Severe adverse events associated with hemoglobin based oxygen carriers: role of resuscitative fluids and liquid preserved RBC.

Severe adverse events have been observed following the infusion of hemoglobin based oxygen carriers 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 resuscitative fluid, Ringer's d,l-lactate in the excipient medium for the stroma free hemoglobin, and liquid preserved red blood cells that had been stored at 4 degrees C for longer than 2 weeks. The Ringer's d,l-lactate solution has been shown to be toxic in both animals and patients. The current formulation of Ringer's lactate contains only the l-isomer which has been shown in animals to be less toxic than the d-isomer of lactate. In a recent publication morbidity and mortality have been reported associated with the length of storage of red blood cells at 4 degrees C in patients subjected to reoperative cardiac surgery. Current clinical studies to assess the safety and therapeutic effectiveness of a hemoglobin based oxygen carrier (HBOC) must consider the effects of the composition of the resuscitation solution (Ringer's L-lactate), the composition of the excipient medium (Ringer's L-lactate or 0.9% NaCl) 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.