Abstract & Commentary
Therapeutic Hypothermia: How Cold Is Cold Enough?
By James E. McFeely, MD
Medical Director, Critical Care Units, Alta Bates Summit Medical Center, Berkeley, CA
Dr. McFeely reports no financial relationships relevant to this field of study.
SYNOPSIS: This large clinical trial of targeted body temperature — 33°C vs 36°C — following cardiac arrest showed no differences in survival or neurological outcome in the two temperature groups.
- SOURCE: Nielsen N, et al and the TTM Trial Investigators. Targeted temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med 2013;369:2197-2206.
Over the last 10 years, induced hypothermia after out-of-hospital cardiac arrest has become the standard of care. This new intervention is based on two studies that were published in 2002 with a total of 352 patients showing improvement in survival and neurologic outcomes in a select group of patients with successful out-of-hospital resuscitation.1,2 These patients were presumed to have arrests of cardiac origin with initially shockable rhythms. Since that time, use of therapeutic hypothermia has been extended to cardiac arrest with other rhythms and for in-hospital arrests. Questions remained, however, regarding the optimal target temperature and whether the treatment effect was due to induced hypothermia or prevention of fever.
This very large trial of targeted temperature management (TTM) was recently published. A total of 950 unconscious adults were randomized to a TTM goal of either 33°C or 36°C. Primary outcomes were all-cause mortality and a composite score reflecting neurologic function at 180 days. A pre-established protocol was used at 72 hours for neurologic prognosis and withdrawal of care. At the end of the trial, 50% of the 33°C group had died, as compared to 48% of the 36°C group (P = 0.51). At the 180-day follow-up, 54% of the 33°C group had died or had poor neurologic function, compared with 52% in the 36°C group. No differences were identified in six predefined subgroups.
This well-done study was unable to show a benefit of TTM to 33°C as compared with 36°C. If two small studies were enough to change our management to TTM at 33°C, this larger, better-controlled study should make us consider returning to a goal of simply avoiding fever. Much has changed for the better in critical care management in the last 10 years. This may be partly why improved outcomes were seen in both treatment groups in this trial. TTM to 33°C, however, comes with its own set of complications, from the potential need for paralytics and pressors to increased resource utilization from the cooling process. Changing to a philosophy of active fever avoidance rather than rapid cooling will be much easier to implement, with fewer side effects, and (based on this excellent study) equal outcomes.
I would hope for rapid modifications to the international guidelines and local practice to reflect the robust result of this study. Further studies may find subsets of patients who benefit from TTM to 33°C, but until then, 36°C should be our TTM goal. Remember: Primum non nocere: first, do no harm.
1. Bernard SA, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346: 557-563.
2. Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002;346:549-556. Erratum in: N Engl J Med 2002;346:1756.