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Reliance on a brisk erythropoietic response to untreated blood loss is an alternative to transfusion of homologous blood. Slow erythropoiesis has been observed in ICU patients who refused blood. Many of these patients received supplemental oxygen therapy and Fluosol-DA, a temporary red cell substitute. This study reports the erythropoietic response, in the baboon, to moderate (Hct 20%) and severe (Hct 10%) anemia. In addition, the effect of oxygen therapy (FIO2 0.6 for 1 wk) and fluorocarbon emulsions (Oxypherol) on erythropoiesis was evaluated. Baboons uniformly survived acute normovolemic anemia with Hct 10%. In all cases, the response to anemia was characterized by a lag period (with no change in Hct), and a nonlinear recovery period. A lag period of 3 days was observed in both moderate and severe anemia for baboons breathing room air or FIO2 0.6. The lag period was prolonged to 1 wk in the presence of Oxypherol. The recovery period exhibited a uniform and negative correlation between the rate of Hct change and the Hct, in all cases. The theoretical maximum rate of increase of Hct was 2.6%/day. In untreated blood loss, shortening the lag period and increasing the slope of the recovery period will decrease the length of time that the patient is anemic.

A co-oximeter study of whole blood samples containing Intralipid concentrations of 100 to 2000 mg/dl found that the light-scattering effect was greater at lower hematocrits. The methemoglobin reading was affected the most, and led to erroneous displays of total hemoglobin and percent oxyhemoglobin. The O2-content value, however, was accurate over the entire hematocrit and Intralipid concentration range tested. We suggest that an unexplained high methemoglobin value in whole blood samples from patients receiving Intralipid may reflect a light-scattering problem in the instrument.

Hemoglobin solutions have potential as temporary red cell substitutes. Their efficacy has been demonstrated by their ability to maintain life-supporting levels of O2 consumption and CO2 production in animals virtually free of red cells. They do not exhibit major toxic effects, but transient alterations in renal function remain a concern. Cardiac output does not increase in the face of acute anemia associated with isovolemic exchange transfusion with hemoglobin solution. However, cardiac reserve does not diminish significantly after infusion of hemoglobin solution. Alterations in production techniques may lead to a polymerized hemoglobin solution that has a hemoglobin concentration and P50 close to fresh whole blood. Though this development is encouraging, it is clear that no perfect red cell substitute currently is available.

The fluorocarbon emulsion Fluosol-DA (20%) is an acellular O2 carrier that has potential as a red cell substitute. Clinical evaluation of efficacy requires knowledge of the ability of the perfluorochemical (pfc) phase to both load and unload O2. A method is described to measure the oxygen dissolved in the pfc and aqueous phases, and the oxygen chemically bound to hemoglobin, during use of this drug. These O2 contents are used to calculate the contribution of the pfc phase to total O2 delivery and O2 consumption (VO2) and the fractional extraction of O2 in the pfc phase. The technique requires a blood gas analyzer, a microhematocrit centrifuge, and a standard co-oximeter found in many blood gas laboratories. This technique appears to be simple and reliable, and should facilitate the evaluation of efficacy of fluorocarbon emulsions.

Cardiovascular responses have been studied in baboons, after total exchange transfusion with hemoglobin solutions having various P50 values. At the end of the exchange transfusion, the hematocrit was 1.5%, the mean hemoglobin concentration was 4.4 g/dl, and the P50 varied between 12 and 26 mm Hg. Cardiac output did not change during the study, although heart rate increased, and stroke volume and MAP decreased. Hemoglobin concentration, per se, does not appear to be the critical stimulus for an increase in cardiac output with hemoglobin solution. In addition, the position of the hemoglobin-oxygen dissociation curve does not appear to influence these hemodynamic responses. The physiological response to anemia in the presence of hemoglobin solution appears different from that observed in the absence of plasma O2 carriers.

Stroma-free hemoglobin (SFH) solution is an acellular oxygen carrier under development as a temporary red blood cell (rbc) substitute. SFH will be of value if it contributes to oxygen loading (delivery) and unloading (consumption). If there is no interaction between red cell hemoglobin and SFH, then the composite oxygen dissociation curve for whole blood (WB) can be written as: SWB = rSSFH + (1 - r) Srbc, where S is the fractional saturation, and r is the SFH/WB hemoglobin ratio. This composite whole-blood curve was compared with the calculated curve, and the root mean square difference was 0.9%. Direct and indirect methods of measuring oxygen concentration ([O2]) of whole blood or plasma were compared. The regression line was [O2]indirect = 0.995 [O2]direct + 0.07 (r = 0.995, N = 16, p less than .01). The adequacy of anaerobic separation of plasma was evaluated by measuring the changes in PO2 and PCO2. The PO2 increased by less than 2 torr and the PCO2 decreased by less than 1 torr during in vitro tests. Both the direct and indirect methodology yielded consistent [O2] values for each carrier.