Hypothermia Therapy for Resuscitation Takes a Hit

In 2002 the American Heart Association came out in favor of hypothermia in cardiac arrest patients resuscitated from a shockable rhythmn based on 2002 research.
Well, like many positive findings in medical research, more research has produced a retreat from that conclusion.

Hypothermia makes sense for brain recovery from hypoxic injury of cardiac arrest. Arrest people also often get a fever in the first 24 hours from loss of normal temperature regulation. The fever and commensurate higher metabolic rate was thought to release more evil humors and substances, inflammatory mediators and free radicals, also calcium displacements that aggravated brain damage.
Hypothermia is standard for open heart/bypass pump operations to decrease metabolic activity and improve tolerance for the circulatory compromise of being on bypass.
However the theory may be on the decline after a recent study published in the New England Journal of Medicine failed to confirm the benefits assumed.
http://pulmccm.org/2013/randomized-controlled-trials/hypothermia-help-hospital-cardiac-arrest-nejm/
A couple of sections from the papers for and against are illuminating.
First the theory behind the premise of hypothermic resuscitation from the authors in 20003:
http://circ.ahajournals.org/content/108/1/118.long
Mechanisms of Action
There are several possible mechanisms by which mild hypothermia might improve neurological outcome when used after reperfusion. In the normal brain, hypothermia reduces the cerebral metabolic rate for oxygen (CMRO2) by 6% for every 1°C reduction in brain temperature >28°C.21 Some of this effect is due to reduced normal electrical activity,21 however, and after cardiac arrest in dogs, CMRO2 is not significantly reduced by mild hypothermia.22 Mild hypothermia is thought to suppress many of the chemical reactions associated with reperfusion injury. These reactions include free radical production, excitatory amino acid release, and calcium shifts, which can in turn lead to mitochondrial damage and apoptosis (programmed cell death).23–25 Despite these potential advantages, hypothermia can also produce adverse effects, including arrhythmias, infection, and coagulopathy.
Here’s what the 2013 authors say in conclusion after detailing their failure to find a benefit from hypothermia in neurologic outcome in a randomized study of adequate power.
They said they found no benefit from hypothermia at the 32-34 centigrade target. The control group was kept at 36 to prevent the problem of fever.
In summary and self critique:
The other possibility is that the findings in the current study do not reflect truth, and the previous trials (Bernard, HACA) do. One argument for this (as also mentioned by Scott Aberegg in his Medical Evidence Blog) could be the higher “dose” of hypothermia in the prior trials: about 4 – 4.5° average temperature difference between groups, as opposed to 3° in the present trial. But that 1° changing this high-powered, firmly negative trial result seems close to inconceivable.
Treatment teams were not blinded to allocation group here either, and it’s possible biases could have also led to care differences between groups. Care was not standardized across all centers, so outlier effects at specific centers could have skewed the overall result from a positive to negative trial. Given the large overall size, number of centers, and total absence of signal, this doesn’t seem likely either.
Clinical Takeaway: Temperature should be maintained at 36° C or below after out-of-hospital cardiac arrest. Despite its physiologic rationale and evidence of benefit in prior smaller studies, targeted temperature management below 36° probably does not improve outcomes after out-of-hospital cardiac arrest of any type. Because average human core temperature is 37° C (98.6° F), maintaining temperature continuously at or below 36° C (96.8° F) still would require targeted temperature management (cooling) in almost all patients.