HYPERION: 33 vs 37 for Targeted Temperature Management

I am going to be all over the place with this takedown. I’m a bit upset at what may happen as a result of this publication. I really wanted it to be a good study but it’s not. You’ll see why shortly when we analyze the HYPERION trial about targeted temperature management. The good news is that there’s no difference in adverse effects to the patient by cooling them, just a lot of added cost. That’s my tidbit for those physicians who are going to take this data and run with it as if it’s gospel. 

My practice prior to this HYPERION article on targeted temperature therapy was to do a normothermia protocol of 36 degrees after the NEJM trial from 2013. Is this one going to change my ways… from the outset it appeared as if it will, but, spoiler alert, it won’t. 

The objective of this study was to sort out whether we should cool our patients to 33 or normothermia of 37 in patients who suffer cardiac arrest with a non-shockable rhythm. Within the methods, they excluded patients who were down for >10 minutes prior to chest compressions. This is hard to determine many times as families are never quite sure. I complement the 25 ICU’s who recruited 584 patients in this study. The fact that they allowed patients to be recruited for 300 minutes from their arrest time gives us insight that you don’t have to make the determination immediately on whether you have to cool the patient. Then again, such a high percentage did poorly that we don’t really know what’s the best time to get started. 

In how they rewarmed patients, it’s important to note from a practice standpoint that the sedation was tapered when the temp got above 36. That’s a nursing question I often hear. 

Within their outcomes, the primary was a favorable 90-day Cerebral Performance Scale where they wanted to see in particular if the patients had either a score of 1 or 2. A score of 1means Good cerebral performance or minor disability. A score of 2 means moderate disability. They called the patients or families on the telephone for follow up. People lie. I wish they would’ve had someone lay eyes on the patients. But people lie in both groups so this should be no big deal. should be. But it isn’t. You’ll see why. 
The secondary outcomes were all the typical ICU stuff: mortality, days on the vent, LOS in ICU and hospital, infections and adverse hematologic events. We know that cooling causes degrees of coagulopathy. 

With in the results, the authors assessed 2723 patients over the course of 4 years. That’s A LOT of cardiac arrests! Then again, 15 ICU’s. I imagine they’re all busy institutions. 

I was happy to see that an intravascular cooling catheter was only used in 14.8% of patients. I have always thought that they were a little too invasive for my tastes, especially if/when they start oozing. 

When looking at the actual outcomes, the best case scenarios still only had a 10.2% incidence of a CPC of 1 or 2. This is not a cure, team. Patients still do terribly. It’s helpful to let families know what to expect when a patient arrives in our ICUs in cardiac arrest. 

More than 80% of patients died in both groups. 81.3% vs. 83.2 in the 33 vs. 37 respectively. All of the secondary outcomes showed no difference. 

The supplementary text on the hyperion trial regarding targeted temperature management provides data as to how they handled withdrawal of care. Imaging was curiously nowhere to be seen anywhere in the paper. They do not mention abnormal CTs or any type of MRIs anywhere in this paper nor the supplementary text. I would be curious if they found anyone with loss of gray-white differentiation who did well. I wonder if they omitted that information so that they could collect a large enough sample size and families wouldn’t withdraw prior to completion of the study. Hmmmmm.  

I respect the heck out of the authors in the way they disclosed their limitations. They admitted that an outcome change in a single patient would make the primary outcome not significant. What am I supposed to do with that?!?! If one person lied about how well they were doing over the phone it would change the conclusions of the entire 4 years of work! This is why I don’t do research. 

The other caveat to the study is that they let the patients in the 37 degree group develop fevers. Correct me if I’m wrong but didn’t a subgroup analysis in the 33 vs 36 study from several years ago show that avoiding fever is the most important component in these patients? In my practice I discuss with the nurses that we need to be prepared for the fever and have meds on the medication list, not for if it will happen, but rather for when it will happen. Considering the study got started in 2014, this is something that hopefully they knew going into the study. 

I’m sticking with 36 in my practice despite what the hyperion trial says about targeted temperature management. What do you all think?  A hat tip to the authors. 



Lascarrou JB, Meziani F, Le Gouge A, Boulain T, Bousser J, Belliard G, Asfar P, Frat JP, Dequin PF, Gouello JP, Lascarrou JB, Merdji H, Le Gouge A, Colin G, Grillet G, Girardie P, Coupez E, Dequin PF, Cariou A, Boulain T, Brule N, Frat JP, Asfar P, Pichon N, Landais M, Plantefeve G, Quenot JP, Chakarian JC, Sirodot M, Legriel S, Letheulle J, Thevenin D, Desachy A, Delahaye A, Botoc V, Vimeux S, Martino F, Giraudeau B, Reignier J; CRICS-TRIGGERSEP Group. Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm. N Engl J Med. 2019 Dec 12;381(24):2327-2337. doi: 10.1056/NEJMoa1906661. Epub 2019 Oct 2. PMID: 31577396.
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