WEBVTT 00:00:00.000 --> 00:00:02.319 So, you know, when we think about survival in 00:00:02.319 --> 00:00:04.740 extreme situations, our minds usually go straight 00:00:04.740 --> 00:00:08.500 to, well, warmth. Right, yeah. Like fire, shelter. 00:00:08.740 --> 00:00:11.119 Exactly. Staying out of the cold. But I want 00:00:11.119 --> 00:00:13.759 to take you back in time for a second to the 00:00:13.759 --> 00:00:17.460 brutal freezing battlefields of the Napoleonic 00:00:17.460 --> 00:00:20.460 Wars. Oh, wow. OK. Yeah. So there is this military 00:00:20.460 --> 00:00:23.260 surgeon there, Baron Dominique Jean -Lauret, 00:00:23.260 --> 00:00:26.780 and he noticed something completely baffling. 00:00:26.859 --> 00:00:29.500 What was it? Well, the wounded officers, the 00:00:29.500 --> 00:00:31.480 ones who were given the best care, kept warm 00:00:31.480 --> 00:00:33.640 and pampered right near the campfire. They were 00:00:33.640 --> 00:00:35.679 dying. Wait, the ones by the fire were dying? 00:00:35.859 --> 00:00:38.820 Yeah. But the poor rank -and -file infantrymen, 00:00:38.880 --> 00:00:40.600 the ones that were just kind of left out in the 00:00:40.600 --> 00:00:43.700 f— freezing mud, they were surviving. That's 00:00:43.700 --> 00:00:46.259 incredible. It's a wild, right? It turns out 00:00:46.259 --> 00:00:49.060 that brutal battlefield cold wasn't killing them. 00:00:49.140 --> 00:00:51.179 It was actually hitting their biological pause 00:00:51.179 --> 00:00:54.079 button. I love that framing. Thanks. And today 00:00:54.079 --> 00:00:57.939 we're taking a massive, comprehensive Wikipedia 00:00:57.939 --> 00:01:00.820 article you sent us on targeted temperature management 00:01:00.820 --> 00:01:04.859 to see how modern hospitals are using that exact 00:01:04.859 --> 00:01:07.819 same pause button to save lives today. It really 00:01:07.819 --> 00:01:10.299 is fascinating. It completely flips our standard 00:01:10.299 --> 00:01:12.620 assumptions about triage and recovery upside 00:01:12.620 --> 00:01:15.519 down. It really does. And just to set the right 00:01:15.519 --> 00:01:18.299 visual tone for our discussion today, I've actually 00:01:18.299 --> 00:01:21.099 changed the backdrop in the studio to a frost 00:01:21.099 --> 00:01:23.200 -covered medical laboratory. I noticed that. 00:01:23.219 --> 00:01:25.609 It looks great. Yeah, because we are looking 00:01:25.609 --> 00:01:29.450 at a highly coordinated systemic medical intervention 00:01:29.450 --> 00:01:32.090 that's basically designed to put human biology 00:01:32.090 --> 00:01:35.349 on ice. OK, let's unpack this. Targeted temperature 00:01:35.349 --> 00:01:38.909 management, or TTM, what are we actually dealing 00:01:38.909 --> 00:01:42.370 with here? So TTM is... Because based on the 00:01:42.370 --> 00:01:44.989 article, it's the active deliberate lowering 00:01:44.989 --> 00:01:47.310 of a patient's body temperature. Exactly. We 00:01:47.310 --> 00:01:48.989 aren't just talking about a slight chill from 00:01:48.989 --> 00:01:51.060 an open window. Right. The target temperature 00:01:51.060 --> 00:01:53.079 is often pushed down to somewhere between 32 00:01:53.079 --> 00:01:55.780 and 34 degrees Celsius. And for context, normal 00:01:55.780 --> 00:01:58.620 body temperature is what, around 37 degrees Celsius? 00:01:58.739 --> 00:02:01.920 Yeah, roughly 37. And this drop is done for a 00:02:01.920 --> 00:02:05.120 very specific reason, to improve health outcomes 00:02:05.120 --> 00:02:07.719 and brain function after blood flow to the brain 00:02:07.719 --> 00:02:09.939 has completely stopped. So we're talking about 00:02:09.939 --> 00:02:12.860 the aftermath of a cardiac arrest. Cardiac arrest 00:02:12.860 --> 00:02:15.819 or, you know, the blockage of an artery by a 00:02:15.819 --> 00:02:19.469 clot during a stroke. Wow. OK, so. While the 00:02:19.469 --> 00:02:22.229 technology we use today to achieve that temperature 00:02:22.229 --> 00:02:25.389 drop is incredibly advanced, the concept itself 00:02:25.389 --> 00:02:28.509 is, um, it's surprisingly ancient, isn't it? 00:02:28.669 --> 00:02:31.770 It really is. If we trace the history back, that 00:02:31.770 --> 00:02:34.169 observation by the Napoleonic surgeon wasn't 00:02:34.169 --> 00:02:36.229 even the first time this phenomenon was noted. 00:02:36.469 --> 00:02:40.110 Really? Who was earlier? Hippocrates. He actually 00:02:40.110 --> 00:02:42.389 advocated for packing wounded soldiers in snow 00:02:42.389 --> 00:02:44.310 and ice to treat their injuries. I mean, that 00:02:44.310 --> 00:02:46.469 sounds more like medieval torture than medicine. 00:02:46.550 --> 00:02:48.949 Right. It does seem harsh. But it took a long 00:02:48.949 --> 00:02:50.849 time for modern medicine to catch up to what 00:02:50.849 --> 00:02:52.789 Hippocrates observed. How long are we talking? 00:02:53.009 --> 00:02:56.069 Well, it wasn't until 1945 that the first formal 00:02:56.069 --> 00:02:58.569 medical article concerning hypothermia was actually 00:02:58.569 --> 00:03:02.189 published. 1945? That late? Yeah. And that was 00:03:02.189 --> 00:03:04.250 focusing on patients with severe head injuries. 00:03:04.839 --> 00:03:08.539 Then, in the 1950s, a doctor named Rosamoff demonstrated 00:03:08.539 --> 00:03:11.280 the positive effects of mild hypothermia after 00:03:11.280 --> 00:03:13.580 brain ischemia in dogs. Brain ischemia, that's 00:03:13.580 --> 00:03:15.439 a restriction of blood supply, right? Exactly. 00:03:15.939 --> 00:03:18.099 And around that same time, doctors started using 00:03:18.099 --> 00:03:21.479 hypothermia in intracerebral aneurysm surgery 00:03:21.479 --> 00:03:24.520 to create what they called a bloodless field. 00:03:24.699 --> 00:03:27.800 A bloodless field sounds less like medicine and 00:03:27.800 --> 00:03:29.939 more like science fiction. It's a very intense 00:03:29.939 --> 00:03:32.219 term. I'm assuming that means they cool the body 00:03:32.219 --> 00:03:34.740 so much that circulation slows down to a crawl, 00:03:34.860 --> 00:03:37.539 which allows surgeons to, like, operate on the 00:03:37.539 --> 00:03:39.900 brain without catastrophic bleeding. Precisely. 00:03:40.340 --> 00:03:42.360 By lowering the body temperature, you reduce 00:03:42.360 --> 00:03:44.280 the heart rate and blood pressure, shrinking 00:03:44.280 --> 00:03:46.780 the blood vessels. Makes sense. But for decades 00:03:46.780 --> 00:03:50.139 after those initial 1950s experiments, the research 00:03:50.139 --> 00:03:52.780 was incredibly sporadic. And honestly, it was 00:03:52.780 --> 00:03:55.909 a bit misguided. How so? Well, researchers initially 00:03:55.909 --> 00:03:58.150 thought that if cold was good, freezing must 00:03:58.150 --> 00:04:01.229 be better. Oh, no. Yeah. They focused on deep 00:04:01.229 --> 00:04:04.030 hypothermia, dropping the body down to 20 to 00:04:04.030 --> 00:04:06.889 25 degrees Celsius. I have to imagine dropping 00:04:06.889 --> 00:04:09.409 a human core temperature by 15 degrees causes 00:04:09.409 --> 00:04:12.169 the body's systems to just start shutting down 00:04:12.169 --> 00:04:15.389 completely. It does. That extreme drop brought 00:04:15.389 --> 00:04:18.290 a whole host of dangerous side effects, primarily 00:04:18.290 --> 00:04:20.589 cardiac arrhythmias. The heart just can't handle 00:04:20.589 --> 00:04:23.569 it. No. The heart simply cannot maintain a normal 00:04:23.569 --> 00:04:26.389 rhythm at 20 degrees Celsius. It often leads 00:04:26.389 --> 00:04:29.189 to ventricular fibrillation, making it entirely 00:04:29.189 --> 00:04:31.810 impractical for most clinical situations. So 00:04:31.810 --> 00:04:33.990 they had to back off from that extreme. Right. 00:04:34.189 --> 00:04:36.470 It wasn't until the 1980s that animal studies 00:04:36.470 --> 00:04:39.149 shifted focus back to mild hypothermia, that 00:04:39.149 --> 00:04:42.769 32 to 34 degree range, as a general neuroprotectant. 00:04:42.870 --> 00:04:45.350 Got it. And that leads us to the real turning 00:04:45.350 --> 00:04:49.350 point in the source material. Two landmark human 00:04:49.350 --> 00:04:51.350 studies were published simultaneously in the 00:04:51.350 --> 00:04:53.850 New England Journal of Medicine in 2002. Wait, 00:04:54.029 --> 00:04:56.829 simultaneously? Yep. One in Europe, one in Australia. 00:04:57.069 --> 00:04:59.829 And they conclusively proved that mild therapeutic 00:04:59.829 --> 00:05:03.050 hypothermia improved both survival and neurological 00:05:03.050 --> 00:05:05.610 outcomes after cardiac arrest. And reading through 00:05:05.610 --> 00:05:08.350 the history, that 2002 publication completely 00:05:08.350 --> 00:05:10.709 changed the game, didn't it? Oh, overnight. Because 00:05:10.709 --> 00:05:13.629 right after that, in 2003, the American Heart 00:05:13.629 --> 00:05:16.029 Association and the International Liaison Committee 00:05:16.029 --> 00:05:18.709 on Resuscitation officially endorsed the use 00:05:18.709 --> 00:05:20.509 of targeted temperature management. They did, 00:05:20.589 --> 00:05:22.709 yeah. So we have the historical anecdotes, we 00:05:22.709 --> 00:05:24.810 have the data. But when I was looking at the 00:05:24.810 --> 00:05:27.600 research... The underlying mechanics tripped 00:05:27.600 --> 00:05:31.420 me up a bit. What part? Wait, doesn't lack of 00:05:31.420 --> 00:05:34.680 oxygen kill a cell directly? Like, how does being 00:05:34.680 --> 00:05:37.160 cold stop a cell from suffocating? That's a great 00:05:37.160 --> 00:05:39.620 question. Is it basically, is chilling the body 00:05:39.620 --> 00:05:42.060 essentially forcing the brain into low power 00:05:42.060 --> 00:05:44.240 mode? Like you're dimming the screen and stopping 00:05:44.240 --> 00:05:46.259 background apps so the battery doesn't die before 00:05:46.259 --> 00:05:48.100 the ambulance gets there? What's fascinating 00:05:48.100 --> 00:05:51.079 here is... The mechanism isn't just about saving 00:05:51.079 --> 00:05:53.160 battery, though that is the foundation of it. 00:05:53.240 --> 00:05:54.959 All right. So the analogy holds up a bit. It 00:05:54.959 --> 00:05:57.279 does. When your phone goes into low power mode, 00:05:57.680 --> 00:06:00.540 it reduces the demand for power. For every one 00:06:00.540 --> 00:06:03.680 degree Celsius drop in body temperature, a cell's 00:06:03.680 --> 00:06:07.019 metabolic rate, its demand for energy and oxygen 00:06:07.019 --> 00:06:10.300 slows down by five to seven percent. Wow. So 00:06:10.300 --> 00:06:13.339 if you drop the temperature by like Four degrees. 00:06:13.600 --> 00:06:16.680 The brain's oxygen demand plummets by up to 28%. 00:06:16.680 --> 00:06:19.120 That is massive. But it goes deeper than that. 00:06:19.339 --> 00:06:21.120 And this addresses your question about cellular 00:06:21.120 --> 00:06:24.339 suffocation. Cell death is not directly caused 00:06:24.339 --> 00:06:27.160 by oxygen deprivation. Wait, really? Yeah. It 00:06:27.160 --> 00:06:29.839 is not an immediate suffocation. It is a slow 00:06:29.839 --> 00:06:31.759 -motion cascade. I need to make sure I'm getting 00:06:31.759 --> 00:06:34.139 this. It's not the lack of oxygen itself that's 00:06:34.139 --> 00:06:37.920 the killer. No. Cells need oxygen for one primary 00:06:37.920 --> 00:06:43.160 reason, to manufacture ATP. And ATP is the energy 00:06:43.160 --> 00:06:45.319 molecule, right? Exactly. It's the molecule that 00:06:45.319 --> 00:06:48.139 cells use to store and transport energy. Without 00:06:48.139 --> 00:06:51.779 oxygen, ATP production just stops. OK. No oxygen, 00:06:51.839 --> 00:06:54.199 no energy. Right. And the reason that is lethal 00:06:54.199 --> 00:06:57.980 is because cells desperately need ATP to fuel 00:06:57.980 --> 00:07:00.339 the microscopic pumps on their surface. Pumps? 00:07:00.480 --> 00:07:02.579 Yeah. These pumps regulate their internal environment. 00:07:02.860 --> 00:07:05.199 They constantly use energy to push necessary 00:07:05.199 --> 00:07:09.060 ions in and harmful ions out. So the oxygen stops. 00:07:09.449 --> 00:07:11.870 factory shuts down, and without that energy, 00:07:11.970 --> 00:07:14.629 the cell loses the ability to pump out the trash. 00:07:14.689 --> 00:07:16.509 That's a great way to put it. It effectively 00:07:16.509 --> 00:07:18.569 poisons itself. That is exactly what happens. 00:07:18.649 --> 00:07:21.250 When those pumps shut down, the intracellular 00:07:21.250 --> 00:07:24.029 environment can no longer be regulated. Calcium 00:07:24.029 --> 00:07:26.370 and sodium ions just flood into the cell. And 00:07:26.370 --> 00:07:28.870 homeostasis is destroyed. Entirely. And that 00:07:28.870 --> 00:07:31.649 toxic internal environment is what triggers apoptosis 00:07:31.649 --> 00:07:34.629 program cell death. It's the catastrophic failure 00:07:34.629 --> 00:07:37.970 of the cell's ion pumps due to the lack of oxygen 00:07:37.970 --> 00:07:41.050 that ultimately kills the tissue. That reframes 00:07:41.050 --> 00:07:43.629 a stroke or a cardiac arrest entirely. It is 00:07:43.629 --> 00:07:45.829 literally a domino effect. It really is. But 00:07:45.829 --> 00:07:47.910 if the dominoes are falling because the pumps 00:07:47.910 --> 00:07:50.490 are broken, what is the cold actually doing to 00:07:50.490 --> 00:07:53.350 the cell structure to stop it? This is the true 00:07:53.350 --> 00:07:56.629 genius of targeted temperature management. Even 00:07:56.629 --> 00:07:59.470 a small drop in temperature physically alters 00:07:59.470 --> 00:08:02.110 the lipid bilayer of the cell membrane. Like 00:08:02.110 --> 00:08:05.000 the outer wall of the cell. Exactly. It strengthens 00:08:05.000 --> 00:08:08.160 and stabilizes it, making the membrane more impermeable. 00:08:08.279 --> 00:08:11.980 Oh, I see. So even when the ATP pumps fail, the 00:08:11.980 --> 00:08:14.420 fortified membrane acts as a physical barrier. 00:08:14.730 --> 00:08:17.509 It becomes rigid enough to help prevent that 00:08:17.509 --> 00:08:20.290 fatal influx of unwanted calcium and sodium ions. 00:08:20.490 --> 00:08:23.069 That is wild. You're essentially freezing the 00:08:23.069 --> 00:08:25.449 dominoes in place before they can topple. Exactly. 00:08:25.509 --> 00:08:27.949 You're buying time. It physically fortifies the 00:08:27.949 --> 00:08:30.089 walls of the cell, but, you know, reading further 00:08:30.089 --> 00:08:32.549 into the source material, the lack of oxygen 00:08:32.549 --> 00:08:34.850 is only half the battle. Right. The reperfusion. 00:08:35.090 --> 00:08:37.990 Yeah. Eventually, a doctor has to restart the 00:08:37.990 --> 00:08:40.509 heart or clear the clot. The blood has to come 00:08:40.509 --> 00:08:43.929 rushing back. And paradoxically, The blood returning 00:08:43.929 --> 00:08:46.509 seems to be just as dangerous as the blood leaving. 00:08:47.190 --> 00:08:49.769 You are bringing up reperfusion injury, which 00:08:49.769 --> 00:08:52.389 is a massive hurdle in emergency medicine. It 00:08:52.389 --> 00:08:55.149 just seems so counterintuitive. It does. When 00:08:55.149 --> 00:08:57.409 blood supply is finally restored to a tissue 00:08:57.409 --> 00:09:00.110 after a period of ischemia, meaning lack of blood 00:09:00.110 --> 00:09:02.870 flow, the body doesn't just return to normal. 00:09:03.330 --> 00:09:06.769 It triggers a massive violent inflammatory immune 00:09:06.769 --> 00:09:10.149 response. But why? Why does the body attack itself? 00:09:10.360 --> 00:09:12.720 just because the blood is back. Because the tissue 00:09:12.720 --> 00:09:15.200 has been starving and its chemistry is fundamentally 00:09:15.200 --> 00:09:18.340 altered. Okay. When a massive wave of fresh oxygen 00:09:18.340 --> 00:09:20.440 suddenly interacts with those altered damaged 00:09:20.440 --> 00:09:23.480 cells, you get immense oxidative stress. You 00:09:23.480 --> 00:09:25.580 get a surge in free radical production. Which 00:09:25.580 --> 00:09:28.860 sounds terrible. It is. This inflammatory response 00:09:28.860 --> 00:09:31.240 causes the brain to swell, leading to increased 00:09:31.240 --> 00:09:33.179 intracranial pressure. And the skull doesn't 00:09:33.179 --> 00:09:36.799 have any extra room. Exactly. That pressure squashes 00:09:36.799 --> 00:09:39.259 the brain against the skull, which causes even 00:09:39.259 --> 00:09:42.110 more injury and death. It's like a rescue squad 00:09:42.110 --> 00:09:44.669 showing up to a house fire but their hoses are 00:09:44.669 --> 00:09:47.289 spraying gasoline instead of water. The rescue 00:09:47.289 --> 00:09:49.669 itself is causing the structural damage. That 00:09:49.669 --> 00:09:53.029 is a brilliant analogy and hypothermia acts as 00:09:53.029 --> 00:09:55.450 a shield against that overzealous rescue attempt. 00:09:55.610 --> 00:09:58.590 How so? The cold moderates that intracranial 00:09:58.590 --> 00:10:01.370 pressure. It suppresses the harmful inflammatory 00:10:01.370 --> 00:10:04.409 immune responses and it drastically reduces the 00:10:04.409 --> 00:10:06.789 production of those damaging free radicals during 00:10:06.789 --> 00:10:09.600 reperfusion. Here's where it gets really interesting 00:10:09.600 --> 00:10:12.740 for me. Knowing why it works on a cellular level 00:10:12.740 --> 00:10:15.879 is incredible, but it begs an almost absurd logistical 00:10:15.879 --> 00:10:17.840 question. Logistics are always the hard part. 00:10:17.919 --> 00:10:20.240 Right. Like, how do doctors practically turn 00:10:20.240 --> 00:10:23.240 a living, breathing human being into an icebox? 00:10:23.360 --> 00:10:25.620 It's not easy. I mean, the human body does not 00:10:25.620 --> 00:10:28.159 want to be cold. We have millions of years of 00:10:28.159 --> 00:10:31.120 evolution designed specifically to keep our core 00:10:31.120 --> 00:10:34.080 temperature at exactly 37 degrees. We do. And 00:10:34.080 --> 00:10:36.220 the body fights back violently against the cooling 00:10:36.220 --> 00:10:38.659 process. Stop that. When the core body temperature 00:10:38.659 --> 00:10:41.320 drops below a certain threshold, typically around 00:10:41.320 --> 00:10:44.460 36 degrees Celsius, the hypothalamus in the brain 00:10:44.460 --> 00:10:47.580 sounds the alarm. And it triggers its primary 00:10:47.580 --> 00:10:50.039 defense mechanism, which is shivering. Exactly. 00:10:50.379 --> 00:10:52.299 Shivering. Because shivering is just intense 00:10:52.299 --> 00:10:54.740 involuntary muscle friction, right? It generates 00:10:54.740 --> 00:10:57.259 heat. Yes. The body is desperately trying to 00:10:57.259 --> 00:10:59.399 warm itself back up, which burns massive amounts 00:10:59.399 --> 00:11:02.259 of energy, the exact opposite of what you want 00:11:02.259 --> 00:11:04.879 when you are trying to put the brain in low power 00:11:04.879 --> 00:11:08.379 mode. Which is why Inducing therapeutic hypothermia 00:11:08.379 --> 00:11:12.179 is an incredibly intense pharmacological process. 00:11:12.799 --> 00:11:14.840 Medical teams cannot just place someone in an 00:11:14.840 --> 00:11:17.019 ice bath. They just shake themselves to death. 00:11:17.539 --> 00:11:20.240 Basically. Before the cooling even begins, they 00:11:20.240 --> 00:11:22.600 have to administer a heavy cocktail of drugs 00:11:22.600 --> 00:11:25.600 just to suppress that shivering reflex. Like 00:11:25.600 --> 00:11:27.799 what kind of drugs? We were talking about medications 00:11:27.799 --> 00:11:30.759 like acetaminophen, opioids like fentanyl, and 00:11:30.759 --> 00:11:33.580 sedatives like propofol. Wow. But I imagine even 00:11:33.580 --> 00:11:36.000 with heavy narcotics, the brain is still trying 00:11:36.000 --> 00:11:38.299 to force the muscles to spasm and generate heat. 00:11:38.659 --> 00:11:40.960 What happens if the shivering won't stop? Then 00:11:40.960 --> 00:11:43.279 the patient is often placed under general anesthesia, 00:11:43.700 --> 00:11:46.220 or given paralytic medications like Vekeronium. 00:11:46.440 --> 00:11:49.340 Yeah. They essentially have to medically paralyze 00:11:49.340 --> 00:11:51.779 the patient to stop the muscles from moving. 00:11:51.960 --> 00:11:55.539 That is intense. It is. Only after that evolutionary 00:11:55.539 --> 00:11:58.399 survival programming is overwritten can the actual 00:11:58.399 --> 00:12:01.360 physical cooling process begin. I am looking 00:12:01.360 --> 00:12:03.840 at the list of ways they actually lower the temperature 00:12:03.840 --> 00:12:06.580 and the physical engineering of it is just wild. 00:12:06.600 --> 00:12:08.879 It's very creative. You can't just throw a bag 00:12:08.879 --> 00:12:11.440 of crushed ice on someone. The methods in the 00:12:11.440 --> 00:12:14.940 sources range from deceptively simple to pure 00:12:14.940 --> 00:12:18.840 sci -fi. The methods are incredibly diverse and 00:12:18.840 --> 00:12:22.399 as of 2013 the research suggests that it's actually 00:12:22.399 --> 00:12:25.059 unclear if one method is definitively better 00:12:25.059 --> 00:12:27.860 than the others. They all have unique engineering 00:12:27.860 --> 00:12:29.919 challenges. What's the most common one? The most 00:12:29.919 --> 00:12:31.919 common and well studied method involves water 00:12:31.919 --> 00:12:34.600 blankets. You wrap the patient's torso and legs 00:12:34.600 --> 00:12:37.360 in blankets or vests that have cold water continuously 00:12:37.360 --> 00:12:39.240 circulating through them. Okay, so it lowers 00:12:39.240 --> 00:12:41.340 the temperature exclusively through skin contact. 00:12:41.399 --> 00:12:43.720 Right, covering about 70 % of the patient's surface 00:12:43.720 --> 00:12:46.200 area. But if you're just putting cold water on 00:12:46.200 --> 00:12:48.779 the skin, doesn't the body temperature plunge 00:12:48.779 --> 00:12:51.799 too fast or unevenly? The source has mentioned 00:12:51.799 --> 00:12:55.179 overshoot is a major complication. Yes. The temperature 00:12:55.179 --> 00:12:57.960 overshoot is a significant engineering flaw. 00:12:58.559 --> 00:13:00.519 Because you are cooling from the outside in, 00:13:00.899 --> 00:13:03.159 it takes time for the cold to reach the core. 00:13:03.379 --> 00:13:06.019 Oh, of course. By the time the core registers 00:13:06.019 --> 00:13:09.019 a stubby three degrees, the skin and outer tissues 00:13:09.019 --> 00:13:12.019 are much colder. And that cooling momentum carries 00:13:12.019 --> 00:13:14.759 their core temperature even lower, dropping them 00:13:14.759 --> 00:13:17.299 below 32 degrees Celsius. Which is getting into 00:13:17.299 --> 00:13:19.399 the danger zone we talked about earlier. Exactly. 00:13:19.580 --> 00:13:22.620 That drastically increases the risk of adverse 00:13:22.620 --> 00:13:25.240 medical events. So how do they fix that? Newer 00:13:25.240 --> 00:13:28.059 machines try to combat this using core temperature 00:13:28.059 --> 00:13:31.240 probes, often rectal probes, that feed continuous 00:13:31.240 --> 00:13:34.000 data back to the blanket software to automatically 00:13:34.000 --> 00:13:36.299 adjust the water temperature. But it remains 00:13:36.299 --> 00:13:38.759 a blunt instrument. So if water blankets risk 00:13:38.759 --> 00:13:40.899 burning the skin and overshooting the target 00:13:40.899 --> 00:13:44.340 temperature, how do doctors bypass the skin entirely? 00:13:44.480 --> 00:13:46.539 Because that's where the engineering gets a bit 00:13:46.539 --> 00:13:49.000 terrifying. You were referring to cooling catheters. 00:13:49.460 --> 00:13:52.460 This is an invasive procedure that must be performed 00:13:52.460 --> 00:13:55.600 by a fully trained physician, often an interventional 00:13:55.600 --> 00:13:59.240 radiologist. OK. They insert a highly precise 00:13:59.240 --> 00:14:02.659 triple lumen catheter directly into the femoral 00:14:02.659 --> 00:14:05.700 vein in the leg. The femoral vein is huge. It 00:14:05.700 --> 00:14:08.940 is. The catheter has a metal coated tube or a 00:14:08.940 --> 00:14:11.600 balloon through which cooled saline solution 00:14:11.600 --> 00:14:14.720 circulates. Wait, injecting cold saline directly 00:14:14.720 --> 00:14:17.399 into the bloodstream? No, no, and that is a crucial 00:14:17.399 --> 00:14:20.360 distinction. The cold saline circulates inside 00:14:20.360 --> 00:14:23.159 a closed loop within the catheter. It never actually 00:14:23.159 --> 00:14:25.889 touches the blood. It just chills the metal or 00:14:25.889 --> 00:14:28.529 balloon. And as the patient's blood flows past 00:14:28.529 --> 00:14:31.169 this incredibly cold surface in the vein, it 00:14:31.169 --> 00:14:33.490 cools down. So you are literally chilling the 00:14:33.490 --> 00:14:35.509 blood from the inside out as it circulates through 00:14:35.509 --> 00:14:37.970 the body. Exactly. That has to be incredibly 00:14:37.970 --> 00:14:40.090 efficient compared to putting a cold blanket 00:14:40.090 --> 00:14:42.429 on someone's chest. Oh, it is. It can reduce 00:14:42.429 --> 00:14:45.470 the body temperature at a rapid rate of 1 .5 00:14:45.470 --> 00:14:48.340 to 2 degrees Celsius per hour. And because the 00:14:48.340 --> 00:14:50.539 control unit is directly monitoring the blood 00:14:50.539 --> 00:14:53.580 temperature inside the vein, it can dial in the 00:14:53.580 --> 00:14:56.399 core body temperature to within 0 .1 degrees 00:14:56.399 --> 00:14:59.279 Celsius of the target level. So no overshoot. 00:14:59.399 --> 00:15:01.379 It completely eliminates the overshoot problem. 00:15:01.519 --> 00:15:04.440 Plus, it allows doctors to rewarm the patient 00:15:04.440 --> 00:15:07.899 at a very slow, steady, controlled rate, which 00:15:07.899 --> 00:15:10.419 is crucial for preventing those dangerous spikes 00:15:10.419 --> 00:15:12.960 in brain pressure we discussed earlier. But the 00:15:12.960 --> 00:15:15.820 trade off is significant physical risk, right? 00:15:16.059 --> 00:15:19.019 You are threading a foreign object into a major 00:15:19.019 --> 00:15:21.399 vein. There are definitely risks. The sources 00:15:21.399 --> 00:15:24.559 note severe risks of infection, vascular puncture, 00:15:24.779 --> 00:15:28.200 and deep vein thrombosis. Like a blood clot forming 00:15:28.200 --> 00:15:30.480 around that catheter in the femoral vein could 00:15:30.480 --> 00:15:33.080 travel to the lungs and cause a fatal pulmonary 00:15:33.080 --> 00:15:36.059 embolism. That is a real concern. So you are 00:15:36.059 --> 00:15:38.179 trading the bluntness of the blankets for the 00:15:38.179 --> 00:15:40.639 precision and physical risk of a catheter. Exactly. 00:15:40.919 --> 00:15:42.779 Which is why engineers look for a way to target 00:15:42.779 --> 00:15:45.580 the brain directly. bypassing the full body complications 00:15:45.580 --> 00:15:48.559 altogether. That led to trans -nasal evaporative 00:15:48.559 --> 00:15:50.480 tooling. This was the method that I just couldn't 00:15:50.480 --> 00:15:52.679 wrap my head around initially. I don't understand 00:15:52.679 --> 00:15:55.899 how cooling the nasal cavity cools the brain 00:15:55.899 --> 00:15:58.700 fast enough to matter in an emergency. It really 00:15:58.700 --> 00:16:00.820 comes down to human anatomy. Yeah. The nasal 00:16:00.820 --> 00:16:03.159 cavity sits directly underneath the base of the 00:16:03.159 --> 00:16:05.419 skull, right underneath the brain. Right. It 00:16:05.419 --> 00:16:08.460 also has an incredibly high surface area and 00:16:08.460 --> 00:16:12.090 massive blood flow. This device uses two small 00:16:12.090 --> 00:16:14.690 cannulae inserted directly into the patient's 00:16:14.690 --> 00:16:18.149 nose. And then what? It sprays a continuous mist 00:16:18.149 --> 00:16:21.070 of a volatile coolant that evaporates instantly. 00:16:21.429 --> 00:16:23.730 It's literally like spraying Freon straight into 00:16:23.730 --> 00:16:26.990 the hard drive. Functionally, yes. As blood passes 00:16:26.990 --> 00:16:29.350 through that incredibly cold area in the nasal 00:16:29.350 --> 00:16:32.710 cavity, it cools down significantly before circulating 00:16:32.710 --> 00:16:35.070 up into the rest of the brain. That is brilliant. 00:16:35.309 --> 00:16:37.149 It's targeted right at the most critical organ, 00:16:37.470 --> 00:16:39.409 and research shows it can drop the brain's temperature 00:16:39.409 --> 00:16:43.019 by 2 .6 degrees Celsius per hour. The practical 00:16:43.019 --> 00:16:45.720 application for you listening right now is amazing 00:16:45.720 --> 00:16:48.840 here. Because this device is so compact, it doesn't 00:16:48.840 --> 00:16:51.639 need a whole hospital room or a surgeon to insert 00:16:51.639 --> 00:16:54.179 a femoral line. No, not at all. It can be used 00:16:54.179 --> 00:16:56.840 by paramedics right at the point of cardiac arrest 00:16:56.840 --> 00:17:00.179 or in the back of a moving ambulance. They can 00:17:00.179 --> 00:17:02.379 start saving the brain before the patient even 00:17:02.379 --> 00:17:05.400 hits the emergency room doors. It's a huge leap 00:17:05.400 --> 00:17:08.059 forward for pre -hospital care. And the last 00:17:08.059 --> 00:17:10.680 method mentioned in the sources shows how adaptable 00:17:10.680 --> 00:17:14.119 this technology is. Cool caps. Yes, these are 00:17:14.119 --> 00:17:16.759 non -invasive helmets or caps made of neoprene 00:17:16.759 --> 00:17:19.519 or silicone, filled with gel or continuously 00:17:19.519 --> 00:17:22.420 circulating liquid, cooled to as low as negative 00:17:22.420 --> 00:17:25.980 25 to negative 30 degrees Celsius. They target 00:17:25.980 --> 00:17:28.430 the scalp and the brain specifically. And they 00:17:28.430 --> 00:17:30.829 aren't just for a cardiac arrest. No, they have 00:17:30.829 --> 00:17:33.650 other very important uses. The sources note they 00:17:33.650 --> 00:17:36.309 are used specifically to prevent cerebral palsy 00:17:36.309 --> 00:17:38.589 in newborns who suffer from oxygen deprivation 00:17:38.589 --> 00:17:40.809 at birth. Yes. And they are also widely used 00:17:40.809 --> 00:17:42.990 by chemotherapy patients to prevent or reduce 00:17:42.990 --> 00:17:45.950 hair loss. By freezing the scalp, it constricts 00:17:45.950 --> 00:17:47.869 the blood vessels, physically preventing the 00:17:47.869 --> 00:17:50.089 toxic chemo drugs from reaching and killing the 00:17:50.089 --> 00:17:53.230 hair follicles. It is a perfect example of taking 00:17:53.230 --> 00:17:56.950 a core physiological principle. cold, causing 00:17:56.950 --> 00:17:59.869 vasoconstriction, and slowing metabolism, and 00:17:59.869 --> 00:18:02.309 applying it across radically different medical 00:18:02.309 --> 00:18:04.369 disciplines. OK, I have to play devil's advocate 00:18:04.369 --> 00:18:06.829 here. Fair enough. It can't be all perfect. We've 00:18:06.829 --> 00:18:08.829 talked about the miracles and the brilliant engineering, 00:18:09.269 --> 00:18:11.809 but what are the downsides? Because freezing 00:18:11.809 --> 00:18:14.730 a critically ill patient, paralyzing their muscles, 00:18:15.069 --> 00:18:17.849 dropping their core temperature, that has to 00:18:17.849 --> 00:18:20.349 come with severe collateral damage. It absolutely 00:18:20.349 --> 00:18:22.269 does. When you drop the body's temperature, you 00:18:22.269 --> 00:18:24.470 suppress everything, including the immune system. 00:18:24.589 --> 00:18:27.250 That makes sense. One comprehensive review found 00:18:27.250 --> 00:18:30.450 an increased risk of pneumonia and sepsis because 00:18:30.450 --> 00:18:32.509 the white blood cells just aren't functioning 00:18:32.509 --> 00:18:34.690 at optimal speeds. They're in low power mode 00:18:34.690 --> 00:18:37.269 too. Exactly. You also suppress the body's ability 00:18:37.269 --> 00:18:40.589 to clot. The enzymes responsible for coagulating 00:18:40.589 --> 00:18:43.710 blood are highly temperature sensitive. Oh, wow. 00:18:44.089 --> 00:18:46.430 Hypothermia lowers the clotting threshold, which 00:18:46.430 --> 00:18:49.190 means there is a trend towards increased bleeding. 00:18:49.490 --> 00:18:52.569 That is obviously incredibly dangerous for trauma 00:18:52.569 --> 00:18:55.450 patients or stroke victims who might already 00:18:55.450 --> 00:18:58.130 have internal hemorrhaging. It's a massive risk 00:18:58.130 --> 00:19:00.609 factor they have to weigh. The source material 00:19:00.609 --> 00:19:04.269 also outlined a complication called cold diuresis. 00:19:04.809 --> 00:19:07.289 Can you explain what is actually happening there 00:19:07.289 --> 00:19:09.890 without getting too deep into the medical jargon? 00:19:09.910 --> 00:19:13.730 Of course When you are cold your body tries to 00:19:13.730 --> 00:19:16.309 conserve heat by constricting the blood vessels 00:19:16.309 --> 00:19:19.269 in your arms and legs Right pushing all your 00:19:19.269 --> 00:19:21.990 blood to your core to protect your vital organs 00:19:21.990 --> 00:19:24.990 Yes, but because all that blood is now squeezed 00:19:24.990 --> 00:19:27.829 into a smaller central area your central blood 00:19:27.829 --> 00:19:30.470 pressure goes up Okay, that makes sense your 00:19:30.470 --> 00:19:33.109 kidneys sense this high pressure and while they 00:19:33.109 --> 00:19:35.809 panic They try to fix it by filtering out massive 00:19:35.809 --> 00:19:38.230 amounts of fluid to lower the overall volume. 00:19:38.670 --> 00:19:40.849 So the patient produces a massive amount of urine 00:19:40.849 --> 00:19:43.730 just because they are cold. Exactly. But because 00:19:43.730 --> 00:19:46.289 the body is flushing out so much fluid, it takes 00:19:46.289 --> 00:19:48.230 essential minerals right out the door with it. 00:19:48.490 --> 00:19:51.049 Like what? We're talking about a dangerous plunge 00:19:51.049 --> 00:19:53.430 in potassium, magnesium, and phosphorus levels 00:19:53.430 --> 00:19:56.000 in the blood. And those are important. incredibly. 00:19:56.559 --> 00:19:58.440 These minerals are critical for heart rhythm 00:19:58.440 --> 00:20:01.160 and muscle function, so it requires constant 00:20:01.160 --> 00:20:03.900 vigilant monitoring and intravenous replacement 00:20:03.900 --> 00:20:06.720 by the ICU team. It's a massive high wire act 00:20:06.720 --> 00:20:08.900 for the doctors, which brings us to a really 00:20:08.900 --> 00:20:10.819 crucial point about the current state of this 00:20:10.819 --> 00:20:13.579 treatment, because the medical consensus on TTM 00:20:13.579 --> 00:20:16.400 isn't as settled as it was 20 years ago. If we 00:20:16.400 --> 00:20:19.339 connect this to the bigger picture, this is exactly 00:20:19.339 --> 00:20:21.900 how medical science self -corrects and evolves. 00:20:22.099 --> 00:20:26.000 For certain conditions, TTM remains the absolute 00:20:26.000 --> 00:20:29.259 standard of care for neonatal encephalopathy 00:20:29.259 --> 00:20:32.579 infants who suffer oxygen loss at birth. Cooling 00:20:32.579 --> 00:20:36.119 the whole body or just the head to 33 or 34 degrees 00:20:36.119 --> 00:20:39.400 for 72 hours is proven to significantly reduce 00:20:39.400 --> 00:20:42.000 mortality and neurological deficit. It is undeniably 00:20:42.000 --> 00:20:44.460 a lifesaver there. Yes. But the Wikipedia article 00:20:44.460 --> 00:20:46.759 highlights that for adults the protocol is being 00:20:46.759 --> 00:20:49.799 heavily questioned. Remember those landmark 2002 00:20:49.799 --> 00:20:52.059 studies that push everyone to cool patients to 00:20:52.059 --> 00:20:54.940 33 degrees? Why is the medical community walking 00:20:54.940 --> 00:20:57.599 that back now? It comes down to how those original 00:20:57.599 --> 00:21:01.259 studies were designed. In 2002, the control group 00:21:01.589 --> 00:21:03.869 The patients who weren't cooled were essentially 00:21:03.869 --> 00:21:05.930 just left alone at room temperature. Which seems 00:21:05.930 --> 00:21:08.109 normal, right? It does. But many of those patients 00:21:08.109 --> 00:21:10.789 naturally develop severe fevers after their cardiac 00:21:10.789 --> 00:21:14.490 arrests. A fever of 39 or 40 degrees cooks the 00:21:14.490 --> 00:21:17.069 already vulnerable brain cells. Oh, wow. The 00:21:17.069 --> 00:21:19.569 group that was cooled to 33 degrees obviously 00:21:19.569 --> 00:21:22.589 didn't develop fevers. So at the time, researchers 00:21:22.589 --> 00:21:25.250 concluded that 33 degrees was a magic number 00:21:25.250 --> 00:21:28.950 for neuroprotection. Ah, I see. But later on, 00:21:29.069 --> 00:21:31.670 they decided to test 33 degrees against just 00:21:31.670 --> 00:21:33.690 keeping the patient at a strictly controlled, 00:21:33.809 --> 00:21:36.750 normal body temperature. Precisely. More recent, 00:21:37.170 --> 00:21:39.269 massive clinical trials tested aggressively cooling 00:21:39.269 --> 00:21:41.970 patients to 33 degrees, again simply keeping 00:21:41.970 --> 00:21:44.410 them at a near normal temperature of 36 degrees. 00:21:44.529 --> 00:21:46.410 And what happened? The results were stunning. 00:21:46.809 --> 00:21:48.930 There was no significant difference in long -term 00:21:48.930 --> 00:21:51.369 neurological outcomes or survival between the 00:21:51.369 --> 00:21:55.299 two groups. That is a massive aha moment. It 00:21:55.299 --> 00:21:57.859 appears that the real benefit of targeted temperature 00:21:57.859 --> 00:22:00.519 management in these adult cardiac arrest cases 00:22:00.519 --> 00:22:03.559 was never the deep freeze. It was simply the 00:22:03.559 --> 00:22:06.079 strict prevention of the fever. By locking the 00:22:06.079 --> 00:22:09.000 body at 36 degrees, you prevent the fever from 00:22:09.000 --> 00:22:11.519 ever occurring, saving the brain from that secondary 00:22:11.519 --> 00:22:14.299 inflammatory damage. And you completely bypass 00:22:14.299 --> 00:22:16.859 the extreme risks of deep sedation, pneumonia, 00:22:17.079 --> 00:22:20.019 and bleeding associated with 33 degrees. It is 00:22:20.019 --> 00:22:22.910 a brilliant refinement of the data. And the sources 00:22:22.910 --> 00:22:25.470 also point out that despite theoretical benefits, 00:22:26.029 --> 00:22:29.210 TTM is completely unproven right now for treating 00:22:29.210 --> 00:22:31.549 strokes or traumatic brain injuries in humans. 00:22:31.930 --> 00:22:34.170 Really? Yeah, these animal models look incredibly 00:22:34.170 --> 00:22:36.670 promising, but the human trials just haven't 00:22:36.670 --> 00:22:39.849 shown clear benefits yet. The human body is infinitely 00:22:39.849 --> 00:22:42.970 complex. A therapy that works perfectly for a 00:22:42.970 --> 00:22:45.630 newborn's brain might not translate at all to 00:22:45.630 --> 00:22:47.859 a six -year -old stroke patient. So what does 00:22:47.859 --> 00:22:50.000 this all mean? For you listening right now, we've 00:22:50.000 --> 00:22:52.099 gone on quite a journey. We really have. We started 00:22:52.099 --> 00:22:54.279 with the surprising survival of freezing soldiers 00:22:54.279 --> 00:22:57.380 on a Napoleonic battlefield. We unpacked how 00:22:57.380 --> 00:22:59.519 a lack of oxygen doesn't kill a cell directly, 00:22:59.819 --> 00:23:02.539 but rather shuts off its ATP power supply, leading 00:23:02.539 --> 00:23:05.740 to a toxic collapse. Right. We explored how the 00:23:05.740 --> 00:23:08.839 cold stabilizes that cell wall, freezing the 00:23:08.839 --> 00:23:11.259 dominoes of death in place and shielding the 00:23:11.259 --> 00:23:13.859 brain from its own toxic rescue attempt. It's 00:23:13.859 --> 00:23:15.420 amazing when you think about it. And we looked 00:23:15.420 --> 00:23:17.940 at the extreme engi - Genearing doctors use cooling 00:23:17.940 --> 00:23:21.500 catheters and transnasal mist just to override 00:23:21.500 --> 00:23:24.880 our body's evolutionary desire to shiver. And 00:23:24.880 --> 00:23:27.140 we saw how the science is constantly refining 00:23:27.140 --> 00:23:29.420 itself, learning that sometimes just preventing 00:23:29.420 --> 00:23:31.799 a fever was doing all the heavy lifting. Exactly. 00:23:32.099 --> 00:23:34.680 It shows us that human biology is incredibly 00:23:34.680 --> 00:23:38.240 malleable. Sometimes deliberately pausing the 00:23:38.240 --> 00:23:40.980 system is the only way to save it. This raises 00:23:40.980 --> 00:23:43.250 an important question. One that I think sits 00:23:43.250 --> 00:23:45.849 at the very frontier of medical science. What's 00:23:45.849 --> 00:23:48.769 that? Well, we have just spent the last 20 minutes 00:23:48.769 --> 00:23:51.230 discussing how dropping our core body temperature 00:23:51.230 --> 00:23:55.109 by a mere few degrees can completely pause a 00:23:55.109 --> 00:23:57.950 catastrophic cellular death cascade. It forces 00:23:57.950 --> 00:24:00.369 you to wonder what other extreme environmental 00:24:00.369 --> 00:24:02.750 triggers are our cells secretly waiting for. 00:24:02.930 --> 00:24:05.019 Oh, that's an interesting thought. If the simple 00:24:05.019 --> 00:24:07.799 application of cold can unlock a biological pause 00:24:07.799 --> 00:24:10.420 button, what other hidden states of survival 00:24:10.420 --> 00:24:12.980 are locked away in our biology, just waiting 00:24:12.980 --> 00:24:14.779 for the right temperature, the right pressure, 00:24:15.140 --> 00:24:17.220 or the right environment to be discovered? Are 00:24:17.220 --> 00:24:19.920 we carrying dormant survival mechanisms that 00:24:19.920 --> 00:24:21.619 we just haven't figured out how to switch on 00:24:21.619 --> 00:24:24.779 yet? That's wild. Thank you for joining us on 00:24:24.779 --> 00:24:26.940 this deep dive into the resilient, surprising, 00:24:27.180 --> 00:24:29.339 and sometimes freezing machinery of the human 00:24:29.339 --> 00:24:32.019 body. Next time you step out into the cold and 00:24:32.019 --> 00:24:34.799 feel that shiver remember the complex biological 00:24:34.799 --> 00:24:37.220 war happening right beneath your skin. Until 00:24:37.220 --> 00:24:37.680 next time.