In this article, we'll review the current evidence surrounding red blood cell (RBC) transfusion practice in the ICU, and the potential adverse events associated with this commonly prescribed treatment. Up to 45% of all ICU patients receive blood transfusions at some time during their admission.1 In critically ill adults, RBC transfusions have obvious clinical benefits, and often may be lifesaving. However, blood product transfusions aren't without risks, such as transfusion-transmitted infectious diseases and serious transfusion reactions. With modern blood banking technology, these complications are exceedingly rare.
Recent literature has revealed that blood transfusions aren't as benign as once thought. Less clinically recognized and potentially overlooked risks are associated with blood product transfusion in critically ill adults. Based on literature to date, researchers accept that transfusions can lead to potentially significant cardiopulmonary complications and immunomodulation. These effects may increase a patient's risk of developing clinical noninfectious complications such as transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), transfusion-related immunomodulation (TRIM), and associated risk related to the increased incidence of healthcare-associated infections.
Transfusion requirements will continue to increase because of the increasing burden of chronic disease in an aging population, improvement in life-support technology, and blood-intensive surgeries.1 Current clinical data support a more conservative transfusion trigger, which is directly associated with lower morbidity and mortality. By understanding the risks and benefits of RBC transfusions, you can provide safer therapy.
Anemia and critical illness
Anemia associated with critical illness is common in the ICU. In one study, 70% of ICU patients evaluated had a hemoglobin concentration less than 12 g/dL.2 (Normal hemoglobin values vary by institution, but generally range between 14 and 18 g/dL for men and 12 to 16 g/dL for women.)
Anemia is defined as a reduced absolute number of circulating RBCs, which clinically manifests as a reduction in hemoglobin, hematocrit, and/or RBC count.3 For patients with anemia, RBC transfusions are aimed at improving oxygen delivery and limiting tissue hypoxia and damage at the cellular level.
In critically ill patients, anemia has many causes: gastrointestinal tract bleeding, trauma, and major surgery are compounded by the less appreciated etiologies of phlebotomy, minor procedures, and patients' physiologic responses to critical illness. In 24 hours, the typical ICU patient has an average volume of 41.1 mL of blood drawn.4 Furthermore, ICU patients often require minor bedside procedures such as arterial line placement and central venous access device placement that may significantly contribute to daily blood loss.
Also, anemia of critical illness is related to decreased RBC production via decreased erythropoietin synthesis, resistance to erythropoietin, or iron deficiency in patients with active, ongoing inflammation. RBC production in critically ill patients is physiologically abnormal. These patients have an inappropriately low erythropoietin concentration, whether they have renal failure or not.5 A variety of inflammatory mediators can cause suppression of erythropoietin production and erythropoietin resistance.5
Signs and symptoms related to anemia are the result of decreased tissue oxygen delivery and hypovolemia. The patient's blood has less oxygen-carrying capacity, so the oxyhemoglobin dissociation curve shifts to the right. Depending on the severity of the anemia, your patient may have dyspnea, fatigue, bounding pulses, palpitations, dizziness, chest pain, dysrhythmia, syncope, hypotension, or shock. Without treatment, the patient is at risk of dying.
Risks of transfusion
Let's take a closer look at some of the risks associated with RBC transfusion.
Transfusion-transmitted infections. Donated blood products are routinely tested for antigens and/or antibodies to HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), human T-cell lymphotropic viruses, syphilis, and West Nile virus.6 The progression of testing technology has significantly reduced the risk of transfusion-transmitted infections. The reported risk from test-negative blood components in the United States is an estimated 1 in 2 million for HIV and HCV, and 1 in 200,000 to 500,000 for HBV.6
TRALI. This potentially life-threatening complication of blood transfusion carries a mortality of 6% to 10%.7 The patient often is misdiagnosed with heart failure or volume overload and may receive loop diuretic therapy inappropriately. TRALI is a clinical diagnosis characterized by respiratory distress and worsening hypoxia within the first 2 to 6 hours of an associated blood transfusion.7 Additional signs and symptoms include hypoxemia, hypotension, fever, cyanosis, and bilateral pulmonary infiltrates in the absence of signs of circulatory overload or an elevated pulmonary capillary wedge pressure (PCWP).
The absolute pathophysiology of TRALI remains unclear, but researchers think that passively transferred donor blood cells containing antileukocyte antibodies and blood storage lipids attack recipient leukocytes. This causes pulmonary fluid sequestration, complement activation, and lung injury resulting in pulmonary edema secondary to increased capillary permeability.7 Treatment of TRALI consists of supportive care with supplemental oxygen, lung-protective low tidal volume mechanical ventilation, and hemodynamic support of hypotension.7
TACO. Pulmonary edema, a potentially serious complication of blood transfusions, is associated with the accumulation of extravascular lung water due to an imbalance of fluid filtration and resorption.8 When pulmonary edema and hypoxemia occur within 6 hours of a blood transfusion, the cause could be TACO or TRALI. TACO may occur in up to 11% of patients undergoing blood transfusions, and has a mortality of 5% to 15%.8
Signs and symptoms of TACO include dyspnea, tachypnea, jugular venous distension, evidence of increased central venous pressure or PCWP, and an elevated systolic BP. Because treatment of TRALI and TACO vary considerably, differentiating the two is crucial. Suspect TACO in a patient with a history of heart disease, positive fluid balance, absence of acute lung injury risk factors, and signs and symptoms consistent with systemic and/or pulmonary hypertension.8
Management of TACO is supportive. Lung protective mechanical ventilatory support and intravascular volume reduction with diuretics and/or ultrafiltration are used when required.
TRIM. TRIM results from infusion of small amounts of foreign antigens and storage proteins that accumulate in blood products when they're stored. These mediators have been shown to downregulate the recipient's own immune system, contributing to the development of immunosuppression and increasing the incidence of healthcare-associated infections.9 Researchers are still studying how transfusion of stored blood products affects patient outcomes.
Because of morphological and functional changes in stored RBCs, a transfusion may improve a patient's oxygen delivery but not necessarily increase tissue oxygenation or oxygen use.10 Blood storage systems approved by the FDA allow RBCs to be stored for up to 42 days.11 The mean calculated age of stored RBCs in the United States is 19.5 days at the time of transfusion.12 Some studies have suggested that posttransfusion complications increase when the blood has been stored for longer periods. One study of cardiac surgery patients found that transfusing RBCs that had been stored for more than 2 weeks was associated with a significantly higher risk of postoperative complications, including prolonged intubation, renal failure, sepsis, and multiorgan failure, as well as an overall reduced survival rate.11 The relationship between adverse outcomes and duration of RBC storage isn't clear. The depletion of 2,3-diphosphoglycerate (2,3-DPG), which shifts the oxyhemoglobin dissociation curve to the left, reducing oxygen delivery, may be a contributing factor. Also, stored RBCs change shape secondary to decreased adenosine triphosphate levels, and this decreased deformability impedes microvascular flow.
The bottom line is that although your patient's hemoglobin levels will increase after a transfusion of packed RBCs, there's no guarantee that the patient has better end-organ oxygenation at the cellular level.
Immunologic blood transfusion reactions
One of the most frequent and avoidable causes of life-threatening adverse reactions to blood transfusions is an acute hemolytic reaction caused when the patient receives an ABO-mismatched unit of blood. Acute hemolytic reaction is a medical emergency, as donor erythrocytes are rapidly destroyed by the patient's existing antibodies. This intravascular hemolysis may lead to disseminated intravascular coagulation, shock, and acute renal failure from acute tubular necrosis.
Signs and symptoms of an acute hemolytic reaction include fever, chills, flank pain, back pain, and hemoglobinuria. Immediately stop the transfusion, start an infusion of 0.9% sodium chloride solution, and provide supportive care. Alert the blood bank, return the bag of RBCs, and follow your hospital blood bank's policy for further interventions.
A febrile nonhemolytic reaction, characterized by low-grade fever, chills, and mild dyspnea, is the most common transfusion reaction.3 Discontinue the transfusion and administer antipyretics and supportive care. Confirm that the patient isn't having an acute hemolytic reaction.
A life-threatening anaphylactic reaction is caused by class-specific IgG, anti-IgA antibodies in patients who are IgA deficient.3 Rapid in onset, this reaction is characterized by shock, hypotension, angioedema, and respiratory distress. Discontinue the transfusion and administer epinephrine, oxygen, volume resuscitation, and vasopressors as prescribed.
Trends in transfusion practice
Anemia is common in critically ill patients, but blood transfusions can lead to adverse reactions. This is why determining when to transfuse patients is a topic of intense interest. The previous arbitrary transfusion trigger (a hemoglobin level of 10 g/dL) has been subjected to rigorous investigation, and various studies have found:
- that about 40,000 severe acute complications associated with transfusions could be avoided, and nearly $1 billion saved annually if facilities adopted a restrictive transfusion policy.13
- overall 30-day mortality was 19% in critically ill patients assigned to a restrictive transfusion strategy (maintaining the hemoglobin level between 7 and 9 g/dL) compared with a 23% mortality in the group assigned to a liberal transfusion strategy (maintaining the hemoglobin between 10 and 12 g/dL).14 Overall hospital mortality was significantly less in the restrictive group—22% compared with 28%.
- patients who received RBC transfusions had higher mortalities than those who hadn't received transfusions (18.5% versus 10.1%),4 and the number of RBC transfusions was independently associated with longer ICU and hospital lengths of stay and an increase in mortality and complications.2
Further support for a restrictive transfusion trigger was established in 2008 when international guidelines for the management of patients with severe sepsis and septic shock were published.15 The Surviving Sepsis Campaign supports a transfusion trigger of less than 7 g/dL and a target hemoglobin level of 7 to 9 g/dL in adults. Special circumstances that may require a higher hemoglobin level include active myocardial ischemia, severe hypoxemia, acute hemorrhage, cyanotic heart disease, or lactic acidosis.15
In 2009, in light of mounting clinical evidence supporting a more restrictive transfusion threshold, a joint task force was convened. Expert clinicians from the Eastern Association for Surgery of Trauma and the American College of Critical Care Medicine of the Society of Critical Care Medicine performed a comprehensive literature review relating to the topic of blood transfusion in trauma and critically ill patients.16 All clinical studies relating to blood transfusion were reviewed and the evidence was subsequently graded using scientific assessment methods.16 The task force developed the first evidence-based recommendations for the use of RBC transfusion in adult trauma and critical care, as summarized in Recommended practices.16
Although more studies are needed, the current best evidence supports a restrictive transfusion trigger of 7 g/dL in most critically ill adult medical, surgical, and trauma patients. As nurses, we can advocate for evidence-based RBC transfusion indications, an evidence-based ICU RBC transfusion policy and protocol, and the implementation of blood conservation techniques to minimize patient blood loss. These techniques may include closed-circuit sampling with all arterial lines, point-of-care microanalysis, use of low-volume adult blood tubes for phlebotomy, and coordination of and responsible phlebotomy for all critically ill and injured patients. By knowing the evidence-based indications for RBC transfusions and advocating for your patients, you can help see that RBCs are only transfused when clinically indicated.
- RBC transfusion is indicated for patients with evidence of hemorrhagic shock.
- RBC transfusion may be indicated for patients with evidence of acute blood loss and hemodynamic instability or inadequate oxygen delivery.
- Consider RBC transfusion if the hemoglobin level is below 7 g/dL in a critically ill medical patient without evidence of active, acute myocardial ischemia, and in trauma patients who have been adequately resuscitated.
- RBC transfusion may be beneficial in patients with active myocardial ischemia who are anemic (hemoglobin level of 8 g/dL or less) on hospital admission.
- A liberal transfusion strategy (that is, transfusing RBCs to maintain a hemoglobin level over 10 g/dL) hasn't been shown to have any benefit.
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