Synthetic Oxygen-Carrying Substances
Various substances that carry or facilitate the transport of oxygen
have been made. The most notable is the perfluorochemical emulsion called Fluosol-DA.
However, it had little use because it carries oxygen (i.e., a small amount) only
when the PaO2
is more than 300 mm Hg.
[160]
A newer perfluoro compound, perfluorooctylbromide,
carries three to four times more oxygen and has a longer half-life and presumably
fewer problems than are associated with Fluosol-DA. However, phase III trials have
not been completed.
The remaining synthetic blood
(a term I use but not one officially accepted by industry and the FDA) or oxygen
therapeutics are labeled as hemoglobin-based oxygen carriers. These products modify
the hemoglobin molecule from humans, animals, or recombinant technology. Only three
products are undergoing clinical trials.[161]
Two
products are from outdated human RBCs and the third from bovine RBCs. However, these
solutions are not without complications.[162]
The
most serious are kidney toxicity and an increase in affinity for oxygen (i.e., left
shift in the oxygen dissociation curve). A variety of approaches are being used,
including crosslinking, pyridoxylation and polymerization, and conjugation and encapsulation,
to decrease oxygen affinity, to increase deposition in the reticuloendothelial system,
and to increase half-life.
Genetic engineering has provided hope for blood products. Initially,
recombinant erythropoietin was developed for treatment of anemias and facilitation
of autologous blood donation. (see Chapter
48
). In 1992, a human recombinant hemoglobin was designed as a blood substitute.
[163]
With the use of genetic engineering techniques,
it was made from Escherichia coli. It functions
as normal hemoglobin in terms of oxygen-carrying capacity, but it does not require
crossmatching, nor does it transmit disease or become rapidly outdated. How much
recombinant material can be tolerated by humans remains to be determined. Unfortunately,
this promising hemoglobin solution is not being examined in clinical trials.
The product that appears to be the initial one possibly approved
for routine clinical practice is Hemopure.[164]
It is from ultrapurified bovine RBCs that have been glutaraldehyde polymerized.
It has a higher P50
(i.e., 43 instead of 26 mm Hg), which means that
is should deliver oxygen to the tissues at least as well, if not better, than human
RBCs.[164]
It has the added advantage of not requiring
type and crossmatch and not transmitting infectious agents such as HIV and hepatitis
virus.[164]
Many clinical trials have been safely
conducted with a few possibly minor complications, the significance of which are
not clear. Complications include a slight increase in mean arterial blood pressure
and a decrease in cardiac index, which
presumably may be from nitric oxide. Hemopure is approved for routine clinical use
in South Africa. Its indication will probably be treatment of acute anemia in some
type of surgery. Most of the clinical trials have shown a decreased use of allogeneic
blood transfusions.[165]
