Benjamin S. Abella, MD, MPhil, presents how Targeted Temperature Management (TTM) is an important therapeutic took for post-arrest care to improve health outcomes during recovery after a period of stopped blood flow to the brain.
Hello. My name is Rebecca Offner. I'm your host from B. D. Today I'm introducing dr Ben Abella. He is the director for the Center of Resuscitation Science and Vice chair for research in the department of Emergency medicine at the University of pennsylvania. His career has focused on cardiac arrest and post arrest care for the past 20 years with authorship of over 200 manuscripts pertaining to cpr resuscitation team training and post arrest targeted temperature management including works in Jama New England Journal Medicine and Circulation. His scholarly efforts have been funded by the National Institutes of Health, Department of Defense and the American Heart Association. Among other sources, he serves as the co chair of the resuscitation Science symposium, the Premier Global American Heart Association Meeting focused on cardiac arrest scholarship and clinical care advances. His work has been featured on CNN Good Morning America and National Geographic Meet Dr Ben Abella. So before I begin today's lecture, it's important to point out my disclosures that I am indeed a paid consultant of Beckton Dixon. And it's important to note that the material I'll be sharing with you today is based on the literature but represents my opinion and not necessarily that of Beckton Dixon. Now To start us off in this discussion on post arrest care often find it's helpful to start with a clinical case. And so this vignette will show you a fairly typical cardiac arrest scenario that you may face on a regular basis at your hospital. So here we have a 57 year old male. They are called in as cardiac arrest with CPR in progress. And the story goes that the emergency medical services found this patient at home with the wife actually doing CPR she was the witness to the victims collapsed. There were no symptoms before the arrest. The patient was found in ventricular fibrillation. They tried to shock the patient. Shaq was unsuccessful. They continued CpR and brought the patient to the emergency department. So this is a fairly common sort of scenario that we find with cardiac arrest. In this case, it's good that by centre CPR was provided. So already we're off to a somewhat better start than many arrests scenarios. Now in the emergency department the patient remains pulseless find ventricular fibrillation is noted and after a variety of interventions which are fairly typical, A CLS approaches to this patient return of spontaneous circulation is obtained. So R. O. S. C. So we get the pulse back the patient's comatose. And many of you may know that there are a couple of key things on the immediate post arrest checklist. One of them is a head Ct. The head C. T. In this case was negative so there's no evidence of trauma or bleeding in the brain. And an E. C. G. That's performed immediately after arrest shows no stem me no S. T. Segment elevation. M. I. So in this case the patient is planned to be delivered to the medical, I see you where care will be ongoing and the question becomes how do we improve outcome in this scenario? So the patient is comatose, the patient's going to the the big risk here is brain recovery and of course what kind of organ injury may occur to delve into this? I think it's important to explain when people actually die from cardiac arrest and so given a certain set of people who go into arrest. As many of you know, despite cpr most patients do not achieve our osc, most people do not get their pulse back. However, among the people who do get initial survival, most of those patients go on to die before hospital discharge. They died during subsequent hospital care. And that's a big problem because unlike the people in arrest the people have their pulse back. These are alive patients, they're in our care, their inner emergency department, their interests you. So what can we do to improve survival? And of course it's not just about survival. It turns out up to half of all the patients who survived to hospital discharge end up with some degree of brain injury. And this can be from the mild some people have cognitive memory deficits or motor deficits to the profound. Some people are bed bound, requiring tube feeds. And so this is this is a real problem. And what can we do to improve survival there? Well that is where T. T. M. Or targeted temperature management has its role. And before we plunge into T. Tm itself, I think it's important to give a little bit of the path of physiological context. Why why is this such a problem? What happens during and after cardiac arrest that leads to such injury? Well here you have a rhythm strip of cardiac arrest and what happens after you get your pulse back. There are a number of things that happen with the uncontrolled return of blood flow. And this is known as ischemia re profusion injury. It's a well described set of phenomena. This occurs after a myocardial infarction after a stroke is reaper fused and if you think about it, cardiac arrest is sort of the ultimate example of global ischemia re perfusion. And in this scenario you get a number of problems. There can be this whole body inflammatory reaction with cytokine storm and activation of white blood cells and they can be injurious. Also mitochondria, the energy powerhouses within cells become dysfunctional and that can lead to a number of cellular problems. And then another third large set of injuries that occur with ischemia profusion. The lining of blood vessels becomes dysfunctional and becomes very leaky. And so patients after cardiac arrest often look like they have sepsis fluid bleeds out into the periphery, patients are hypotensive, they have a drop in systemic vascular resistance. So these are all major problems that occur with ischemia re profusion. Now these biologic phenomenon lead to clinical problems and these include brain swelling include cardiac stunning kidney injury, acute kidney and J. K. I. And of course one of the biggest things we worry about his brain injury and indeed brain swelling and herniation is a major cause of death during the post arrest phase. So if you're an ICU physician or nurse and you're watching this, understand that brain swelling and brain injury are the number one problem we face in the first few days following resuscitation from cardiac arrest and we need to think about how to address this and that's where targeted temperature management has his role. Now, a brief nomenclature point. Many of you may know this therapy as therapeutic hypothermia or th that term has largely been replaced by T. T. M. For reasons that will become clear a little later. But just know that in the literature, you'll see both of those terms th or T T. M. Now in T T. M. The concept is that we lower The core body temperature after cardiac arrest. And based on a variety of studies, 33°C.. That's about 1992. Fahrenheit seems to be the ideal target temperature. This is based on many laboratory studies. The idea is, we lower core body temperature. We keep people cool for a period of time and then we re warm them. And so where is the evidence behind T T. M. Well, there have been a number of randomized trials that have shown that TPM is effective. In fact three major ones. And I show you the references here have shown that lowering core body temperature improves outcomes after cardiac arrest. There was one trial that will get into called the T. T. M. Trial or the Nielsen trial from 2013 balance hard to interpret because it showed two different targeted temperatures were equally effective 33 or 36. There's not a single randomized trial showing that T T. M relates to worse outcomes. So this in one slide is the balance of all the RCT evidence surrounding these poster S T T M. Now to show you the two foundational trials, this is from 2000 and two, the Bernard and hacker trials. These were randomized trials of one done in europe, one done in Australia. That looked at whole body cooling to 33 Celsius after resuscitation community and caressed. And then they looked at outcomes. They looked at how did people survive when they were randomized? Either cooling or no cooling after arrest. And you can see here in a brief little summary that survival was much better when T. TM. Applied to patients after cardiac arrest. These two studies only enrolled patients after ventricular fibrillation, cardiac arrest and those of you who are aware of this shock double rhythms are one subset, of course of all of the cardiac cross rhythms. These studies did not enroll patients pulseless electrical activity recently. The last group study more recently did, and I'll get to that shortly. Um but for a period of time, T T. M. Was thought to be mostly useful for shock double rhythms that has changed and I'll explain what I mean by that. But in any case, these two foundational trials showed that both survival and neurologic outcome were improved. So brain recovery was better. People had what was called a higher CPC or cerebral performance category score. They were more likely to walk out of the hospital of their own powers. So that was excited. No things got a little confusing. In 2013 with the introduction of the T. T. M. Trial. The first author, Nicholas nelson and his colleagues, largely out of Sweden. Although a number of countries were involved. This was a large study that looked at two different targets, two different temperature targets for post arrest care 33 or 36 and the rationale here Was that they felt there might be some side effects at 33. We believe that and we'll get to side effects by the way a little later in this lecture. But We believe that at 33 there's a slightly increased risk of bleeding. There may or may not be a slightly increased risk of shivering. We'll get to that. So they felt well if a lot of the benefit of targeted temperature management is fever prevention and I'll explain why they felt that way. Maybe we could have a lesser degree of T. T. M. A smaller dose if you will and have the same benefit without the harms. Now, let me explain this a little further. It turns out after cardiac arrest people mount these wicked fevers known as neurogenesis fevers. And this is not a fever from infection. This is not a fever that's productive but rather a damaging fever that's from brain stem dysfunction and energetic fevers are very hard to manage and they're actually bad for the brain. So it turns out when patients have a significant brain injury and this could be A T. B. I. Or stroke or post cardiac arrest. Fevers are very bad and then they can lead to worsen brain injury. And so the authors felt, well, if we did a milder version of T. T. M. And we just really aggressively controlled temperature at 36 where people wouldn't have fevers, maybe we could have the same benefit and minimize harms. Well, indeed, that's what they found and I show you hear their survival occurred from their study published New England Journal of Medicine in 2013. Survival was identical at 33 or 36. Now this confused many people because they felt, well, maybe t t m. Doesn't work at all. After all, 36 is close to body temperature. But it's important to note that everybody in this study and both groups got targeted temperature management, it was just a different dose of T. T. M. So it's not like one group was norma thermic and allowed to do whatever their temperature wanted to do. So we have to understand this trial And here I show you a brain and the brain stem and this is the source of these neurogenesis fevers. But in this trial, the 36° group, unlike the prior hack on Bernard trials received active temperature management with a cooling device to prevent these neurasthenic fevers. And so this trial has been massively misinterpreted. Many hospitals around the world felt well. Maybe team doesn't work and we don't have to cool people or manage temperature at all. But that's not the case. The TPM child didn't show that T t. M. Doesn't work. It only shows that 36 degrees is acceptable. That that's an equally reasonable option. Well of course get into why uh certain people have chosen 36 or 33 at our hospital. We have stayed with 33 as a target temperature. And I will explain why shortly. But first I wanted to cover this issue of the rhythm of arrest and when you can apply T. T. M. And so I mentioned how the prior trials only enrolled patients with shock kable rhythms. Well then came along this study in 2019 out of France. Lasker and colleagues looked at cooling for pe a in a systolic initial rhythms. And as you know, assistant is not a good rhythm. You don't want to have that pia is also um more difficult rhythm to manage in cardiac arrest. But they found that when they cooled patients after resuscitation who initially apiary sisterly that they improved neurologic survival with T. T. M. So this was the first randomized trial showing that cooling had its benefit independent of initial rhythm. Which leads us to our current guidelines recommendation in the american Heart Association guidelines in 2020 which I'll get to shortly cooling is recommended for any patient after out of hospital cardiac arrest whether or not they have a shock double rhythm. And this is this is the evidence underneath that guideline recommendations. So let's talk a little bit about the guidelines. So the guidelines first listed. T. TM is a level one indication that is to say a strong recommendation to use T. T. M. In 2015. But then in 2000 and 20 there was an update. The update largely confirmed That T. T. M. was useful. So there wasn't a lot of change. honestly between 2015 and 2020 targeted temperature management is recommended for any patient with out of hospital cardiac arrest. Now in the hospital cardiac arrest is a more complicated entity. We won't have time in today's lecture to go deep into that. The data are much weaker. So in hospital cardiac arrest there's some scenarios where it may be useful. Other scenarios where it may not be useful but for out of hospital cardiac arrest if you get the pulse back targeted temperature management is a strong recommendation irregardless of rhythm and it's recommended for people who remain unresponsive and by unresponsive we mean in Glasgow motor score less than six so they cannot follow volitional commands. Um Moving around a little bit or or groaning in the ambulance or in the E. D. Does not mean they're responsive. They have to be able to respond to commands to not need T. T. M. So that's what the guidelines state. And these can be found as a free online resource at the american Heart Association. Yeah now a little bit more about this initial rhythm because there's still some confusion out there that people think that T. T. M. Is only for shock algorithms. If you think about it. Um The brain doesn't really care what the electrical rhythm of the heart is. It just cares that there's no blood coming from the heart to the brain. So in laboratory studies has been clearly shown that this brain injuries irrespective of arrest rhythm. Many lab models of cardiac arrest are actually assistant in P. A. Um And indeed this is what it worked out. So so the lab data is very consistent now with this last grew study this clinical study. And we strongly recommend that asystole your P. A. If you get them back. We I recommend in my opinion based on the science that you should use T. T. M. Now let's get to some of the practical issues involved in T. T. M. And many of you listening today are probably involved in some fashion with the T. T. M. Protocol at your hospital. And I strongly recommended going to formalize TPM protocol. So everyone can be working off the same principles in many hospitals. This takes the form of an E. H. R. Order set, electronic health record order, set an epic or sooner or whatever you use. And I think that's an excellent idea as well. The basic phases or components of the TPM protocol are the initiation or how you start cooling people maintenance or what you do during maintaining people at a given target temperature. And as you'll hear shortly I recommend 33 then um the rewarming phase, how you come out of T. T. M. And go back to normal temperature. And then finally what kind of adjuncts? What kind of things you do in addition to T. T. M. Such as sedation paralytic. So what kind of monitoring you might do? So those are four components you need to think about and need to address in a protocol. Uh And and of course some of these adjuncts relate to other elements you need to think about. Such as what should the role of cardiac cath maybe we'll get to that. What should the role be of getting neurologists or you're a critical care involved in these patients? And and the reason why is these patients go through this complex progression of care. So as you all know, they come into the emergency room, sometimes they need the Cath lab and that's a little controversial. We'll get to that and why it's controversial. Uh some patients then go right to the ICU and then to the floor and they often have a lot of consultants involved. These are complex patients who need input from neurologists from cardiologist. So this is really a team effort and you need to think about is a team effort. And so one thing I've seen, some hospitals do poorly is they have separate protocols or uh not great collaboration from the er to the ICU. And I think that's really important to strive for. So if you're listening to this and you work in the emergency department, you really need to reach out to your, I see you folks and make sure you all agree on the principles of care and the guidelines. If you're listening to this from the cardiology realm where the icy realm, similarly, you need to get the emergency department on the same page as well, especially because increasing evidence shows that this therapy needs to be started in the emergency department. And I'll show you some data supporting that statement shortly. No, it's also I think really important from a practical matter based on my experience. And I've been teaching and doing work in this field since 2002, since those initial studies came out. And I've learned over the years that the hospitals that do this well have a diet of a physician and nurse, a duo involved in developing and managing the protocols that is a nurse and physician champion. The hospitals that only have a physician champion. Um Sometimes they don't have enough sort of buying from staff or they don't understand nursing staff issues and implementation concerns well enough. And those who only have a nurse champion sometimes don't have sort of the political heft with administration or physician leaders sometimes to make things happen. So in my experience it just works really well when you have both physicians side and the nurses had involved in managing and implementing protocols. So in short from the slide teamwork is everything in the world of T. T. M. And teamwork is where often healthcare falls short as as many of you know. Now I made the statement that T. T. M. Should really start in the emergency department. And and this is one of the studies that shows why there are others like it. But this was a fairly recent study that looked at door to T. T. M. Time. That is to say how quickly did T. T. M. Need to get started to improve survival and the history Graham here I show you is just a distribution in a large set of patients of when cooling got started. And you know like any clinical care, there's some variability. A lot of patients got cooling started in the first two or three hours. But some it took 34 or five hours. And the question becomes, doesn't matter do you need to start it right away? And what they found was it really did matter if you got cooling started within the first two hours. Post arrest survival was much better than if it got started later. So this really suggests that patients benefit from starting T. T. M. In the emergency department. Many emergency departments have a bit of a cop out where they say well we have an ICU bed available so we'll just started up there. But we all know in the reality of things having an ICU bed available and arriving in the icy or two very different things and it still takes a while to package up the patient, get them upstairs, get them settled. So patient care in my opinion goes much better and survival can be improved if we start T. T. M. In the emergency department. Now could you Certainly I see. Well I suppose if you have a really quick transport time and the beds immediately available, you could do that. But as I say in my experience in the real world, it's often better to get patients cared for in the emergency department so that the transition goes better. Now, how soon should we consider starting targeted temperature management? Well, first for those of you listening in the emergency medical services or pre hospital community, I should dispense with the notion of whether you should cool in the ambulance. The current data from several randomized controlled trials has pretty clearly shown that cold I. V. Fluids given in ambulances before hospital arrival do not impact outcomes. And indeed one study suggested some degree of harm and so given cold fluids to induce T. T. M. In the pre hospital environment is probably not going to be a indicated thing for quite some time. What might change this however are newer technologies um given cold fluids and using ice packs, they just don't cool quickly enough in the pre hospital setting. Um And even in the emergency department setting, one might as well go right to a cooling device. However there are newer technologies for rapid cooling that are under development and I do suspect in future we may return to the notion of pre hospital cooling once clinical studies of some of those technologies have been undertaken. That said, when you start to cool with a device, when I do recommend is that you use a feedback loop device that is to say just packing people in ISIS to crude. There a number of excellent devices on the market. Currently that have feedback loops. Um and to remind you full disclosure, I am being paid as a consultant by one of those companies. Um I won't mention any commercial devices. However, in this talk however, there are a number of such devices with temperature sensing Foley's or for that matter, esophageal probe attachments so that you can have carefully controlled temperature management now. So when you initiate you want to set a goal temperature. And the question remains, should you pick 33 36 I alluded earlier to the fact that we in our hospital recommend 33. Now, why is that? Well, a large body of laboratory evidence exists showing that the cooler you go, the better the outcome if you're a pig, a rat or a dog. So so but we're humans. And so the question becomes, is that true in humans as well? Well, we weren't the only ones to think that 33 might be better. This is a survey study done in european issues asking after the TPM trial came out, what did people pick? And and most I see you stuck with 33 is the main goal temperature. And I think they did so for our rational as well, that there's this large laboratory evidence based showing that it's a dose effect Is present, that the lower you go, the better the outcomes. In addition, the hack and Bernard clinical studies both chose 33. In the Nielsen study, 33 and 36 had equivalent outcomes. But here's the part, I didn't tell you yet, they both had equivalent side effects. So in the Nielsen study, 36 did not spare you any amount of shivering. It did not spare any amount of bleeding. So the side effect profiles the same. So why change care based on a neutral study? Whereas neutral, both for adverse effects and neutral for benefit. So we were gratified to see that other hospitals felt the same as us. But here's where it gets more important, a number of hospitals switched to 36 based on the strength of the Nielsen study. And the question then became, how did they do? And this is a study from Seattle Harbor View Hospital in Seattle. This hospital based on the Nielsen study switched their primary default target temperature 36. And you know what? They found survival worsened. So several got worse. And here is the data from their study. And you see the two columns here, T. T. M. At 33 T. T. M. At 36. So sort of a before and after study and their neurologic recovery fell from 35 to 21%. So they basically worsened brain outcomes from cardiac arrest. After they made the switch, they've now switched back to 33. Um and and they were brave enough to sort of air their dirty laundry as it were in this publication. So, this is sort of a warning shot suggesting switching to 36 may not be the best approach for patient care. So, how do we explain this? You know, and how do we ultimately make sense of these two different gold temperatures? Well, for now, I I do recommend sticking to 33 However, this very recent study, this provocative retrospective study suggests that there may be a future compromised. Now, this is not a trial. I wouldn't change what you do based on this study, but this is just to get us thinking. So, this was a large retrospective study out of Pittsburgh and the University of Pittsburgh, like we do at Penn and follows our cardiac arrest patients, their cardiac arrest patients. And and they wanted to look at the use of 33 or 36 based on how injured the patients were. They tracked something in Pittsburgh called the P C A C, the Pittsburgh cardiac arrest uh severity score basically, and a category, if you will. And and so the, the catalog this one patients come in and in their centers, some physicians believe in 33. Some believe in 36. And so it creates a natural experiment. And what they found was when they looked at these categories. And the larger numbers, Peacock four is more injured. Peacock one is less injured. And what they found was patients who are less injured did better when they were managed at 36. And patients who are more injured patients who were in the higher categories of Peacock. That is to say they were more deeply comatose. They were already showing signs of shock or brain injury. They did better at 33. So this is not perhaps too surprising. Sicker patients need more aggressive therapy. Less sick patients need less aggressive therapy. This is not proven, but this does suggest that in the future of cardiac arrest care we may be tailoring our approach, which absolutely makes sense. If you're nice to you, nurse or physician listening, you know that you don't give everybody 10 of doobie to mean you taylor and titrate the doobie too. Mean to blood pressure effects similarly, we may be in a situation coming years where we titrate the temperature target based on how sick the patient would be. And I think that's that's a good goal to shoot for now. What about the maintenance face and and the duration of T. T. M. Well many of you may know that we typically choose 24 hours as our goal, maintenance duration. And as a key a technical point. This clock starts when you reach goal. So most hospitals to find that as once you get under 30 for you start your 24 hour clock for rewarming. Um And and then 24 hours later you start the rewarming process. Were any other questions of course is would cooling for longer be beneficial. And one study did look at this in a randomized fashion. This is out of uh Scandinavia. They looked at 24 versus 48 hours and they found no significant difference in outcomes. Although there was a trend towards better survival with 48 hours of cooling. So there's some pervasive thought out there that longer cooling may be beneficial. We just don't know yet. And there's a large trial NIH funded going on in the United States. Right now. My site is part of that study called the ice cap trial. That's going to be looking at different durations of cooling to see if a longer duration can improve brain recovery. What about some of the side effects we mentioned briefly shivering and bleeding. There are a number of potential side effects from lowering temperature. The good news is, most of these are pretty uncommon and manageable, shivering is probably the most common, but also fairly straightforward to manage. In most cases The bleeding risk is largely talked about in T. T. M. But it's really modest. The best evidence we have suggests that less than five of patients have any clinical bleeding. So less than one in 20 of your critical patients are bleeding. And indeed the studies that found some patients increased bleeding. Most did not need a therapy. Um And and none of that was related to mortality. So at worst some patients needed a platelet or or career precipitate infusion. Um But or other management of kogel apathy. But that was it the most common way this applies. So it turns out when you lower core body temperature, you prolonged PTT. So if people are in heparin for whatever reason, you just need to lower the heparin dose when you cool them anyway. It's a fairly specific point. But other side effects. Sometimes Q. T. Interval can be prolonged very common but no great clinical consequences bradycardia. Most T. Tm patients get greater critic but it does not seem to have run toward human dynamic effects. So anyway this is a list and certainly there are studies that catalog these and go through them in great detail. Let's talk about a few of them shivering. It turns out can occur even at 36. So don't think by choosing 36 that you're listening shivering because you're not. Many patients will shiver robustly at 36 as well. Now why do we worry about shivering? Well several reasons one is shivering fights cooling after all, shivering generates a lot of heat. It's designed to be a heat uh temperature defensive mechanism of your body to maintain body temperature. So so first off it just counteract your T. T. M. But also it increases metabolic rate. and thirdly it can lead to some muscle breakdown. So rhabdomyolysis when shivering is really bad and of course we want to avoid that. Um So so there's a lot of reasons why we don't want shivering and we want to address it during clinical care. And so many of you may have something called the bss or bedside shivering assessment score. I highly recommend you use that in your protocol for bedside nursing care in the I. C. U. How do you manage shivering well most hospitals including ours in our Protocol have a scaled approach. Paralytic work beautifully. Some hospitals are a little nervous about using paralytic routinely so that's often considered either appear in for when shivering is very bad. Um Although in our hospital sometimes we just start paralympics as a drip and maintain it throughout. Nonetheless if you don't like that approach there are some medications that are quote unquote, more mild, I suppose you could say that that worked well, abuse bar has been known to reduce shivering. Certainly opioids can reduce shivering, so adequate levels of sedation alone can help either through opioids and of course also through sedatives. Then there's also this non pharmacologic approach which is really useful known as counter warming, where you actually put hot pads or warming packs on the hands and feet doesn't have a lot of big effect on overall temperature, but it tricks the brain to thinking you're warm. It's sort of a life hack for for brain and shivering. Um as I mentioned, we use paralytic. Sometimes it's a continuous approach, although there's no great evidence that that's necessary to manage shivering. Although the reason why we like it is it makes for uniform, carried everyone paralyzed and then then shivering is off the table. People will not shiver. Of course when they're paralyzed. Of course the downside there is if you paralyzed patients you won't be able to see if they seize and why? Why do we mention seizures? Well up to a quarter of patients after cardiac arrest have some degree of seizure activity. It has nothing to do with cooling. It's just part of the ischemia, re profusion injury of the brain. And so that may be an issue to keep in mind as well. Now, as far as going Lamptey I mentioned the bleeding risk is small, says less than 10%. That's the broadest risk range really. Most studies have shown less than 5%. And in most cases mild bleeding, you might just have a little bit of using at a central line site or in the foley uh urine drainage bag. So it's pretty small and less than 2% significant bleeding rate. So it's much safer say than T. P. A. For stroke. Um What can we do? Well you can minimize heparin use in some patients and consider um compression devices instead of heparin for D. V. T. Prophylaxis. Uh Some patients and F. F. P. Or blood transfusions of course. Um uh And if bleeding is really bad you can always raise the target temperature. Uh This quagga apathy does less than 35 or 36. So you can raise the temperature. But as I said in most cases it's not really a big problem. And I mentioned earlier sort of a key pro tip that if you do need heparin say the patient in cardiac arrest from A. P. E. Uh No that PTT. Is prolonged at 33. So you may need to reduce your heparin dozing to get the same therapeutic effect. Yeah. One other issue during TT M. And specifically during rewarming is Hipaa cally mia. I'm sorry. During cooling I should say is typically mia. So it turns out when you cool people you create something called a cold diaries. Is people lose potassium in their urine and cooling is a diuretic effect. Many of you may know this personally if you've ever been out in the snow all day or you go skiing, you pay attention to your need to go to the bathroom. People tend to need to urinate more when they're really cold. It's a well known phenomenon and you lose potassium that way. So it's just important to be attentive to this. It turns out that this happens during cooling and maintenance. It's usually not a big clinical problem. And you can replete potassium normally as you would following standardized protocols but just be aware that that can happen. Hyper kelly McCann occurred in rewarming, although it's much less common. So just be aware of that as well. So we recommend checking electrolytes every six hours through the cooling and rewarming process. Okay, now, what about this issue of of cardiac arrangements with T. T. M. Well, you can't have QT prolongation. Again, this is not really a clinical concern in most cases, it's more of just something you'll note. However, however, we do worry more. Of course if people have inherited a long QT syndrome that baseline, sometimes that's why they had their cardiac arrest or they may not be on medications that also prolong QT intervals. So if Q. T. Becomes really pronounced, we might raise the target temperature based on that alone. So this might be one of the reasons we might choose 36 or at least an intermediate cold temperature of 35. If people already have a long Q. T. Because we wouldn't want to worsen that problem and increase the risk of subsequent ventricular fibrillation. But in most cases you don't have to do anything about it slightly prolonged Q. T. Is not particularly dangerous. And indeed since most of these people are braided critic their risk of having an are anti phenomena and having ventricular fibrillation are very small but but certainly you can raise the target temperature if you're concerned. As I mentioned, bradycardia is extremely common with T. T. M. Many times. You'll see heart rates in the forties or fifties and this may be protective. This may actually be a good thing. Um So don't reach for the atropine as a pro tip. Don't you know don't treat the number. What you need to ask yourself is what the Meaner chill pressure. What's the urine output with the cardiac out. But if all the parameters are good it's fine. Just just leave that brady cardio well enough alone. It's not really a clinical consequence. One of the big issues that is worth addressing as far as practical topics around post arrest care is prognostication and this is probably one of the most important and and misunderstood issues in post arrest care that isn't related to T. T. M. Itself, but rather one of these adjunctive issues. And so this is a study from our group where we just asked the question, when do people wake up after cardiac arrest? That is to say when do they open their eyes? When can they squeeze someone's hand to command? And we found that in fact it takes a while. Some people don't have this until 23 or four or even five or six days following arrest. So it takes a long time for people to wake up. And so the guidelines clearly recommend that you have to wait at least three days, at least three days before you can consider withdrawal of care based on clinical exam. So how does this come up as a problem that I see? Well, we all have deeply embedded in our educational uh data bank. That fixed and doubted pupils are a bad thing and I would agree. However many post arrest patients have no gag or fixed pupils for days following cardiac arrest and it is not necessarily mean that they will do poorly. So I'm constantly receiving phone calls from residents at various hospitals in our system saying, oh, we're thinking withdrawn care because someone is fixed and dilated pupils on day one post arrest. That is an incorrect reading. The science. Um, some patients will still make a full recovery despite having fixed pupils. So we strongly urge you have in your protocol to avoid early withdrawal. And this is right out of the guidelines in 2015, this was first put in and and it remains in the 2000 and 20 guidelines that the earliest you can use the clinical exam. The bedside exam to make determinations of outcome is 72 hours after arrest. But in fact, it may even be longer if you're cooling sedating, doing all these other things. So, so we actually recommend not doing a clinical exam as a, as a guide for uh withdrawal for three days falling rewarming. Now, that's a tough nut to swallow for many because after all, all of our issues are full in this era of covid even more so. But nonetheless, just know that brain recovery after cardiac arrest is a slow process and if we withdraw patients early we may lose the chance to have meaningful survival and people who would do so if we give them the time. Well how do we then neural prognosticate? How do we tell our people are going to do? And one of the really important tools at our disposal, E. G. And many hospitals including ours use continuous EEG monitoring to assess the brain much better than the clinical exams in the first few days following cardiac arrest and E. G. Reactivity is really important. And this is one of many papers, a lot of pink is being spilled on different approaches to E. G. Fund cardiac arrest. And it's although there's some questions you do continuous, do you do it intermittent? What are the markers that are most predictive? All this is being investigated? What is clear is E. G. Is important and if your hospital has the availability of continuous E. G. I strongly recommend that you use it in patients following cardiac arrest now. Well what about the Cath lab? Uh There's a question about whether or not we should be sending people into the Cath lab full on cardiac arrest and the reason why of course is that many out of hospital cardiac arrests are due to coronary lesions after all, people have to arrest him something. And if people collapse in the field very often it's related to coronary disease, acute coronary syndromes or myocardial infarction. And in this meta analysis that summarizes a large literature of studies where patients were aggressively sent to the Cath lab fallen cardiac arrest survival seems to be better in these studies when aggressive cardiac cath immediately post arrest is considered. Now, these are not randomized trials. If pieces went to the Cath lab because someone felt it might be beneficial. So these are flawed studies. But at least it raises the possibility that maybe we need to send some of these people to the Cath lab right away to look for their acute coronary occlusion. Well, there was one major randomized trial on this topic that just came out this last year and this is called the co act trial out of uh this was out of the Netherlands. And in this trial they asked the question well if patients need to go to the catholic falling arrest, should they go right away or can it be delayed? Can they go later? And they found that survival was the same whether they went immediately or later. And this of course made cardiologist around the world very happy because it suggested they don't have to get out of bed at two in the morning. They can wait several days before catholic the patients. But it turns out most patients in the study did not have significant coronary lesions that needed treatment and the Netherlands, they of really excellent uh systems of hospital care. Many patients were well medically maximized and had very little significant coronary disease. So I don't think this is the final story and it's hard to know whether this would generalize to the United States population, for example. So there's much yet to be learned about the role of cardiac cath fond cardiac arrest. Now, as as a sort of final side note, there may be rules for TM and other critical illness. This is outside the scope of today's lecture, but it's just worth mentioning if you're going to have a TPM protocol, you may as well realize that TM may be useful in other conditions. So, in Sabra accurate hemorrhage and stroke and T. B. I, a number of studies have shown that neurogenesis fever is common in the same T T. M. Technologies are superb at managing these fevers and improving outcomes from significant brain injury. So many neuro issues around the world are starting to use TPM devices for management of your a critical illness more generally. And this is often known as therapeutic. Normal thermal because it's not so clear need to cool in this case 36, maybe just fine. It's more to aggressively avoid fever because those of you who work in a neuro issues no rectal Tylenol, for example, is really not effective at controlling neurasthenic fever. So in summary, TTM is really an important tool, especially for post arrest care. And there's really strong evidence now from multiple randomized trials showing the TTM is effective. Some key points from this lecture, of course we support a target of 33° as a TPM goal for most parts arrest patients. We believe that you should start teaching promptly ideally within several hours. So you really want to start in the emergency department. You want to maintain T. T. M. for 24 hours at least maybe longer, but at least 24 hours shivering and others adverse effects you have to be mindful of. But they are relatively mild and infrequent. And and very importantly we want to avoid early withdrawal and we talked about how the pupil exam is really not helpful in the first several days following arrest. And of course the ultimate goal here is to improve survival and quality of life after significant brain injury. That comes about from cardiac arrest resuscitation. So that sort of summarizes the evidence that I can share with you today. Of course, there's much more we could share, which is why uh we started something called the T. T. M. Academy at Penn, which is a larger educational program or and post arrest care. We offer one day workshops, encourage you to think about joining us for one of our workshops through the TDM Academy. But what I'd like to do now is answer some questions that come up all the time because we're not interactive and live today. I thought I'd anticipate some of your questions. So one question I get often as well. Doc I hear you that 33 is a good gold temperature in most cases, but when should we choose 36? Are there times that 36 would be better? And I would say yes, there 36. Certainly acceptable. The evidence supports 36. So, so it's not wrong to choose 36. And in some situations that may be safer. We talked about patients with Long QT syndrome, also patients with actual hemorrhage. So for example, let's say you get someone back from cardiac arrest from A. G. I bleed, so they died From bleeding. Well, in that situation, the risk benefit analysis is such that 36 might be preferred. However, no randomized trial shows 36 has improved outcomes versus 33 or less side effects. So which is why we recommend 33 for most patients now is 36 easier. I hear this. Sometimes hospitals feel like, well 36 is easier for for ice used to do. Um Well, I'm not so sure that's true. Actually, there's no evidence for that and and there's no difference in shivering or bleeding side effects. So maintaining people at 36 is still sub physiologic set points, meaning people don't walk around at 36 the lowest people tend to walk around as 36 5, 36 8, 36 4. So you still have to push Physiology to do 36 and they both require active closed loop cooling devices. So I would respectfully ask, is it really easier? I haven't seen evidence that it is. So now what about this issue of paralytic? So I do get a lot of questions around that. It's important to point out that the evidence is still unclear. No randomized trial has shown that continuous neuromuscular blockade or continuous use of paralytic actually improves outcomes. It's often used as an escalation options. So when shivering is really bad, you can use, for example, bullets, vecuronium, you can choose other agents as well to manage that. Uh, if you're not going to use paralympics, it's very important to adequately sedate to control shivering. Of course you want to adequately sedate even when you use paralytic, but at least from a shivering standpoint. Uh Sometimes you can control shivering with with aggressive sedation. The other question I get a lot is. What about antibiotics for T. T. M. Or as an adjunct to T. T. M. Use? Uh Should antibiotics be routinely? Well, it is true that ventilator associated pneumonia is very common after cardiac arrest and with T. T. M. Um But no studies really clearly shown that routine antibiotic use improves outcomes. One study has shown recently the antibiotic use did reduce the rate of pneumonia. Um But it's not clear in our center, we do not routinely use antibiotics for all post arrest T. Tm patients, but when we looked at it as a practical matter, we find that the majority are on antibiotics within a day or two anyway for something either a urinary infection or pneumonia or or a presumptive management of such. So once you have a low threshold to start antibiotics. And what about the timeline of T. T. M. As we had mentioned, the 24 hour maintenance periods begin when you reach your goal temperature. Not when you first initiate T. T. M. Because it does take sometimes several hours to cool people. It's okay to go a little bit longer. Uh There may be practical reasons why going to 28 hours or 30 hours is better. For example, I do not recommend rewarming at three in the morning. Bad things happen at three in the morning. So if if a patient reaches goal at three in the morning, I recommend rewarming maybe at seven or eight in the morning and going to 27 or 28 hours. There's clearly no evidence of harm and it may actually even be better now another question I get is should rewarming be done quickly or slowly. It's pretty clear that you want to cool quickly. However, rewarming quickly is a bad idea for a variety of reasons. It can increase human Denham against ability from skin vaso dilation. So we recommend rewarming at a quarter of degree per hour. So slow rewarming quick cooling, slow rewarming and then a final set of questions. I often get the question to all post arrest patients need a head ct. Well, you have to ask yourself, why do we get a head ct? The main rationale is to look for trauma that may have occurred when someone collapsed in the field. So for in hospital cardiac arrest, we do not feel you need a head ct because these are witnessed arrest patients are in their bed and they almost certainly didn't get trauma. Uh and it's not particularly useful for prognostication. We often see brain swelling on a head ct. Yes, in general, that may suggest a worse outcome, but it's not really clear. So do not use that initial head ct for mirror prognostic purposes. So how do you know, prognosticate with imaging? Well, there's some evidence that MRI can be done on day 3-7 post arrest. And that may be helpful, but this is still a very, very active area of research. So, hopefully those uh frequently asked questions may have helped you. As you think about T T. M. I'm certainly happy to answer questions via email. You can find me pretty easily through internet searches. Um, and uh we hope that through this resource and others provided by TDM Academy or by our sponsor, today, Beckton Dixon. Um, we can help you improve your care for patients after cardiac arrest and ultimately return them to their families and the quality of life that we all strive for. Thank you very much.
