From Wiki Journal Club
Jump to navigation Jump to search
Moler et al. "Therapeutic hypothermia after out-of-hospital cardiac arrest in children". New England Journal of Medicine. 2015. 372:1989-1908.

Clinical Question

Amongst comatose children aged 2 days to 18 years with return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest of any cause, does mild hypothermia (32-34ºC) lead to improved neurological outcomes at 12 months as compared to normothermia?

Bottom Line

Among comatose children 2 days to 18 years who survived in-hospital cardiac arrest from any cause, mild therapeutic hypothermia (32-34ºC), as compared with targeted temperature control at normothermia (37ºC), does not improve favorable functional outcome at 12 months and cannot be recommended in these patients.

Major Points

The Therapeutic Hypothermia after Out-of-Hospital Cardiac Arrest in Children (THAPCA-OH) trial was designed to answer the question if mild hypothermia is neuroprotective in children with ROSC after out-of-hospital cardiac arrest. In the adult literature leading up to this trial it was suggested that patients may benefit from hypothermia or just fever prevention.

This trial, randomized patients to either hypothermia (target temperature, 33.0°C, n=155) or normothermia (target temperature, 36.8°C, n=140). Their primary outcome was survival with a good neurobehavioral outcome at 12 months, defined as a Vineland Adaptive Behavior Scales, second edition (VABS-II) score of at least 70. Enrolling children between the ages of 48 hour and 18 years old who experience cardiac arrest outside of hospital and received at least 2 chest compressions, they found no difference in their primary outcome with 20% of hypothermic patients vs. 12% of normothermic patients (95% CI -1.5 to 16.1; P = 0.14), as well as their secondary outcomes of all-cause mortality at 28 days (57% vs. 67%; P = 0.08) or alive at 1 year (38% vs. 29%; P = 0.13). They found no difference in the 1-year change in VABS-II score from baseline (P = 0.13) but found that the hypothermic patients had longer survival time of 149 days vs. 119 days (P = 0.04). For their safety analysis, there was no statistical difference for utilization of blood products, arrhythmias, and culture proven infections within 7 days of randomization.

This trial may have run the risk of being under-powered. Screening over 1400 children only 88% of the original 295 sample were included in the modified-intention-to-treat. The clinicians were/could not be blinded to treatment allocation and thus may have delayed clinical assessment and prolonged aggressive treatment in the hypothermia group. The findings of this trial are consistent with the THAPCA-IH Trial, the out-of-hospital sibling to this trial.


As of November 2022, no guidelines have been published that reflect the results of this trial.


  • Multicenter, randomized, controlled trial
  • N=295
    • hypothermia [target temperature, 33.0°C] (n=155)
    • normothermia [target temperature, 36.8°C] (n=140)
  • Setting: 36 sites in Canada and the USA
  • Enrollment: 1 September 2009 – 31 December 2012
  • Follow-up: 1 year
  • Analysis: modified-intention-to-treat
  • Primary outcome: Survival with a good neurobehavioral outcome at 12 months (VABS-II score ≥70)


Inclusion Criteria

  • Children between 48 hours and 18 years of age
  • cardiac arrest requiring chest compressions for at least 2 minutes
  • occurring outside of hospital walls
  • remained dependent on mechanical ventilation after return of circulation

Exclusion Criteria

  • inability to be randomized within 6 hours after the return of circulation
  • Glasgow Coma Scale motor-response subscale of 5 or 6
  • decision by clinical team to withhold aggressive treatment
  • major trauma associated with the cardiac arrest

Baseline Characteristics

Hypothermia Group displayed

  • Demographics: Median age 2.1, 49% less than 2 years, 31% between 2 to 12 years, 20% greater than 12 years, 34% female
  • Pre-existing medical condition: 52% no pre-existing medical condition, 21% lung or airway disease, 19% neurological condition, 12% gastrointestinal disorder, 10% prenatal condition, 9% congential heart disease, 22% other
  • Characteristic of cardiac arrest: 72% respiratory event, 9% cardiovascular event, 7% other, 12% unknown, 40% bystander witnessed, 68% bystander performed CPR, time to CPR median 3 minutes
  • Initial rhythm observed by EMS or hospital: 55% asystole, 6% bradycardia, 16% PEA, 9% VFib or VTach, 14% unknown
  • Doses of epinephrine: median 2, median given by hospital 1, median given by EMS 3


  • Targeted temperature management actively maintained for 120 hours.
  • hypothermia [target temperature, 33.0°C]
    • pharmacologically paralyzed and sedated, mechanically cooled to maintain core temperature (range, 32.0 to 34.0) for 48 hours, then rewarmed over 16 hours or longer to 36.8°C and maintained through rest of 120 hours.
  • normothermia [target temperature, 36.8°C]
    • same therapy as hypothermic group but temperature (range, 36.0 to 37.5) maintained for entire 120 hours.


Comparisons are Hypothermia group vs. Normothermia group.

Primary Outcomes

Alive with VABS-II score ≥70 at 1 year
20% vs. 12% (risk difference 7.3; 95% CI -1.5 to 16.1); P = 0.14

Secondary Outcomes

Alive at 1 year
38% vs. 29% (risk difference 9.1; 95% CI −1.8 to 19.9; P = 0.13)
1-yr change in VABS-II score from baseline
P = 0.13 (calculated by means of the Mann-Whitney test on basis of continual change)
Survival over time
149 days vs. 119 days; P = 0.04
All-cause mortality at 28 days
57% vs. 67%; P = 0.08

Adverse Events

No statistical difference for utilization of blood products, arrhythmias, and culture proven infections within 7 days of randomization


  • Trial may have been underpowered to detect a difference
  • Treatment allocation was not blinded for clinicians but assessors were blinded
  • Modified ITT analysis only included 88% of the total sample, thus potential false negative results


  • National Heart, Lung, and Blood Institute

Further Reading