A Pilot Study of Intra-arrest Therapeutic Hypothermia in Patients Suffering Non-Traumatic Out of Hospital Cardiac Arrest
Condition: Out-of-Hospital Cardiac Arrest
MeSH terms: Heart Arrest; Out-of-Hospital Cardiac Arrest; Hypothermia
Study type: Interventional

Summary: 
      The objective of this study will be to assess the frequency of return of spontaneous
      circulation (ROSC), survival to admission, survival to discharge from the hospital, and
      neurologic function at time of discharge from the hospital among patients experiencing out of
      hospital cardiac arrest randomized to receive either intra-arrest induction of therapeutic
      hypothermia (IATH) or post-arrest therapeutic hypothermia (TH).
    

Detailed description: 
      Therapeutic hypothermia improves mortality and functional neurologic outcomes in patients
      resuscitated from pulseless ventricular tachycardia and fibrillation (VT/VF), with several
      studies validating the safety of prehospital induction following successful (return of
      spontaneous circulation) ROSC by the rapid infusion of 2 liters of 4ºC intravenous fluids.
      However, the optimal timing for inducing hypothermia remains uncertain. Early studies
      demonstrated the efficacy of therapeutic hypothermia despite delays of 4 to 8 hours from the
      time of ROSC to the initiation of cooling. The post-resuscitation reperfusion injury evolves
      quickly and was thought to be best attenuated by hypothermia induction immediately following
      return of spontaneous circulation (ROSC). This was supported by animal data which
      demonstrated that improved neurologic outcome was associated with reduced time to goal
      temperature following ROSC. More recently this hypothesis has been called into question by 2
      clinical trials which suggested that time to initiation of cooling was not associated with
      improved neurologic outcome at discharge.

      There may be another benefit to early therapeutic cooling. Animal data suggest that
      intra-arrest induction of therapeutic hypothermia (IATH) improves rates of ROSC from cardiac
      arrest. This is corroborated by a report describing an impressively high ROSC rate of 60.9%
      among patients receiving IATH. This was a higher frequency of ROSC than reported in similar
      patient groups. It has been demonstrated that mild hypothermia exerts a stabilizing effect on
      the myocardium, decreasing the rate of refibrillation following ROSC. Mild hypothermia has
      also been shown to prolong ventricular refractoriness and repolarization, possibly
      facilitating electrical defibrillation by slowing repolarization ion currents.

      Recently we conducted a retrospective observational study that demonstrated an association
      between the administration of IATH and ROSC.22 We found that the likelihood of ROSC with IATH
      was 2.4 (95% CI 1.41-4.24) time higher in the subset of patients who received > 700ml of 4º C
      normal saline compared to those who did not receive IATH. Our study lacked sufficient power
      to demonstrate a difference in survival to admission or discharge; however, we noted trends
      towards improved survival. Current intra-arrest treatments do not obtain ROSC rates greater
      than those seen in our study with IATH. These associations were noted in all rhythms,
      including asystole and pulseless electrical activity.

      Obtaining ROSC quickly with the resulting decrease in time spent in a low or no flow
      circulation would have obvious downstream effects on both hospital mortality and neurologic
      function, independent of the effect of mild hypothermia in the post-arrest inflammatory
      state. Surprisingly these associations were seen even with fluid volumes that were too low to
      change core body temperature suggesting that the benefits of therapeutic hypothermia on the
      myocardium may be possible even at relatively low fluid volumes.
    

Intervention name(s): 4 degree chilled saline
Intervention type(s): Drug
Intervention description(s): 4 degree chilled saline up to 2L in the prehospital setting
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment