Effects of Resuscitation Fluids: The HBOC Excipients, And Length of Storage of RBC at 4 ̊c on the Toxicity of Hemoglobin Based Oxygen Carriers (HBOC)

Severe adverse events have been observed following the infusion of Hemoglobin Based Oxygen Carriers (HBOCs) in patients subjected to elective orthopedic procedures, cardiopulmonary bypass surgery, and vascular surgical procedures. Along with all three of the hemoglobin based oxygen carriers, the patients received Ringer’s D,L-lactate as the resuscitation fluid, Ringer’s D,L lactate in the excipient medium for the stroma-free hemoglobin, and liquid preserved red blood cells that has been stored at 4 ̊C for longer than 2 weeks. The Ringer’s D,L lactate solution has been shown to be toxic in both animals and patients. In a recent publication morbidity and mortality have been reported and associated with the length of storage of red blood cells at 4 ̊C for longer than 2 weeks in patients subjected to re-operative cardiac surgery. Current clinical adverse events with HBOCs may be associated with the composition of the resuscitation solution (Ringer’s lactate), the composition of the excipient medium (Ringer’s lactate) for the hemoglobin based oxygen carrier, and the length of storage of the liquid preserved red blood cells infused with the hemoglobin based oxygen carrier. Two billion dollars have been spent on attempts to develop Food and Drug Administration (FDA)-approved safe and therapeutically effective hemoglobin based oxygen carriers. Despite the significant investment, the clinical studies performed in elective orthopedic surgical patients; in patients subjected to cardiopulmonary bypass surgery; and in patients subjected to major vascular surgical procedures have all been associated with severe adverse events. The combination of the Ringer’s D,L lactate resuscitation fluids administered to these patients, the Ringer’s D,L lactate excipient medium for the HBOC, and the length of storage at 4 ̊C of the liquid preserved RBC infused into these patients who received HBOC may be responsible for severe adverse events that have been observed. Received: October 12, 2015; Accepted: November 20, 2015, Published: November 28, 2015 *Corresponding author: C. Robert Valeri, Naval Blood Research Lab Inc, 195 Bournehurst Drive, Plymouth, MA 02360, United States; E-mail: [email protected]