By Alexander E. Merkler, MD

Assistant Professor of Neurology and Neuroscience, Weill Cornell Medical College, and Assistant Attending Neurologist, New York-Presbyterian Hospital

Dr. Merkler reports no financial relationships relevant to this field of study.

SYNOPSIS: Therapeutic hypothermia is beneficial and increases the probability of brain recovery in patients with coma due to cardiac arrest with a nonshockable heart rhythm.

SOURCE: Lascarrou JB, Merdji H, Le Gouge A, et al. Targeted temperature management for cardiac arrest with nonshockable rhythm.
N Engl J Med 2019;381:2327-2337.

In 2002, two landmark studies found that targeted temperature management with hypothermia was beneficial for improving neurological outcomes in patients in coma after cardiac arrest with shockable rhythms (ventricular fibrillation and ventricular tachycardia).^1,2 These studies completely changed the paradigm for the management of cardiac arrest, as therapeutic hypothermia became the standard of care in patients with cardiac arrest. However, recent studies have raised skepticism regarding the use of therapeutic hypothermia in patients with cardiac arrest, and specifically in those found in cardiac arrest with nonshockable rhythms.

In 2013, the authors of the Targeted Temperature Management (TTM) trial suggested that targeted temperature management to 33°C vs. 36°C was equivalent for patients in coma after cardiac arrest. In this trial, 19% of patients had an initial nonshockable rhythm. The lack of a dose-response relationship with therapeutic hypothermia questioned its benefit and suggested that avoidance of fever may be equivalent to cooling.³ In addition, in an observational study of in-hospital cardiac arrest survivors in whom the majority had a nonshockable rhythm, there was no benefit of therapeutic hypothermia on survival.⁴ Thus, further data were necessary to evaluate the role of therapeutic hypothermia in patients with cardiac arrest and, specifically, in those with nonshockable rhythms.

HYPERION was a randomized clinical trial to evaluate the effectiveness of moderate therapeutic hypothermia in adults with coma after resuscitated out-of-hospital cardiac arrest with nonshockable rhythms. Investigators performed a randomized, controlled trial comparing moderate therapeutic hypothermia (33 degrees) vs. normothermia (37 degrees). The primary outcome was survival with a favorable neurological outcome 90 days post-arrest, defined as a score of 1-2 on the Cerebral Performance Category (CPC) scale.

A total of 581 patients were randomized and included in the analysis. Bystander cardiopulmonary resuscitation (CPR) was performed in 70% of
patients. On day 90 after cardiac arrest, there was a significant improvement in neurological outcomes in patients who underwent therapeutic hypothermia. Of the 284 patients in the therapeutic hypothermia group, 29 (10.2%) had a favorable neurological outcome compared to 17 (5.7%) of the 297 patients in the normothermia group (P = 0.04). Mortality and adverse outcomes also were similar between the two groups.

COMMENTARY

HYPERION was the first randomized clinical trial to clearly demonstrate a benefit of therapeutic hypothermia for patients in coma after cardiac arrest with nonshockable rhythms. Moreover, the results of the trial provide reassurance regarding the benefit of therapeutic hypothermia for patients with cardiac arrest in general. After the publication of TTM, skepticism grew in regard to whether therapeutic hypothermia was beneficial or whether avoidance of fever was the necessary ingredient to improve neurological outcomes. The HYPERION trial supports the use of therapeutic hypothermia in all patients in coma after out-of-hospital cardiac arrest and buttresses the 2015 International Liaison Committee on Resuscitation guidelines, which recommend moderate therapeutic hypothermia for all patients with coma after successful resuscitation from cardiac arrest. However, given the low rates of favorable neurological outcomes in patients with cardiac arrest, particularly in the United States, and only a 70% rate of bystander CPR, improvement in public education of CPR is necessary to further improve outcomes.

REFERENCES

1. Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346:557-563.
2. Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002;346:549-556.
3. Nielsen N, Wetterslev J, Cronberg T, et al. Targeted temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med 2013;369:2197-2206.
4. Chan PS, Berg RA, Tang Y, et al. Association between therapeutic hypothermia and survival after in-hospital cardiac arrest. JAMA 2016;316:1375-1382.