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In February 2011, a much-anticipated school trip went disastrously wrong for a group of Danish students. The dragon boat carrying the pupils across Præstø Fjord capsized, plunging the passengers into the icy water below. By the time paramedics got there two hours later, seven of the students’ hearts had stopped and they were pronounced dead at the scene.
But once the teenagers arrived at the hospital in Copenhagen, doctors made a last-ditch attempt to revive them, even though the group had been technically ‘dead’ for two hours. The medics knew that when you're that cold (one student’s temperature had dropped to 17.5 degrees Celsius), there’s still a chance of resuscitation. Using cardiopulmonary bypass – a procedure that uses a machine to take over the functioning of the heart and lungs – medics very slowly warmed the victims’ blood by one degree every ten minutes. Six hours after the incident, all seven teenagers had come back to life.
It’s not unheard of for cold water drowning victims to be successfully resuscitated. One of the most high profile cases was in 1999 when Swedish radiologist Anna Bågenholm fell through a frozen stream while skiing, her temperature plunging to 13.7C, yet lived to tell the tale. It led Mads Gilbert, the doctor who saved her, to coin a phrase: “nobody is dead until warm and dead”. Such incidents raise an unlikely possibility: can the science of cold help us bring back people from the brink of death?
Around 4,000 miles away from Præstø Fjord, instead of warming patients up, trauma surgeon Samuel Tisherman is cooling them down. In November 2019, New Scientist reported that Tisherman’s team at the University of Maryland School of Medicine in Baltimore had placed a patient in suspended animation for the first time. The person was rapidly cooled to around ten to 15C, temporarily stopping their vital functions and putting them into a state somewhere between life and death.
“There are numerous reports of people who drown in cold water and do fine, because they cool fast enough to protect the brain and heart,” Tisherman says. He wanted to see if simulating the same conditions in the hospital could help his patients.
If you’re unlucky enough to experience a serious injury that causes cardiac arrest, such as a gunshot or stab wound, your odds aren’t good. Once you’ve lost half your blood (around 2.5 litres), Tisherman explains that you would have just a five per cent chance of survival. This scenario would cause irreversible brain damage within just five minutes, and permanent heart failure after twenty — leaving surgeons with an almost impossibly short window in which to operate.
“Despite very aggressive, very active things that we do to try to save these people, like giving them blood and opening the chest, it just doesn't work,” says Tisherman. “Surgically, it's a race against time to get the bleeding stopped so you can resuscitate the person before their internal organs are damaged irreversibly by not having enough blood flow.”
He wanted to try something else for these patients and knew from animal studies that turning down the heat was associated with better survival. The beauty of cooling is that time effectively slows down. At normal body temperature, cells need a constant supply of oxygen — which can’t happen if the heart has stopped. Without oxygen, the brain can only cope for a few minutes before it is irreversibly damaged. But cool the body down to 15C and the brain can survive for at least two hours, says Tisherman.
But cooling down humans by twenty degrees isn’t easy. To do so, the University of Maryland team drains the person’s remaining blood and replaces it with ice-cold saline solution. Once the patient is cold enough, their body — which would otherwise be classified as dead — is moved to the operating theatre. Suspended animation buys the surgeons far more time to operate before blood is reintroduced, the person is slowly warmed up and their heart restarted.
Right now, Tisherman is declining to reveal how many people have survived this procedure, which is officially called emergency preservation and resuscitation (EPR). And he’s still unclear on how long you can keep someone in suspended animation without causing reperfusion injuries (damage to vital organs when the person is warmed back up). But his team is gathering data for an FDA-approved trial which will look into whether this experimental method could eventually help acute trauma patients all over the world.
There are quite a few details to iron out first before suspended animation becomes commonplace in medicine, though.
Karim Brohi, head of research at the Centre for Trauma Sciences at Barts Hospital, London, agrees that the idea makes sense in principle. But he wonders how feasible the procedure really is, especially as blood won’t be able to clot at the temperatures Tisherman’s team is proposing.
“There's all sorts of problems with it because in order to operate we need to have blood that clots around stitches and things,” he points out. “And even if you can reduce somebody's temperature to that level, how do you fix them after that and how do you safely rewarm them?”
However, he does admit that it’s not a million miles away from a procedure that’s performed regularly on some patients with brain injuries, which relies on mild hypothermia (cooling the body by just a few degrees) to reduce tissue damage.
“If you've got a cerebral aneurysm in a critical case, the patient can be put on bypass, and the machine cools their blood down to stop their heart. You do the surgery, warm them back up and the heart starts again,” Brohi reveals. “But the difference there is that it's a controlled procedure done over some period of time, with the patient's own blood in their system.”
But when a trauma victim is brought into an emergency room, the one thing they don’t have is time. What if doctors could trick the human body into slowing down its own biological processes, instead of relying on cooling techniques? While Tisherman is focusing on EPR, other researchers are looking to the animal kingdom to find out if human healthcare could take any tips from hibernating animals.
One researcher doing just that is University of Oxford neuroscientist Vladyslav Vyazovskiy. He explains that hibernation (or torpor) usually causes an animal to reduce their metabolism before they reduce their body temperature. In torpor, the chemical reactions in the body slow right down too.
“The endpoint effect is similar [to suspended animation] and may be indistinguishable to some extent but I think there is an important distinction about how this is achieved,” he points out. “Animals know the trick and we don't.”
Large mammals like bears, and even some primates can hibernate. This suggests to Vyazovskiy that humans could potentially do it too. He hopes scientists will figure out what allows some mammals to enter torpor without any harmful lasting consequences so we might be able to find safer ways to induce suspended animation in people.
The phrase ‘suspended animation’ is starting to get to Tisherman. “We've tried and failed to get away from the term, but it makes it sound like science fiction, where we're trying to help astronauts make it Jupiter or something,” he says.
But one area where trauma and hibernation research could intersect is in space travel. Earlier this year, Elon Musk, CEO of SpaceX, announced that he plans to send one million people to Mars by 2050. A bold claim. But to send even a fraction of this cohort to the Red Planet within the next few decades will be a considerable task.
“We could probably make a rocket go to Mars that could carry people. But what are these poor people going to do in this tiny little space for six months?” asks Sandy Martin, from University of Colorado Denver, who studies the molecular mechanisms responsible for torpor.
Placing humans into a synthetic hibernation could reduce engineering demands for long-duration space flights and also make the experience less stressful for the astronauts. And again, cooling the body down might do the trick here. But as Martin points out, the strain doing that would place on the humans would likely cause problems when they do reach their destination.
“You don't put healthy people that have to jump out and do the best work of their lives the day they land on Mars into this state that is basically only used for people about to die,” she says. “But the hibernator really does just pop out of its burrow and get going with life. So if we could do that, it would be huge.”
Unfortunately, researchers like Martin and Vyazovskiy are still struggling to work out exactly how hibernators flick the switch.
“We have no idea how animals enter into torpor state,” says Vyazovskiy. “We can produce a very artificial physiological state by injecting some drugs that prevent you from regulating your body temperature, and then you would cool down and this would look pretty much like hibernation. But this is very dangerous,”
If scientists can figure out the molecular mechanisms behind torpor, this could perhaps lead to safer medicines that both medics and space agencies could exploit in future. “It’s very tricky to take a normal-sized person, and cool them down to 15C,” admits Tisherman. “It would be amazing if somebody came up with a drug that could lead to the same effect.”
But for now, with the survival rate of acute trauma victims being so paltry, he is committed to seeing his project through and gathering enough data to demonstrate the feasibility of the procedure. Then he’ll work on long-term troubleshooting and expanding it to other hospitals. His goal is to get ten patients to undergo EPR to compare to ten controls. Once this number is reached, he’ll share his findings with the public.
Tisherman knows he’s pushing the boundaries of trauma medicine, but with such low chances of recovery, he says he has little other choice. “The response so far has been: ‘things are so bad right now with all we’re doing in trauma medicine, that this is worth looking at’,” he says. “People might think it’s crazy — but it’s so crazy it just might work.”
Samuel Tisherman will be one of the speakers at WIRED Health in London on March 25, 2020. For more details, and to book your ticket, click here
This article was originally published by WIRED UK
