Trial Supports Therapeutic Hypothermia in Nonshockable Cardiac Arrest

Batya Swift Yasgur, MA, LSW

October 14, 2019

The use of moderate therapeutic hypothermia can significantly improve chances of survival with a favorable neurologic outcome in patients remaining in a coma after resuscitation from cardiac arrest with nonshockable rhythm, a new randomized trial suggests.

Of 584 adult patients in the study, about 10% of those who received targeted hypothermia had a favorable neurologic outcome at 90 days as indicated by scores on the Cerebral Performance Category (CPC) scale. That compares to only 5.7% of those randomly assigned to receive targeted normothermia.

The results of the Therapeutic Hypothermia after Cardiac Arrest in Nonshockable Rhythm (HYPERION) trial were presented at the 2019 Annual Congress of the European Society of Intensive Care Medicine (ESICM) and simultaneously published October 2 in the New England Journal of Medicine.

Moderate therapeutic hypothermia, that is to a target of 32°C to 36°C (89.6°F to 96.8°F), is "currently advocated for all patients with coma after successful resuscitation from cardiac arrest," note the authors, led by Jean-Baptiste Lascarrou, MD, Nantes University Hospital, France.

But previous studies of hypothermia in patients with nonshockable rhythm (defined as asystole or pulseless electrical activity) have been "inconclusive" and inconsistent, they write.

"This uncertainty requires resolution, because nonshockable rhythms now predominate among patients with cardiac arrest" and are associated with a poor neurologic prognosis, compared to shockable rhythm, the authors note.

HYPERION is "a very important study that could influence how we treat cardiac arrest patients going forward," Lars W. Andersen, MD, PhD, MPH, DMSc, Aarhus University and Aarhus University Hospital, Denmark, told theheart.org | Medscape Cardiology.

Patients with cardiac arrest and nonshockable rhythms, especially those with in-hospital cardiac arrest, "have rarely been included in previous trials," said Andersen, who was not involved with the current research. "As such, this new study adds important information."

He added, "Current guidelines already suggest that targeted temperature management can be used in patients with nonshockable rhythm, in and out of [the] hospital."

The current study "emphasizes this message and suggests that targeted temperature management is potentially useful for this patient group."

Patients in HYPERION were admitted to the intensive care unit (ICU) following resuscitation from cardiac arrest with nonshockable heart rhythm. Of those, 284 were randomly assigned to receive moderate therapeutic hypothermia (to 33°C) and 297 to targeted normothermia (37°C).

Out of all patients, 27.4% experienced cardiac arrest in the hospital and 72.6% experienced it outside of the hospital.

Patients in the two groups were similar with respect to age, sex, comorbidities, whether arrest was in-hospital or out-of-hospital, whether cardiopulmonary resuscitation was used, and percentages of first-monitored rhythm (asystole, pulseless electrical activity, or unknown), as well as causes of cardiac arrest and Glasgow Coma Scale (GCS) score at enrollment.

Hypothermia was induced and maintained for 24 hours, and temperature in the normothermia group was maintained for 48 hours.

After 90 days, significantly more patients in the hypothermia group than in the normothermia group had a CPC score of 1 or 2, signifying favorable neurological outcomes: 10.2% vs. 5.7% respectively, P =.04.

But mortality in the two groups was similar at 81.3% and 83.2%, respectively. Causes of death were also similar between the hypothermia and normothermia groups. The most common was withdrawal of life support in 61.9% and 65.2%, respectively.

The two groups had not differed substantially in duration of mechanical ventilation or the length of stay in the ICU; that was also the case separately for those who survived and those who died during the follow-up.

"We detected no significant harmful effects of hypothermia at 33°C [91.4°F], as compared with targeted normothermia," the authors note. The two groups fared similarly with respect to incidence of adverse events, including early renal replacement therapy and severe cardiac arrhythmias, and bacteremia during the first month.

Andersen cautioned that the trial was "relatively small" and the findings "will have to be replicated." The ongoing Target Temperature Management-2 (TTM-2) trial "will provide some additional answers within this field."

HYPERION was supported by independent research grants from the  French Ministry of Health, the nonprofit health care institution Centre Hospitalier Départemental Vendée, and the Laerdal Foundation. Lascarrou has received grants from the Laerdal Foundation, the French Ministry of Health, and the District Hospital Center, La Roche Sur Yon, France. He has disclosed no relevant financial relationships. The other authors' disclosures are listed in the original article. Andersen is a volunteer member of the Advanced Life Support task force at the International Liaison Committee on Resuscitation (ILCOR), an international organization that reviews cardiac arrest literature. He has disclosed no relevant financial relationships.

N Engl J Med. Published online October 2, 2019. Abstract

32nd Annual Congress of the European Society of Intensive Care Medicine (ESICM): Presented October 2, 2019.

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