Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children

Your pager startles you awake. Blurry eyed, you see the message — CODE BLUE, PEDIATRIC ICU. You arrive at the bedside of an 18-month-old girl who was admitted with severe bronchiolitis. She had been in respiratory distress, and despite high-flow oxygen and inhaled bronchodilators, minutes after arriving in the ICU she became bradycardic, then pulseless. As the overnight pediatric resident, you are responsible for leading the code. The nurses and interns perform chest compressions, the anesthesiologist intubates, and the ICU fellow doses the epinephrine. After 10 minutes, the patient regains circulation. What else can you do to ensure the best possible outcome for this child?

Pediatric cardiac arrest is an unimaginable tragedy for most people, but a daily reality for pediatric intensivists and emergency physicians. Many interventions have been studied to prevent cardiac arrest and improve outcomes when it does occur. In the early 2000s, results from clinical trials demonstrated that therapeutic hypothermia (cooling) improved neurologic outcomes in adult patients with out-of-hospital cardiac arrest. Subsequent trials extended these findings to pediatric patients and demonstrated that therapeutic normothermia (fever prevention) was as effective as hypothermia in adult and pediatric patients. For example, the Therapeutic Hypothermia after Pediatric Cardiac Arrest in the out-of-hospital setting (THAPCA-OH) trial, published in 2015, found that therapeutic normothermia and hypothermia were associated with similar outcomes in children who had suffered out-of-hospital cardiac arrest. Based on these findings, current guidelines recommend either therapeutic normothermia or hypothermia for both adult and pediatric out-of-hospital arrest. In this week’s NEJM, the results of a parallel study to the THAPA-OH trial — the Therapeutic Hypothermia after Pediatric Cardiac Arrest in the in-hospital setting (THAPCA-IH) trial — are reported.

THAPCA-IH was conducted in pediatric ICUs in 37 children’s hospitals in the US, Canada, and the UK. Children enrolled in the study were aged 48 hours to 18 years, had experienced cardiac arrest in the hospital, received chest compressions for at least 2 minutes, and remained mechanically ventilated with a poor initial neurologic exam. The patients were randomized to receive therapeutic hypothermia (to achieve a core temperature of 33.0°C) or normothermia (with a goal temperature of 36.8°C). The primary outcome was survival with a favorable neurobehavioral outcome at 12 months of follow-up.

The trial was stopped early for futility. At the time, 329 patients had been randomized (166 to hypothermia and 163 to normothermia). Among those patients, the percentage of children with a score ≥70 on the validated Vineland Adaptive Behavior Scale at 12 months follow-up was similar in the hypothermia and normothermia groups (36% vs. 39%, P=0.63). The rate of survival at 12 months also did not differ significantly between the two groups (49% vs. 46%, respectively; P=0.56).

The authors note that the lack of differences between groups could be a result of the low enrollment and wide confidence intervals for outcomes due to early termination of the trial, as well as the relatively long time (median, 6 hours) required to achieve therapeutic hypothermia. However, the results are consistent with other recent trials that have found no benefit from therapeutic hypothermia compared with therapeutic normothermia for out-of-hospital arrest. The authors add that many unanswered questions remain about targeted temperature management for pediatric cardiac arrest and state, “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.”

In conclusion, the THAPCA-IH trial found that therapeutic hypothermia did not result in a significant neurobehavioral benefit at 1 year, as compared with therapeutic normothermia, in children with in-hospital cardiac arrest. For the patient you successfully resuscitated overnight, these results can guide your management. It seems that therapeutic hypothermia and normothermia are both reasonable options for management, and you remain hopeful that the child has a good neurologic outcome.

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Rebecca is a 2016-2017 NEJM Editorial Fellow and a hospitalist at Massachusetts General Hospital. She graduated from Columbia University College of Physicians and Surgeons in 2013 and completed internal medicine residency at Massachusetts General Hospital in 2016. Her interests include medical education, quality improvement, patient safety, health care delivery innovation, and teaching value in health care.