Why Are We Giving Our Patients Blood?

Abstract & Commentary

By Andrew M. Luks, MD Pulmonary and Critical Care Medicine, University of Washington, Seattle Dr. Luks reports no financial relationship to this field of study. This article originally appeared in the January 2008 issue of Critical Care Alert. It was edited by David J. Pierson, MD, and peer reviewed by William Thompson, MD. Dr. Pierson is Professor, Pulmonary and Critical Care Medicine, Harborview Medical Center, University of Washington, and Dr. Thompson is Staff Pulmonologist, VA Medical Center; Associate Professor of Medicine, University of Washington. Drs. Pierson and Thompson report no financial relationships relevant to this field of study.

Synopsis: This retrospective analysis of data on patients with acute lung injury shows that transfusion of red blood cells in such patients is associated with increased in-hospital mortality, and that the risk is highest with transfusion of non-leukoreduced blood and transfusion following the onset of acute lung injury.

Source: Netzer G, et al. Association of RBC transfusion with mortality in patients with acute lung injury. Chest. 2007;132:1116-1123.

Multiple, recent studies have demonstrated that red blood cell (RBC) transfusions may be deleterious to critically-ill patients, as they have been found to be associated with increased mortality following coronary artery bypass surgery, increased rates of ventilator-associated pneumonia, and worse outcomes in patients with burn injury and trauma. Netzer and colleagues sought to build on this literature and determine if RBC transfusion had an effect on in-hospital mortality in patients with acute lung injury (ALI). They performed a retrospective analysis on previously collected data from a cohort of 248 patients with ALI or acute respiratory distress syndrome (ARDS) at a single center between 1999 and 2002. All patients over the age of 13 admitted to the medical or surgical ICU at this center were enrolled if they met American European Consensus criteria for ALI/ARDS. They did not include patients with heart failure, respiratory diseases such as diffuse alveolar hemorrhage-mimicking ARDS, significant burns, or transplant recipients.

RBC transfusion was the primary exposure variable, and this was evaluated dichotomously (any transfusion), as well as linearly (total number of RBC units transfused). The primary outcome was in-hospital mortality. Because mechanical ventilation strategies changed over the course of the study due to the results of the ARDSNet trial, and because the use of leukoreduced blood increased over the same time period, appropriate adjustments were made in the statistical analysis to account for these changes in practice. Netzer et al also investigated whether the timing of transfusion, relative to the onset of ALI, had any effect on mortality.

Overall mortality among the 248 patients analyzed in the study was 39%, consistent with that seen in the placebo group of the ARDSNet trial. Transfusion was associated with an increased risk of mortality. Transfusion of any RBC was associated with an unadjusted odds ratio (OR) for mortality of 2.90, a value that remained significant when adjusted for various factors such as age, gender, and APACHE III score. The mortality risk per unit of RBC transfused, adjusted for length of stay, was 1.06. Put in other terms, a patient who received 4 units of blood over the course of admission had a 24% increase in mortality risk. With regard to timing of the transfusions, transfusion of blood after the onset of ALI was associated with an OR of mortality of 1.13 per unit transfused, while administration prior to ALI onset was not a risk factor for mortality. The risk of mortality was higher, however, with non-leukoreduced blood; the OR for non-leukoreduced RBC per unit transfused was 1.14 compared to only 1.04 for the leukoreduced products. Finally, when adjusted for RBC transfusion, platelet administration was not associated with a higher risk of mortality.

Commentary

The study by Netzer et al is yet another entry in a growing list of studies that leaves one wondering why it is that we are transfusing RBC in critically ill patients. Basic cardiopulmonary physiology teaches us that increasing a patient's hemoglobin levels improves oxygen delivery, a key goal in the critically ill. Yet, studies on a wide variety of critically ill patients, such as post-cardiac surgery, burn, trauma, and now ALI patients, demonstrates that RBC transfusion may have deleterious effects, such as increased mortality, increased ventilator-associated pneumonia, and decreased organ function. The etiology of these effects has not been definitively established, but may relate to transfusion-related amplification of lung injury or immunosuppressive effects.

It should be noted that there are some methodological issues of concern in the paper, such as the fact that Netzer et al were not able to separate cases of Transfusion-Related Acute Lung Injury (TRALI) from pure ALI, as well as the fact that it was a retrospective analysis, but in light of all the previous studies with similar conclusions, this paper's results warrant consideration.

The Transfusion Requirements in Critical Care (TRICC) trial1 has previously demonstrated that using a restrictive transfusion strategy, in which patients are only transfused when their hemoglobin values fall below 7 mg/dL, is not associated with increased morbidity or mortality when compared to a more liberal transfusion threshold. Given the large number of studies noted above demonstrating potential deleterious effects of RBC transfusion, increased attention should be devoted to stricter transfusion practices along the lines of those used in this important, prospective, randomized trial. There are situations in which RBC transfusion is likely to be beneficial, warranting deviation from strict thresholds — acute coronary syndrome and early goal-directed therapy2 are two good examples — but in general, the growing evidence now indicates that we need to be more careful about our use of RBC transfusions in the ICU.

References

1. Hebert PC, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med. 1999;340:409-417.

2. Rivers E, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368-1377.