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October - 2019

   

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Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm

J.-B. Lascarrou, H. Merdji, A. Le Gouge, et al for the CRICS-TRIGGERSEP Grou New Eng J Med, 2019, Online first Oct 2019

Comment

The 2015 ILCOR guidelines recommend targeted temperature management between 32 and 36 C for all patients successfully resuscitated from cardiac arrest who remain in coma. The interpretation of the evidence behind these recommendations remains debated, and practice varies. 

The application of TTM to patients with non-shockable rhythm is even less clear. This cohort are the majority, and overall outcomes are very poor. So, the Therapeutic Hypothermia after Cardiac Arrest in Nonshockable Rhythm (HYPERION) trial was designed to assess whether moderate therapeutic hypothermia at 33°C, as com- pared with targeted normothermia (37°C), would improve neurologic outcome in patients with coma who had been successfully resuscitated after cardiac arrest with nonshockable rhythm.

What did they do;

  • A total of 584 patients from 25 French ICUs were enrolled in this open- label, blinded-outcome-assessor, pragmatic, multi- center, randomized, controlled trial 
  • Enrolled patients were adults resuscitated from OHCA / IHCA from any cause, GCS ≤8. Of note exclusion criteria included no-flow time (collapse to CPR) > 10 minutes; a low-flow time (CPR to ROSC) > 60 minutes; and major hemodynamic instability
  • Patients were randomised to;
    • moderate therapeutic hypothermia (33°C) for 24-hours, with slow rewarming at a rate of 0.25 to 0.50°C per hour, to 36.5 to 37.5°C, maintained for further 24 hours.
    • targeted normothermia (37°C) for 24-hours, maintained 36.5 to 37.5°C, maintained for further 24 hours.
  • Cooling was  achieved at a median of 16 minutes, and was effectively maintained for the 24-hour period 
  • The primary outcome was proportion of patients alive at day 90 with CPC score of 1 (good cerebral performance or minor disability) or 2 (moderate disability). This was 10.2% hypothermia vs 5.7% normothermia (difference, 4.5 percentage points; 95% CI 0.1 to 8.9; P=0.04). This effect was consistent across prespecified subgroups. 
  • 90-d mortality did not differ significantly 81.3% hypothermia vs 83.2% normothermia (difference, −1.9 percentage points; 95% CI, −8.0 to 4.3). 
  • CPC 3 was 7.7% (hypothermia) vs 10.4% (normothermia), CPC 4 was 0.4 and 0%.
  • Prespecified adverse events did not differ significantly between groups. This included duration of MV or ICU LOS in those who died and survived.

Overall moderate TTM for patients with coma who had been resuscitated from cardiac arrest with nonshockable rhythm, led to a higher percentage of survivors with CPC 1 or 2 at day 90. The NNT is 22. There was no difference in mortality, and eyeballing of the overall results looks like the increase in CPC 1 and 2 came from CPC 3 and 5 patients. This study supports moderate TTM for 24 hrs.

 

Abstract

BACKGROUND

Moderate therapeutic hypothermia is currently recommended to improve neuro- logic outcomes in adults with persistent coma after resuscitated out-of-hospital cardiac arrest. However, the effectiveness of moderate therapeutic hypothermia in patients with nonshockable rhythms (asystole or pulseless electrical activity) is debated.

METHODS

We performed an open-label, randomized, controlled trial comparing moderate therapeutic hypothermia (33°C during the first 24 hours) with targeted normothermia (37°C) in patients with coma who had been admitted to the intensive care unit (ICU) after resuscitation from cardiac arrest with nonshockable rhythm. The primary outcome was survival with a favorable neurologic outcome, assessed on day 90 after randomization with the use of the Cerebral Performance Category (CPC) scale (which ranges from 1 to 5, with higher scores indicating greater disability). We defined a favorable neurologic outcome as a CPC score of 1 or 2. Outcome assessment was blinded. Mortality and safety were also assessed.

RESULTS

From January 2014 through January 2018, a total of 584 patients from 25 ICUs underwent randomization, and 581 were included in the analysis (3 patients withdrew consent). On day 90, a total of 29 of 284 patients (10.2%) in the hypothermia group were alive with a CPC score of 1 or 2, as compared with 17 of 297 (5.7%) in the normothermia group (difference, 4.5 percentage points; 95% confidence interval [CI], 0.1 to 8.9; P=0.04). Mortality at 90 days did not differ significantly between the hypothermia group and the normothermia group (81.3% and 83.2%, respectively; difference, −1.9 percentage points; 95% CI, −8.0 to 4.3). The incidence of prespecified adverse events did not differ significantly between groups.

CONCLUSIONS

Among patients with coma who had been resuscitated from cardiac arrest with nonshockable rhythm, moderate therapeutic hypothermia at 33°C for 24 hours led to a higher percentage of patients who survived with a favorable neurologic outcome at day 90 than was observed with targeted normothermia.

October


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