Hypothermia Protects Brain Function, Increases Survival After Nonshockable Cardiac Arrest

Deborah Brauser

November 24, 2015

AURORA, CO — Using therapeutic hypothermia to treat comatose patients who have experienced an in- or out-of-hospital cardiac arrest and who have nonshockable initial rhythms can increase their chance of survival neurologically intact, new research suggests[1].

A retrospective registry study of more than 400 post–cardiac-arrest patients showed that those who received this treatment strategy were almost three times more likely to survive to hospital discharge and 3.5 times more likely to have better neurologic function, defined as having a Cerebral Performance Category (CPC) of 1 or 2, than those who did not receive the treatment.

"In research we often talk about 'survival to hospital discharge.' But those of us in this field of work recognize the importance of also arriving at your neurologic baseline," lead author Dr Sarah M Perman (University of Colorado School of Medicine, Aurora) told heartwire from Medscape.

"We didn't just want to get people to survive to home but to survive and thrive somewhere to where they were prior to the arrest event."

For clinicians, Perman recommends that all post–cardiac-arrest patients who are comatose be evaluated for application of therapeutic hypothermia to improve neurologic recovery. "The therapy has a very low adverse-event profile. So our hope is that the work we've done will somewhat quiet some of the hesitancy or concerns, and people will be more proactive about using it."

The findings were published online November 16, 2015 in Circulation.

Updated Guidelines

"Therapeutic hypothermia or targeted temperature management (TTM) has been widely accepted as the only known therapy to impart neuroprotection to the post–cardiac-arrest patient with anoxic injury resulting in coma after return of spontaneous circulation," write the investigators.

Although "the landmark studies" showing these benefits were in patients with an initial shockable rhythm, the incidence of this type of rhythm "has been declining over recent years," they write.

However, past observational studies looking at using this treatment strategy in patients with pulseless electrical activity (PEA) and asystole "have yielded conflicting results." This, plus 2010 guideline recommendations from the American Heart Association (AHA) assigning therapeutic hypothermia a class IIB recommendation, have led to low adoption of the practice—especially during in-hospital arrests, note the researchers.

In part 8 of its updated guidelines released last month[2], however, the AHA is now recommending TTM for all adult comatose patients with return of spontaneous circulation after cardiac arrest regardless of rhythm type.

Perman reported that there have been strong calls for a randomized controlled trial to assess the utility of therapeutic hypothermia in these patients with unshockable rhythms. However, because conducting a true randomized controlled trial that would withhold this type of treatment in some participants "felt unethical," they created a simulated trial "with advanced statistical modeling so we could mimic an ideal study."

The researchers first examined data on 519 post–cardiac-arrest patients from the 2000–2013 Penn Alliance for Therapeutic Hypothermia (PATH) registry, which includes records from 16 contributing institutions.

Then, using propensity-score matching that accounted for various confounding variables, 402 patients (51% men; mean age 63 years) were split into two subgroups. This included 201 patients who received therapeutic hypothermia with standard goal temperatures of 32ºC to 34ºC (mean arrest duration 23 minutes; 68% of arrests witnessed) and 201 who received usual care only (arrest duration, 25 minutes; 73% witnessed).

Useful "for All Comers"

Significantly more of the hypothermia-receiving group survived to hospital discharge (29%) vs the nonreceiving group (15%, P=0.001) and were discharged with a CPC of 1 or 2, signifying a "good" outcome (21% vs 10%, respectively; P=0.003).

In addition, the adjusted odds ratio (OR) for survival was 2.8 for hypothermia-group members (95% CI 1.6–4.7) vs their matched counterparts. Their OR for better neurologic outcomes was 3.5 (95% CI 1.8–6.6).

Further subgroup analysis showed that location of cardiac arrest did not affect the results. The OR for survival to discharge neurologically intact was 2.1 (95% CI 1.0–4.4) for the hypothermia vs nonhypothermia groups who had an out-of-hospital arrest; it was 4.2 (95% CI 1.2–14.9) in those who had an in-hospital arrest.

"The findings suggest that [this] is a beneficial treatment for comatose postarrest patients when the initial rhythm was either PEA or asystole," write the investigators, noting that the results "should encourage its use in this patient population while awaiting data from randomized trials."

"It's fair to say that the [AHA] is endorsing the utilization of therapeutic hypothermia for patients who have cardiac arrest who have any rhythm. And we think our data support that guideline," added Perman. "Hopefully people will recognize that this therapy can be used for all comers."

Perman was supported by a training grant from the National Institutes of Health. She and the coauthors report no relevant financial relationships.


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