The #TTM2trial was published today in the @NEJM
nejm.org/doi/full/10.10…
Here’s a summary of what we did, what I think the trial means, and what next.
@ttm2trial @nielsen_niklas @CritCareReviews @NEJM
We enrolled 1900 adults with a coma after an out of hospital cardiac arrest with a presumed cardiac or unknown cause
We assigned them to hypothermia at 33°C followed by controlled rewarming OR to normothermia with early treatment of fever (body temp ≥37.8°C)
The primary end point was death from any cause at six months.
Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale
In the 33°C arm we aimed for “gold standard” therapeutic hypothermia with cooling initiated early, slow rewarming, and care taken to avoid rebound fever.
In the early treatment of fever arm, fewer than half of the patients were cooled with a cooling device.
There was substantial separation in temperature by treatment group and the hypothermia arm was likely as good as can be achieved in clinical practice
Some of the patients in the normothermia group developed fever and the temperatures in this group were broadly similar to those recorded in the control group of the pivotal Hypothermia after Cardiac Arrest trial in which no temperature management was used.
nejm.org/doi/full/10.10…
Despite this, at 6 months, 50% in the hypothermia group and 48% in the normothermia group had died (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P=0.37).
At 6 months, a total of 54% in the hypothermia group and 54% in the normothermia group had a poor functional outcome (relative risk in the hypothermia group, 1.00; 95% CI, 0.91 to 1.08).
Pre-specified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission.
There was no evidence that therapeutic hypothermia benefited any patient subgroup in terms of death
...or disability
Therapeutic hypothermia was associated with a significantly higher risk of arrhythmia resulting in hemodynamic compromise.
The @TTM2trial has many strengths including a sample size that was five times the combined enrolment of the earlier “positive” trials, centralised assessment of outcomes by trained assessors, multimodal neuroprognostication, and protocolisation of withdrawal.
Here are my take home clinical points…
(1) Therapeutic hypothermia is associated with a higher risk of arrhythmia and does not appear to benefit any patient group. The @TTM2trial data should herald the end of the era of therapeutic hypothermia for adult cardiac arrest.
(2) Core temperature should be monitored and current standard of care could reasonably be considered to be normothermia and early treatment of fever (body temp ≥37.8°C); however, here are a few things to think about…
Is normothermia better than no temperature control at all? The reality is that the evidence supporting normothermia over no temperature control is, at this point, very weak.
Given that fewer than half of the patients needed active cooling, do patients actually need to be sedated for a fixed period?
Why not just desedate patients who do not require cooling to avoid fever? This might mean patients who will do well can avoid unnecessarily prolonged ventilation. We need to study this.
Prior cardiac arrest trials that suggested benefit from therapeutic hypothermia were small and they were less methodologically rigorous than the @TTM2trial – all evidence is not equal and the @TTM2trial is the trump card.
For more discussion and to watch the results presentation check out criticalcarereviews.com

• • •

Missing some Tweet in this thread? You can try to force a refresh
 

Keep Current with Paul Young

Paul Young Profile picture

Stay in touch and get notified when new unrolls are available from this author!

Read all threads

This Thread may be Removed Anytime!

PDF

Twitter may remove this content at anytime! Save it as PDF for later use!

Try unrolling a thread yourself!

how to unroll video
  1. Follow @ThreadReaderApp to mention us!

  2. From a Twitter thread mention us with a keyword "unroll"
@threadreaderapp unroll

Practice here first or read more on our help page!

More from @DogICUma

17 Jan 20
Here’s what we did in the #PEPTICtrial, what we found, and what I think it all means. #CCR20 @jama_current
We conducted an international, randomized, open-label, cluster crossover, registry-embedded trial to compare strategies of stress ulcer prophylaxis in mechanically ventilated adults implemented at the level of the ICU jamanetwork.com/journals/jama/…
The primary outcome was in-hospital all-cause mortality up to 90 days. Secondary outcomes were clinically significant upper GI bleeding, C. difficile infection, ICU and hospital length of stay.
Read 28 tweets
14 Oct 19
The #ICUROXtrial has been published today in @NEJM. The 1st author (and our #ICUROXtrial project manager extraordinaire) is @dianemackle
nejm.org/doi/full/10.10…
This #tweetorial is to highlight what we did, what we found, what I think is means, & what next.
We enrolled 1000 mechanically ventilated adults who were anticipated to require ventilation in ICU beyond the calendar day after randomisation.
Read 27 tweets
22 Oct 18
Results of the #TARGETtrial, the largest critical care nutrition trial ever undertaken, are now online @NEJM
nejm.org/doi/full/10.10…
What we did, what we found, and what it means follows…
Please RT to help translate this new knowledge.
Thanks to funding from @HRCNewZealand & @NHMRC we randomised 4000 participants from 46 Australian and New Zealand ICUs in less than a year and a half!
Adults mechanically ventilated & expected to require enteral nutrition in ICU beyond the calendar day after randomisation were assigned to energy dense enteral nutrition (1.5kcal/mL) or standard care enteral nutrition (1.0kcal/mL) at a dose of 1mL/kg/hr based on ideal body weight
Read 27 tweets

Did Thread Reader help you today?

Support us! We are indie developers!


This site is made by just two indie developers on a laptop doing marketing, support and development! Read more about the story.

Become a Premium Member ($3/month or $30/year) and get exclusive features!

Become Premium

Too expensive? Make a small donation by buying us coffee ($5) or help with server cost ($10)

Donate via Paypal Become our Patreon

Thank you for your support!

Follow Us on Twitter!

:(