Targeted Temperature Management in Cardiac Arrest with Nonshockable Rhythm

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.

WHAT

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.

WHERE

25  intensive care units in France.

METHODS

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.

OUTCOMES

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.

RESULTS

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.

LIMITATIONS

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.

DISCUSSION

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.