Richard DeWoskin

The first randomized trial of human polymerized hemoglobin as a blood substitute in acute trauma and emergent surgery

BACKGROUND Human polymerized hemoglobin (PolyHeme) is a universally compatible, disease-free, oxygen-carrying resuscitative fluid. This is the first prospective, randomized trial to compare directly the therapeutic benefit of PolyHeme with that of allogeneic red blood cells (RBCs) in the treatment of acute blood loss. STUDY DESIGN Forty-four trauma patients (33 male, 11 female) aged 19-75 years with an average Injury Severity Score (ISS) score of 21+/-10 were randomized to receive red cells (n = 23) or up to 6 U (300 g) of PolyHeme (n = 21) as their initial blood replacement after trauma and during emergent operations. RESULTS There were no serious or unexpected adverse events related to PolyHeme. The PolyHeme infusion of 4.4+/-2.0 units (mean +/- SD) resulted in a plasma [Hb] of 3.9+/-1.3 g/dL, which accounted for 40% of the total circulating [Hb]. There was no difference in total [Hb] between the groups before infusion (10.4+/-2.3 g/dL control vs. 9.4+/-1.9 g/dL experimental). At end-infusion the experimental RBC [Hb] fell to 5.8+/-2.8 g/dL vs. 10.6+/-1.8 g/dL (p < 0.05) in the control, although the total [Hb] was not different between the groups or from pre-infusion. The total number of allogeneic red cell transfusions for the control and experimental groups was 10.4+/-4.2 units vs. 6.8+/-3.9 units (p < 0.05) through day 1, and 11.3+/-4.1 units vs. 7.8 +/-4.2 units (p = 0.06) through day 3. CONCLUSIONS PolyHeme is safe in acute blood loss, maintains total [Hb] in lieu of red cells despite the marked fall in RBC [Hb], and reduces the use of allogeneic blood. PolyHeme appears to be a clinically useful blood substitute.

Clinical utility of human polymerized hemoglobin as a blood substitute after acute trauma and urgent surgery.

We have previously documented the safety of 1 unit (50 gram) of human polymerized hemoglobin (Poly SFH-P) in healthy volunteers. This report describes the first patient trial to assess the therapeutic benefit of Poly SFH-P in acute blood loss. Thirty-nine patients received 1 (n = 14), 2 (n = 2), 3 (n = 15), or 6 (n = 8) units of Poly SFH-P instead of red cells as part of their blood replacement after trauma and urgent surgery. There were no safety issues related to the infusion of Poly SFH-P. The plasma hemoglobin concentration ([Hb]) after the infusion of 6 units (300 gram) of Poly SFH-P was 4.8 +/- 0.8 g/dL (mean +/- SD). Although the red cell [Hb] fell to 2.9 +/- 1.2 g/dL, the total [Hb] was maintained at 7.5 +/- 1.2 g/dL. Poly SFH-P maintained total [Hb], despite the marked fall in red cell [Hb] due to blood loss. The utilization of O2 (extraction ratio) was 27 +/- 16% from the red cells and 37 +/- 13% from the Poly SFH-P. Twenty-three patients (59%) avoided allogeneic transfusions during the first 24 hours after blood loss. Poly SFH-P effectively loads and unloads O2 and maintains total hemoglobin in lieu of red cells after acute blood loss, thereby reducing allogeneic transfusions. Poly SFH-P seems to be a clinically useful blood substitute.

Scope and Limitations of Stroma-Free Hemoglobin Solution as an Oxygen-Carrying Blood Substitute

One hundred years of study of stroma-free hemoglobin have generated much information regarding its scope and limitations as an oxygen-carrying blood substitute. The most important development in recent years is the development of a truly stroma-free hemoglobin solution. At this time, we know that SFH can readily bind, transport, and unload oxygen. It does not appear to be nephrotoxic or significantly antigenic. It may not be converted to methemoglobin in the body in significant amounts. Its short in vivo half-life may have important advantages.

Application of self-modeling nonlinear regression to ventricular pressure data

This paper is concerned with the application of Self-Modeling Nonlinear Regression to pressure data from left ventricles of awake, intact baboons. The baboons were subjected to either an experimental (endotoxin) protocol or a control protocol. Pressure segments of the cardiac cycle from the QRS complex to the systolic plateau were the input data. Families of such segments were formed in several ways. A very good fit was obtained in the sense that both the individual residuals and their rms values were comparable with the noise in the data acquisition system. The model used was: p(t)=f(t, θ) + ϵ f(t, θ) = θo + θ1g((t−θ2θ3). Here p is pressure, t is time, the θs are location and scale parameters, and the g is the “shape invariant model.” There were some variations of physiological interest in the θ parameters and in the time derivatives. We were unable to show variations in the shape function (g) from endotoxin to control or over time.