Therapeutic Hypothermia in Children With In-Hospital Cardiac Arrest

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Therapeutic hypothermia did not improve survival outcomes in pediatric patients with in-hospital cardiac arrest.
Therapeutic hypothermia did not improve survival outcomes in pediatric patients with in-hospital cardiac arrest.

Therapeutic hypothermia for in-hospital cardiac arrest in children was not significantly beneficial, according to results from the Therapeutic Hypothermia After Pediatric Cardiac Arrest (THAPCA) clinical trial (ClinicalTrials.gov identifier: NCT00880087) published in the New England Journal of Medicine.1

The investigators conducted the randomized trial in 37 children's hospitals throughout the United States, Canada, and the United Kingdom to determine whether the efficacy of therapeutic hypothermia would be different in patients who experienced in-hospital vs out-of-hospital cardiac arrest. According to other trials, therapeutic normothermia may be just as efficacious as therapeutic hypothermia in fever prevention.2,3 The researchers in the present study noted that published data on these therapies in patients who had in-hospital cardiac arrest are limited. They wrote that patients who experience in-hospital cardiac arrest represent a “pathophysiologically distinct population from those who have out-of-hospital cardiac arrest[s].”

The primary outcome was survival with a “favorable neurobehavioral outcome” (defined as an age-corrected standard score of 70 or higher on the Vineland Adaptive Behavior Scales, second edition [VABS-II]) at 12-month follow-up. Secondary outcomes included survival at 12 months after cardiac arrest and neurobehavioral functional change (defined as the difference in VABS-II scores between baseline and 12 months).

Of the 2791 patients (children older than 48 hours and younger than 18 years of age) screened, 746 were eligible for trial enrollment. Due to family consent issues, the total final study cohort consisted of 329 patients. Patients also had to have received chest compressions for at least 2 minutes and required mechanical ventilation after circulation returned. The patients were randomly assigned (1:1 ratio) to therapeutic hypothermia (target temperature: 33° C) or therapeutic normothermia (target temperature: 36.8°C). The investigators randomly assigned patients via permuted blocks stratified by facility and age (younger than 2 years of age, 2 to 12 years of age, or 12 years of age and older).

On February 25, 2015, the trial was halted because of futility after the data and safety monitoring board conducted a review of interim efficacy. The 2 treatment groups had similar baseline characteristics (mean age, 1 year; 60% male; 91% had a preexisting medical condition). Bradycardia was present in 57% of patients and ventricular fibrillation or ventricular tachycardia in 10% of patients. From cardiac arrest to cardiopulmonary resuscitation (CPR), the median time was 0 minutes and CPR lasted a median of 22 minutes. In addition, treatment initiation from the return of circulation occurred at a median of 4.9 hours in the hypothermia group and 4.7 hours in the normothermia group.

At 12 months, the percentages of children with VABS-II scores of 70 or higher were not significantly different between treatment groups (36% of the hypothermia group vs 39% of the normothermia group; relative risk [RR]: 0.92; 95% CI, 0.67-1.27; P =.63). The change in VABS-II scores were also not significantly different (P =.70). Survival rates at 12 months were 49% in the hypothermia group and 46% in the normothermia group (RR: 1.07; 95% CI, 0.85-1.34; P =.56).

The primary causes of death were brain death or life support withdrawal as a result of “poor neurological prognosis” in 39% of the hypothermia group vs 33% of patients in the normothermia group. Meanwhile, 31% of patients with hypothermia treatment died due to cardiovascular failure compared with 38% of patients with normothermia treatment.

Safety outcomes — including infection, blood-product use, and serious arrhythmias within 7 days after randomization — were similar between treatment groups.

“Unanswered questions remain regarding the role of targeted management in children after in-hospital cardiac arrest,” the researchers concluded. “A different therapeutic window for attaining the target temperature (shorter), a different duration of temperature control (longer or shorter), and different depths of temperature control (higher or lower) are modifications that have been suggested previously and might be considered for future trials.”

References

  1. Moler FW, Silverstein FS, Holubkov R, et al; for the THAPCA Trial Investigators. Therapeutic hypothermia after in-hospital cardiac arrest in children [Published online January 24, 2017]. N Engl J Med. doi:10.1056/NEJMoa1610493
  2. Nielsen N, Wetterslev J, Cronberg T, et al; for the TTM Trial Investigators. Target temperature management at 33 degrees Celsius vs 36 degrees Celsius after cardiac arrest. N Engl J Med. 2013;369(23):2197-2206. doi: 10.1056/NEJMoa131051
  3. Moler FW, Silverstein FS, Holubkov R, et al; for the THAPCA Trial Investigators. Therapeutic hypothermia after out-of-hospital cardiac arrest in children. N Engl J Med. 2015;372(20):1898-1908. doi: 10.1056/NEJMoa1411480
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