Mind the evidence gap: The need for trials in the prevention and management of perioperative anemia in noncardiac surgery

Red blood cell (RBC) transfusions are the most widely administered inpatient therapeutic intervention in medicine. Transfused RBCs increase oxygen delivery to tissues in situations such as anemia from perioperative bleeding. Each year, 108 million units of blood are transfused globally, with major surgical procedures accounting for approximately 20% of the utilization based on an estimate from the United States. Internationally, surgical procedures have been estimated to account for a quarter to nearly a half of all RBC transfusions among hospitalized patients. Although often lifesaving because major bleeding is the leading cause of perioperative death, blood products have been associated with adverse outcomes, and their use has a significant impact on our health system. Based primarily on observational studies, patients who receive transfusions have longer lengths of hospital stay and higher infection rates, spend more time in intensive care, and have a higher risk of acute respiratory distress.7–9 Thus, clinicians attempting to balance the perceived benefits and risks of RBC transfusion is likely a factor that has produced considerable practice variation within and across institutions. Very little evidence exists in the noncardiac perioperative setting as to the most effective blood management strategies to reduce inappropriate transfusions and improve patient outcomes. Anemia is well tolerated by a majority of patients undergoing surgical procedures; thus the benefits of potentially corrective treatments such as RBC transfusions or pharmacologics need to be weighed against their risks. For noncardiac surgical procedures, recommendations to guide perioperative RBC transfusion practice are limited and nonspecific. For instance, clinical guidelines from AABB recommend a restrictive RBC transfusion threshold of a hemoglobin (Hb) level of 8 g/dL in patients undergoing orthopedic and cardiac procedures but do not define its applicability to other surgical procedures. Thus, surgeons and anesthetists are left to generalize findings from critical care, orthopedic, and cardiac surgery populations demonstrating that restrictive transfusion thresholds are as safe and effective as liberal thresholds. In the absence of robust trial evidence in other noncardiac surgical populations, extrapolation and application of a restrictive strategy seems prudent. Yet, it is not ideal as surgery-specific evidence is necessary to reduce practice variation resulting from a physicianʼs uncertainty or unwillingness to accept evidence from other populations. A recent observational study of more than 6.6 million surgical patients captured in the American College of Surgeonsʼ National Surgical Quality Improvement Program identified 19 noncardiac procedures at very high risk of perioperative transfusion. Given the incidence of major noncardiac procedures and the risk of perioperative transfusion, thorough and contemporary evaluations of the clinical impact of perioperative anemia with population-based data are warranted. In this issue of TRANSFUSION, Kerfeld and colleagues from the Mayo Clinic in Rochester, Minnesota, undertook a large retrospective cohort study of more than 3000 non–cardiac surgery patients residing within 120 miles of Rochester. Their objective was to evaluate the association between anemia at hospital discharge and important posthospitalization outcomes using routinely collected and well-validated perioperative, clinical, and administrative data. Based on a patientʼs discharge Hb, the authors categorized anemia as severe, moderate, mild, or none. As expected, the wide range of acceptable Hb levels at discharge reflected the current variation in clinical practice. Contrary to their hypothesis, the authors found that hospital readmissions, strokes, myocardial infarctions, and mortality rates were not significantly associated with anemia. They did demonstrate higher posthospitalization transfusion rates in patients categorized as severely anemic (Hb <8 g/dL). While it is somewhat surprising that moderate to severe levels of anemia at hospital discharge did not translate into increased morbidity and mortality, the authorsʼ “real-world” observational data are in keeping with results from large pragmatic trials evaluating different levels of anemia tolerance. Contrary to widely held beliefs, the majority of large trials to date do not establish that increased transfusions via a liberal Hb threshold strategy result in higher morbidity and mortality. Received: 10 September 2020 Accepted: 10 September 2020