J.B. Lascarrou, H. Merdji, A. Le Gouge et el published the results of HYPERION (Hypothermia after Cardiac Arrest in Nonshockable Rhythm) trial in NEJM.
Open-label, randomized, controlled trial comparing moderate therapeutic hypothermia (33°C during the first 24 hours) with targeted normothermia (37°C) in adult patients with coma(GCS <8) after resuscitation from cardiac arrest with a NON shockable rhythm( both out of hospital and in-hospital cardiac arrest). Primary outcome was favorable neurological outcome assessed by cerebral performance category scale( 1-5, with the CPC score of 1-2 is favorable neurological outcome) at 90 days.
25 intensive care units in France.
In patients who were assigned to the hypothermia group, hypothermia at 33° C was maintained for 24 hours. Cooling was achieved active internal cool in with device, Active external cooling with a device or without a device depending on the ICU. Slow rewarming was then performed at the rate of 0.25-0.5 C per hour.
In patients who were assigned to the normothermia group, body temperature was maintained at 36.5-37.5 degrees C.
Following patients were excluded- patient who had collapsed to initiation of CPR more than 10 minutes, initiation of CPR to return of spontaneous circulation more than 60 minutes, major hemodynamic instability( defined as continuous epinephrine/ norepinephrine infusion at 1 micrograms/kilogram body weight per minute), delay in the screening for enrollment for more than 300 minutes, moribund condition, cirrhosis of liver with Child Pugh class C category, pregnancy or if the patient was a prisoner.
According to the French law, both strategies used in the trial were considered to be components of standard care, therefore consent was not required.
Primary outcome was arrival with a favorable 90 days neurological outcome. secondary outcomes were mortality, mechanical ventilation duration, length of stay in ICU and Hospital, infection and hematological adverse effects.
A total of 584 patients were randomized. 29 out of 284 patients in hypothermia group had CP C score of 102 as compared to 17 out of 297 in normothermia group( 10.2 versus 5.7% p = 0.04).
27.4% had in hospital cardiac arrest and 72.6% had out of hospital cardiac arrest. There was no difference in mortality in 2 groups. 82.3% (478 patients) died during follow up. There was no difference in duration of mechanical ventilation, length of stay between 2 groups.
Primary outcome was assessed using a telephone interview. Many patient said body temperature above 38° centigrade, also the targeted temperature management was used up to 64 hours.
International Liaison Committee on Resuscitation (ILCOR) recommends a targeted temperature of 32 to 36 degree C in all patients with coma after successful resuscitation from cardiac arrest. These recommendations were based on two pioneer trials(Trial 1, Trial 2) comparing hypothermia with normothermia in patients with cardiac arrest with shockable rhythm, neurologic outcomes were good in 26% and 39% of patients who were treated with normothermia. Temperature target was selected based on trial published in 2013.
However, at trial published in 2015 showed inconclusive effects of hypothermia in patient who had non shockable rhythm.
Following this, several case series have been published which showed variable results of hypothermia in patients with non shockable rhythm.
In spite of his limitations, this trial proves that moderate hypothermia with a temperature of 33° centigrade in patients with non shockable rhythm( both in and out of hospital cardiac arrest) may improve neurological outcome. Furthermore, this therapy does not show any adverse effects.