June 25, 2006 With research funded by the Department of Defense, two scientists have taken novel approaches with IV resuscitation fluids to find ways to save Soldiers' and civilians' lives.
Joseph Messina of the University of Alabama at Birmingham and Patrick Kochanek of the University of Pittsburgh don't collaborate with one another, but they both are interested in improving patients' chances of surviving trauma, be it on a battlefield or in a Buick.
"I want to take my basic science background and training and apply it to a problem that can help a lot of other people," Messina said.
As an undergraduate at Dartmouth College, Messina started working with the "master metabolic hormone" insulin, he said. He's been hooked ever since. Rather than focusing on diabetics, however, the endocrinologist has studied the effects injuries have on the body's insulin levels and how those levels in turn affect a patient's chance of surviving.
When a person hemorrhages or experiences major trauma, the body can undergo severe changes in its metabolism and immune system, like becoming resistant to insulin. This insulin resistance causes poor outcomes in critically ill patients. Messina's research focuses on reducing the amount of damage that's done to a body's organs during hemorrhage or trauma by using drugs that are commonly used by type 2 diabetics, who are also resistant to insulin.
"I asked myself where or when this would be most practical, and it occurred to me that it would be in situations outside of the ICU (intensive care unit). … For instance, in the battlefield there would (be) the potential need for a treatment that would require less dependency on high-tech equipment," he said.
A graduate of the University of Michigan Medical School and the University of Virginia School of Medicine, Messina thought that drugs rather than insulin would be the better choice on the battlefield.
"These drugs are insulin sensitizing agents, and most also have the added benefit of being anti-inflammatory," he said. "The idea is that normalizing metabolism would be beneficial, but using insulin would be difficult. Therefore the drugs may be easier to use in the field."
Messina has been testing a class of drugs, thiazolidinedione, for almost a year. Cautioning that there's just a little data right now, he said that if the drugs he's testing prove useful, they could be given as a pill, injected or added to IV resuscitation fluids. If all goes well, his work could move into clinical trials in a few years to determine for what situations this therapy would be practical
Messina's research endeavors were funded, in part, by a grant from the DoD's Peer Reviewed Medical Research Program. Congress created the program in 1999 to promote research in health issues the military faces. Since its inception through 2005, the program has spent almost $300 million to fund nearly 200 projects in a range of medical topics, including combat casualty care and technology and infectious disease research.
Kochanek's research, funded by the same DoD program, focuses on which resuscitation fluid to use after a traumatic brain injury occurs and hemorrhagic shock ensues. In Operation Iraqi Freedom and Enduring Freedom, he said, 22 percent of casualties have traumatic brain injuries, a rate higher than any earlier conflict. Treatment typically involves cutting open the skull to let the brain swell in a procedure called a decompressive craniectomy. Kochanek believes there's a better solution, especially when the patient is also contending with the effects of blood loss.
"The development of novel neuroprotective resuscitation fluids could have an important impact on the treatment of blast-injured victims … and in many other victims of traumatic brain injury in the military and civilian sectors," he said. "The importance of the combination of TBI (traumatic brain injury) with HS (hemorrhagic shock) is established in civilian trauma and has gained interest in the military setting in light of the recent increase in TBI from blast injury – where shrapnel in improvised explosive devices can produce secondary HS."
For the past two decades, the graduate of the University of Chicago's Pritzker School of Medicine and director of the Safar Center for Resuscitation Research has worked with the Navy and the Army on topics including traumatic brain injury, cardiac arrest and shock. His current research explores the effect that new nitroxides-based resuscitation fluids have on traumatic brain injury and hemorrhagic shock. This study area, he said, has been neglected in the past because researchers often look for a "pure" study group in which too many variables aren't at work. Further, the Safar Center, named for the Peter Safar "the father of CPR," has extensive experience with animal models of traumatic brain injury and hemorrhagic shock, and looks for opportunities to improve long-term patient outcomes.
"The dramatic exacerbation of damage in experimental traumatic brain injury by superimposing relatively mild shock suggests a potential important therapeutic target – particularly since hemorrhagic shock often complicates blast induced traumatic brain injury," he said.
Research on these new fluids, Kochanek said, will add more information to the ongoing discussions about what the best resuscitation fluid is for military and civilian trauma cases.
"There is indeed much debate on this question – which becomes even more complex in the setting of combined traumatic brain injury and hemorrhagic shock," he said.
Currently, Kochanek and his research team are working on optimizing their models to test the fluids, which link antioxidants to the blood components hemoglobin and albumin. "We are testing two novel solutions, a novel polynitroxylated albumin and a novel polynitroxylated hemoglobin," he said. "It is probably most likely that one will be best in the setting of TBI (traumatic brain injury) plus hemorrhagic shock." .
His early data look good, he said.
"Our preliminary data suggest a very powerful detrimental effect of a modest level of hemorrhagic shock on even a relatively mild traumatic brain injury," he said. "These findings could have important ramifications even before treatment trials commence in our models."
The Peer Reviewed Medical Research Program is one of the Congressionally Directed Medical Research Programs directed by Colonel Janet R. Harris. The Peer Reviewed Medical Research Program is an administrative funding agent for the U.S. Army Medical Research and Materiel Command. The command is the Army's medical materiel developer, with lead agency responsibility for medical research, development and acquisition. The command's expertise in these critical areas helps establish and maintain the capabilities required by the Army to fight and win on the battlefield.
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