Wednesday 20 May 2020

Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm

The literature regarding cooling of comatose survivors of cardiac arrest is mixed. But even more controversial is the role of therapeutic hypothermia in the group of patients with non-shockable rhythm.

Enter the HYPERION trial published in the high impact New England Journal of Medicine.

This mammoth effort was an open-label pragmatic RCT comparing hypothermia (33 degrees) vs normothermia (37 degrees) in comatose survivors of cardiac arrest with non-shockable rhythms (PEA or asystole).

As if PEA and asystole were not bad enough, they excluded the sicker patients who would have highly likely died anyway- regardless of cooling or no cooling. These were patients who had no CPR for >10 minutes, CPR for more than 60 minutes, those with high vasopressor requirements etc.

The primary outcome was a good one; survival with a favorable day-90 neurologic outcome. This was defined as independent & able to perform ADL’s (CPC score 1-2). Unfortunately, it was possibly poorly determined by a single blinded psychologist by phone interview.


Over 4 years, 581 patients were included from 25 French ICU’s. On day 90, 10.2% of the hypothermia group vs. 5.7% of the normothermia had a good outcome (difference 4.5% 95%CI 0.1 to 8.9; P=0.04 and a NNT of 22.) Overall mortality did not differ between the groups at 80%.

Cooling wins!?

Despite the results, I am a bit less enthusiastic about this one.

The literature is still conflicting, and this is far from overwhelming data.

The primary result has a fragility index of 1. If only one of the patients that did well in the hypothermia group were reclassified as unfavorable at 90 days, the results would not have been statistically significant… we would be talking about a negative trial.

There are other issues with the measurement of the primary outcome, external validity and a few other things.

In the end, it is probably fine if your ICU wants to cool these patients. But please make sure it does not distract & get in the way of providing adequate resuscitation and supportive care. Stay cool (or not) and do the right things first.


Lascarrou JB, Merdji H, Le Gouge, A, et al. Targeted Temperature Management for Cardiac Arrest with Non-Shockable Rhythm. New Engl J Med; 2019: 381:2327-2337. [link to article]

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