Conference Coverage

Studies question benefits of induced hypothermia after cardiac arrest

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Care advances – including hypothermia – driving success in cardiac arrest

Dr. Niklas Nielsen and his colleagues found no real benefit of induced hypothermia over near-normothermic temperature maintenance in patients with out-of-hospital cardiac arrest, Dr. Jon C. Rittenberger and Dr. Clifton W. Callaway wrote in an editorial published along with the study (N. Engl. J. Med. 2013 Nov. 17 [doi:10.1056/NEJMe1312700]).

"This superbly executed study is more than twice the size of the original trials combined (which enrolled a total of 352 patients) and was conducted with meticulous attention to modern intensive care," the colleagues wrote, saying that there are multiple possible explanations for its finding.

The largest factor among these, they said, is probably the immense progress made in emergency care since the original hypothermia studies were published nearly a decade ago. "There has been evolution of intensive care over the past decade and improvements in patient care may have reduced the potential incremental benefits of a single intervention. In addition, illness severity varies greatly among patients with cardiac arrest, and there may be subgroups of patients who do benefit from induced hypothermia but who were not designated in advance. Particularly if the degree or duration of hypothermia must be adjusted to match the severity of brain injury, the benefits to a subgroup may be missed in a trial of one regimen of hypothermia for all comers."

The most important message of this trial, they wrote, "is that modern, aggressive care that includes attention to temperature works, making survival more likely than death when a patient is hospitalized after CPR.

"In contrast to a decade ago, one-half instead of one-third of patients with return of spontaneous circulation after CPR can expect to survive hospitalization. Few medical situations have enjoyed such absolute improvement over the same time period."

Dr. Clifton W. Callaway is the Ronald D Stewart Endowed Chair of Emergency Medicine Research at the University of Pittsburgh. He disclosed receiving speakers fees from several cardiac health groups and holding two patents on devices related to cardiac resuscitation. Dr. Jon C. Rittenberger is director of residency research in the emergency medicine department of the University of Pittsburgh. He has received honoraria and lecture fees for speaking on emergency medicine.


 

FROM THE AHA SCIENTIFIC SESSIONS

Most (76%) had temperature management with a surface cooling system; the rest were cooled by an intravascular catheter. Three patients in the 33°C group and four in the 36°C group didn’t get the assigned intervention; 16 in the 33°C group were rewarmed sooner than the protocol, at the discretion of their physician.

During the first week of hospitalization, 247 patients (132 in the 33°C group and 115 in the 36°C group) had life support withdrawn. Reasons for withdrawal included brain death, multiorgan failure, and ethical concerns.

At final follow-up, 50% of patients in the 33°C group and 48% in the 36°C group had died – a nonsignificant difference. There were no significant differences in the composite outcome of death or poor neurologic outcome whether measured by the CPC or the modified Rankin scales.

These results were similar in all adjusted analyses, in the intent-to-treat population, and in the per-protocol population.

Adverse events were common, occurring in 93% of the 33°C group and 90% of the 36°C group. The most common was hypokalemia, which was more significantly more common in the 33°C group (19% vs. 13%).

The study differed in one important way from others that have supported the use of induced hypothermia – and this might have had a key impact on the overall finding.

"We did not allow the natural trajectory of temperature evolution in either group," the authors said. "We actively controlled the temperature during the intervention period and aimed to prevent fever during the first 3 days after cardiac arrest."

It’s difficult to compare these results with those of the Hypothermia After Cardiac Arrest Study – the 2006 trial which first found in favor of the practice, the authors said.

Mortality in both groups of the current study was lower than that seen in 2006 – probably because of the recent advances in prehospital and in-hospital critical care management for cardiac arrest patients.

"We did not find any harm with a targeted temperature of 33°C as compared with 36°C," the investigators wrote. "However, it is worth recognizing that for all outcomes, none of the point estimates were in the direction of a benefit for the 33°C group. On the basis of these results, decisions about which temperature to target after out-of-hospital cardiac arrest require careful consideration."

Dr. Kim had no financial disclosures. Several of his coauthors disclosed financial relationships with medical device companies. Dr. Nielsen had nothing to disclose. Five of his coauthors disclosed financial relationships with outside entities; however, none appeared to be related to the study.

msullivan@frontlinemedcom.com

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