Co-oximetry interference by hemoglobin-based blood substitutes

The blood substitutes now being developed from molecularly modified hemoglobin interfere with a wide variety of clinical analyzers, but their effects on cooximeters are unknown. Therefore, we investigated the effects of five hemoglobin-based blood substitutes on the measurements of eight different oximeters and cooximeters: the AVL Omni 6, the AVOXimeters 1000 and 4000, the Ciba Corning (now Bayer) CC270 CO-Oximeter, the Instrumentation Laboratory Synthesis 35, the IL482 and IL682 CO-Oximeters, and the Radiometer OSM3 Hemoximeter. The five blood substitutes in this study were obtained from Apex Bioscience (Research Triangle Park, NC), Baxter Healthcare Corp. (Deerfield, IL), Biopure Corp. (Cambridge, MA), Hemoglobin Therapeutics, and Hemosol, Inc. (Etobicoke, Ontario, Canada). A cooximeter control was used to compare the eight different instruments' measurements on unaltered human hemoglobin. The instruments yielded measurements of total hemoglobin concentration in undiluted blood substitutes that were generally not more variable than those on the control material. By contrast, when compared with readings on controls, the test instruments yielded measurements of the fractional concentrations of oxy-, deoxy-, carboxy-, and methemoglobin that showed greater instrument-to-instrument disparities and larger standard deviations about the all-instrument means. In some cases, the interference was even more obvious: five of six cooximeters gave negative carboxyhemoglobin readings on one particular product. Our findings indicate that the instruments will give less accurate but clinically useful measurements in the presence of these hemoglobin-based blood substitutes.