San Diego, CA, April 29, 2008 -- Intravenous administration of isotonic fluids is the standard emergency treatment in the U.S. for patients with severe blood loss, but UC San Diego bioengineering researchers have reported improved resuscitation with a radically different approach. Building on earlier studies in humans that have shown benefits of intravenous fluids that are eight times saltier than normal saline, the researchers combined hypertonic saline with viscosity enhancers that thicken blood.
Reporting in the journal Resuscitation in an article that is available online, the researchers describe dramatic increases in beneficial blood flows in the small blood vessels of hamsters with the combined hypertonic saline and viscosity enhancement approach. The fluid was given to animals after as much as half of their blood was removed to simulate human blood losses on the battlefield, in traffic accidents and in operating rooms.
The team led by Marcos Intaglietta, a professor of bioengineering at the Jacobs School of Engineering, reported that the news approach sharply improved the animals’ functional capillary density, a key measure of healthy blood flow through tissues and organs.
“Of course, trauma physicians want to get the blood flowing as soon as possible, and increasing the viscosity of blood may not make any sense to them,” said Intaglietta. “However, our results are highly suggestive that increasing viscosity rather and partially restoring blood volume is a better way to increase blood flow through tissues. These findings also are consistent with recent discoveries showing that higher shear forces of more viscous blood leads to dilation of small blood vessels.”
Treating blood loss is a critical medical issue because trauma is the leading cause of death among North Americans 1 to 44 years old. Whether injured on the freeway or wounded in battlefield, loss of 40 percent or more of a patient’s blood is immediately life-threatening. Physicians and emergency workers must act quickly.
The bible of trauma physicians and emergency workers, the Advanced Trauma Life Support (ATLS) guidelines, emphasize that physicians first control bleeding and then provide limited fluid resuscitation, a strategy known as "permissive hypotension" until control of hemorrhage is obtained. The ATLS guidelines, developed by the American College of Surgeons and adopted in more than 30 countries, were modified to lower the volume of isotonic fluids given after several studies demonstrated that sudden increases in blood pressure (without immediate bleeding control) would "pop" clots that the body forms to control bleeding.
Over several decades, studies involving humans and animals have evaluated hypertonic saline (up to 7.5 percent sodium chloride) versus isotonic saline (0.9 percent sodium chloride). Given intravenously, hypertonic solutions act like magnets, drawing fluid from tissues into the bloodstream, thereby increasing blood volume. Such hypertonic saline has not received the approval of the Food and Drug Administration for clinical use in the United States. Therefore, it is not part of ATLS guidelines.
However, several medical research teams, including one led by Dr. Raul Coimbra, professor of surgery and chief, Division of Trauma, Surgical Critical Care and Burns at UC San Diego Medical Center, have investigated the effects of hypertonic saline for almost 20 years.
In Intaglietta’s study with hamsters in the Jacobs School of Engineering’s Department of Bioengineering, 90 minutes after hypertonic saline was given to blood-depleted hamsters about 30 percent of normal flow was reconstituted through skin arterioles, tiny branches of arteries that lead to the even smaller capillaries. The bioengineering researchers quantified blood flow with special microscopic procedures.
“Our findings suggest that elevating the viscosity of blood after severe blood loss is beneficial in resuscitation,” said Intaglietta. “In fact, our studies indicate that Hextend and similar plasma extenders could produce even greater benefit if they were formulated with higher viscosities.”
Arterioles regulate blood flow by constricting and dilating. A variety of factors in the body influence the process, including the viscosity of plasma, the fluid portion of blood. For example, higher viscosity plasma causes arterioles to dilate.
Studies such as Intaglietta’s are important because it uses not only hypertonic saline,” said Coimbra, “but also other adjuncts which may increase the effects of hypertonic saline in treating those patients and in advancing our knowledge about shock resuscitation.”
Co-authors of the Resuscitation report with Intaglietta are Pedro Cabrales, a senior investigator at the La Jolla Bioengineering Institute, and Amy G. Tsai, a research professor in the Jacobs School’s Department of Bioengineering. The research was supported by the National Heart, Lung and Blood Institute and the U.S. Army. Dr. Coimbra’s research was supported by the National Institutes of Health.