No Benefit From Cooling in Pediatric Cardiac Arrest

Jim Kling

April 27, 2015

SAN DIEGO — In children who experienced out-of-hospital cardiac arrest, survival and cognitive outcomes are not significantly better with therapeutic hypothermia than with normothermia, according to new research presented here at the Pediatric Academic Societies 2015 Annual Meeting.

Therapeutic hypothermia is recommended for infants with brain injury caused by a lack of oxygen at birth and for adults who have experienced cardiac arrest.

But no studies have looked specifically at the therapy in children who experience cardiac arrest. And, according to the American Heart Association, there are more than 6000 such cases annually in the United States.

Adult guidelines were developed on the basis of two studies that showed the therapeutic benefit of hypothermia in adults who experienced cardiac arrest (N Engl J Med. 2002;346:549-556 and 2002;346:557-563). However, a more recent study showed no therapeutic benefit of hypothermia (N Engl J Med. 2013;369:2197-2206).

In the 2013 study, the use of fever-prevention strategies might have eliminated the difference between therapeutic hypothermia and normothermia; in the 2002 studies, there was no fever control.

"What we did in kids was similar to the 2013 trial, and we couldn't show a difference," said Frank Moler, MD, from the University of Michigan at Ann Arbor. The study results were published online in the New England Journal of Medicine to coincide with their presentation.

Dr Moler and his team evaluated 295 young people who had been admitted to a children's hospital after cardiac arrest. The children had chest compressions for at least 2 minutes and were dependent on mechanical ventilation. Patients whose cardiac arrest was the result of trauma were excluded from the analysis.

Cooling Blankets

All patients were pharmacologically paralyzed and sedated during the 120-hour treatment period. Physicians used cooling blankets to maintain body temperatures at 89.6 to 93.2 °F for the 155 patients randomized to the hypothermia group and at 96.8 to 99.5 °F for the 140 patients randomized to the normothermia group. In the hypothermia group, temperatures were kept low for 2 days, slowly returned to normal over a period of at least 16 hours, and maintained in the normal range until the end of the treatment period.

At 1 year, the difference in survival between the hypothermia and normothermia groups was not significant (38% vs 29%; relative likelihood, 1.29; 95% confidence interval [CI], 0.93 - 1.79; P = .13).

Survival with good neurobehavioral outcome — the primary end point — was assessed with the Vineland Adaptive Behavior Scales, second edition (VABS-II). A VABS-II score of 70 or higher (on a scale of 20 to 160) indicated a good neurobehavioral outcome.

At 1 year, the difference in the proportion of patients with a VABS-II score of at least 70 between the hypothermia and normothermia groups was not significant (20% vs 12%; relative likelihood, 1.54; 95% CI, 0.86-2.76; P = .14).

"I'm surprised by the results showing no difference between the two groups," said Kanwaljeet Anand, MD, from the University of Tennessee Health Sciences Center in Memphis, who attended the presentation.

Nevertheless, he took heart in the data. "There does seem to be a trend toward a benefit of hypothermia consistent with what we see in newborns and in adults," he told Medscape Medical News.

It is possible that fever control in the normothermia group made it harder to detect a statistically significant prevention of death or neurologic injury. "You lose signal-to-noise ratio and make it more difficult to show a therapeutic effect," Dr Anand explained. If the sample size had been larger, "we may have seen a positive result."

Dr Anand said he hopes to see secondary analyses that will pinpoint specific populations that could benefit from hypothermia. "This is the only thing we have available to treat children with cardiac arrest," he lamented.

The International Liaison Committee on Resuscitation is expected to update its treatment guidelines for cardiac arrest at the end of this year. Dr Moler, who has no involvement with the committee, predicted that the recommendations will suggest that both normothermia and hypothermia are viable treatment strategies.

Normothermia therapy is at least as challenging to maintain as hypothermia, because patients at normal temperature are more likely to shiver, which affects body temperature, according to Dr Moler.

The choice might come down to the individual patient. Either way, "you can't do nothing," he pointed out. "You have to sedate them and paralyze them and put them on cooling equipment to keep their temperature under control."

This study was funded by the National Heart, Lung, and Blood Institute. Dr Moler and Dr Anand have disclosed no relevant financial relationships.

Pediatric Academic Societies (PAS) 2015 Annual Meeting: Abstract 1360.5. Presented April 25, 2015.

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