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.
