Transcript Video What Happens if We Stop?Prof. Wilhelm Behringer < Back to Boundaries of Temperature Session 3: Utility What Happens if We Stop? Presented by Professor Wilhelm Behringer I can now announce Professor Perino I think he has not really have to be introduced. We saw his name already on numerous publications shown actually today he is the head of the department of emergency medicine at the university hospital in Vienna please. Good morning. Also from my side and thank you very much for the nice introduction and the topic of my talk is uh what happens if we stop and the nice thing on such events is that you hear different opinions and also in this session you will hear different opinions so you will see a lot of the same slides but interpret it differently. So that's the nice thing on science. Ah these are my potential conflicts of interest and I was supposed to say what happens if we stop And I extended because I think this was the question of the organizers, what happens if we stop using 33° in our patients after categories. Ah in the beginning, what I want to say is that T T M. Is dead. So the expression T T M we should not use any more. Sorry for the organizers probably they put their T T M. In the title before the inquiry recommendations because they said we shouldn't use this term anymore. Um Back to the history, it was in 2009 when some expert met in Puerto Rico and I was lucky enough to be part of this panel and there we as experts decided, you know therapeutic hypothermia. This word We shouldn't use it, let's use targeted temperature management and this was published in 2011. And since then we use this targeted like a tank breaker, targeted temperature management in German it's even worse to say, temperature management. Very difficult to say. But we used it until recently. When and you saw yesterday Bodil carries is his mother or going to a father or parent organization and the expert in this round, they said, well, TtMT that's too much associated with the T. T. M. Trials. So we shouldn't use any more of this expression. Let's use other words like we did before. Hypothermic temperature control, normal thermic temperature control, fever prevention, temperature controls. All should be controlled or no temperature control at all. So these are the new words we should use from now on. We should not use any more T T. M. Except we speak about the T. T. M. Trials. So just for the books and for the ones among you who are not so familiar with all these trials, the history of hypothermia. Give me only two minutes to give a very short history of the development of the guidelines. This was good old times 2005, 2010, just after the hack a study and the study, the two randomized clinical trials showing the benefit of 33 degrees and based on this too. And there was a third small study by also showed the benefit of hypothermia. 33. There was no temperature control. And at that time the guidelines recommended to use the temperature range between 32 to 34 degrees. Um This is the original temperature curve of the hacker trial. This is the hypothermia 33 degree and the so called normal ther mia. But it was not really normal thermic it was slightly slightly hypothermic. So the argument was maybe with its enough to prevent this hypothermia and that's why Nicholas Nielsen that T. T. M. One trial investigated a temperature of Ah stopped. Okay 36°. Can I operate it from here? No 36 degrees in the red line versus 33 degree in the blue line. And as you heard a couple of times there was no difference in survival and the study had some limitations. Probably penna Bella. In the next session we'll speak about most long time for random ization up to four hours, took a long time to reach target temperature. We heard today very high rate of basic life support. So good patients, very short, no flow time. So some limitations. However, the guidelines recommended them based on this one study to change the temperature range. So it was 32 to 36 degree and then Came to T. T. M to trial published in 2021 and this start investigated the temperature of 37.5. So normal for me, a controlled normal hermia versus 33 degrees. And to our surprise or to my surprise um this study also showed no difference in outcomes. So to randomize trials showing no difference and that's why the most recent guidelines then changed to recommend preventing fever and in very light gray as marco said before, The guidelines leave the possibility to use lower temperatures in the range of 32-34°. But the main messages prevent fever. These are the guidelines we heard and we have different opinions. So I agree that we should monitor the core temperature but I do not agree with the target temperature. I agree that we should control the temperature for 72 hours but not with the level of hypothermia and with the other ones I would need. Now another two hours presentations To give you the arguments why I think we should reconsider these recommendations. However, so my strong belief is we should use in our patient 33°. Uh now the title of the talk was what happens if we stopped using 33° and this was already shown yesterday. What happens if we comment or if guidelines give a change. Sometimes these guidelines are misinterpreted and this is uh an example from from the US. Huge database 37,000 categories patients across 10 rock means resuscitation outcomes consortium sites. And this is the use of target temperature management at that time. And you can see that over the years the use of Temperature control decreased for Chaka bill written. And if you look at non chargeable written from 2015 on almost no use of temperature in these patients. But this was not, the study did not show if it's associated with outcome. Just the observation that they use degrees. This will show our speaker before I show this slide already. This is from also the U. S. Almost 50,000 patients. To a huge observational study. And it also shows The use of hypothermia after 2013 the use decreased is only eight absolute decrease. So it's not a lot of change but there is a change in the use of hypothermia over the years. And the authors also presented the mortality in these patients. Um Actually it's it's survival and the survival in this large patients group slightly decreased due to the large number. This was statistically significant. But they also mentioned that we don't know if it's associated with the use of hypothermia or not. So it's not it's uncertain but at least there is an observation that it might be associated Now. Then after the first DTM study, some centers really changed. They changed from 33 to 36. And they published the results, what happened after these centers changed the temperature liberal And they will show you only a few of them very fast. So this was the first one actually from Australia was published around 2017. And what they showed is that so in in dark blue that's the 33 degree. It was uh from 2012 to 2013. And then the classic before after study. Then they changed to 36 degree. In 2014. They also observed that the patients with 36 degree, they had more fever. So the temperature control was not that good. And they observed a trend in uh less hospital survival and less good neurologic outcome at discharge. So CPC 12, this means real performance category and one and two is supposed to be good outcome and 345 is supposed to outcome. So they observe this trend in various outcome. That's a huge database from from the US from Pittsburgh um From 2010 to 2013. The study group, they used 33° and from 2014 on it was up to the treating physician if they used 33 or 36 degree and then um they mixed all together and made an analysis and They showed a little bit different the opposite. So this is hospital survival with 36. Degreed seems to be a little bit better and concerning the outcome, neurologic outcome. That's the modified ranking scale 0- three which is good outcome. That was the same. No difference. Then he studied from Holland Out of possible categories uh before after 33 degree until 2014. And then two years of 36 degree and they showed the opposite like the T. T. M. Not the T T. M. Study but they showed that 36 degree there is a trend of petr survival and there is a trend of peter neurologic outcome. So the opposite knee retrospective, the problem of retrospective data. Um Another study from johnson also the U. S. Before after study 33°2014 and then 36 degree. And like the other first two studies, they showed a trend of verse outcome concerning survival and verse neurologic outcome. And this is the last one I show you it's from the Czech Republic and has the same pattern as most of the other studies, a trend of less survival and a trend of less or worse neurological outcome. Now these are single studies. Most of them have few patients included. So they were not statistically significant. Ah That's a study from Japan from a from a big database and they showed survival was the same. But a trend of verse neurologic outcome. Now what are you doing If you have many small studies, you do a meta analysis, you put all the studies together and this was oh that's the rookie mistake. Sorry uh you do a meta analysis and you put all these studies together for the ones of you are not so familiar with reading a meta analysis. What does it mean? So here you have the single studies I showed you before, I showed you each study this is the effect. The blue point favors 33 degree or favors 36 degree And this is the 95% confidence interval of the effect. And here if they affect this one Which is the odds that you improve it. If it's one there's no change. Because if the odds is 1121 means like flipping a coin. And if the 95% confidence in crosses the line, one means it's not statistically significant. Okay. So as you can see only the study by johnson, this is the only one where the effect is statistically significant. All the other studies show the trend but not significant. And the diamant On the bottom here, that's the total effect and the 95% confidence in the bar. And if this diamond does not cross the line one means it's statistically significant. So if you put all the retrospective studies together, the summary effect Shows that 33° might be better than 36 degree. It's statistically significant. So that's how you read a meta analysis for the ones who are not familiar with it. Ah This is from Australia New Zealand um 16,000 categories patients. And um you can see that the temperature over the years, slightly slightly degrees c it's 34 to 35 degrees. So it's 34.5 to 34 degrees. So only very slight change over the years in the temperature and then with time trial Australia New Zealand changed Targeting 36 degree. But the temperature actually It went up but also only slightly. You see that 35 degree. So it's never reached 36 degree. It's a very slight change in temperature, it looks big because of the scale here. But it's actually clinically very small change in temperature. And if you put the mortality to that temperature change over the years with a slight decrease in temperature also mortality slightly decreased. And with the change in temperature up only 35° a very small change in temperature. This trend of decreased type of mortality stopped and even converted up again. So this slight change in temperature was associated with an increasing mortality. And This might be an explanation by a body temperature of 36° might not be our optimal target. This is study from from the US where they put in patients after categories, temperature probes into the brain and compared it with the social temperature and record temperature. And these are the different patients. 11 patients. And overall the temperature in the brain was higher than in the body temperature up to two degrees. Some patients even up to three degrees higher brain temperature. So if you target a body temperature of 36 degree could be a brain temperature of 38 degree. Could be a brain temperature of 39 degrees. And as we heard from a previous speaker that higher temperature might be associated with worse outcome. So this might be an explanation by if you look in the daily use of of temperature in all these studies. If you put them together, there's a trend or a little signal that uh higher temperature might not be the best choice. Ah That's a very interesting study I found only yesterday. That's why I put it on. It's goes back to attempt to feedback devices we heard before. How how important it is to use the feedback device. And I kind of put the slide under the topic. What happens if we stop using feedback devices? What did they do? It was a korean database and they looked at 33° with the temperature feedback device. The green line. 36 degree with a temperature feedback device and 33 degree without the feedback device or no feedback device and 36 degree with feedback device. So if you look at the survival curves there seems to be no difference between 33 36 degree. If you use a feedback device. But if you use 33 degree without the feedback mortality seems to be higher. This might be as you said before, that unintentionally over cooling might not be good for the brain. So, uh if you use temperature control, then I think this study is a very good one to show it should be uh with feedback. So, coming to the end of my talk was a very small window namely what happens if we stop. Ah Well, If you look what happened in the change in the center's changing from 33 to 36° overall. There's a signal there is a signal that outcome might be verse. Might if you look at the retrospective studies, if you look at randomized trials, well we have three at least three randomized trials showing a benefit of hypothermia versus no temperature control. Actually, it's for very small studies. Almost forgotten. We have two randomized trials showing no difference in outcome and we have no study, not one study showing that hypothermia is worse. The normal thermal. So signals That 36 might not be good signals. No studies showing that hypothermia improves mortality. So based on all these literatures, I personally think we should keep the 33° until we have more evidence and we can be more certain that 36 or normal for me, a 37.5 Is equal to 33°. Thank you. Created by
