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Dying to Live

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Suspended animation

Hasan Alam, a Safar Center collaborator, trauma surgeon and director of trauma research at the Massachusetts General Hospital, has achieved similar results in multiple studies. Alam uses ice-cold fluid to induce suspended animation in exsanguinated animals, but unlike the Safar Center scientists, he works in the laboratory with human-size Yorkshire pigs. His latest findings, described in the April 2007 issue of the Journal of the American College of Surgeons, confirm that a temperature of 50°F preserves vital organs while surgeons repaired inflicted wounds to the colon, spleen and vascular system. Each surviving animal recovered without brain damage, future learning impairments or evidence of organ dysfunction.

Bolstered by success in animal models, Tisherman is preparing to test EPR in humans, with one of the most daring clinical trials ever attempted in trauma care. The idea is to rush victims of gunshot wounds and other penetrating injuries to participating trauma centers. If a patient’s heart stops after transfer to a trauma center, a medical team will employ the same method developed in animals, using a roller pump to circulate through the patient’s body as much as 30 liters of ice-cold saline saturated with dissolved oxygen and glucose. Time is of the essence, Tisherman emphasizes. His animal studies suggest cooling won’t save brain function if it’s delayed by more than eight minutes after cardiac arrest.

During the procedure, the fluid enters through a large catheter, usually inserted into the femoral artery that runs from groin to knee. But if the patient’s chest has already been opened by an emergency thoracotomy (in the field or after arrival in the ER), the catheter can be threaded into the aorta, which serves as an arterial pipeline from the heart to other vessels. (Thoracotomy is a standard procedure for locating and stopping internal bleeding from chest wounds.) The goal is for the cold saline, pumped at a rate of two to three liters per minute, to saturate the brain, heart and other organs, reducing core temperature to roughly 50°F. 

With the body fully cooled, its biochemical processes should pause, bringing metabolism to a virtual standstill and reducing the demand for oxygen by as much as 95%. In the operating room, wounds will be plugged and vessels repaired, and then cardiopulmonary bypass equipment will begin circulating blood through a heat exchanger, slowly raising the body temperature so that a heartbeat can be restored.

“I think this could be the beginning of something huge,” says Thomas Scalea, physician-in-chief at the R. Adams Cowley Shock Trauma Center in Baltimore, considered one of the best in the world. “It’s a fantastic leap in sophistication.”

Tisherman concedes the approach carries substantial risk. Hypothermia reduces clotting, which can be problematic when trying to save a patient who has already lost a great deal of blood. And cold raises the threat of infection because immune cells that protect the body from viruses and bacteria lose their effectiveness when body temperature drops. But the biggest worry is that the patient might suffer permanent brain damage.

The best way to avoid poor outcomes, Kochanek asserts, is to select the right patients—those who have been healthy and strong; haven’t had extensive brain trauma; are already at an appropriate trauma center; and can be prepped for EPR within the critical eight-minute window. It’s that last part that will be especially difficult. “The technical feasibility of doing this fast enough is our biggest stumbling block,” Kochanek says.

Tisherman hopes to launch the trial in five top trauma centers, in which EPR will be compared with the standard treatment for trauma victims who have lost a pulse: blood infusions, emergency thoracotomy and CPR. Surgeons will be trained to perform the new procedure, which involves some skills—using cardiopulmonary bypass equipment, for example—that may not figure in their clinical repertoire.

The trial faces additional challenges, including regulatory hurdles at the FDA and the Department of Defense, which is providing funding. Unlike ordinary clinical trials where patients can give informed consent, the trauma victims in this trial will be unconscious and near death, and there likely won’t be time to ask relatives to agree to the procedure. So researchers will have to secure in advance what’s known as an exception from informed consent, an authorizing statement from each community served by the trauma centers in the trial. Assuming most communities assent and federal agencies give the green light, a launch is expected later this year, Tisherman says.

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1.“Hypothermia and Injury,” by Samuel A. Tisherman, Current Opinion in Critical Care, December 2004. An introduction to the concept of inducing suspended animation with profound hypothermia during the treatment of exsanguination cardiac arrest.

2. “Induction of Profound Hypothermia for Emergency Preservation and Resuscitation Allows Intact Survival After Cardiac Arrest Resulting From Prolonged Lethal Hemorrhage and Trauma in Dogs,” by X. Wu et al., Circulation, April 25, 2006. A detailed surgical description of the saline flush method.

3.“Inhaled Hydrogen Sulfide: A Rapidly Reversible Inhibitor of Cardiac and Metabolic Function in the Mouse,” by G.P. Volpato et al., Anesthesiology, April 2008. An intriguing report that hydrogen sulfide can suspend animation in mice without lowering body temperature or blood pressure, thus avoiding hypothermia’s attendant problems (increased infection risk, decreased blood clotting).

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