In the future, however, a unique blood plasma volume expander may reduce or eliminate the need for blood transfusions in situations such as these. Plasma expanders, including those being presented at an upcoming meeting, are now being studied by a number of military researchers seeking the ideal surgical fluid to treat combat casualties, and are also in use by the US military overseas.
Four studies involving blood plasma volume expanders performed in animals is the subject of a presentation by Paul E. Segall, Ph.D., Hal Sternberg, Ph.D., Stephen Kehrer and Mark A. Voelker, Ph.D. all of BioTime Inc., Berkeley, CA. They will discuss the results of their work, entitled, “An Animal Model for Eliminating Battlefield Transfusions,” during the American Physiological Society’s (APS) annual meeting, part of the "Experimental Biology 2002” conference. More than l2,000 attendees will attend the conference , which is being held April 20-24, 2002 at the Ernest N. Morial Convention Center, New Orleans, LA.
Methodology
Over a series of four studies the investigators used a unique six percent hetastarch-based blood plasma volume expander in lactated electrolyte injection containing a physiological amount of glucose. The first two experiments modeled hemorrhagic shock followed by extended periods of apnea. Rats were resuscitated with plasma volume expander and then either maintained and ventilated with 100 percent oxygen at elevated pressures, or ventilated with 100 percent oxygen at ambient pressure.
In the third series of experiments, the plasma volume expander was used to replace most or all of the rats’ circulating blood. The rats were then maintained and ventilated in hypebaric oxygen. In the final series, the plasma volume expander was used to replace most of the rats’ circulating blood while they were at normothermia in room air. The rats were then further hemodiluted with a mixture of plasma expander and oxygen carrier solution, and finally with the oxygen carrier solution alone, until their initial circulating blood had been completely replaced.
Results
In the experiments involving shock, some rats rescued with hyperbaric oxygen revived and survived at least 7 days after severe hemorrhagic shock followed by various periods of apnea: 10 minutes (5 of 8 rats), 12 minutes (10 of 16 rats), 15 minutes (2 of 10 rats), and 18 minutes (4 of 10 rats). The last series of 10 rats were rescued using a revised protocol, which kept them warm after their return to the cage. The surviving animals, all of which were ventilated with 100% oxygen at 30 psig until spontaneous respiration was achieved, appeared normal following their recovery.
Hypothermia may have been an important factor in the resuscitation of hemorrhagic, apneic rats. Rats treated but rescued with ambient pressure ventilation instead of hyperbaric ventilation, also survived after 10 minutes of apnea (1 of 3 rats) and 15 minutes of apnea (3 of 17 rats). However, the fraction of these ambient pressure-treated rats which began spontaneous respiration (5 of 17) was substantially less than the fraction beginning spontaneous respiration treated with hyperbaric oxygen (8 of 10).
In the experiments involving isovolemic hemodilution and blood substitution, all rats (n=8) survived long term (at least seven days) subsequent to replacement of 85-89 percent of their circulating blood with plasma expander followed by maintenance overnight at hyperbaric oxygen pressures gradually reduced from 18-30 psig to ambient.
In a second group of 35 rats, 22 rats lived long term subsequent to replacement of 94-99 percent of their circulating blood with plasma expander followed by maintenance for 3-6 hours at l00 percent oxygen pressures at 30 psig to ambient. These rats were then decompressed and transfused with their own blood. All but one rat which regained consciousness survived, the other 12 not surviving were those which never regained spontaneous respiration.
In a third group of six rats, maintained at normal temperatures in room air, ¾ of their initial circulating blood was first replaced with plasma expander. They were then hemodiluted with a 2:1 mixture of plasma expander and oxygen carrier solution sold for veterinary purposes, and finally with oxygen carrier solution, until all their blood had been replaced. Each regained consciousness and became active, and 4 of 6 survived at least one week.
Conclusions
Based on these findings, the researchers concluded that:
· It is possible to resuscitate some rats following massive hemorrhage with extended periods of respiratory arrest (10-18 minutes) using a physiologically balanced plasma volume expander and ventilation with 100 percent oxygen or ventilation in hyperbaric oxygen. No subsequent blood transfusions were needed to allow these survivors to live long term, and hyperbaric oxygen may confer some advantages over using oxygen at ambient pressures.
· Hyperbaric oxygen can be used to maintain rats in which nearly all (85-89 percent) of their initial circulating blood is replaced with plasma expander, until they can reproduce enough red blood cells to allow survival in room air.
· Hyperbaric oxygen can be used to maintain, for several hours, rats in which essentially all (94-99 percent) of their initial circulating blood volume was replaced with plasma expander.
· Hypothermia, with body temperature declining to as low as 230C, appears to play an important role in these results following severe hemorrhage.
· Massive isovolemic hemodilution with plasma expander, followed by an equal hemodilution with a 2:1 mixture of plasma expander and oxygen carrier solution, and a third hemodilution with oxygen carrier solution alone, can allow long term survival in most rats maintained in room air without any subsequent blood transfusion.
In summary, techniques such as resuscitation with physiologically balanced plasma expanders, coupled with hypothermia and ventilation with oxygen, or ventilation in hyperbaric oxygen, or used in large volumes in conjunction with oxygen carrier solutions, warrant further study for applying these methods to the human population.
The American Physiological Society (APS) is one of the world’s most prestigious organizations for physiological scientists. These researchers specialize in understanding the processes and functions underlying human health and disease. Founded in 1887 the Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals each year.
Contact: Donna Krupa
703.967.2751 (cell) or
djkrupa1@aol.com
APS Newsroom: April 20-24, 2002
Morial Convention Center, New Orleans
Room: Level 2, Room B211
Telephone: 504.670.6534