Therapeutic Hypothermia – current evidence

Bethan OwenSCGH ED CME 23/1/14

Background

• 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.

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.

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.

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

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

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

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 ?

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– 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

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

Current ARC guidelines:

• Therapeutic Temperature Management (TTM) is recommended and remains currently at 32-340C

• However if clinicians are not cooling to 32-340C fever should be avoided and aim for temperature of 360C

• Temperature management should not be abandoned

References: