This document summarizes current evidence on therapeutic hypothermia after cardiac arrest. It discusses two key trials from 2002 that found improved outcomes with targeted temperature management between 32-34°C. However, these trials were small. A large recent randomized controlled trial found no difference in outcomes between a target temperature of 33°C versus 36°C. While therapeutic hypothermia remains recommended, the study challenges its widespread adoption based on only two small trials. Further research is still needed to determine the optimal target temperature range.

1. Therapeutic Hypothermia –
current evidence
Bethan Owen
SCGH ED CME 23/1/14

2. Background
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Modern CPR come a long way since 1960’s
In early 2000’s OOHCA survival was 7-8%
Now estimated 9-12%
Brain ischemia often causes catastrophic
outcomes in those who survive.

3. Background
• Patients frozen to cardiac arrest seemed to be
protected.
• Two trials in 2002 showed improved outcome
of therapeutic hypothermia.
• Since then therapeutic hypothermia been
recommended by international resuscitation
guidelines targeted temperature management
(TTM) 32-340C.

4. However 2002 trials…
• Were small (273 & 77 patients)
• One trial showed that fever developed in
many patients of the control group. Which is
associated with poor outcome in ROSC.
Also
• Case reports of ‘frozen’ OOHCA patients were
hypothermic pre arrest, therefore brain was
already cooled.

5. Original Article
Targeted Temperature Management at
33°C versus 36°C after Cardiac Arrest
Niklas Nielsen, M.D., Ph.D., Jørn Wetterslev, M.D., Ph.D., Tobias Cronberg, M.D., Ph.D.,
David Erlinge, M.D., Ph.D., Yvan Gasche, M.D., Christian Hassager, M.D., D.M.Sci.,
Janneke Horn, M.D., Ph.D., Jan Hovdenes, M.D., Ph.D., Jesper Kjaergaard, M.D., D.M.Sci.,
Michael Kuiper, M.D., Ph.D., Tommaso Pellis, M.D., Pascal Stammet, M.D., Michael
Wanscher, M.D., Ph.D., Matt P. Wise, M.D., D.Phil., Anders Åneman, M.D., Ph.D., Nawaf
Al-Subaie, M.D., Søren Boesgaard, M.D., D.M.Sci., John Bro-Jeppesen, M.D., Iole Brunetti,
M.D., Jan Frederik Bugge, M.D., Ph.D., Christopher D. Hingston, M.D., Nicole P.
Juffermans, M.D., Ph.D., Matty Koopmans, R.N., M.Sc., Lars Køber, M.D., D.M.Sci., Jørund
Langørgen, M.D., Gisela Lilja, O.T., Jacob Eifer Møller, M.D., D.M.Sci., Malin Rundgren,
M.D., Ph.D., Christian Rylander, M.D., Ph.D., Ondrej Smid, M.D., Christophe Werer, M.D.,
Per Winkel, M.D., D.M.Sci., and Hans Friberg, M.D., Ph.D. for the TTM Trial Investigators
November 17, 2013DOI: 10.1056/NEJMoa1310519

6. Design
• Randomised (unblinded) controlled trial
• ICUs in Europe and Australia (36 in total)
• Adult patients post OOHCA (all rhythms)
– cardiac cause presumed, ROSC for 20mins, GCS<8
• Treatment Temperature Targets
– Intervention - cooled to target of 330C by 6hrs, rewarm after
28hrs, maintain temp <37.50C until 72 hrs.
– Comparison - active maintenance of 360C for 28hrs then
maintain temp <37.50C until 72 hrs.
• Outcome assessment (by blinded assessors)
– 10 mortality at 180 days
– 20composite of death & poor neurological outcome assessed by
Cerebral Performance or Rankin Scale

7. Outcomes
• 473 pts in 330C group, 466 in 360C
• Groups mostly well matched at baseline
– Features include: mean age 64, male~80%, ~½ at home,
bystander CPR in 73%, ALS at median 10 mins, 80%
shockable rhythm (mostly VF), temp at time of
reqruitment 350C .
• No difference (50% vs 48%) in 10 endpoint (death)
• Similarly no difference in 20 (neuro) outcomes
• Some minor 20 outcomes differences
– Less mechanical ventilation in 360C group
– More hypokalaemia in 330C group

8. Critique
• Rigorous methods in a study population and medical
systems similar to our own
• Included non-VF rhythms unlike previous studies
• One country excluded many pts – consent issues
• High survival rate a concern to some but explained by
inclusion criteria (>20mins ROSC)
• ICU care not controlled or blinded
– But final outcome assessors & authors were
• Only powered to detect a relative risk reduction of 20%
(ie 50% deaths decreased to 40%)
• Not powered for neurologic outcome assessment
• Tested 2 temps – might the answer lie between ?

9. Applicability
• Therapeutic hypothermia has become a widely
accepted standard and is in all resus guidelines
– Adopted following results of 2 relatively small trials
– Recently challenged by (mostly) observational studies
• This study probably is a “Game Changer” at least
from an ED perspective
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We want them to get a little cold
Don’t aggressively pursue getting them very cold
Never let them get hot
Further studies might tell us what the “best” temp is

11. Prehospital cooling
• 1359 pts randomised to receive 40C NaCl or
not by paramedics
• Reduced the cooling time by ≈ 1hr
• No change seen in survival or neurological
outcome

13. Current ARC guidelines:
• Therapeutic Temperature Management (TTM)
is recommended and remains currently at 32340C
• However if clinicians are not cooling to 32340C fever should be avoided and aim for
temperature of 360C
• Temperature management should not be
abandoned

15. References: