Therapeutic Hypothermia: Delightful Brain Freeze


Main Points:

  1. This study demonstrates that the number needed to treat with therapeutic hypothermia to prevent one unfavorable neurological outcome is 6. The number needed to treat to prevent a single death is 7.


  1. Overall 75 of the 136 patients in the hypothermia group had favorable neurological outcomes as defined by the Pittsburgh cerebral performance grading scale. Only 54 of 137 patients in the control arm had favorable neurological outcomes recorded.Mortality in the hypothermia group at six months was 41 percent compared to 55 percent in the normothermic group.



The exact mechanism for the beneficial effects of therapeutic hypothermia are unclear with regards to favorable neurological outcomes, but it has been postulated that a reduction in cerebral oxygen consumption or a disruption in the inflammatory and acute phase cascade helps to prevent further brain injury following cardiac arrest. At the time of this study over 375,000 people in Europe were being treated annually for cardiac arrest with overall poor neurological outcomes. The study data clearly demonstrates that there is significant benefit for improved brain recovery with therapeutic hypothermia; however, current debate in the literature exists as to the exact target temperature, rate of cooling and rewarming.



This study was a randomized controlled trial with a blinded outcome assessment at six months evaluating for neurological recovery. It was impossible to blind the medical teams involved directly in patient care during their index hospital visit, but the treatment assignment was randomly generated by a computer in blocks of 10 once study eligibility was met. The study’s primary outcome was a favorable neurological outcome defined by the Pittsburgh cerebral performance category of either one or two. The Pittsburgh cerebral performance scale is comprised of 5 categories: 1 (good recovery), 2 (moderate disability), 3 (severe disability), 4 (vegetative state), 5 (death). Overall 3,551 patients were assessed for eligibility, but 3,246 did not meet the inclusion criteria. The inclusion criteria was defined as: a witnessed arrest, ventricular fibrillation or a nonperfusing ventricular tachycardia as the initial rhythm, age 18-75 years old, only 5 to 15 minutes of down time prior to EMS intervention and no more than 60 minutes from collapse to return of spontaneous circulation. The goal in the timeline of care was to appropriately select out patients and reach a target bladder temperature of 32-34°C within 4 hours of ROSC. The patient was to remain at this level of therapeutic hypothermia for the following 24 hours and then experience passive rewarming, estimated to take approximately 8 hours. The median time, however, between ROSC and the attainment of the temperature goal was 8 hours and in 19 patients out of the 137 in the hypothermia arm the target temperature could not be reached. Hypothermia needed to be discontinued in 14 patients due to significant complications ranging from death to hemodynamic instability as well as technical challenges. Both arms of the study lost a single patient to follow up. Nonetheless reviewing the data collected from the 275 patients enrolled in the study, 137 in the hypothermia arm and 138 in the normothermia group, shows marked improvement in outcomes. The number needed to treat with therapeutic hypothermia to prevent one unfavorable neurological outcome is 6. The number needed to treat to prevent a single death is 7. Few interventions in medicine provide such high yield results at relatively little cost.


Level of Evidence:

Based on the ACEP grading scheme for therapeutic questions this study receives a level 1 grade of evidence.

 Relevant articles:


Bernarnd, SA. Jones, BM. Horne, MK. “Clinical Trial of Induced Hypothermia in Comatose Survivors of Out-of-Hospital Cardiopulmonary Arrest.” Ann of Emerg Med 1997; 30:146-53


Source Articles:

Holzer, M.and The Hypothermia After Cardiac Arrest Study Group. “Mild Therapeutic Hypothermia to Improve the Neurologic Outcome After Cardiac Arrest.” NEJM, February 2002; 436(8): 549-56

Anatoly Kazakin MD

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