Apr 052017

Therapeutic hypothermia after cardiac arrest was almost immediately accepted as standard care in 2002 when two smallish, unblinded randomized trials (n=77 and n=273) showed a significant benefit from hypothermia after out-of-hospital ventricular fibrillation cardiac arrest. Hospitals and their cardiac care units quickly adopted resource-intensive protocols to manage patients' special needs while being cooled to an icy 33° Celsius.

Then the much larger 2014 TTM trial (n=950) contradicted the initial two hypothermia studies, showing no benefit of deep cooling over maintenance of core temperature at 36° C (96.8° F; essentially fever suppression). For physicians and centers that accepted the more convincing data, post-cardiac arrest care became a lot easier.

But others argued that the absence of benefit seen in TTM was not because deep hypothermia doesn't help -- it was because the patients weren't cooled quickly enough in TTM. Enter the RINSE trial, published in Circulation.

Authors randomized ~1200 patients with out of hospital cardiac arrest in Australia to either therapeutic hypothermia initiated pre-hospital with 2 liters of 3° C saline infusion or usual prehospital care. All patients were then transported to cardiac care centers where therapeutic hypothermia was performed as standard post-arrest care. Temperature targets at the cardiac centers changed during the trial, with many centers switching from a 36° to a 33° target based on the TTM study.

What happened? Patients with shockable rhythms receiving the cold saline did worse immediately, with 41% achieving return of spontaneous circulation, vs. 50% achieving ROSC who did not receive cold saline.

But the standard care patients caught up, unfortunately: equivalent proportions of patients survived to hospital discharge (a dismal 10% vs 11%).

It was hypothesized that the extra fluid bolus in patients with cardiac failure may have resulted in the initial deaths after unsuccessful CPR.

Everyone agrees that hyperthermia must be prevented following cardiac arrest, as fevers are associated with worse neurologic outcomes. Fevers earlier post-arrest are believed to be particularly damaging (compared to fevers occurring later). Thus some kind of temperature control is advisable for all victims of cardiac arrest.

Some experts advise 36° for 24 hours for uncomplicated cardiac arrest patients, with 33" reserved for those with no motor response, abnormal EEGs, or cerebral edema on CT. (There is no clear evidence of benefit of hypothermia for this sicker subgroup, either.) No evidence suggests one cooling method (cold saline, cold surface blankets, cool baths, or a combination) is better than another.

Patients cooled to 33° shiver, raising body temperature, and must be deeply sedated, requiring intubation. Neuromuscular blockade stops shivering but can mask status epilepticus and requires continuous EEG monitoring. Hypothermia can cause diuresis resulting in volume depletion and electrolyte loss (K, Phos, Mg) and so also requires frequent chemistry lab draws. In other words, deep hypothermia is complicated.

The RINSE trial isn't definitive; given the concerns about fluid boluses in cardiac failure, the logical next step in testing pre-hospital hypothermia is use of surface cooling. More clinical trial results for pre-hospital hypothermia after cardiac arrest are on the way.

Read more:

Induction of Therapeutic Hypothermia During Out-of-Hospital Cardiac Arrest Using a Rapid Infusion of Cold Saline (The RINSE Trial). Circulation. August 2016. [PubMed]

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Pre-hospital hypothermia hurt, not helped after cardiac arrest