The publication of this study provides valuable insights into the clinical use of HBOCs, which may inform the risk-benefit analysis of future research design and clinical recommendations. (Image source: Thinkstock)
The publication of this study provides valuable insights into the clinical use of HBOCs, which may inform the risk-benefit analysis of future research design and clinical recommendations. (Image source: Thinkstock)

There was a lot of interest, particularly in the 1990s, in hemoglobin-based oxygen carriers (HBOCs) as a substitute for blood transfusions. HBOCs eliminate the need for cross-matching prior to use, they don’t require refrigeration, and they have a longer shelf life than banked blood. However, these cell-free hemoglobin oxygen substitutes have been shown to be more risky than blood transfusions since both the risk of death and MI are higher compared with RBC transfusions.

Dr. Jan Van Hemelrijck, currently affiliated with the Department of Cardiovascular Sciences, Katholieke Universiteit Leuven, Leuven, Belgium, and colleagues from South Africa, the United States, and Germany, present the results of a single-blind, head-to-head comparison between RBC transfusion and HBOCs in a population of noncardiac surgery patients in the article titled “A Safety and Efficacy Evaluation of Hemoglobin-Based Oxygen Carrier HBOC-201 in a Randomized, Multicenter Red Blood Cell–Controlled Trial in Noncardiac Surgery Patients,” which was published in this month’s issue of Anesthesia & Analgesia. The work was done in the late 1990s, prior to the bankruptcy of the company developing HBOC-201. It was resurrected for presentation due to continued interest in developing hemoglobin therapeutics for use when transfusion is not possible.

In this study, patients needing transfusion were randomized to receive up to 7 units of HBOC-201 or 6 units of RBCs. The primary endpoint was transfusion avoidance, which was achieved in 43% of patients in the HBOC group. There were substantially more minor adverse events in the HBOC group, notably hypertension and jaundice. Serious adverse events and mortality were similar in both groups.

In discussing this study 15 years after it was conducted, the authors acknowledge that “blood substitutes” are unlikely to ever supplant transfusion therapy as the first-line therapy for life-threatening anemia. This is due both to the overall excellent safety record of transfusions and to side effects intrinsic to stroma-free hemoglobin molecules. All artificial hemoglobin solutions to date have induced some degree of hypertension due to enhanced scavenging of nitric oxide, leading to the possibility of serious cardiovascular complications such as stroke and myocardial infarction. At present, the only ongoing studies of hemoglobin solutions are in settings in which patients refuse transfusion (e.g., a Jehovah’s Witness) or where it is logistically infeasible (e.g., in prehospital care). It is unlikely that any further head-to-head comparisons with RBC transfusions will be conducted.

The publication of this study provides valuable insights into the clinical use of HBOCs, which may inform the risk-benefit analysis of future research design and clinical recommendations.   Indeed, as Dr. Richard B. Weiskopf, Department of Anesthesia, University of California, San Francisco, San Francisco, California, writes in the accompanying editorial titled “Hemoglobin-Based Oxygen Carriers: Disclosed History and The Way Ahead: The Relativity of Safety,” “We may hope that…continued development of HBOCs will be allowed for the revised indications that do not rely on RBCs as the comparator, and, thus, may alter the subjective view of HBOCs’ ‘safety.’”