In nineteen sixty seven, I was treated with hypothermia by immersion in ice cold water as part of a local study, and then developed subcutaneous fat necrosis. Both myself and one other case were reported by the neonatal team who looked after me to have had otherwise favorable short term outcomes, but on the basis of this complication, these early studies of hypothermia were stopped. I was born weighing three thousand, nine hundred seventy grams at full term after an uncomplicated pregnancy,
labor and delivery. As reported, at one minute after birth, I became apnic and did not respond to resuscitation. After five minutes, I was placed in an ice water bath. My breathing was reported to recover after twenty eight minutes of hypothermia. At forty five minutes of life, my capillary pH was six point nine but recovered steadily, and I was discharged at day three. Subcutaneous fat necrosis developed between two and four weeks of age. The calcium deposits were
largely cleared by six months. My serum calcium remained normal, and my weight gain and in development were considered appropriate at that age, but no further follow up was reported fifty three years after these events. I have had a very normal life. Although my mother tease me about my skin in childhood, I never had any apparent skin problems as a child or later. I was a keen sportsman at school. My handwriting was never a strength, and so I taught myself to touch type, which turned out to be
an advantage in the computer age. At the same time, it is interesting to note that I can easily thread a needle. Academically, I did very well throughout school and university. I was awarded my PhD in nineteen ninety eight and have served at my current institution as department chair and
faculty Senate president. In retrospect, I strongly believe that the benefits of treatment clearly outweighed the costs, and that the abrupt cessation of these early studies of therapeutic hypothermia represented a missed opportunity. If the opinion of my parents had been sought at the time, or subsequently my opinion, we
would have favored continued trialing of this promising treatment. Fascinating, it's really an interesting I don't know that I've ever read a report or like of someone who had been a recipient of therapeutic hypothermia, like especially from so long ago, Like it's really interesting. Yeah, it's really good. Fine, Darren, thank you. I don't remember how I found it, but well I can tell you where it's from.
Do.
That was by Robert Carlson in Pediatric Research from twenty twenty one and article titled fifty three years of follow up of an infant with neonatal encephalopathy treated with therapeutic hypothermia.
It's fascinating and I feel like that, yeah, the first hand account much much later because it's not like he remembers this happening.
Right, It's like he's clearly reading some of the like medical, you know, records of his birth and treatment thereafter, and then and then talking about his life since Like it's so interesting.
Yeah, and I'm I'm so curious to know how this episode shakes out with like what you find. But like the point I feel like, I feel like the thing that stuck out to me when it comes to that is that maybe it was a little bit of missed opportunity, Maybe it was a little bit of you know, understandable hesitation to pursue trials, but ultimately it's like, how do you, how do you make scientific discoveries that do not harm people or have the potential to harm people? And that's yeah.
You know, we've come a long way in the twentieth century because of that. So yeah, anyway, Hi, I'm Aaron Welsh.
And I'm Erin alman Updyke.
And this is this podcast will kill You.
And we're coming back with our second part on hypothermia, as promised.
As promised, this is hypothermia can be good, Cold can be good.
Cold is not always bad.
Yeah, yeah, however you want to say it. Yes, it's the history of therapeutic hypothermia. It's really so much to learn.
I am thrilled. I know literally nothing about the history prior to two thousand and two.
Oh yep, oky dook. Well, I'll teach to some things that I have discovered. Great, but we've got a few a few things. This is off to a great start erin, we've got a few things to tackle before we can get into like the meat of the episode. It's quarantin any time.
It's quarantin any time. We're still we changed it. Yeah.
Oh, uncommon cold, the uncommon cold.
Yeah, that's what we're drinking. That's what we're drinking. Yep, we should probably do that again though, right, Nah, Okay.
This is gold erin, this is gold It's an uncommon cold. It's a hobn arrow margarita, spicy margarita because it's blended. It's cold, there's ice in it, but also there's like a little bit of warmth, you know. Yeah, and also alcohol does not make is not a treatment for hypothermia, as we covered last episode as the Room. Yeah, it's on our website, this podcast will kill You dot com. It's on our social media channels, toy.
This is going really well, really well.
Our website has lots of good things. It's got transcripts, it's got sources for all of our episodes, links to merch links to Patreon, bookshop, dot Orgiphilia account, Goodreads list, music by Bloodmobile. If I haven't already said that, contact us form firsthand account form reach out, reach out. We love to hear from you.
We also love to hear when you have a great rating or review to write about us, So if you could leave us one of those, we'd really appreciate it. I haven't done that already, Thank you if you have, and subscribe on YouTube exactly right, channel. Can we get into the episode.
Certainly, but it's like a break. I left off last week with the story of the amazing recovery of Anna Bagenholm, whose body temperature dropped to thirteen point seven degrees celsius or fifty six point six degrees fahrenheit. What I still can't get over it.
Yeah, it is that, like the is that in the Guinness Book of World Records? Like is that the record?
Or I don't trust the Guinness Book of World Records anymore the g I ever did, but like, yeah, not after a gallstone.
Missaply hugely lost faith.
But yeah, she might be in there.
Wo.
But in that episode Arin last week, you also took us through all the ways that the cold can hurt or even kill us, and how we can reverse or halt some of that damage. But it would be unfair to the cold for us to end the story there just showing its villainous side, Because while the cold has claimed many lives and fingers and toes and noses, it
has also saved many as harnessed by modern medicine. And so this week I want to tell the story of how humans have attempted to use cold, successfully or unsuccessfully, to save or prolonged lives. We have long used cold as a topical treatment for various aches and pains, swollen joints, battle trauma, and fever. Ancient Egyptian, Greek, and Roman physicians all called for cold to be used in various ailments.
You know, the oldest medical writing hailing the benefits of cold comes from the Edwin Smith Scroll dating to sixteen hundred BCE. It details a recipe to cool blisters, so it's more about like a cooling sensation in the cold itself, but still.
Like still, yeah, cold can feel good.
Cold can feel good. And Hippocrates, of course was a big liver in cold, especially for those of a warmer temperament. And he also wrote that this is yeah, infants left out in winter like left out infants survived longer than babies left out in the summer months.
That's I'm sorry, I wrote, yeah, like, first of all, what also second of all, I could miss this a little bit, but you just said of a warmer temperament.
Oh yeah, you know, like tempers or not tempers? Oh like humors? Humors, Oh my god, you just did a whole.
Episode, just did a whole episode on it.
Honestly, this sweater is making me overheat.
Well maybe you have a warm temperament and you need.
Some cold next week hyperthermia. Just kidding, but no, so I I have no idea.
Was this experiment?
Was this just like lore?
You know?
Yeah, I don't know.
I mean so like babies can definitely overheat, yes, in warmer temperatures, in many cases more quickly than they will. But like we said last week, because of their body surface area to volume ratio, they're also you know, going to get be more susceptible to hype both roma too, So it's it is both. And how about that both?
And I mean really anything is possible with Hippocrates, Like it's like I yeah, I don't know. But beginning in the sixteen hundreds or so, there was a shift in thinking like if a little localized cold was helpful to relieve joint pain and whatnot, that a full body cold
soak would be even better. Right. Cold baths became all the rage, and advocates claimed that they cured every ailment under the sun, especially fevers, which honestly, maybe they did, I don't know, But by the way, this made me think I was I did a little digging in this episode because I was like, oh, yeah, fevers that sometimes can be adaptive, that sometimes can help us to fight off infections. Can hypothermia ever be adaptive in that way?
Is there any reason that it would be protective? So I did some digging, and yes, I did find that a few people suggested that maybe a hypothermic response, like sometimes people get hypothermic incepsis, for instance, could be a last ditch effort to conserve energy and protect it gets
damage from inflammation. But I also see your face right now, which is very questioning, and that's that's how I feel too, because how do you disentangle that from the body just not having the energy to maintain a fever or even just like normal body temperature?
Right And I will say, like, what is the what is the driver of it? I don't know, but what is the outcome of it? We do know that hypothermia in case like unintentional hypothermia, We're going to talk later and today about like intentionally reducing someone's body temperature. But if someone is so sick with an infection and they end up hypothermic, it's usually quite a bad sign that things are not going well and they're usually poor outcomes.
Yeah, so it's yeah, it's not like it seems to me that we have no evidence to suggest or very little and not none that I found that it's an adaptive response and it's more just the body shutting down.
Yeah, it's not like our It's not like a fever where our hypothalmis is like, hey, let's raise the body temperature. Our hypothemist doesn't go, hey let's lower the body temperature.
Didn't.
I didn't find any data that happens in humans and other animals like you talked about, they're doing all the time.
They're doing it for other reasons too. It's like not, it's yeah, exactly. Yeah, okay, anyway, I love this one of already. I'm glad, don't we love to just like some easy swing and just bat down ideas. Yeah, hypotheses, No,
I got Okay. So, one of the biggest cheerleaders for cold baths was this guy named James Curry, and I mentioned him in our Fever episode last year as the mastermind behind many enthusiastic cold water treatments, where he continually doused people with freezing water, even past the point where they were like no, please, no, no, more.
Remember this.
Well, I don't know. I don't remember if I got into this in the episode. But one of the reasons that he became so evangelical about cold water treatment is because in the early seventeen seventies he observed a shipwreck in the freezing waters of the North Channel. When rescue finally came, the survivors tended to be those who stayed in the water, while those who waited on top of
the ship more often perished. And that made me think of Titanic and Jack and Rose, you know, because by this logic, shouldn't Jack have survived.
Spoilers, He doesn't.
He doesn't spoilers. Sorry if that's a spoiler for it, And it got spoiled for me by a neighborhood friend in when it came out and it was trauma like that, like has made me hate spoilers so much, you know how I feel like would be I do like dealers, But.
Yeah, it also I just want to say that that does not make any sense because of what we talked about last week with how water is a much better conductor of heat than air, and so immersion in even I mean, the water in Titanic was like below freezing, very cold. But even immersion in like water that's like sixty or seventy degrees can cause hypothermia in a number of hours, where it would take a very very prolonged exposure with no clothes at all to be hypothermic in those temperatures in air.
Yeah, I mean, you know, if only we had Curry himself here to question only only bro.
Yeah, what was your sample size?
And I think he was watching from a distance, and how he could even know were the people who were on the shipwreck like or on the remains of the boat where they also soaked in water? Did they fall off occasionally?
You know?
Like right, was it that they were soaking wet and then there was wind chill or something like that? Maybe was the air temperature colder and the water temperture was not that cold and then there was a winch maybe.
I mean the bottom line is that he was like convinced cold water is where it is at.
Well, we know you can't change their minds, you can't.
Yeah. And oh, by the way, speaking of Titanic, so of the nearly fifteen hundred deaths from the Titanic, from that Titanic, I mean, I don't need to say, anymore were classified as drowning when in fact they were probably hypothermia. Yeah, makes just an interesting I think that kind of but it shows to me it demonstrates sort of the public's understanding of hypothermia and what was happening in that situation. Yeah, okay.
So the other reason that Curry was psyched about cold baths was reading about the experience of this guy, doctor William Wright, who used cold water to treat a fever that he had, which was likely typhoid fever. All right, quote September ninth. Having given the necessary directions, about three o'clock in the afternoon, I stripped off all my clothes and threw a sea cloak loosely about me till I got upon deck. When the cloak was also laid aside.
Three buckets full of cold salt water were then thrown at once on me. The shock was great, but I felt immediate relief. The headache and other pains instantly abated, and a fine glow and diaphoresis succeeded. Towards evening, however, the febrile symptoms threatened return, and I had recourse again to the same method as before, with the same good effect. I now took food with an appetite and for the first time had a sound night's rest en.
I love that image. What is a sea cloak? Can I have one?
I'm assuming towel. No, I'm picturing.
I'm picturing something quite much more majestic than a towel.
I'm calling my towel sea cloak. From this point forward, can you help me fold the sea clad folks? Please?
Do you know that never in a million years would I assumed that it's a towel.
I have no idea. Somebody, we need to look this up.
Of course it's a towel, but I never.
Know it might not be. It's just a branding opportunity. It really is.
Someone make a seat cloak, Okay, but also like that's a hih so that is the account that made this guy Curry be like cold baths, cold bass for everyone, cold bass for everything.
Yeah, I mean it's it's not that much different than like watching a TikTok video today and being like cold baths.
I think you can find a lot of those videos on tiktoks. People are really into cold baths.
Yeah, yes, yeah, yep, uh and so, but this like really took many different places by storm spas sprung up where you could alternate between hot and cold waters, which is quite delightful, and the benefits of cold water plunges widely hailed even before the TikTok bros you know, came on the scene. But cold treatments weren't always used with consent. In the sixteen hundreds, cold water dunking was occasionally employed as a cure for mental illness, where it proved not
only ineffective but also cruel, torturous, and even deadly. In some cases, there were dunking stations built on the grounds of some asylums.
Oh my gosh, that's awful.
The logic behind this was that, okay, well, if mental illness is caused by a fevered brain, you need to cool it by any means necessary. So as an example, in seventeen twenty five, a woman who was accused of neglecting her husband was forced, while restrained, to stand under a torrent fifteen tons of freezing water for ninety minutes until she promised she would become a loving and obedient wife. Torture. That's like, I mean, what else do you call this?
Really?
Torture? Just actual torture? Yeah, yeah.
What uh, and not to mention ineffective on medical grounds, but even if it were effective, it's not like that would justify its use.
Also, it's not a mental disorder to not be nice to your husband.
I know.
I I told my husband this, and he was like, what is neglectful? Like what what does that? What does that mean?
Right?
Yeah?
Right, so many questions. Sandwich wasn't made crispy enough, or like it was too crispy and it you know when it scratches the.
Top, Yeah, the Captain crunch syndrome. Yeah, just shreds the roof of your mouth.
She made his sandwich like that?
Mm hmm. I mean, well, yeah, I still don't think it deserves fifteen tons of freezing water. But you know that's just my opinion, just.
Our opinion, just our opinion, Okay.
But yeah, And so as as much as I would like to tell you that this type of thing fell out of favor and was never used again by anyone in medicine, unfortunately I I cannot. In fact, it was the tortuous use of cold on non consenting individuals that led to cold therapy being dismissed as an illegitimate and groundless therapy, even when one doctor showed evidence to the contrary. While in medical school in the early twentieth century, Temple Fay was stumped by a question on a quiz, why
does metastatic cancer rarely appear in the limbs? He had no idea. He was like, I don't know what to put here. So he asked his professor, like, hey, what's the answer to this? And his professor was like, I don't know either.
Actually, why did they put it on the quiz?
I don't know, I don't know.
Okay, yep.
But the puzzles stuck with him, and so in the nineteen thirties, Fay decided that he wanted to try to solve it. His primary hypothesis had to do with temperature, so he figured that parts of the body with higher temperatures were more likely to promote cancer growth, while cooler parts the extremities discouraged growth. It would stand to reason, then, that if you cooled a metastatic growth, you could arrest
cancer development. So, operating under this logic, Fay devised a few local refrigeration experiments, first in chicken embryos than tissue culture, and then in humans. His first patient was a woman who was experiencing extreme pain from a cervical carcinoma. He inserted a device of his own making into the mass, like a hollow metal capsule through which water flowed in
a closed system, and he set it to cooling. Forty eight hours later, the patient was pain free, and within five days the tumor had actually shrunk a fair bit around the edges of wow. The results encouraged Fay to invent more cooling instruments and setups rubber bags, tubing ice baths, and he tested out his hypothesis on other cancer patients.
His results suggested he was onto something. Ninety five percent of his patients reported an alleviation in pain, and twenty to twenty five percent reported that their tumors shrank or grew more slowly. I mean, this was the nineteen thirties, so keep in mind that, like other treatment options for cancer were really limited. Yeah, and when he presented his results,
the broader medical community was stunned. They had dismissed his ideas initially as just quackery, Like what do you mean, You're just going to refrigerate that body part and suddenly you're all healed. And now they're like, hey, actually, maybe there is something to therapeutic cooling. What other applications can we find for this? And Fay himself would have likely gone on to develop his cold therapy further if a
couple of things had not happened. The first was a series of cold therapy programs that began in the nineteen forties at a few hospitals in the US, notably McLain Hospital in Belmont, Massachusetts. Doctors would administer barbiturates to the patients of theirs who were the most seriously debilitated by mental illness, and then place them in cold water for
periods ranging from ten to thirty eight hours. Oh jeez. Yeah, and yes there were warming blankets on hand and the patients were being monitored.
But still, this is this is patients with mental illness. Yes, these like this is these are not consented. This is not a correct correct this is not an institutional review board which doesn't exist approved done.
Right, Yeah, body temperature would drop into the seventies fahrenheit twenties celsius. Outcomes were allegedly positive, but it's not clear who's making the assessment, right, Like, is it the doctor who's like bio to think, Oh, I want this therapy to work, you know, is it the person's self reporting, right, And it's also not clear how long any you know, positive effects, if they did exist, how long they lasted, But they were encouraging enough for scientific American to rave
about them quote for the first time. This new therapy, popularly known as human hibernation and technically as hypothermia, has apparently found a definite, valuable application in treating insanity, particularly schizophrenia or dementia praecox. Results in the case of study have been remarkable, so that more extensive investigation of the possibilities and limitations of this treatment will surely be forthcoming at the war's end, if not before end.
Quote Okay, Yeah, a little bit of unchecked enthusiasm there that went a bit too far, as it often does.
And as more hospitals started cold therapy program to treat mental illness, there was several of them that got started. Illnesses, injuries, and deaths, even deaths occurred. So for example, at the University of Cincinnati in nineteen forty three, sixteen people were put into refrigerators for forty eight hours, Two died, and others suffered permanent brain damage. Yeah, jeez, this, This had the understandable effect of halting interest in therapeutic hypothermia for
any reason or for any condition. But it was it wasn't the only thing to do, so it wasn't the only thing to kind of pump the brake. So I mentioned that it was a couple of things that prevented therapeutic hypothermia from being like more investigated. The first being these US based programs, and the second was Nazis.
Yeah, so that's what I knew about.
Yeah. In nineteen thirty nine, temple Fay submitted a manuscript to a publisher in Belgium, and somehow the Nazis, who had captured Belgium in nineteen forty came across it. They were already interested in hypothermia because their pilots often died in frigid waters after being shot down, and they wanted to better understand how long come someone could survive, at what temperatures, which revival methods worked best, and when the point of no return was there, like what that point
looked like, what it was? And they took inspiration from phase paper to set up cold water immersion tanks at Dochau concentration camp, where they held people in the tanks at varying temperatures ranging from thirty six point five degrees fahrenheit, which is two and a half degrees celsius, to fifty four degrees fahrenheit or twelve degrees celsius. Sometimes they gave
people pilot suits or flotation devices. Other times they stripped them and held them there naked for up to fourteen hours, and over the course of the war, three hundred and sixty to four hundred experimental sefts were carried out, involving three hundred individuals. It's yeah, there are many, many more horrifying details of this torture that emerged after the war during the Nuremberg Trials, and the news of these trials
really poisoned any remaining interest in therapeutic hypothermia. For almost two decades, no one wanted to be seen doing what had become characterized as Nazi science. Eventually, though, that characterization faded as people realized that cold therapy may still hold some promise, and as World War two became more distant, some researchers grew more comfortable with using the data generated by these torture sessions, believing that it could quote advance
contemporary research on hypothermia and save lives end quote. And it became and really still is quite a controversial topic. Some people advocate for free, unrestricted use of this type of data, and others saying that a ban is actually more appropriate. No one, no one should be able to use this data.
I mean you're essentially benefiting from torture, torture in one way, in one way or another.
By nineteen eighty four, though over forty five publications had cited the hypothermia experiments at Dacau implicitly or explicitly endorsing
the use of such data. And I found a paper published in the New England Journal of Medicine in nineteen ninety that discusses these hypothermia experiments specifically and the controversy surrounding them, and the author concludes with this quote on analysis, the Dacou hypothermia study has all the ingredients of a scientific fraud, and rejection of the data on purely scientific
grounds is inevitable. If the shortcomings of the Dacou hypothermia study had been fully appreciated, the ethical dialogue probably would never have begun. Continuing it runs the risk of implying that these grotesque Nazi medical exercises yielded results worthy of consideration and possibly of benefit to humanity. The present analysis
clearly shows that nothing could be further from the truth. Basically, like the author, I feel like he is saying that if it's a question of using the data, first of all, the data is worthless scientific, right. But even if it was you know, had even if the experiments were done in a way were quote unquote experiences were done in a way that was controlled and all the variables, it doesn't mean that it's okay to use.
Yeah.
So.
And also and also on top of that, it's trash data.
It's trash. Yeah, it's just yeah yeah, so yeah, there's it is a really interesting paper.
Yeah.
So, therapeutic hyperthermia joins the ranks of so many other scientific advancements that have been built on the backs of those who did not have the power to say no or have their no heard. And hopefully it's somewhat of a consolation that overall, very few papers exploring the use of therapeutic hypothermia make reference to Dacau, at least like directly from data. They may mention this is where things you know, this is what YEP was done, but they don't say, and this is how we know.
Is where we've got our data right right.
And the therapy came crawling back slowly with a few papers here and there in the mid to late nineteen fifties, first the discovery by Hubert, Rossumov and Duncan holiday that when a person is hypothermic, their brain consumes less oxygen. It was a major breakthrough. It opened the door for new avenues to protect the brain during times where oxygen might be restricted like stroke, heart attack, aneurism, certain surgeries. By just reducing the brain's oxygen demands with hypothermia, you're
protecting the brain from long term injury. And shortly after a few physicians started playing around with us hypothermia after cardiac arrest others during cardiac surgery, although the routine use of therapeutic hypothermia wouldn't happen for a long time, especially as physicians grew aware and wary of certain complications with
the practice. In the nineteen fifties and nineteen sixties, again the therapy was used in a few small studies for infants that had trouble breathing shortly after birth, like Apgar scores of one this is our first hand account. Animal studies had shown promise in this regard, so doctors tried it out on humans. And also it has a deeper history, like there are some reports from the sixteen hundreds using cold water immersion for infant For infants, it seems successful.
So when one of the studies, nine out of ten of the infants survived and none showed any developmental delay. And I couldn't find any indication that the baby that did not survive died because of hypothermia. But I, yeah, I don't think that that was the case. But these studies were really small and they weren't well controlled, and so combine that with the potential for complications, and you've got another decades long delay in this becoming a standard of care.
Interesting.
Yeah, And ultimately in two thousand and five, I believe it did become a routine and has since saved lives and prevented injuries. But what about prolonging lives. So someday, Aaron, we should do an entire episode on cryonics. As a teaser. For now, let's just say that while researchers were trying to figure out how to use the cold to protect the body from injury. Other folks were wondering whether we could use hypothermia to put the body in a suspended state.
The space race had begun, after all, so like, who was going to be the first to traverse light year's worth of distances exactly? So a bunch of cryonics come and he sprung up in the nineteen sixties, with the first volunteer dying on January twelfth, nineteen sixty seven, and which was a little bit earlier than the company that he had. The Life Extension Society it was called, had thought that they were going he was going ready for dot. Yeah, they were not ready at all. Like his doctor was like,
he's on ice. You got to get him now. And they didn't have anything set up. They were still in building the pods or whatever. And so they stored this person in one of the Life Extension Society guy's garages in his station wagon and then was like, don't tell my wife. And then his wife went into the garage and was like, what, get this out of here. So he found a couple of friends who would store the body for a few days. But yeah, cry on.
Sorry, all I can do is blinga sorry, this is a this is a I just so, I'm so I understand. Sure, this was a person who died, yes, of some other cause, some cause cancer, Yes, I believe cancer. And then they made him cold and stored him in a hatchback.
There was some profusion of various substances. I forget what got Yeah it might have been dmso sounds familiar.
Yeah okay in the sixties, in nineteen sixty seven, yeah cool, okay, but.
They didn't have the pods ready for like long term storage, so the station wagon.
Was the thing pod. Yeah, okay, yep.
But this came out, like the news of this came out, and cryonics never quite recovered from this first mishap, And really it was like, over the years, it seems like our way to extort money from grieving people who don't know how to accept that their loved one died or that they themselves are mortal.
Going to die. Yeah.
So there you have it, Aaron, the history of cold, the good, the bad, and the weird. So, okay, tell me how therapeutic hypothermia works. Does it work?
I love that that's what you're leaving me with. Yeah, I also have to tell you I am not going to talk about cryonics at all.
I didn't think, so that's okay.
Literally, as you were like, as you were even starting, I was like, gosh, I wonder if I should have looked into like I didn't. So, if that's what you're expecting from this episode, listeners, you're about to be disappointed. I'm going to talk about real life and not science fiction. Yeah, maybe it will be science reality someday. Right now, it's science fiction.
Okay.
Wouldn't it be nice if we could wake up in the morning anyways, so.
The Salm Beach boys, Oh, didn't it be nice?
Okay.
What I am going to actually focus on today, not cryonics, is how we use therapeutic hypothermia. I'm putting it in air quotes because we don't call it that anymore. Oh, there's there's been a multiple evolutions of this term for a while, and a kind of depends on the like what scenario you're looking at, So sometimes it still is induced hypothermia or therapeutic hypothermia, but more commonly targeted temperature management is used.
Okay, this might explain why I could find so few papers on the history of therapeutic hypothermia.
Yes, it's why it took me so long to find the papers that I finally found about how we do it. It's because targeted temperature management and now newly just temperature control. Why the change in rhetoric erin let me tell you. Oh, I'm going to tell you, but it's going to take me a while to get there because I'm verbose, and I'm going to focus mostly on the broad strokes of like what are the contexts in which we use therapeutic hypothermia,
how do we do it, and things like that. The point of it, really big picture is what you mentioned, Aaron. It is to reduce the risk of ischemic injury, meaning reduce the risk that a lack of oxygen to our tissues causes actual and irreversible damage because of the theoretical fact, which is like, it's not just theoretical, it is true, but because of the fact that as our body temperature cools, our metabolic rate decreases, our need for oxygen in our
tissues decreases. That is the theory by which therapeutic hypothermia works. But how does it end up working in practice? Like
what is it really doing to protect our tissues? We think that in the brain, this decrease in our metabolic rate decreases blood flow to the brain, which can also decrease intra cranial pressure, which is something that often goes up during damage in our heart because of changes to the heart muscle and the heart tissues itself, as well as the changes that we see in our blood vessels. With cold. Right, we're vaso constricting a lot of our
blood vessels. We see a decrease in our heart rate, but you can maintain blood pressure to a certain degree.
Okay.
And these are two of our organs, our heart and our brain that we are wanting to protect the most with therapeutic hypothermia, because our heart and our brain are two organs that a are going to be impacted first due to aeschemic damage. Right, lack of oxygen is going to end up damaging those tissues irrevocably, and if we we can protect those, then we could potentially recover from any other insult to other organs or other tissues.
So we're still in the hypothetical thing, the thought of how this should go and why we think that that recooling a body a core temperature is going to be beneficial, Okay, got it.
So to understand the specific situations where we might use therapeutic hypothermia or targeted temperature management or whatever. We also have to think about the ways in which this lack of oxygen ends up causing damage. Okay, because what that tells us is there's different time periods at which you could potentially use hypothermia to try and reverse or prevent this damage.
Right, So tell we ah elaborate.
Okay, let me elaborate, and we can use if we want, we can use an example. Let's say your heart stops. Okay, Okay, this is one possible situation. If your heart stops beating, you're not pumping blood, so your tissues are not going to get oxygen. That's all of your tissues, your brain, your heart, all of your tissues are going to not get oxygen. There's three phases to the damage that that
is going to cause. The first is when that heart stops, you're going to have the lack of oxygen, right because our cells require oxygen for metabolism. Without oxygen, your cells start to become damaged. Okay, step one. But then if we are in medicine and we're like trying to bring somebody back and you can restart their heart after a cardiac arrest, you're going to all of a sudden reperfuse that area, yep, okay, which means you're going to have
a flow of oxygen to the area. You're doing CPR, you're using a defibrillator, whatever it is you're now reperfusing. That process actually causes its own sort of damage, because as our cells start working again, they end up creating reactive oxygen species. The way that I think of it is like you know, if you turn your water off in your house for a while, yeah, and then when you turn it back on, it's like grody, like sputtery and like brown water at first before it runs clear.
Thank you.
That's my analogy. That's like the immediate reperfusion injury that you can get okay, okay, and then after that there's a final stage that you can also get, like a delayed reperfusion injury. Think of it like a few hours after you start to get blood flow back, there's inflammation. There's our body reacting to this insult that it just received, so you can get additional damage to that time as well.
I don't have a Sealskis analogy. How does the what about pipes in the house water.
It doesn't. Yeah, it doesn't. I don't have an equivalent there. Sorry, okay, okay, sorry, okay. So that so that's that's the example with cardiac arrest. But it's true in any scenario where you are have lack of blood flow, right if you think of a stroke, all of those same scenarios are going to happen. You have blocking blood flow to a part of the brain
that causes tissue damage in the brain. Then if you're able to reperfuse that area by say breaking up that clot or something like that, you're going to get reperfusion injury, and then you'll have delayed reperfusion injury as well. So it is that's the ways that damage are caused. So you could potentially, in theory use hypothermia at any of those stages to decrease the risk of injury, depending on when you can initiate it, how long you initiate it for.
Because in addition to decreasing our over a metabolism, this hypothermia also just like attenuates all of our cellular responses. It's going to reduce the inflammatory response. You'll have vaso constriction, so you're not going to have as much edema or fluid like collection outside of our vascular system. And there is a lot of animal data to support the use of therapeutic hypothermia in a really wide variety of situations.
Okay, real quick though, So if someone has their heart stops, then there already will be damaged because of the reperfusion and then the second reperfusion situation whatever. So then when is hypothermia? When when do you target the use of hypothermia? And also how realistic is that from like a hospital situation.
So that is why this gets so complicated. Okay, right, because that's the exact right question. But if you think about the survival story that you told last episode, Darren, Oh, because her he hair just stopped, her heart stopped, right, but she was already cold at that point. Yes, she was cold and her heart stopped because of that cold.
So there was already a decrease. So you potentially in that case, because she recovered so well, you already had protection against anoxic injury, You had protection against lack of oxygen because the tissues were already cold before that initial insult. Right, in most realistic scenarios, that's not going to happen. Right.
Yeah, So the cases.
That we are going to potentially be able to use therapeutic hypothermia were probably not going to be able to do it before that initial injury, before the onset of the lack of oxygen. Okay, so it's the second two scenarios that were thinking about targeting. Can we use it to reduce the risk of that initial reperfusion injury? Well, to do that, you would have to cool the body before you reperfuse it, right right, Okay, so before you
restart the heart. That's not a thing that people do because if someone's heart stops, your first thought is to
restart it, restart us. Yeah. Right, So the way that therapeutic hypothermia, or the way that targeted temperature management often ends up being used is in that third phase to try and reduce the risk of that delayed reperfusion injury after the heart or whatever it is gets restarted or things like that, Can we can we reduce the risk of that further damage by cooling the body, slowing down the metabolism, slowing down the need for oxygen.
Does that make sense? It does? And so like, because I feel like there are two main well, I mean obviously you're going to tell me more. But like in an emergency situation, there's it's like the use of therapeutic kypothermia or whatever. We're good temperature control, yeah whatever, Yeah, the thermostat in an emergency situation, And like we need to decide, right now, what do we do versus a we're going into surgery type of situation, Like is that you know, like a more planned right use?
So when do we when do we actually use it? Right? What are the situations that we actually use it today? And do we have data that it's actually helpful? Because that was all like the theory of like this is how it should work, we should be able to use it in these scenarios. Can we actually use it in these scenarios? Surgeries? So, in a surgical situation, you could, because you're in total control there, you could cool the body before any kind of a schemic insult. Right, Yeah,
you can do that. And if we are talking about a heart surgery, you might need to actually stop the heart in order to do a surgery on the heart. Right, In those situations, a person is put on cardiopulmonary bypass, so their blood is still being pumped. It's being oxygenated outside.
Of the body.
But could we by reducing their body temperature also decrease the risk that if we're not oxygenating it quite well enough, or just you know that the heart itself which is stopped, it's not going to be as injured. That is something that is sometimes used, but there is much more mixed data on whether or not it's truly protective, both for like neuroprotection as well as just like generally protective against dschemia.
And so right now, the guidelines for you know, if someone is doing a heart surgery and is going to be on cardiopulmonary bypass, do you do intentional hypothermia or do you not? It depends on the situation.
In what and like in what way.
It might depend on that particular person, how high of risk are they for eschemia to begin with. It might depend on the capabilities of where you're doing the surgery. Do you have the ability to cool somebody or not. But the data is not like a clear cut like you need to do it in order to improve outcomes
and it's okay if you don't do it. Essentially, in most other surgeries, the data is more clear that hypothermia should actually be avoided, okay, because your body is going to be under more stress trying to warm itself up, and surgery is already a very stressful situation. So it's really only like heart surgeries. There also was like there's been trials on using it for brain surgeries, especially like
aneurism clips and things like that. There's not really data that hypothermia is beneficial necessarily in those scenarios.
It's so interesting because I feel like, I mean, and maybe this just speaks to the papers that I found that were you know, out of date, but how so many how it is talked about in terms of like this is a really promising thing. It's case by case, but like it does, it does really work. And I think also just the fact it's the human body, Like we have these controls. These these are are homeostasis or whatever.
We're trying to maintain temperature for our benefit, even if that does end up hurting us, And so I see, yeah, causing more stress by trying to override those controls. That makes sense.
Yeah, yeah, So that's really from what I could find, at least, that's the only scenario where if you could do therapeutic hypothermia, you would be trying to prevent that initial injury. Everything else that we use it for is kind of post injury. Can we prevent you know, worse Sequele When it comes to neurologic stuff, because there's a lot of interest in like protecting our brain using hypothermia, the data is much more mixed and not as strong
as I kind of expected. So after stroke, after traumatic brain injury, after you know, hemorrhagic aneurism or aneurism, rupture, any of these things, the data is unclear and guidelines
right now do not support universal therapeutic hypothermia. Okay, they do support avoiding fever, and that is part of why, and I'll get into it even more, but that is part of why the kind of naming of this has changed more to let's not think as much about you know, intentionally cooling the body, but to like a degree lower than a typical body temperature of thirty seven, but let us do make sure that we don't go above thirty seven point five, because then we do see that there's more damage.
That makes sense. What about babies?
Okay, I was going to talk about cardiac arrest next. You can do a basory No, I love it. Those are the two. Those are the two big areas. So that's all the things that we maybe sometimes kind of use it for. There's two areas that at least for a while, Oh spoilers, this therapeutic hypothermia actually cooling the body to around thirty two thirty three thirty four degrees. So mild hypothermia was considered standard of care for almost
twenty years for out of hospital cardiac arrest. Okay, so if somebody heart stops outside of the hospital and you're doing CPR or you have access to a diffibrillator and they have a shockable rhythm, so you can different relate them.
There was a big paper that came out in two thousand and two that showed big benefit to once you get circulation back, once you have rosc which is return of spontaneous circulation, once you bring that person back to life, if you cool them for at least twenty four hours I think it was twelve to twenty four hours at first, you have improved outcomes, better survival.
Okay, survival, that's the outcome, got it.
Survival is the outcome, because that's yeah, And so that became standard of care. And then there was other papers that came out later that showed even if the person initially did not have a shockable rhythm, meaning if their heart stopped, but it was because of other things. It could be because of substance use, it could be because of a pulmonary issue, it could be like just so many different things. But their initial rhythm wasn't one that you could differ relate like they do on er.
Huh.
Yep, they've moved past the Oh that's good. The paddles, Yeah, that's good.
Yeah. But so there were other papers that came out in like the early two thousands that showed even in those situations there was some benefit to therapeutic hypothermia, so that was the standard of care. However, since very recently, like a paper came out in twenty twenty one that looked at a pretty big swath of people regardless of their initial rhythm out of hospital cardiac arrest and did not find that therapeutic hypothermia was beneficial compared to just
ensuring that they don't have a fever. So targeting thirty seven point five and not allowing it to go higher than that but not necessarily lowering it wasn't any more beneficial. There were a couple of other papers that came out since then that were similar that kind of just showed maybe this because there were papers that looked at, okay, well, if lowering the body temperature is beneficial, what's the ideal temperature? Is it thirty two? Is it thirty three? Could it
be thirty six? How low do we need to go? And those papers found that like thirty six and thirty three, Eh, no big difference, And so that led to more and more of these papers looking at how cold do we need to get people to have a benefit to try and keep them alive with minimal neurologic damage once we bring them back after their heart stops.
Okay, so this is once you bring them back after their heart stops, administer therapeutic hypothermia, but you don't anymore. It's just make sure they don't have a fever.
So right now, as of twenty twenty three, the guidelines is to pick a temperature somewhere between thirty two and thirty seven point five and keep them there, so temperature control but not necessarily therapeutic hypothermia.
I have a question, how do we do that? Ooh, such a good question.
There's a lot of different ways. It all does have to be very tightly monitored, especially during the induction and maintenance phase, so as you're cooling that body down and then once you get to that temperature that you're targeting, one of the things you have to do is avoid shivering, right because that's an automatic response that's going to rewarm
the body and increase metabolic demand. You also have to keep very close eye on like their blood counts, making sure that all of the things that can go wrong during hypothermia, getting increased blood clotting, electrolyte abnormalities, diarrhasis, acid base disorders, from things shifting in and out of cells. You have to monitor all of those things. But how
do you actually do it. You can do it almost the opposite of how we can warm your body, So you can externally cool with like water baths or these fancy gel pads that like circulate temperature controlled water. You can do internal cooling like the opposite of what we would do to warm it up. You can infuse cold ivy fluids or cold like peritoneal or levage. You can also I know you can also do have you ever
donated plasma only blood? If you ever donate plasma they take out circulate, yeah, yeah, and so when it goes back into you, it is a little it's not cooled, but it is just colder than your body temperature usually, and it does it makes you feel cold. But you can also do that. You can do extra corporeal blood cooling, so you can take someone's blood out, cool it down and then and then infuse it back in. So there's
a number of different ways. And like I mentioned, it's usually a very mild hypothermia that is targeted, so like thirty two to thirty four degrees celsius, right, okay, pascinating, Okay,
I know. And then there is babies, you asked, Aaron, And this is the area that I think therapeutic hypothermia is truly still the correct term because it is the area that is still used Okay, whole body cooling or sometimes just head cooling, so just cooling of the head is used and is considered standard of care for full term newborns that are born and suspected of having hypoxic ischemic encephalopathy or HIE. And this is suspected brain damage that's due to lack of oxygen to the brain in
a newborn okay, and that can happen. I'm not going to go into a lot of deep detail on this because I think it deserves its whole own episode. But this can happen in a variety of different contexts, either just before delivery or kind of during delivery, or shortly
after delivery. Right, There's a lot of situations. Whether it's placental abruption when like the placenta comes off of the uterus before the baby is delivered, that is going to disrupt oxygen flow to the fetus, other cord issues like the cord getting compressed or prolapsing, uterine rupture, the heart rate of the fetus just dropping and then not recovering,
or even during or after delivery. Anything that causes the baby to stop breathing or not have access to oxygen is going to lead to potentially hypoxic a ischemic encephalopathy. And we use that Appgar score that you mentioned, which is a composite score of like how well they're breathing, their skin color, Turger reflexes all of these things to
give a sense of how a baby is doing. And it's usually at that ten minute mark if a baby's heart rate is still really low or if it's not there at all, and if they're not breathing or they're requiring continued ventilation support, there is good data that cooling these babies can help prevent severe disability or death. Okay,
and I specifically mentioned full term infants. Yes, because a relatively recent study from I think it was actually published this year in twenty twenty five, was actually one of the first ones that looked at preterm infants and did not find any statistically significant improvement in outcomes for preterm infants by using therapeutic hypothermia.
Why why do you think that is?
I mean, babies, newborn babies are so different in their physiology, and so like a premature newborn has different physiology than a non premature like a full term newborn, and so we don't know, I mean the short answers, we just
don't know. But that's why it was so important that this study was actually done, because there certainly were all of the studies previously had only used full term infants, and yet therapeutic hypothermia I think was often maybe used in some situations in preterm infants just based on the data of full term infants. Right, But because we know they're so different. It was important that this data actually came out and it doesn't show improvement in outcome.
So okay, and what is like the the effect size, I guess or like what you know, it's a good question.
A meta analysis from twenty one found for full term infants a pooled reduction in risk of mortality of about twenty six percent in infants who were cooled compared to ones who weren't. And this was similar whether it was whole body cooling or just head cooling that was used. Okay, yeah, it's not nothing.
It's not nothing, and it's pretty amazing that, yeah, that there are there is I don't know there are uses for this because it does seem like fairly, I know, it's not straightforward that there are many different home approaches that you can use to do this and administer this and monitor this, and that it's about the degree and all this stuff. But it's like it's just I don't know, it's it's fascinating to me that it's like we use temperature in this way.
Also, what you had mentioned, Aaron about the use in cancer is so interesting because I didn't find anything about it's you. I mean, I know you know, people do sometimes like ice on the head to try and reduce hair loss during chemo therapy or things like that. The mechanism that's going to be very different than what you had mentioned, but someone using it to try and reduce
cancer growth. I think probably because we have better options today is why there's not really a lot of data that I could find, at least on modern uses of that. We do use a different kind of crowd therapy like liquid nitrogen to kill small skin cancers or other growths all the time. Yeah, I forgot about that after the fact.
I also did find a paper on cold plunges and that kind of crowd therapy for muscle recovery have to work out by the way, there's not really good data to support it, but I can give you a paper if you want to read about it.
Well, And you know, I'm not against cold plunges. If you enjoy jumping into an icy lake or tub or whatever it, do it safely, have a buddy whatever you know.
No, but there's not like for like the muscle recovery stuff, like, there's not a lot of data that it's really beneficial. But you can read about it if you want to know more. We have so many sources for you.
We do okay again, I'm going to shout out that book by Phil Jakol called out Cold Chilling Descent into the macabre, controversial, life saving History of Hypothermia. And then a paper about doctor temple Fay called Breaking the Thermal Barrier Doctor temple Fay by al Saga at All from two thousand and six and then by Gunn from twenty seventeen Therapeutic Hyperthermia Translates from Ancient History into Practice and more papers.
I had a couple of older papers, one from twenty fourteen that old but called Clinical Applications of Targeted Temperature Management by Perman at All and another one from two thousand and eight that was just called Therapeutic Hypothermia by Varren and Acosta. And then the two papers two biggest
papers that I had on hypothermia in infants. One of them is Whole Body Hypothermia for Neo nail and Cephalopathy and Preterm Infants thirty three to thirty five weeks in GEMI Pediatrics, and the other one was from PLUS one. And it was that twenty twenty one paper that was the systematic review and meta analysis. But then what's fun
is I have guidelines. So many of the guidelines, like the two thousand and two paper that led to the guidelines initially of being yes, do therapeutic hypothermia for out of hospital kardiac arrest, and then all the subsequent papers that were like, yes, it's beneficial. No wait, maybe it isn't. Maybe it's not as good to be thought. Now Here are the new guidelines. So many guideline papers. You can find them all on our website, This podcast will kill You dot com.
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