Hibernation drug increases survival after extreme blood loss

A lifesaving treatment for trauma patients who have sustained extreme blood loss is one step closer to reality. For the first time, Dr. Mark Roth and colleagues in the Basic Sciences Division have demonstrated that the administration of minute amounts of inhaled or intravenous hydrogen sulfide, or H2S—the molecule that gives rotten eggs their sulfurous stench—significantly increases survival from potentially lethal hemorrhage in an animal model.

Roth, in collaboration with Dr. Robert Winn of the University of Washington Medicine's Harborview Medical Center, reported the findings last week online in The Journal of Trauma Injury, Infection and Critical Care. The print edition of the journal will be published on July 10.

The researchers successfully used H2S to induce a state of reversible metabolic hibernation as a way to reduce death from insufficient blood supply to organs and tissues in a rat model. (Federal regulations mandate the use of such animal models in preclinical research to test the safety and effectiveness of various procedures and treatments before they can be tested in humans.)

They found that 75 percent of rats (18 of 24) given inhaled hydrogen sulfide and 67 percent (eight of 12) given intravenous hydrogen sulfide survived at least two weeks—the duration of the monitoring period—after losing more than half of their blood for an extended period. In contrast, long-term survival rates for the untreated rats in the two control groups were 23 percent and 14 percent, respectively.

"Our goal is to develop lifesaving treatment for critically ill people suffering from acute, sustained blood loss, such as in a car accident or on the battlefield," Roth said. "These findings have obvious implications for the military, but they also have tremendous implications for the civilian population."

The U.S. Defense Advanced Research Projects Agency and the U.S. Defense Services Office funded the research. The ultimate goal: designing self-injectable hydrogen-sulfide kits that critically injured soldiers could use in the field to temporarily dim their metabolism and reduce their oxygen demand. This would help buy time until they could get medical attention.

"The military feels that if a soldier can be kept alive for at least three hours, that would allow time for the situation to be stabilized and the scene of the incident secured enough to allow evacuation of that soldier to an area where he or she can get medical attention," Roth said.

How does hydrogen-sulfide treatment prevent death from profound and sustained blood loss? One possibility is that in reducing metabolism, H2S also reduces oxygen demand, which allows crucial neurons in the hippocampus, the part of the brain that controls autonomic functions such as breathing and heartbeat, to withstand low oxygen levels due to hemorrhage.

Another mechanism may be that hydrogen sulfide, which is naturally present in the blood, is lost during hemorrhage and must be replaced to maintain life processes.

In 2005, Roth and colleagues made headlines worldwide when they reported, in the journal Science, the first use of H2S to induce a state of reversible hibernation in mice. The latest findings represent the next step in demonstrating hydrogen sulfide's potential to treat ischemic injuries caused by conditions such as severe blood loss, hypothermia, cardiac arrest and stroke.