52 in 52 – #21: The Hyperion Trial

Question:

Does moderate hypothermia improve neurologic outcomes in cardiac arrest patients with non-shockable rhythm?

Design: A multicenter open-label randomized controlled trial

PICO

Population:

• Enrolled patients in 25 ICUs (11 academic, 14 community)
• Inclusion criteria
  • Age ≥ 18
  • Enrolled in and out of hospital cardiac arrest patients resuscitated from non-shockable cardiac arrest with any cause
  • GCS ≤ 8
• Exclusion criteria
  • A no-flow time (from collapse to initiation of cardiopulmonary resuscitation [CPR]) of more than 10 minutes
  • A low-flow time (from initiation of CPR to return of spontaneous circulation) of more than 60 minutes
  • Major hemodynamic instability
    • Continuous epinephrine or norepinephrine infusion >1 μg per kilogram of body weight per minute
  • Time from cardiac arrest to screening of more than 300 minutes
  • Moribund (terminal/ near fatal) condition
  • Child-Pugh class C cirrhosis of the liver (severe hepatic dysfunction)
  • Pregnancy or breast-feeding
  • Status of being under guardianship
  • Status of being an inmate at a correctional facility
  • Previous inclusion in another randomized, controlled trial involving patients with cardiac arrest in which the neurologic outcome at 90 days was assessed as the primary endpoint
  • Lack of health insurance
  • A decision by the next of kin for the patient not to participate

Randomization:

• Normothermia group with slightly more arrest at home, asystole as initial rhythm, and post-ROSC shock state
• Slightly longer median time to randomization in the hypothermia group
• Roughly the same temperature at randomization between the groups

Intervention:

• 24 hours of hypothermia at 33ºC following each ICU’s own standardized protocol
  • Treatment began a median of 16 minutes post-randomization
  • Treatment was stopped prematurely in 12.7% of patients
  • Patients were warmed at a rate of 0.25-0.5ºC/hour

Comparator:

• 48 hours of normothermia 36.5-37.5 ºC following each ICU’s own standardized protocol
  • Over 5 % of patients were unable to be maintained at 36.5-37.5 ºC, and had documented fever (≥38ºC)

Outcome:

• Primary outcome survival with a good neurologic outcome (CPC score of 1 or 2 at 90 days)
  • 2% of hypothermia patients
  • 7% of normothermia patients
  • Fragility index of 1
    • A fragility index of 1 indicates that if 1 patient in the control group were “converted” from NOT having the primary endpoint to HAVING the primary endpoint, the study would lose statistical significance (p > 0.05). The higher the fragility index, the more robust the results of a study.

Take Aways: