Lit of the Week – Therapeutic Hypothermia

Holzer M, et al. “Mild Therapeutic Hypothermia to Improve the Neurologic Outcome After Cardiac Arrest”. The New England Journal of Medicine. 2002. 346(8):549-556.

 

Clinical question / background:

  • In patients with ROSC following cardiac arrest due to ventricular fibrillation, does mild systemic hypothermia increase the rate of neurologic recovery after resuscitation?

 

Design:

  • Unblinded, parallel-group, randomized, controlled trial
  • 275 participants in 5 European centers
  • Inclusion criteria:
    • Witnessed cardiac arrest
    • Initial rhythm of Vfib or non-perfusing ventricular tachycardia
    • Presumed cardiac origin of arrest
    • Age 18-75
    • Interval of 5-15 minutes from patient collapse to first attempt at resuscitation by emergency medical personnel
    • Interval of less than 60 minutes from collapse to ROSC
  • Exclusion criteria:
    • Temp< 30 C on admission
    • Prior to arrest, comatose due to CNS depressant medication
    • Pregnancy
    • Response to verbal commands after ROSC
    • MAP<60 for more than 30 minutes after ROSC
    • Hypoxemia for more than 15 minutes after ROSC (SpO2<85%)
    • Terminal illness prior to arrest
    • Cardiac arrest after arrival of emergency medical personel
    • Known pre-existing coagulopathy

 

Intervention:

  • Reduce core temperature (bladder temp) to 32-34 C within four hours of ROSC. Maintain temperature goals for 24 hours, at which point allow for passive rewarming.

 

Control:

  • Normothermia

 

*Both groups sedated with midazolam and fentanyl. Paralyzed with pancuronium.

 

Primary endpoint:

  • Favorable neurologic outcome within 6 months after cardiac arrest defined as Pittsburgh cerebral performance categories 1 (good recovery), 2 (moderate disability). Poor outcome defined at category 3 (severe disability), 4 (vegetative state), 5 (death).

 

Secondary endpoints:

  • Mortality within 6 months
  • Complication rate within 7 days

 

Results:

  • TH associated with improved neurologic outcome at 6 months: Pittsburgh cerebral performance category 1 or 2
    • 55% vs 39% (p=0.009)
  • TH associated with decreased rate of death at 6 months
    • 41% vs 55% (p=0.02)
  • No difference in rate of complications
    • 73% vs 70% (p=0.09)

 

Take-home:

  • Witnessed cardiac arrest, VF and ROSC within 1 hour should be treated with therapeutic hypothermia for 24 hours for improved neurologic outcome.

 

Weaknesses / Critiques

  • Small trial
  • Unblinded
  • Only 8% of eligible patients enrolled in trial
  • Follow-up study in 2013 shows no difference between 33 C and 36 C, suggesting that hypothermia not of benefit, but hyperthermia dangerous.

 

Real World Application

  • Improved neurologic outcome: NNT of 6
  • Mortality benefit: NNT 7

 

Further reading

  • Nielsen N, et al. “Target Temperature Management 33°C vs. 36°C after Out-of Hospital Cardiac Arrest”. The New England Journal of Medicine. 2013. 369(23):2197-2206.

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