In Cold Blood

We all know that hy­pother­mia can kill – but in­creas­ingly, it’s also be­ing used to save lives

BBC Earth (Asia) - - Contents - WORDS BY TOM IRE­LAND

Hy­pother­mia is known to be fa­tal, but in­creas­ingly, it’s also be­ing used to save lives

Early on the morn­ing of 30 De­cem­ber 2007, a drunk 41-year-old man left a party in the city of Stok­mark­nes, in north­ern Nor­way. Soon after, he slipped and fell into a steep-sided ditch. Plunged neck-deep in the freez­ing wa­ter, he was un­able to get out and spent nearly an hour in the ditch be­fore passers-by spot­ted him and hauled him out.

De­spite their best ef­forts to warm him up, the man re­mained se­verely chilled, largely thanks to the air tem­per­a­ture be­ing a bit­ing -2°C. Shortly after the paramedics ar­rived, he fell un­con­scious, stopped breath­ing and went into car­diac ar­rest. It would be seven hours be­fore his heart started beat­ing prop­erly again, and for five of those he was tech­ni­cally dead. Some­how the ex­treme cold – the very thing that had caused the man’s heart at­tack in the first place – had saved his life.

In healthy hu­mans, the body main­tains a core tem­per­a­ture of be­tween 36.5 and 37.5°C – any­thing be­low this is a dan­ger­ous con­di­tion known as hy­pother­mia. When some­one’s body en­ters a hy­pother­mic state, their me­tab­o­lism slows down, their heart rate slows, or­gans start to shut down and even­tu­ally, their heart stops beat­ing. Within a few min­utes of the heart stop­ping, the body’s oxy­gen re­serves are de­pleted and cells start to pro­duce toxic chem­i­cals. This quickly starts to cause ir­re­versible dam­age to the del­i­cate tis­sues of the brain. Even if re­sus­ci­ta­tion is suc­cess­ful, the dan­ger is not over: most car­diac ar­rest pa­tients whose hearts are restarted end up dy­ing in hos­pi­tal from the dam­age caused by the re­turn of oxy­genated blood through­out the body; up to 30 per cent suf­fer per­ma­nent brain dam­age.

How­ever, there’s an old say­ing in the med­i­cal pro­fes­sion: “No one’s dead un­til they’re warm and dead”. In cases of car­diac ar­rest caused by ex­treme cold, an ex­tra­or­di­nary thing can hap­pen: the re­duc­tion in body tem­per­a­ture re­duces the brain’s need for oxy­gen. If cool­ing is rapid enough, it can help pre­vent toxic chem­i­cals ac­cu­mu­lat­ing while the heart has stopped, and con­tin­ues to pro­tect the brain when oxy­genated blood re­turns.

The Nor­we­gian man ar­rived at a nearby hos­pi­tal at 5am, with a tem­per­a­ture of just 25.5°C – eas­ily in the most se­vere cat­e­gory of hy­pother­mia. After at­tempts to warm him failed, medics called for a he­li­copter from the Univer­sity Hos­pi­tal of North Nor­way (UNN), a bet­ter-equipped med­i­cal cen­tre over 250km away. Doc­tors con­tin­ued to do CPR on the man, but by the time the he­li­copter reached UNN with the pa­tient on­board it was nearly 9am. He had been tech­ni­cally dead for nearly five hours.

At 11.37am, after hours of work by teams of

UNN staff, the man plucked from the icy ditch was fi­nally re­vived, and weaned off ma­chines that had been ar­ti­fi­cially pump­ing blood around his body.

It had been nearly seven hours since he had en­tered car­diac ar­rest – one of the long­est re­sus­ci­ta­tion pe­ri­ods ever recorded. Mirac­u­lously, he went on to make a full re­cov­ery, with no signs of brain dam­age at all.

“His me­tab­o­lism had de­creased by 60 to 70 per cent,” says Lars Bjert­naes, a pro­fes­sor of crit­i­cal care at The Arctic Univer­sity of Nor­way, who ex­am­ined the case in de­tail. “His oxy­gen needs prob­a­bly could be met by a car­diac out­put of about a quar­ter of nor­mal.”

BACK TO THE COLD SCHOOL

Sto­ries like this have in­spired a range of med­i­cal treat­ments that de­lib­er­ately in­duce cold states in pa­tients. It’s seen as a cut­ting-edge treat­ment, but re­ports of doc­tors us­ing ex­treme cold to keep peo­ple alive ac­tu­ally go back cen­turies. A pa­per on ‘the Rus­sian method of re­sus­ci­ta­tion’ from 1803 de­scribes cov­er­ing car­diac ar­rest pa­tients with snow to boost their chance of sur­vival. Mean­while, in 400 BC, Greek physi­cian Hip­pocrates ad­vo­cated pack­ing wounded sol­diers in ice and snow when mov­ing them.

Since the 1990s, putting pa­tients into a state of hy­pother­mia has been stan­dard prac­tice in open heart

“THERE’S AN OLD SAY­ING IN THE MED­I­CAL PRO­FES­SION: NO ONE’S DEAD

UN­TIL THEY’RE WARM AND DEAD”

surgery, and in the treat­ment of ba­bies born with heart de­fects. Here, doc­tors must ‘turn off’ the cir­cu­la­tory sys­tem in or­der to op­er­ate on the heart; re­duc­ing body tem­per­a­ture al­lows them to do this for long pe­ri­ods with­out caus­ing tis­sue dam­age.

Over the past decade, the use of ‘ther­a­peu­tic hy­pother­mia’ – also known as tar­geted tem­per­a­ture man­age­ment (TTM) – has be­come wide­spread in the treat­ment of heart at­tacks and strokes. The con­cept is the same: use low tem­per­a­tures to pro­tect against the dam­ag­ing cel­lu­lar re­ac­tions that oc­cur when the oxy­gen sup­ply is cut off, and per­haps more im­por­tantly, pre­vent dam­age when blood and oxy­gen re­turn after treat­ment.

“We try to reach hy­pother­mia as soon as pos­si­ble,” says Gla­dys Janssens, a car­di­ol­ogy re­searcher at VU Univer­sity Am­s­ter­dam who has stud­ied dif­fer­ent meth­ods of cool­ing heart at­tack pa­tients. “After reach­ing hy­pother­mia, we try to keep the tem­per­a­ture as close to the goal tem­per­a­ture as pos­si­ble for 12 to 24 hours. Lower tem­per­a­tures can be a risk for bleed­ing com­pli­ca­tions and heart rhythms, and higher tem­per­a­tures might negate the pro­tec­tive ef­fect.”

While the idea of cool­ing crit­i­cally ill pa­tients is now widely ac­cepted, the op­ti­mal tem­per­a­ture to keep them at, and the method of get­ting them cold, is still be­ing de­bated. Older meth­ods cooled heart at­tack pa­tients to 33°C, but more re­cent stud­ies have shown cool­ing by just one de­gree to 36°C could be equally as ef­fec­tive, with fewer risks. There are also a num­ber of dif­fer­ent meth­ods to get pa­tients cold – the most sim­ple be­ing wa­ter-cooled blan­kets or ad­he­sive pads placed on the body, with

more ad­vanced tech­niques in­volv­ing the in­ser­tion of catheters into the body and bal­loons cir­cu­lat­ing icecold saline. Both have their pros and cons.

“The blan­kets are cheap, quick and less labour­in­ten­sive. But fast ap­pli­ca­tion does not au­to­mat­i­cally mean pa­tients reach hy­pother­mia more rapidly,” says Janssens. “The dis­ad­van­tage of the catheters is that a trained physi­cian has to insert them.”

Through­out treat­ment, drugs must also be ad­min­is­tered to stop pa­tients’ nat­u­ral shiv­er­ing re­sponse. Com­mon com­pli­ca­tions of be­ing kept cold for so long in­clude se­vere fever, in­fec­tions and dam­age to the skin. After the dan­ger pe­riod is over, pa­tients must be warmed slowly – no faster than 0.5°C per hour. It’s an or­deal for the body to go through, but

TTM is the only post-re­sus­ci­ta­tion tech­nique that can sig­nif­i­cantly de­crease the chance of brain dam­age after a car­diac ar­rest.

FIRE AND ICE

With cool­ing equip­ment in­creas­ingly com­mon in med­i­cal cen­tres, doc­tors are now ex­plor­ing what other con­di­tions in­duced hy­pother­mia may help to treat. Dr Sam Tish­er­man, a sur­geon and pro­fes­sor of crit­i­cal care medicine in Bal­ti­more, has started tri­als to dras­ti­cally cool pa­tients who ar­rive in his emer­gency de­part­ment bleed­ing to death – of­ten from mul­ti­ple gunshot wounds.

“Trauma pa­tients nor­mally en­ter car­diac ar­rest be­cause they have lost so much blood there just isn’t enough for the heart to work,” says Tish­er­man. “The prob­lem is we just can’t sew them up fast enough – for se­vere blood loss their chances of sur­vival are around 5 to 7 per cent.”

Tish­er­man’s ex­per­i­men­tal tech­nique in­volves pump­ing ice-cold saline di­rectly into the body to re­place lost blood, in­duc­ing a very deep state of hy­pother­mia – as low as 15°C – not un­like the state known in science fic­tion as ‘sus­pended an­i­ma­tion’. This is not cool­ing by a few de­grees after a con­trolled car­diac re­sus­ci­ta­tion; it’s more like freez­ing some­one and oper­at­ing on them while they’re tech­ni­cally dead.

“The is­sue for us is time,” says Tish­er­man. “This is very dif­fer­ent from teams who have re­sus­ci­tated some­one hav­ing a car­diac ar­rest and are try­ing to pro­tect the brain from dam­age. We have some­one with no pulse, who’s los­ing so much blood CPR is not ef­fec­tive. We’re just try­ing to buy time.”

Some­body with no blood reach­ing the brain might nor­mally ex­pect to die or suf­fer ir­re­versible brain dam­age within five min­utes. Tish­er­man says his tech­nique has en­abled peo­ple to sur­vive after up to an hour of surgery be­fore be­ing slowly warmed and re­vived. “In the lab, we’ve even seen as much as two or three hours,” he says.

Tish­er­man be­lieves it may be pos­si­ble to use cool­ing to treat a range of other con­di­tions, even at the scene of an emer­gency. “There are now teams that will try to start the cool­ing out­side the hos­pi­tal,” he says. “There’s an image be­ing shared on­line of paramedics in Ger­many at­tend­ing to a man suf­fer­ing car­diac ar­rest in a gro­cery store. They piled bags of frozen French fries on him to cool him down.”

A range of stud­ies are now in­ves­ti­gat­ing cool­ing as a way to pro­tect against dam­age caused by con­di­tions as var­ied as head in­juries, menin­gi­tis, spinal cord in­juries and liver fail­ure. In the US, a woman ar­riv­ing at hos­pi­tal clin­i­cally brain-dead after com­mit­ting

“WE HAVE SOME­ONE WITH NO PULSE, WHO’S LOS­ING SO MUCH BLOOD CPR IS NOT EF­FEC­TIVE.

WE’RE JUST TRY­ING TO BUY TIME”

sui­cide with a cock­tail of seda­tives and an­tifreeze was suc­cess­fully ‘man­aged’ with ther­a­peu­tic hy­pother­mia for 36 hours while doc­tors worked on her. She awoke within 48 hours of be­ing warmed up and made a full re­cov­ery.

The power of cold to stave off death might even mean we need to re-eval­u­ate our def­i­ni­tion of death. Re­searchers such as Dr Sam Par­nia, a pro­fes­sor of crit­i­cal care medicine, have sug­gested that tech­niques like ther­a­peu­tic hy­pother­mia are mak­ing it dif­fi­cult to tell what ‘dead’ re­ally means. In his book Eras­ing Death,

Par­nia ar­gues that cur­rently, the point at which med­i­cal staff stop try­ing to re­vive pa­tients and de­clare them dead is en­tirely ar­bi­trary.

In the near fu­ture, Tish­er­man hopes that the mirac­u­lous ef­fects of cold tem­per­a­tures could be repli­cated by a more prac­ti­cal med­i­cal equiv­a­lent. “We don’t use the term ‘hy­pother­mia’, be­cause the hope is that we could even­tu­ally find a drug that stops the brain and body need­ing oxy­gen like cold does,” he says. “That would be a lot eas­ier.”

ABOVE: A mol­e­cule of hu­man haemoglobin, the pro­tein that car­ries oxy­gen in the blood

ABOVE RIGHT: The darker ar­eas in this CCT (coloured com­puter to­mog­ra­phy) image of a car­diac ar­rest pa­tient’s brain show where dam­age has been caused by a lack of oxy­gen

ABOVE LEFT: Dr Sam Par­nia, of New York’s Stony Brook Univer­sity Hos­pi­tal, be­lieves ther­a­peu­tic hy­pother­mia has the po­ten­tial to change our un­der­stand­ing of death

ABOVE: Chill­ing the body to tem­per­a­tures as low as 12°C is now com­mon prac­tice dur­ing open heart surgery

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