All in a lather over TTM

In case you have been hiding under a rock the last 72 hours…here is a run down on Targeted Temperature Management (TTM) – not to try and sell you either way, but to highlight the amazing way in which the conversation has evolved.

I am really interested in the outcomes of the discussion – but even more interested in the way the discussion takes place - the way the evidence is dissected and the means by which the global community rally together to debate the future direction of TTM and other pressing issues.

Papers are published then discussed and dissected, whilst the controversial aspects, the stats, the machinations and the implications are all openly being evaluated on a global scale in real time – as a persistent 24/7/365 journal club

There was a time not so long ago that the Journals were inaccessible online, a paper version had to be ordered, distributed and debated in parochial isolated silos over weeks and months…now we see the process happening in real time, online…immediately through FOAM

  • Distribution – free open access articles, online ahead of print
  • Dissemination – twitter, podcast, blog
  • Discussion - FOAMed groups, social media platforms
  • Analysis – academic analysis, statistical review and commentary
  • DebateTTM survey, storify, FOAM

Publication

  • The key articles are freely available online – easy to access, review, analyse and share.

  • Bernard SA et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346:557-63. doi: 10.1056/NEJMoa003289
  • The Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002;346:549-56. doi: 10.1056/NEJMoa012689
  • Nielsen N et al. Targeted temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med Nov 17 2013 doi: 10.1056/NEJMoa1310519
  • Rittenberger JC, Callaway CW. Temperature Management and Modern Post–Cardiac Arrest Care. N Engl J Med Nov 17 2013 doi: 10.1056/NEJMe1312700
  • Kim F et al. Effect of Prehospital Induction of Mild Hypothermia on Survival and Neurological Status Among Adults With Cardiac ArrestA Randomized Clinical Trial. JAMA Nov 17 2013  doi:10.1001/jama.2013.282173
  • Granger CB, Becker LB. Randomized Clinical Trial Progress to Inform Care for Out-of-Hospital Cardiac Arrest. JAMA Nov 17 2013 doi:10.1001/jama.2013.282174

Dissemination

  • The telegram is dead.
  • Long live podcasts, blogs and FOAM

EM:RAP Audio - On the morning of publication the inimitable Mel Herbert of EM:RAP gave us a brief summary update of the hypothermia debate.

 

EMcrit Audio - Scott Weingart provides enlightening commentary on the major issues in critical care, interviewing the leading lights in critical care. He provided an early EMCrit Wee on TTM


…and then got straight on the line with  Jon Rittenberger


The SGEM Audio – Ken Milne put the TTM concept into clinical context adding the JAMA article to the debate

 

Backed up with myriad blogposts including Intensive Care Network, KIDocs, AmboFOAM, ResusMe, ScanCrit, EMLit of Note, Emergence Phenomena, Meritus, Clinical EM just to name a few - all with different target audiences and differing points of view…but with one common aim of disseminating the information and promoting discussion.

Analysis

Then we have the UberNerds with the statistical analysis, the in depth review of the power and the stats. The academic reprise if you will. Now I don’t understand statistics very well, and in the past would read every paper as gospel bowing to the greater analytical academic minds that wrote, reviewed and analysed the data – but not anymore. Now we have open discussion on every element from study design, to power analysis and detailed statistical evaluation.

  • TTM and OOHCA cooling evidence - “Sorry folks, but this is a negative study of difference NOT a positive study of similarity…”
  • The Adventure of the Empty House” Well before Han Solo was frozen in carbonite, before Sigourney Weaver crossed galaxies in cryostasis, or Walt Disney was cryopreserved, we have been fascinated by the stasis-like powers of hypothermia…

The power is not just in the posts and podcasts – but in the commentary and discussion inline through comments and online throughout the blogosphere on twitter, Facebook, G+ and beyond. It really is an amazing opportunity for us to take emergency medicine and critical care management to the next level of understanding and practice.

To change or not to change – good evidence or poor analysis – we now have a place to debate the outcome and be part of the development of Critical Care management moving forward.

Journals are not dead, textbooks are not dead, academic peer-review is not dead…we have just fundamentally changed the way we can distribute, disseminate, discuss, debate and analyse medical education and research…forever

Glossary of Terms:

  • OOHCA – Out Of Hospital Cardiac Arrest
  • ROSC – Return Of Spontaneous Circulation
  • TTM – Targeted Temperature Management
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Comments

  1. says

    Great to see all this FOAMiness bubbling up. The world of knowledge translation has changed. It can be a global conversation. Thanks for aggregating this information. Welcome to the future…

  2. says

    Equally fascinated -- not just with the debate (it’s not that big a deal -- keep ‘em at 36, avoid hyperthermia and continue to avoid hyerpoxia) -- but more fascinated with the way it’s drawn together input from clinicians working in very different fields

    - emergency medicine
    - intensive care
    - retrieval
    - ambulance
    - rural practice

    We are united by a common theme -- to bring “quality care, everywhere”, regardless of background

    As Parker highlighted in smacc2013′s ‘MacGyver Dilemma’ -- none of us want to be the ‘weak link’ in care for our patients.

    After all, “critical illness does not respect geography”

    Tim Leeuwenburg
    http://www.ruraldoctors.net & KIdocs.org

    • says

      Cheers Tim
      I think the rural aspect of FOAM is especially important -- as rural practitioners become more engaged -- so the conversation becomes even more practical and useful. So much to contribute as a result of dealing with what might fit, rather than what must fit.
      vive la FOAM

  3. Matt Astin - @mastinmd says

    Best example of how FOAMed has affected and can affect medicine. As Ken Milne frequently states, it is about accelerating knowledge translation. This new article increases the debate and the current use of the internet and social media has increased the number of participants in the debate. Long live FOAMed!!!

    • says

      Certainly IST-3 had a lot of discussion and a lot of change resulted…
      This feels similar -- it feels like we can really make a practical contribution to the discussion and increase the ‘knowledge translation’ as we go…

  4. says

    Thanks for this article Mike.

    I completely agree that this process of information dissemination, analysis and debate in such a rapid time frame has been truly incredible.

    A fantastic victory for this process which you have pioneered and has now taken off in an amazing fashion.

    You should be proud!

  5. says

    I am presenting a talk next week at my hospital and wanted a great story to convince people of the power of FOAMed and social media -- guess I have found it! I am continually amazed at how much easier it is to keep ‘up to date’ with what is going on in the latest literature by watching my twitter feed. Although news agencies and pop stars have known the power of SoMe for a while, it seems the medical community is finally catching up!

  6. Bill Soares says

    I am a first time poster -- long time follower. The rapid and free access to a potentially important article in Emergency Medicine is truly incredible and demonstrates the power of the new FOAM era. Thanks to you and all the other founders who have made this possible.

    While the availability of the article and commentary are impressive, I am concerned about the quick interpretations people appear to be making. The fact that, per your survey, approx 47% of people would change their practice NOW is a bit scary, especially when the following have yet to be addressed about the article:

    1) This was not a fully blinded study -- this may be impossible in this type of design, however, the doctors that were administering the therapies knew which group their patients were in -- we know this can lead to bias -- maybe the group at 36C was more closely watched because this was the experimental therapy.

    2) The authors admit this was not an intent to treat analysis -- granted, their follow up and explanation were very good -- but it also deviates from the gold standard

    3) Finally, most importantly, the authors conclusions aren’t proven by the current study. This was not a therapeutic hypothermia / no therapeutic hypothermia study, both groups had the same protocol bundle, the only difference was the temperature maintained. We cannot then, say that this was just about avoiding hyperthermia because that was not the study protocol. We dont know, maybe 36 degrees is the same, but maybe in the real world, it is harder to avoid fever when maintained at 36 degreees vs 33 degrees, leading to higher mortality.

    Overall, the dissemination of information has been incredible, however, there appears to be little in depth discussion about the details of the article, especially given a significant number of people seem to indicate they would change their practice. This rapid consensus on the validity of primary articles is a scary side of the FOAM revolution for many of us observing the process.

    thanks for the time.

    • says

      Thanks for taking the time to post William

      All of this is really an observational study into the real-time decisions and actions taken with the production of new information.

      When lignocaine was removed from ACLS I was perturbed…I read the papers, questioned the evidence…then complied with the mantra.

      At least now I feel I am privy to some of the internal machinations that will occur as the brightest brains discuss, analyse and debate the issues at hand -- the validity of the studies, the analytics, the stats, the consequences…

      The initial stats of 50%, then 47% and currently 38% allow us to see into the early fragmented and cursory views of the physicians as they troll through the data and question the last 10 years of protocols. Initially yes -- it is in the NEJM, it is written by important clever people…it must be true -- then wait a minute…is it? Have I been wrong all these years…it is like the 7 stages of grief…and we can see them all unravel in real-time online

      I agree at this stage (80 hours in…) there has been few in depth reviews of the stats and implications…but at least there is discussion, emotion, pros, cons, debate…at least it feels a bit more transparent than waiting three years for ILCOR to hand down their verdict

      It is still early days and we are all finding our feet -- but I feel there is a lot of positive in the opportunity to read, review and comment to a wider and more interested audience than engage in local debate with individuals more interested in the price of fuel at the gas station…

    • says

      Great comment Bill

      RE: your comments

      (1) True, the physicians caring for the patients were unblinded, but some would argue that the placebo effect would work the other way.

      (2) The study actually performed modified ITT analysis, ITT and per protocol analysis with little difference -- it cannot be criticised on this basis.

      (3) The study showed that targeted temperature management is equivalent at T36 and T33, within the limits of the study’s power. T33 is likely to be associated with more complications, but your point is interesting -- fever from inadequate temperature control may be less likely. In my experience though if I want a patient to be T36 the patient will be T36… the problem area is often in controlling the rate of rewarming.

      I suspect we will see further waves of analysis hit the shore in the next few weeks. This study is very, very impressive methodologically.

      Chris

      • Bill Soares says

        Thank you both for the thoughtful replies. It is amazing that so many people are having this discussion days after release of the article, a testament to the powerful platform you and others have created.

        Like the sepsis bundle, it will be interesting to see what variables in the targeted temperature management actually reduce mortality. Is is fever prevention? Is it sedation / paralysis / decreased metabolic function? Is it just the increased resources devoted to post arrest patient care? This article seems to provide strong evidence that specific temperature is non-inferior.

        My hope is that these initial discussions are not misinterpreted by some as disproving targeted temperature management as a whole. It will be interesting to see how this FOAM discussion evolves and is interpreted by the larger online community.

      • Matt says

        IMHO…

        1. Correct me if I’m wrong but from a completely stats standpoint -- this study was powered to look at a mortality difference of 11% -- all we can really take from a mortality standpoint it that there is not a 11% difference between groups. We don’t know if there’s a 6%, 9% or 1% difference between groups because it was not powered to assess anything other than a 11% difference in mortality.

        2. The study was based upon a difference in mortality and not neurologic outcomes. From my standpoint, neuro outcomes are what matters and not mortality in these patients. Moreover, the study wasn’t powered to assess a difference in neurologic outcomes so there well may be a 5%, 8%, or 0% difference between groups — we simply don’t know from the stats that we have in the study, correct?

        3. How do we not know that 34C or 35C ie mild hypothermia doesn’t have a neurologic benefit… we don’t and simply throwing out — no more TH or other “blanket” statements being made by a number of highly followed people are quite dangerous IMHO. By saying that “TH has no role other than in EBM RCTs” is dangerous -- people who simply follow these comments may simply “follow these comments” ie the may do nothing or pass along inaccurate information. Are people abandoning taking people to cath with NSTEMI or UA with continued chest pain or a severe cardiac hx even though we know that they have no mortality benefit though it helps their chest pain? Have people stopped using octreotide or PPIs for UGIBs despite evidence that they don’t work? EGDT is still going strong ie the actual protocol at many large institutions some evidence that the protocol in its original form may be off?

        4. 36C is not exactly physiologic -- this study still controlled temperature. It wasn’t like these patients were getting no care.

        5. I think the verdict is still out on what temperature, duration, etc is appropriate and simply abandoning TH is too soon however a more appropriate terminology may be “temperature controlled post-cardiac arrest care” that based upon neuro deficits on initial presentation may dictate how long, deep, etc to take these patients.

        IMHO…

        • Suneth Jayasekara says

          Dear Matt,

          I would like to comment on your point number 1.

          Power calculations are all about probability. It tells you about the probability of a type II error (the probability of us making the conclusion there is no difference between the treatments, when there really is one)

          The power calculation in this study deemed a 90% power to detect a 11% mortality differnce at the p=0.05 significance level.

          What this means is that if there actually is a mortality difference of 11% or greater, we have a 10% (100% -- 90%) chance of incorrectly concluding that there is no difference from the trial (at the p=0.05 significance level)

          So in summary we cant say there is “not” a 11% or greater mortality benefit. We can say that at the time of designing the trial, they deemed that if it were to show that there was no significant difference between the treatments, there is a 90% chance that the true difference was not at least 11%

          At least that my understanding of it!

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