Therapeutic HypothermiaCurrently, guidelines recommend therapeutic hypothermia for comatose adults with out-of-hospital cardiac arrest (OHCA). A recent trial of adults with OHCA showed that therapeutic hypothermia with the use of a targeted temperature of 33°C vs maintained therapeutic normothermia of 36°C, did not improve outcomes. There is a paucity of randomized trials of therapeutic hypothermia in children with OHCA, but sometimes adult trials get extrapolated to pediatrics. There are differences between adult and pediatric populations with OHCA, which makes it difficult to extrapolate the results of the adult trials to a pediatric population.

Published Study

The New England Journal of Medicine just published the results of a study  entitled “Therapeutic Hypothermia after Out-of-Hospital Cardiac Arrest in Children” featuring the THAPCA-OH trial (Therapeutic Hypothermia After Pediatric Cardiac Arrest Out-of-Hospital).1 The registered clinical trial information can be found at


Therapeutic Hypothermia

What They Did

  • Randomized clinical trial of children admitted after OHCA conducted in 38 pediatric intensive care units (ICUs) in the United States (36) and Canada (2)
  • Children age >48 hours but < 18 years of age were eligible for inclusion
  • Patients randomized in a 1:1 ratio to either therapeutic hypothermia 33°C vs therapeutic normothermia 36°C
  • Target temperature management was actively maintained for 120 hours in both groups


  • Primary Outcome was survival with a good neurobehavioral outcome at 12 months
    • Good neurobehavioral outcome was defined as an age-corrected standard score ≥70 on a scale of 20 to 160 on the Vineland Adaptive Behavior Scales, second edition (VABS-II)
  • Secondary Outcomes:
    • Survival at 12 months after OHCA
    • Change in neurobehavioral function
  • Safety Outcomes:
    • Incidence of blood product use
    • Incidence of Infection
    • Incidence of serious arrhythmias through 7 days
    • 28-day mortality


  • 155 patients randomized to therapeutic hypothermia (33°C) vs 140 patients randomized to therapeutic normothermia (36°C)
  • No statistical difference in the following areas of :
    OutcomeTherapeutic Hypothermia (33°C)Therapeutic Normothermia (36°C)p-value
    Mean time from ROSC to Initiation of Treatment5.9 hrs5.8 hrs
    Survivors with VABS-II Score ≥70 at 12 Months20%12%0.14
    1 Year Survival38%29%0.13
    28 Day Mortality57%67%0.08
  • No statistical difference in the secondary outcome of change in the VABS-II score from baseline to 12 months (p = 0.13)
  • Similar incidences of infection, bleeding, and serious arrhythmias within 7 days after randomization between two groups
  • Hypokalemia (23% vs 14%) and thrombocytopenia (10% vs 1%) did occur more frequently in the hypothermia group, but renal replacement therapy (2% vs 7%) was used more often in the normothermia group.


  • Both arms received identical care with the exception of core temperature
  • Similar baseline patient characteristics between the two arms of the study


  • Potentially important clinical benefits of of less than 15-20% cannot be ruled out despite the lack of a significant difference in the primary outcome measures in this study. A larger trial may have been able to detect smaller intervention effects.
  • Caregivers and research staff could not be completely blinded to the treatment assignments of the patients, but they were blinded to the primary outcome assessments. This could have led to some bias in the study.


  • The duration of temperature control was much longer in this trial compared to the prior counterpart adult study (120 hours vs 36 hrs).2
  • The leading cause of cardiac arrest in this study was a respiratory condition in 72% of patients.
  • There was a lower proportion of patients with a shockable rhythm in this trial compared to the prior counterpart adult study (8% vs 80%).2

The Bottom Line

Bottom Line

In comatose children who survive OHCA, therapeutic hypothermia vs therapeutic normothermia DOES NOT confer a significant benefit or harm with respect to survival with good neurologic function at 1 year.

Moler F, Silverstein F, Holubkov R, et al. Therapeutic hypothermia after out-of-hospital cardiac arrest in children. N Engl J Med. 2015;372(20):1898-1908. [PubMed]
Nielsen N, Wetterslev J, Cronberg T, et al. Targeted temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med. 2013;369(23):2197-2206. [PubMed]
Salim Rezaie, MD

Salim Rezaie, MD

ALiEM Associate Editor Clinical Assistant Professor of EM and IM University of Texas Health Science Center at San Antonio Founder, Editor, Author of R.E.B.E.L. EM and REBEL Reviews