Artificial oxygen carriers and red blood cell substitutes: A historic overview and recent developments toward military and clinical relevance.

Packed red blood cells are a critical component in the resuscitation of hemorrhagic shock. The availability of donor-derived blood products, however, suffers from issues of supply, immunogenicity, and pathogenic contamination. Deployment in remote or austere environments, such as the battlefield, is further hindered by the inherent perishability of blood products. To address the significant limitations of allogenic packed red blood cells and the urgent medical need for better resuscitative therapies for both combat casualties and civilians, there has been significant research invested in developing safe, effective, and field deployable artificial oxygen carriers. This article provides a comprehensive review of the most important technologies in the field of artificial oxygen carriers including cell-free and encapsulated hemoglobin-based oxygen carriers, perfluorocarbon emulsions, natural hemoglobin alternatives, as well as other novel technologies. Their development status, clinical, and military relevance are discussed. LEVEL OF EVIDENCE: Systematic review.