Thursday, November 11, 2010

From lab bench to the battlefield

MGH researchers work to improve trauma care for servicemen and women

With modern improvements to body armor and other protective equipment, the number of soldiers killed in action has decreased over the years. Still, the primary cause of death – blood loss as the result of traumatic injury – remains the same. At the MGH, a team of scientists led by Hasan Alam, MD, an MGH trauma surgeon and director of research for the Division of Trauma, Emergency Surgery and Surgical Critical Care, is developing novel tools, techniques and treatments to help save the lives of soldiers traumatically injured on the battlefield. The projects they've focused on aim to control lethal hemorrhaging or at least prolong the body's response to severe blood loss.

"When we put these young men and women in harm's way, we have an obligation to do everything possible to help protect them," says Alam. "In times of war, agencies like the Department of Defense and the Office of Naval Research dramatically increase funding for trauma research. Increased funding leads to advancements in care."

Though they may be the impetus behind them, men and women in the armed forces aren't the sole benefactors of breakthroughs in trauma care research. Innovative treatment techniques developed with soldiers in mind are eventually used to care for traumatically injured patients in civilian settings. And that's no small number of lives saved: Traumatic injury is the leading cause of death for individuals under the age of 44.

A battle against timeThe faster a traumatically injured patient receives appropriate medical treatment, the more likely it is he or she survives. In developed countries like the United States, after an individual sustains serious injury, a reliable system springs into action. An emergency number is called, and an ambulance arrives at the scene. First responders provide initial care and then transport the victim to a nearby emergency room.

On the battlefield, however, care is not as easily accessible. Tools and techniques that buy an injured victim time are all the more valuable.

"Traumatic injury-related deaths usually occur within the first six hours after injury," says Alam. "What happens during these six hours, especially the first 60 minutes – known as the 'golden hour' – is pivotal to whether someone survives."

Addressing the issue

Military physicians have faced the same challenges in stopping and controlling blood loss for centuries. Up until about a decade ago, servicemen and women carried simple cotton gauze into combat as their main tool for dressing wounds.

Just before the start of the war in Afghanistan in 2001, Alam was contacted by the Office of Naval Research. They asked him to identify agents that could quickly control bleeding, protect the wound from bacterial or viral transmission and at the same time be portable, cost-effective and easy to use.

After several months of rigorous research and testing, Alam and his team identified a new hemostatic product with a type of mineral that could absorb water from the blood and promote clotting to stop the bleeding. This advanced hemostatic dressing was used by the special operations forces in Afghanistan in 2002 and was put in the individual marine first aid kit that accompanied all the marines deployed to Iraq in 2003. The dressing has been credited with saving numerous lives.

Back from the brink

Even the best hemostatic dressing can only do so much in stopping severe blood loss. Building on concepts already utilized in cardiovascular and transplant care, Alam and his team are honing in on an innovative process which uses cooling methods to help slow down the body's response to injury.

In this resuscitation technique, known as suspended animation, an ice-cold solution is injected into one of the major blood vessels soon after trauma occurs. Rapidly inducing a low body temperature pauses metabolic activity, decreasing the amount of oxygen needed to sustain vital organs and tissues. This allows caregivers more time to locate and repair what would otherwise be a fatal injury – and time is of the essence.

Researchers in Alam's lab have successfully performed the technique in animals for years. And though there is no heartbeat, blood flow or brain activity in animals in the induced cooled-down state, after slowly raising the body temperature back to normal, they have been shown to come back from the brink of death without brain damage, learning impairments or organ dysfunction. Once the technique is fully tested and refined, it could be used in combat settings to provide wounded soldiers with the vital extra time they need while being transported from the battlefield to a proper facility for care.

Time capsule

MGH researchers are developing even more immediate ways to prolong life during the first few hours after traumatic injury. Recently they uncovered a drug injection that can alter the body's response to trauma at the most basic level: genetics.

After losing a large quantity of blood, the body goes into shock. When it does, certain proteins react and change their expression. Approximately six to seven percent of the genes in the body change their expression by removing chemical additions to the genome known as acetylations. Researchers have found that an injection of valproic acid, a common histone deacetylase (HDAC) inhibitor, can prevent the removal of these acetylations, thereby slowing down the process in which the vital organs fail and death occurs.

Such an injection – which is relatively inexpensive and might eventually be developed in capsule form – could easily be carried by military personnel in war zones.

"Right now, there are 15 to 20 different studies pushing this project toward clinical application," says Alam. "It's very exciting."

Moving forward

As many opportunities as there are to advance trauma care, there also are enormous challenges. For one – perhaps because traumatic injuries can't be prevented or predicted – trauma care does not receive the widespread support and attention many disease areas do.

In addition, moving trauma care studies to clinical trial is extraordinarily difficult. The nature of traumatic injury is that it occurs suddenly and without advance warning. There's no chance for victims to learn about a trauma care trial, weigh its risks and benefits, and then enroll in it.

"Injuries are the leading cause of death in civilian and battlefield environment. More young Americans die of injuries than all other diseases combined," says Alam. "We must increase awareness about this silent epidemic and get the public involved in order to raise funding that can support injury prevention initiatives, as well as develop novel life-saving techniques."

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