A Study in Scarlet Restrictive Red Blood Cell Transfusion Strategy

by Leon Chen, MSc, AGACNP-BC, CCRN, CPEN

Anemia due to various etiologies occurs in critically ill patients requiring blood transfusion. Traditional transfusion goals guide our transfusion to achieve a hemoglobin goal of at least 10 g/dL. However, it is becoming increasingly evident that a restrictive transfusion goal of 7 g/dL may improve survival outcome, reduce infection, and reduce health care expenditure. Moreover, this strategy has been proven to be effective in a variety of patient population, including those who are critically ill, septic patients, those with a history of cardiac disease, those with gastrointestinal blood, or those who suffered traumatic injury. This article reviews some of the evidence supporting the restrictive transfusion strategy.

…therefore it seems right, as the operation now stands, to confine transfusion to the first class of cases only, namely those in which there seems to be no hope for the patient unless blood can be thrown in the veins.

Although descriptions of blood transfusion experiments date back to the 1600s, the first successful human-to-human blood transfusion is credited to Dr. James Blundell, a British obstetrician. He used blood transfusion to treat several patients with post-partum hemorrhage and was able to resuscitate them in 1818. Through his work, it was established that blood transfusions must be conducted between subjects of the same species, it be transferred through a syringe, and that a small amount of air injected into the vein is tolerated but large amounts would be lethal. In modern critical care medicine, blood transfusion is a common practice used to treat anemia due to various etiologies. Anemia of critical illness is a multifactorial phenomenon that is extremely prevalent. The cause of this condition is a combination of bone marrow suppression due to infection/inflammation, frequent phlebotomies, inadequate nutrition, neocytosis, and hemodilution. However, it is becoming increasingly evident that supraphysiological transfusion goals increase hospital-acquired infection, increase mortality, and increase health care expenditures.

Critically ill patients

The perceived benefit of blood transfusion is built on the concept of maximizing oxygen delivery by increasing oxygen-carrying capacity with red blood cell infusion. The benefit of blood transfusion on mortality was demonstrated in several studies that showed that anemia is an independent risk factor in cardiac surgery and critically ill patients. In 1999, the TRICC (Transfusion Requirements in Critical Care) trial published in the New England Journal of Medicine changed practice and demonstrated that for critcally ill patients in the intensive care unit (ICU), a restrictive transfusion goal of 7 g/dL of hemoglobin is not inferior to the traditional goal of 10 g/dL, with beneficial trend toward the restrictive goal. The TRICC trial did not, however, establish a clear beneficial threshold for patients with cardiac disease. Therefore, many cardiologists still recommend a transfusion goal of 10 g/dL for patients with cardiac disease.

Cardiac patients

The majority of available randomized controlled trials that have evaluated transfusion strategies in adult ICU patients with cardiac disease have found that restrictive transfusion approach is noninferior to a liberal transfusion strategy. Most of these studies used a restrictive goal of 7 or 8 g/dL as their transfusion threshold and have found it to be safe. In addition, there are other retrospective studies that associate blood transfusions and higher hemoglobin (>11 g/dL) goals with increased mortality and ischemic events in adult cardiac patients. Numerous factors explain why blood transfusion does not lead to beneficial effects in patients. In observational studies of Jehovah’s Witness patients and African children in resource-scarce areas, anemia based on 5 g/dL of hemoglobin is noted to be well tolerated. Blood transfusions lead to an increase in viscosity and thus an increase in systemic vascular resistance. Oxygen delivery does not increase after blood transfusion despite a theoretical increase in oxygen-carrying capacity. This is potentially due to the altered oxygen-carrying capacity in transfused red cells while in storage, termed “storage lesion.” In addition, blood transfusion has immunomodulating effects that lead to decreased immune system in patients already vulnerable to infection. This effect has been associated with increased ICU stays and mortality. Finally, other complications suchas TRALI (transfusion-related acute long injury), volume overload, and infections are all considerations when the decision to transfusion is made.

Septic patients

In the landmark Early Goal Directed Therapy for Sepsis and Severe Sepsis Trial, patients who had hemoglobin levels of less than 10 g/dL were transfused. The rationale behind this was to maximize oxygen delivery for these septic patients who have theoretical oxygen deficit. As mentioned previously, this theoretical benefit is impaired in practice due to the storage lesion. Later, large randomized controlled trials have firmly established that restrictive strategy with a hemoglobin threshold of 7 g/dL is the definitive treatment option for septic patients.

Patients with upper gastrointestinal bleeding

In a fascinating study, Villaneuva and colleagues, at a single center in Spain, randomized patients with hematemesis or melena to a restictive strategy group with a hemoglobin threshold of 7 g/dL versus a liberal strategy group with a hemoglobin threshold of 9 g/dL. THe outcome showed that the group with restrictive strategy is that with less transfusion, splenic pressure is lower, therefore leading to a less propensity of bleeding.

Trauma patients

In the trauma world, damage control resuscitation has become the standard of care. This resuscitation strategy emphasizes on stopping the hemorrhage, correcting acidosis, hypothermia, and coagulopathy to improve outcome. A key part of damage control resuscitation is permissive hypotension by restricting crystalloid infusion and also using a restrictive transfusion strategy. Restricting transfusion has been shown to decrease bleeding by decreasing splenic pressure and breaking existing clots.

Clinical implication

The latest trend in medicine seems to point toward a restrictive approach in the management of various conditions. Transfusion studies in critical illness, sepsis with gastrointestinal bleed, and even trauma all seem to suggest that restrictive transfusion protocols are not only safe but also beneficial. Unless the patient is having active acute coronary syndrome or bleed or is hemodynamically unstable, the available evidences suggest that a lower hemoglobin goal of 7 to 8 g/dL should be the transfusion goal. Less is more may emerge to be the best strategy in medicine.

This article and references can be found in Critical Care Nurse Quarterly Volume 38, No. 2, pp 217-219 with permission from Leon Chen.


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