusted for, the association remained significant (P=.01). Additionally, when adjusted for length of stay in bivariate (P<.001) and multivariate (P<.001) models, the association remained significant. In all 3 studies, researchers found that blood transfusions are associated with increased mortality despite severity of illness or injury. Ruttinger et al 30 reported that transfusion was associated with mortality when admission variables were used in the analysis; however, no association was found when ICU variables of duration of mechanical ventilation, vasoactive medications, and renal replacement therapy were included. Vincent et al, 26,27 after using a multivariate regression analysis to adjust for illness severity, reported that blood transfusions were not significantly associated with an increase in mortality. Additionally, after using propensity score matching, a significantly lower 30-day risk of death was found in patients who received a transfusion compared with patients who did not. 26,27 Discussion Researchers in 2 studies 2,30 reported a higher rate of blood transfusion than reported in the other studies, which is most likely attributed to timing. In the TRICC study, 6 published in 1999, the researchers advocated for a restrictive blood transfusion policy. The data used by Corwin et al 2 and Ruttinger et al 30 were from 1996 to 2003 and 1993 to 2003, respectively, whereas the other studies all took place after the results from the TRICC study were published. The 6 analyzed studies were all observational; therefore, a causeeffect analysis cannot be made regarding blood transfusions and increased mortality. However, a correlation was found between blood transfusions and mortality in all 6 studies. Statistical analysis revealed controversial results in the study by Vincent et al. 26,27 These results may have a few explanations. That study included patients admitted to numerous ICUs in Europe, whereas most of the other studies included patients admitted to ICUs in the United States. Perhaps practice patterns are different in Europe. Additionally, in the study by Vincent et al, 26,27 more than 75% of the ICUs were transfusing leukoreduced blood. Taylor et al 25 and Netzer et al 28 also reported an association between leukoreduced blood and decreased rates of mortality. Clinical Implications On the basis of the significant risks of blood transfusions and the conflicting results from the analysis of the 6 studies, we recommend that judicious use of RBC transfusions be continued until further research is conducted. Nurses and other members of the health care team can be influential in forming practice management guidelines and/or in developing hospital policies regarding blood transfusions in critically ill patients. Transfusion Practices Transfusion Trigger. The hemoglobin value that should trigger a transfusion of RBCs is currently under debate. The Surviving Sepsis Campaign Guidelines recommend giving patients a transfusion when the hemoglobin level is less than 7 g/dl with a goal of maintaining a hemoglobin level of 7 to 9 g/dl; however, this does not include patients with active hemorrhage, myocardial ischemia, or lactic acidosis. 23 On the other hand, the American Society of Anesthesiologists Task Force does not recommend giving a patient a transfusion on the basis of the patient s hemoglobin value, but rather recommends that the decision be based on the clinical situation. 31,32 Because of the continuing debate over transfusion, health care providers should continue to monitor each patient s clinical picture. The health care team should watch for blood loss, monitor for signs of inadequate perfusion and ischemia in the form of vital signs and urine output, and track the patients hemoglobin values. 31 Number of Units Transfused. The number of units of RBCs appears to correlate with increased mortality, so the number of units transfused should be as few as possible. 2,26,27,29,30 When a provider decides to give a patient a transusion of RBCs, 2 units are often transfused. It is, however, not always necessary to transfuse 2 units of blood. The expected response in hemoglobin level should be an increase of 1 g/dl per unit of blood www.ccnonline.org CriticalCareNurse Vol 31, No. 1, FEBRUARY 2011 31

transfused. If a stable patient with no known history of heart disease or active hemorrhage has a hemoglobin level of 7 g/dl and is given a transfusion of 1 unit of blood, the hemoglobin level should increase to 8 g/dl. One unit of blood should be transfused, and then the hemoglobin level should be measured. If an appropriate response in the level is noted, it may not be necessary to transfuse more blood products. However, if an appropriate response is not noted, then more blood should be transfused. This advice may not apply in emergency situations, in patients with active hemorrhage, or in patients showing signs of ischemia. Transfusing only 1 unit of blood decreases the risk of mortality and also decreases the risk of transfusion-transmitted infections. Age of Stored Blood and Leukoreduction. Taylor et al 25 reported that 65.3% of patients received blood products close to or over their expiration date, which highlights the importance of noting the expiration date before administration. As previously discussed, health care providers should know whether their institution uses leukoreduced or nonleukoreduced blood products. Leukoreduced blood is given universally in some countries and institutions; however, leukoreduction is associated with a significant cost. The cost for each unit of blood that undergoes leukoreduction ranges approximately from $30 to $100. 33,34 To learn more about blood transfusions in the critical care setting, read Long-term Survival in the Intensive Care Unit After Erythrocyte Blood Transfusion by Engoren M and Arslanian-Engoren C in the American Journal of Critical Care, 2009;18:124-131. Available at www.ajcconline.org. Phlebotomy Practices Phlebotomy practices also contribute to anemia and blood transfusions. Chant et al 35 reported that phlebotomy volume is an independent predictor of transfusion. Patients in the ICU for more than 21 days were twice as likely to get a transfusion when the phlebotomy volume increased by 3.5 ml a day. 35 Therefore, small reductions in phlebotomy volume may greatly decrease the need for transfusion. Health care providers should have a judicious and prudent approach in prescribing and obtaining samples for laboratory tests. Also, studies 36 have shown that using child-sized phlebotomy collection tubes in adults decreases the occurrence of anemia yet still allows collection of sufficient blood to perform laboratory tests. Bedside providers can communicate with their laboratory technicians to determine how much blood is necessary to run certain tests. For instance, does the technician need the entire tube to be filled with 10 ml of blood in order to run a chemistry panel or can less blood be collected? When collecting blood from an arterial or central venous catheter, a waste sample is needed. The amount of volume in a waste sample may be decreased or the waste sample can even be preserved. The amount of necessary waste volume is 2 times the amount of the catheter dead space or 2 ml for an arterial catheter. 36,37 Nurses should be aware of this small amount of waste needed and be mindful when collecting blood from a catheter. Furthermore, new arterial catheters have been developed that return the waste sample to the patient. These systems decrease the volume of wasted blood and decrease the amount of blood that must be transfused. 36 Future Research Analysis of the studies highlighted an inconsistency in mortality rates in ICU patients who received blood transfusions. Therefore, it is recommended that more research be conducted in this area. The study by Vincent et al 26,27 showed a decrease in mortality in patients who received transfusions; however, unlike the other studies, most of the transfused blood in that study had been subjected to leukoreduction. Research has been conducted on leukoreduction in the past; however, the results have been inconclusive. It is suggested that research emphasis be placed on studying the value of leukoreduction. Additionally, results of 2 of the analyzed studies indicated that the blood transfused was a mean of more than 3 weeks old. Taylor et al 25 reported that more than 65% of the patients in their study received at least 1 unit of blood that was more than 4 weeks old. Therefore, research focusing on the adverse effects of RBC storage time should be completed. Blood substitutes, which include polymerized human hemoglobin based oxygen carrier solutions and bovine hemoglobin, were thought to be a great alternative to blood products because of their long shelf life, decreased risk of infection, and elimination of requiring a cross match before transfusion. However, a recent meta-analysis indicated that these products are associated with an increased risk of myocardial infarction and death. 38 Further research and development of safe blood substitutes will be needed before blood substitutes become available. 32 CriticalCareNurse Vol 31, No. 1, FEBRUARY 2011 www.ccnonline.org

Increasing hemoglobin levels in ICU patients by using recombinant human erythropoietin could be another alternative. Corwin et al 39 performed a randomized controlled trial to determine whether ICU patients given recombinant human erythropoietin weekly would have a decrease in transfusion rates. They did find an increase in hemoglobin levels and a decrease in the rate of transfusions in the erythropoietin group as compared with the placebo group. In a recent prospective, randomized, placebo-controlled clinical trial, however, the same authors reported that epoetin alfa did not reduce the incidence of RBC transfusions. 40 They also reported an increase in thrombotic events with the use of epoetin alfa. 40 Conclusion Both anemia and blood transfusions have many risks and adverse effects in critically ill patients. This analysis of studies did show an association between RBC transfusion and increased mortality rates. When disease state was adjusted for in 2 studies, however, RBC transfusion correlated with decreased mortality. On the basis of these findings, further research should be conducted before a change in practice can be implemented. To improve patients outcomes, it is vital that bedside providers stay up to date on this research. CCN Now that you ve read the article, create or contribute to an online discussion about this topic using eletters. Just visit www.ccnonline.org and click Respond to This Article in either the full-text or PDF view of the article. Financial Disclosures None reported. References 1. Corwin HL, Carson JL. Blood transfusion: when is more really less? N Engl J Med. 2007; 356:1667-1669. 2. Corwin HL, Gettinger A, Pearl RG, et al. The CRIT study: anemia and blood transfusions in the critically ill: current clinical practice in the United States. Crit Care Med. 2004;32:39-52. 3. Vincent JL, Baron JF, Reinhart K, et al. Anemia and blood transfusion in critically ill patients. JAMA. 2002;288:1499-1507. 4. Ho J, Sibbald WJ, Chin-Yee IH. Effects of storage on efficacy of red cell transfusion: when is it not safe? Crit Care Med. 2003;31:S687-S697. 5. Napolitano LM, Corwin HL. Efficacy of red blood cell transfusion in the critically ill. Crit Care Clin. 2004;20:255-268. 6. Herbert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med. 1999;340:409-417. 7. Shander A. Anemia in the critically ill. Crit Care Clin. 2004;20:159-178. 8. Taylor RW, Manganaro L, O Brien J, Trottier SJ, Parkar N, Veremakis C. Impact of allogenic packed red blood cell transfusion on nosocomial infection rates in the critically ill patient. Crit Care Med. 2002;30:2249-2254. 9. DeBellis R. 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. 10. Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005;352:1011-1023. 11. Hebert PC, Van der Linden P, Biro G, Hu LQ. Physiological aspects of anemia. Crit Care Clin. 2004;20:187-212. 12. United States Food and Drug Administration. Blood bank inspections. http://www.fda.gov/ora/inspect_ref/igs/blood.html. Accessed January 21, 2008. 13. AABB. Blood FAQ. http://www.aabb.org /resources/bct/pages/bloodfaq.aspx#a10. Accessed November 4, 2010. 14. Schulman CI, Cohn SM. Transfusion in surgery and trauma. Crit Care Clin. 2004;20: 281-297. 15. Vincent JL, Sakr Y, De Backer D, Van der Linder P. Efficacy of allogeneic red blood cell transfusions. Best Pract Res Clin Anaesthesiol. 2007;21:209-219. 16. Zallen G, Offner PJ, Moore EE, et al. Age of transfused blood is an independent risk factor for post injury multiple organ failure. Am J Surg. 1999;178:570-572. 17. Malone DL, Dunne J, Tracy K, et al. Blood transfusion, independent of shock severity, is associated with worse outcome in trauma. J Trauma. 2003;54:898-907. 18. Dunne JR, Maline DL, Tracy J, Napolitano LM. Allogenic blood transfusion in the first 24 hours after trauma is associated with increased systemic inflammatory response syndrome (SIRS) and death. Surg Infect. 2004; 5:395-404. 19. Gould S, Cimino MJ, Gerber DR. Packed red blood cell transfusion in the intensive care unit: limitations and consequences. Am J Crit Care. 2007;16:39-47. 20. Cervia JS, Wenz B, Ortolano GA. Leukocyte reduction s role in the attenuation of infection risks among transfusion recipients. Clin Infect Dis. 2007;45:1008-1013. 21. Kuiryan M, Carson JL. Blood transfusion risks in the intensive care unit. Crit Care Clin. 2004;20:237-252. 22. Dellinger RP, Carlet JM, Masur H, et al. Sur- viving sepsis campaign: guidelines for the management of severe sepsis and septic shock. Crit Care Med. 2004;32:858-873. 23. Dellinger RP, Levy MM, Carlet JM, et al. Surviving sepsis campaign: international guidelines for the management of severe sepsis and septic shock: 2008. Crit Care Med. 2008;36:296-327. 24. Rauen CA. Blood transfusions in the intensive care unit. Crit Care Nurse. 2008;28(3):78-80. 25. Taylor R, O Brien J, Trottier S, et al. Red blood cell transfusions and nosocomial infections in critically ill patients. Crit Care Med. 2006;34:2302-2308. 26. Vincent JL, Sakr Y, Sprung CL, et al. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med. 2006;34: 344-353. 27. Vincent JL, Sakr Y, Sprung C, Harboe S, Damas P. Are blood transfusions associated with greater mortality rates: results of the sepsis occurrence in acutely ill patients study. Anesthesiology. 2008;108:31-39. 28. Netzer G, Shah CV, Iwashyna TJ, et al. Association of RBC transfusion with mortality in patients with acute lung injury. Chest. 2007; 132:1116-1123. 29. Croce MA, Tolley EA, Claridge JA, Fabian TC. Transfusions results in pulmonary morbidity and death after a moderate degree of injury. J Trauma. 2005;59:19-24. 30. Ruttinger D, Wolf H, Kuchenhoff H, Jauch KW, Harti WH. Red cell transfusion: an essential factor for patient prognosis in surgical critical illness? Shock. 2007;28:165-171. 31. Marik PE, Corwin HL. Efficacy of red blood cell transfusion in the critically ill: a systematic review of the literature. Crit Care Med. 2008;36(9):2667-2674. 32. Practice guidelines for perioperative blood transfusion and adjuvant therapies: an updated report by the American Society of Anesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies. Anesthesiology. 2006;105:198-208. 33. Shaprio M. To filter blood or universal leukoreduction: what is the answer? Crit Care. 2004;8:S27-S30. 34. Phelan H, Sperry J, Friese R. Leukoreduction before red blood cell transfusion has no impact on mortality in trauma patients. J Surg Res. 2007;138(1):32-36. 35. Chant C, Wilson G, Friedrich JO. Anemia, transfusion and phlebotomy practices in critically ill patients with prolonged length of stay: a cohort study. Crit Care. 2006;10:1-9. 36. Fowler R, Rizoli S, Levin P, Smith T. Blood conservation for critically ill patients. Crit Care Clin. 2004;20:313-324. 37. Rickard CM, Couchman BA, Schmidt SJ, Dank A, Purdie DM. A discard volume of twice the vascular line deadspace ensures clinically accurate arterial blood gases and electrolytes and prevents unnecessary blood loss. Crit Care Med. 2003;31(6):1654-1658. 38. Natanson C, Kern SJ, Lurie P, et al. Cell-free hemoglobin-based blood substitutes and risk of myocardial infarction and death: a metaanalysis. JAMA. 2008;299(19):2304-2312. 39. Corwin HL, Gettinger A, Pearl RG, et al. Efficacy of recombinant human erythropoietin in critically ill patients: a randomized controlled trial. JAMA. 2002;288:2827-2835. 40. Corwin HL, Gettinger A, Fabian TC, et al. Efficacy and safety of epoetin alfa in critically ill patients. N Engl J Med. 2007;357(10): 965-976. www.ccnonline.org CriticalCareNurse Vol 31, No. 1, FEBRUARY 2011 33

CE Test Test ID C1112: Packed Red Blood Cell Transfusions in Critically Ill Patients Learning objectives: 1. Describe the cause of anemia in critical illness 2. Describe the effects of storage on red blood cells 3. Review the current literature on blood transfusions in critically ill patients 1. Critically ill patients often have inflammatory markers that lead to which of the following? a. Splenic sequestration b. Decreased iron absorption c. Increased erythropoiesis d. Severe vasoconstriction 2. When it is determined that a blood transfusion is necessary, blood banks do which of the following? a. Issue units of blood on the basis of expiration date b. Reserve units of blood related to adenosine 5 -triphosphate levels c. Issue units of blood on the basis of deformability d. Reserve units of blood related to storage lesions 3. Which of the following effects of storage of packed red blood cells is the result of a decrease in 2,3-diphosphoglycerate? a. Occlusion of the microvasculature and organ failure b. An increased risk of hospital-acquired infection c. Hemolysis of red cells with potassium leakage d. Decreased levels of oxygen move into the tissues 4. Which of the following is a proven benefit of leukoreduction of transfused blood? a. Reduced mortality rate 30 days after transfusion b. Reduction in transfusion-transmitted bacteria c. Reduced risk of febrile nonhemolytic reactions d. Reduction in transfusion-associated lung injury 5. The use of blood substitutes, such as bovine hemoglobin and polymerized human hemoglobin carrier solutions, has been found to be associated with which of the following? a. An increased risk of myocardial infarction b. An overall decrease in oxygen-carrying capacity c. A decrease in production of erythropoietin d. A concern over increased economic expense 6. Which of the following independent nursing interventions may help reduce anemia in critically ill patients? a. Sampling blood via an arterial catheter b. Administering synthetic erythropoietin c. Elevating blood pressure with fluid bolus d. Use of child-sized phlebotomy tubes 7. Transfusion of packed red blood cells (RBCs) is of concern for nurses working in critical care areas because of which of the following? a. Approximately 95% of all patients in the intensive care unit (ICU) are anemic on their third day. b. Transfusion of packed RBCs maintain the standard of care expected for critically ill patients. c. Increasing oxygen-carrying capacity, packed RBCs decrease a patient s length of stay. d. RBCs are replaced around every 120 days in response to renal release of erythropoietin. 8. Results of the Transfusion Requirements in Critical Care study included which of the following findings? a. Administering 2 units of packed RBCs when hemoglobin drops to 10g/dL optimizes care of cardiac patients. b. A transfusion trigger of hemoglobin level less than 7g/dL decreases rates of mortality and organ dysfunction. c. Maintaining a hemoglobin level of 7-9 g/dl is adequate in clients with an active hemorrhagic incident. d. Increased units of blood administered decreases client length of stay and mortality rate in the ICU. 9. Which of the following nursing interventions decrease blood loss when collecting samples from catheters? a. Selecting arterial catheters that return the waste sample to the patient b. Discarding 2 times the volume contained in the catheter dead space c. Filling the entire 10-mL tube in order to run accurate chemistry panels d. Increasing phlebotomy volume by 3.5 ml each day the patient is in the ICU 10. Storing RBCs contributes to a decrease in antioxidants, resulting in which of the following? a. Less oxygen moving into the tissues b. Microvascular occlusion and organ failure c. A decrease in oxygen available to tissues d. Possible immunomodulation and infection 11. Which of the following is most likely related to receiving a blood transfusion in the ICU? a. Bacterial contamination b. Pulmonary edema c. Hepatitis A infection d. Contact dermatitis 1. a Test answers: Mark only one box for your answer to each question. You may photocopy this form. 2. a 3. a Test ID: C1112 Form expires: February 1, 2013 Contact hours: 1.0 Fee: AACN members, $0; nonmembers, $10 Passing score: 8 correct (73%) Synergy CERP: Category A Test writer: Shelba Durston, RN, MSNc, CCRN For faster processing, take this CE test online at www.ccnonline.org ( CE Articles in this issue ) or mail this entire page to: AACN, 101 Columbia Aliso Viejo, CA 92656. 4. a 5. a Program evaluation 6. a Yes No Objective 1 was met Objective 2 was met Objective 3 was met Content was relevant to my nursing practice My expectations were met This method of CE is effective for this content The level of difficulty of this test was: easy medium difficult To complete this program, it took me hours/minutes. Name Member # Address City State ZIP Country Phone E-mail RN Lic. 1/St RN Lic. 2/St Payment by: Visa M/C AMEX Discover Check Card # Expiration Date Signature The American Association of Critical-Care Nurses is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center s Commission on Accreditation. AACN has been approved as a provider of continuing education in nursing by the State Boards of Nursing of Alabama (#ABNP0062), California (#01036), and Louisiana (#ABN12). AACN programming meets the standards for most other states requiring mandatory continuing education credit for relicensure. 7. a 8. a 9. a 10. a 11. a