Impact of More Restrictive Blood Transfusion Strategies on Clinical Outcomes A Meta-analysis and Systematic Review

SUMMARY: The traditional hemoglobin trigger to recommend blood transfusions for majority of the Health Care Providers is between 7.5 and 9 g/dl. The clinical rationale is based on the premise that increasing Hgb levels increases blood oxygen content and possible oxygen delivery to the tissues. However, there are no randomized trials validating improved oxygen delivery to tissues or better clinical outcomes in any setting at this hemoglobin transfusion trigger. The authors in this provocative study conducted a comprehensive research and performed a Primary and Secondary meta-analysis. In their primary meta-analysis, they reviewed the pooled data from 3 randomized clinical trials with 2364 patients and in these trials, a less than 7g/dl hemoglobin as a transfusion trigger (restrictive transfusion strategy) was compared with a more liberal transfusion strategy and outcomes were evaluated. These endpoints included mortality, acute coronary syndrome, pulmonary edema, infections and re-bleeding risk. The combined data from these 3 trials showed that a restrictive transfusion strategy resulted in a 26% mortality reduction in hospitalized patients, 20% reduction in total mortality, 36% reduction in the risk of re-bleeding, 56% reduction in acute coronary syndrome, 52% reduction in the incidence of pulmonary edema and 14% reduction in bacterial infections, compared with a more liberal transfusion strategy. The secondary meta-analysis evaluated patients in 16 trials (these were excluded from the primary meta-analysis) that used a less restrictive transfusion trigger (hemoglobin transfusion triggers of 7.5-10g/dl) and the authors noted that outcomes were not improved with a more liberal transfusion strategy. Further it was also noted that several observational studies have shown that Hgb levels of 5-6g/dl was well tolerated in normovolemic patients without effecting oxygen delivery. Contrary to clinical presumptions, these counter-intuitive findings can be explained based on sound physiologic principles. Normovolemic hemodilution following administration of crystalloid or colloid solutions, to replace blood loss, has been associated with a reduction in systemic vascular resistance, increase in cardiac output, coronary and cerebral blood flow and synthesis of 2,3-diphosphoglycerate in red blood cells thus maintaining movement of oxygen from red blood cells to body tissues. Liberal blood transfusions may in fact impair oxygen uptake by vital tissues by increasing the blood viscosity and the resulting loss of RBC function during preservation and storage of blood. Studies have also shown that in patients with gastrointestinal bleeding, restrictive transfusion strategy results in a lower portal blood pressure and less recurrent bleeding, as higher blood pressures might disrupt a thrombus plug. The authors following this clinically relevant meta-analysis concluded that restrictive transfusion strategy resulted in better outcomes and transfusion triggers should be evidence based. Salpeter SR, Buckley JS and Chatterjee S. The American Journal of Medicine 2014;127:124-131