Five Minutes with Jon Rittenberger on the TTM Trial


Just posted a wee on the game-changing TTM Trial

Managed to get Jon Rittenberger, MD on the line to discuss the implications. Jon wrote the editorial that accompanied the TTM trial and he is an accomplished Resuscitationist and a clinical leader for the U. Pitt post-arrest management team.

Here are Jon’s thoughts on what we should do with this trial tomorrow. I add my own opinion at the end. In the next couple of weeks, you’ll hear from Stephen Bernard to get his take on the study.

The 2nd article mentioned by Jon is this one:

Kim, F et al. Effect of Prehospital Induction of Mild Hypothermia on Survival and Neurological Status Among Adults With Cardiac Arrest A Randomized Clinical Trial JAMA 2013

Prehospital hypothermia in this study and the Bernard trial has not seemed to pan out. Intra-arrest is still in play however.

My Take as of Now

  • In the setting of advanced post-arrest care, active temperature management, and protocolized neuro-prognostication; the TTM trial demonstrated no significant outcome difference or trend towards outcome difference when patients were cooled to either 33 or 36C
  • Hemodynamics were poorer in the 33C group (This was not mismatching, SOFA-C same on day 1 and much worse in 33C group on day 3; this was a secondary outcome and therefore the study can’t demonstrate if this was a significant finding) [Table S2 Supplement]
  • Complications were less frequent in the 36C group
  • A majority of patients are probably best managed at or near 36C
  • In the neurocritical care literature, 35C seems to offer moderation of intracranial pressure
  • At Janus General, we will target a temperature range between 35-36C for our V-fib, V-tach, and PEA patients in whom we are pursuing an aggressive treatment path
  • Unwitnessed asystolic arrest patients were left out of the HACA, Bernard, and TTM trial. In this group there is little guidance and it may be reasonable to continue cooling to 33C as this group is most likely to have the most severe post-arrest neurologic injury.

Interview with the Lead Author of Trial from the ICN

Matt MacPartlin interviewed Niklas Nielsen, the author of TTM. He is joined by Anders Aneman, one of the local site investigators to discuss this game-changing study.

Other Thoughts

See this great post from the folks at the Intensive Care Network as well.

The folks at St. Emlyn’s offer a  more cautious approach.

Now on to the Wee…

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  1. Benjamin Dowdy says

    Looks like prehospital TH is going away…thanks science :)

    In all seriousness, to Dr. Weingart and other viewers, do you all now think that prehospital cooling still has a place? From the TTM article it looks like the median temp on arrival was relatively normal, and the JAMA article found no benefit to prehospital versus in-hospital cooling.

  2. Josh Farkas says

    Hi Scott,

    Very interesting, thanks for weighing in.

    Seems like critical care is moving in a less-is-more direction these days… less hypothermia, less IV fluid resuscitation, less steroids, less Xigris, less intensive insulin, less sedation, less HFOV, less IABP, less transfusion…

    Currently there is substantial equipoise between 36 and 33 degrees. Since 36 degrees is easier to achieve without a lot of complications/manipulations, my bias would be to favor 36 for most folks while we await more data. Less being more.

    One fringe benefit of 36 degrees as a target is that it may be possible to prognosticate earlier. It can be enormously stressful on families having to wait to see if their loved one will wake up. One strength of the Nielsen et al. approach was neuroprognostication at the 72 hour mark.


  3. Matt Morgan says

    It is also important to wait for the cognitive outcome study part of TTM to be published. 33 may offer some advantages here despite no difference in survival.

  4. Joshua Bucher says

    I have to disagree with these studies findings. If you look at the NEJM study, their rates of bystander CPR is 80% and there time to BLS is a mean of 1 minute. Where in America outside of Washington and Arizona do we see these numbers? Their survival to neurologically favorable discharge is also in the 40s – 50s %, again not numbers that are replicated by most communities in the USA.
    Until we are producing outcomes and numbers as good as the ones in these studies, I don’t think that we should change hypothermia as of just yet.

    • says

      50% neuro intact survival is pretty much industry standard for V-FIB/V-TACH pts with ROSC. That was seen in the Bernard and HACA trials as well (+-). If you are not achieving this, need to QA post-arrest protocol.

  5. Trent says

    This study might be more of a “perspective changer” than a “practice changer” (though it’s probably a little of both). It probably has always been less about the cold than it is the control.

    I guess this applies to control of both the temperature itself (i.e. preventing wide temp swings in a brain-injured patient) AND more aggressive control of the effects post-arrest inflammation in general. The latter may also have been at least partially responsible for the difference seen in the “VSE” trial.

    Unlike in sepsis (when there’s an infection to fight), post-arrest inflammation doesn’t serve much of a purpose and might be more detrimental. This might be where we go with post-arrest management over the next few years.

  6. Mike Jasumback says


    Was interested in your statement that for the most part you would shoot for 36. Kinda surprised that you are such an early adopter given that the 33 degree threshold is supported by 2 reasonably well done studies of a particular set of ROSC pts and the TTM trial was less particular and more pragmatic I guess. I would think we should wait for replication before jumping on this bandwagon.

    UNLESS, there is some backstory to the hypothermia literature which, I will admit, I am woefully unfamiliar with.


    • says


      If this study was contradictory to HACA and Bernard, it would require a step back and waiting for more. This study directly supported the conclusion of HACA and Bernard. This was a dose-finding study.

  7. Tripp Winslow says

    I spoke to some of the medical directors in my state and they brought up to point that most of the systems in our state do not paralyze the patients and they often don’t bolus the fluids and instead infuse the fluid in a little more slowly than done in the study.

    Tripp Winslow
    Medical Director NC Office of EMS
    Wake Forest University Health Sciences

  8. says

    Great stuff as usual Scott. It’ll be interesting to see what the next ILCOR guidelines do with this. Already some speculation.

    I got to sit down with Niklas Nielsen and Anders Aneman earlier this evening, so watch out for that podcast on the ICN in the next few days.

    See you at SMACC Gold

  9. Andy Elsberg says

    I am wondering what you are basing the thought to continue to cool sicker or asystole patients to 33. Is there a sub analysis that would support that? Or is it theory based and this study did not demonstrate harm with deeper cooling.


  1. […] got in on the act with an interview with the NEJM’s editorialist to see what he really thinks: Five Minutes with Jon Rittenberger on the TTM Trial after Scott also claimed that EMCrit Wee – The Targeted Temperature Trial Changes Everything. […]

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