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was developed for HemaGen as an oxygen transport agent, for use in surgical hemodilution,
trauma resuscitation, and cardiopulmonary bypass. The active agent in Oxyfluor is
perfluorodichlorooctane (PFDCO), designed in collaboration with 3M scientists to avoid
problems previously associated with intravenous infusions of perfluorochemicals. This
collaborative effort resulted in the screening of over 100 perfluorochemicals prior to the
selection of PFDCO as the premier candidate. Pre-clinical studies of Oxyfluor indicated
that it did not cause pulmonary hyperinflation, and was readily eliminated from the liver,
lung and spleen. These results were corroborated by Phase I human clinical trials in which
Oxyfluor was successively administered to healthy human volunteers at dosages of 0.50 and
1.00 cc/kg of PFDCO (pure perfluorocarbon basis), with no evidence of pulmonary disorder.
Subsequent surgical studies employed dosages as high as 2.00 cc/kg of PFDCO, again with no
significant pulmonary side effects.
||Oxyfluor's oxygen content increases in
direct proportion to fractional inspired oxygen content (FiO2), whereas hemoglobin
saturates at low FiO2. By taking advantage of standard supplemental oxygen therapy,
Oxyfluor can deliver twice as much oxygen to the tissues as a comparable volume of
Oxyfluor transports oxygen immediately upon infusion,
whereas stored blood cells do not release bound oxygen until 12 hours after transfusion.
||Oxyfluor can be heat sterilized and is
completely free of viruses (AIDS, hepatitis), and other blood borne pathogens. Whole blood
cannot withstand terminal heat sterilization.
Oxyfluor can be given to
any recipient regardless of blood type, eliminating the antigenicity testing and cross
matching requirements of whole blood.
Oxyfluor's perfluorochemical, PFDCO is unique in that it does not cause significant
pulmonary hyperinflation and has a favorable tissue elimination profile.
||Oxyfluor can be stored at room temperature for long periods,
whereas whole blood must be store refrigerated, with a maximum shelf life of 42 days.
||Oxyfluor is manufactured using equipement and materials commonly
found in large volume parenteral (LVP) production facilities.
Clinical Applications of Oxyfluor
Cardiopulmonary Bypass (CPB)
A substantial body of literature documents permanent neuropsychologic adverse events
associated with CPB. Psychometric testing indicates cognitive
dysfunction in at least 30% of CPB patients, with another 3-4% suffering severe stroke.
Current research points to gaseous microemboli (bubbles similar to those induced during
the bends) and poor post-bypass cerebral blood flow as the cause of these deficits.
Pre-clinical data suggest that very low dosages of perfluorocarbons improve oxygen
delivery and increase the solubility of gases in blood, greatly reducing the consequences
of gas embolization.
Prompt restoration of blood volume and oxygen delivery are the
two critical requirements for resuscitation from trauma with attendant blood loss and
hypovolemic shock. Currently used crystalloid solutions can satisfy volume needs, but
cannot transport oxygen. Furthermore, refrigeration and cross-matching requirements
prevent emergency vehicle usage of whole blood, often resulting in life threatening
transfusion delays. In contrast, Oxyfluor's stability will allow administration from an
emergency vehicle at the site of trauma.
Oxyfluor is uniquely suited for use in surgical anemia. During surgery, acute blood
loss is compensated for by infusion of Oxyfluor, which maintains tissue oxygenation
with improved perfusion. This hemodilution provides the additional advantage of reducing
the percentage of red cells that might be lost during any subsequent surgical blood loss.
Therefore, the use of Oxyfluor reduces or eliminates the need for allogeneic
transfusion while providing safe, effective oxygen transport during the stress of surgery.