Gunshot victims to be suspended between life and death

[Reefa]

Doctors will try to save the lives of 10 patients with knife or gunshot wounds by placing them in suspended animation, buying time to fix their injuries.

NEITHER dead or alive, knife-wound or gunshot victims will be cooled down and placed in suspended animation later this month, as a groundbreaking emergency technique is tested out for the first time.

Surgeons are now on call at the UPMC Presbyterian Hospital in Pittsburgh, Pennsylvania, to perform the operation, which will buy doctors time to fix injuries that would otherwise be lethal.

"We are suspending life, but we don't like to call it suspended animation because it sounds like science fiction," says Samuel Tisherman, a surgeon at the hospital, who is leading the trial. "So we call it emergency preservation and resuscitation."

The technique involves replacing all of a patient's blood with a cold saline solution, which rapidly cools the body and stops almost all cellular activity. "If a patient comes to us two hours after dying you can't bring them back to life. But if they're dying and you suspend them, you have a chance to bring them back after their structural problems have been fixed," says surgeon Peter Rhee at the University of Arizona in Tucson, who helped develop the technique.

The benefits of cooling, or induced hypothermia, have been known for decades. At normal body temperature – around 37 °C – cells need a regular oxygen supply to produce energy. When the heart stops beating, blood no longer carries oxygen to cells. Without oxygen the brain can only survive for about 5 minutes before the damage is irreversible.

However, at lower temperatures, cells need less oxygen because all chemical reactions slow down. This explains why people who fall into icy lakes can sometimes be revived more than half an hour after they have stopped breathing.

Just before heart and brain surgery, doctors sometimes lower body temperature using ice packs, and by circulating the blood through an external cooling system. This can give them up to 45 minutes in which to stop blood flow and perform surgery. However, the cooling process takes time and can only be done with careful planning and preparation.

When someone reaches an emergency department with a traumatic gunshot injury or stab wound, slow cooling isn't an option. Often their heart has stopped beating due to extreme blood loss, giving doctors only minutes to stop the bleeding and restart the heart. Even if the bleeding can be stopped, it's not like filling up an empty gas tank. Resuscitation exposes the body to a sudden onslaught of oxygen, which can cause tissues to release chemicals that damage cells and cause fatal "reperfusion" injuries.

Finding ways to cool the body until it reaches a state of suspended animation – where people are not alive but not yet dead – could give doctors more time in an emergency.

The technique was first demonstrated in pigs in 2002 by Hasan Alam at the University of Michigan Hospital in Ann Arbor, and his colleagues. The animals were sedated and a massive haemorrhage induced, to mimic the effect of multiple gunshot wounds. Their blood was drained and replaced by either a cold potassium or saline solution, rapidly cooling the body to around 10 °C. After the injuries were treated, the animals were gradually warmed up as the solution was replaced with blood.

Vital Signs

The pig's heart usually started beating again by itself, although some pigs needed a jump-start. There was no effect on physical or cognitive function (Surgery, doi.org/dvhdzs).

"After we did those experiments, the definition of 'dead' changed," says Rhee. "Every day at work I declare people dead. They have no signs of life, no heartbeat, no brain activity. I sign a piece of paper knowing in my heart that they are not actually dead. I could, right then and there, suspend them. But I have to put them in a body bag. It's frustrating to know there's a solution."

That solution will be put to the test in humans for the first time. A final meeting this week will ensure that a team of doctors is fully prepared to try it. Then all they have to do is wait for the right patient to arrive.

That person will have suffered a cardiac arrest after a traumatic injury, and will not have responded to attempts to start their heart. When this happens, every member of Tisherman's team will be paged. "The patient will probably have already lost about 50 per cent of their blood and their chest will be open," he says. The team sees one of these cases each month. Their chance of survival is less than 7 per cent.

The first step is to flush cold saline through the heart and up to the brain – the areas most vulnerable to low oxygen. To do this, the lower region of their heart must be clamped and a catheter placed into the aorta – the largest artery in the body – to carry the saline. The clamp is later removed so the saline can be artificially pumped around the whole body. It takes about 15 minutes for the patient's temperature to drop to 10 °C. At this point they will have no blood in their body, no breathing, and no brain activity. They will be clinically dead.

In this state, almost no metabolic reactions happen in the body, so cells can survive without oxygen. Instead, they may be producing energy through what's called anaerobic glycolysis. At normal body temperatures this can sustain cells for about 2 minutes. At low temperatures, however, glycolysis rates are so low that cells can survive for hours. The patient will be disconnected from all machinery and taken to an operating room where surgeons have up to 2 hours to fix the injury. The saline is then replaced with blood. If the heart does not restart by itself, as it did in the pig trial, the patient is resuscitated. The new blood will heat the body slowly, which should help prevent any reperfusion injuries.

The technique will be tested on 10 people, and the outcome compared with another 10 who met the criteria but who weren't treated this way because the team wasn't on hand. The technique will be refined then tested on another 10, says Tisherman, until there are enough results to analyse.

"We've always assumed that you can't bring back the dead. But it's a matter of when you pickle the cells," says Rhee.

Getting this technique into hospitals hasn't been easy. Because the trial will happen during a medical emergency, neither the patient nor their family can give consent. The trial can only go ahead because the US Food and Drug Administration considers it to be exempt from informed consent. That's because it will involve people whose injuries are likely to be fatal and there is no alternative treatment. The team had to have discussions with groups in the community and place adverts in newspapers describing the trial. People can opt out online. So far, nobody has.

Tisherman says he eventually hopes to extend the technique to other conditions.

For now, suspended animation is limited to a few hours. But that's not to say that more lengthy suspension isn't possible (see "Will human hibernation ever happen").

"We're trying to save lives, not pack people off to Mars," says Tisherman. "Can we go longer than a few hours with no blood flow? I don't know. Maybe years from now someone will have figured out how to do it, but it will certainly take time."

Will human hibernation ever happen?

Is long-term suspended animation possible? Humans may soon be held at death's door for a few hours (see main story), but what about more lengthy "human hibernation"?

Clues could be found in our genes. The fat-tailed dwarf lemur is the only primate known to hibernate. Its brain might hold clues to the genetic mechanisms behind such metabolic flexibility. Kathrin Dausmann at the University of Hamburg, Germany, who made the discovery with her colleagues in 2004, reckons that humans may have the genes to hibernate, but we just don't switch them on (New Scientist, 21 January 2006, p 28).

Chemicals could also help slow metabolism. Mark Roth at the Fred Hutchinson Cancer Research Center in Seattle, Washington, and his colleagues have used hydrogen sulphide to put mice into suspended animation for 6 hours. The gas slows the metabolism by limiting oxygen uptake by cells. They are now studying a metabolism-decreasing chemical found naturally in the body.

It may all be down to economics, says Peter Rhee at the University of Arizona. "When I was in medical school, 5 minutes of brain death and you were dead. Now we can increase that to hours. With the time and money, maybe we could start to think about extending [suspended animation] to months and years."

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Edited March 27, 2014 by F3dupsk1Nup