A Quicker Kind of Cool

By now no one questions the value of therapeutic hypothermia among the treatments given to victims of sudden cardiac arrest. With a belief that earlier initiation may be better, many systems are even starting it in the field. That’s typically done after return of spontaneous circulation. But now a handful of systems, including that of the nation’s largest city, are trying it even earlier than that.

Paramedics in New York City are giving cardiac arrest patients ice-cold saline as “the first drug out of the bag,” John Freese, MD, chief medical director for the Fire Department of New York, told attendees at the EMS State of the Sciences Conference in February. The department’s early data suggest it’s safe and associated with an increased rate of return of spontaneous circulation.

“Therapeutic hypothermia has various physiologic benefits, some of which act upon cellular mechanisms that kick in within 10 minutes of the arrest,” explains Freese. “If we can stop those processes, we may actually provide further benefit to patients beyond what typical hypothermia may provide.”

The earlier-cooling protocol began in 2010 with Phase 2 of NYC’s Project Hypothermia, an initiative of the city’s EMS and Greater New York Hospital Association. The project’s first phase brought hypothermia for cardiac arrest to hospitals; the second brought it to ambulances. The specifics for EMS: Large volumes of cooled saline (30 cc/kg up to 2 liters, delivered at around 4ºC) delivered via large-bore IV or IO access. Excluded are SCA victims with pulmonary edema, neurologically intact following initial resuscitation, whose providers couldn’t maintain IV/IO access, and for whom saline wasn’t available. It’s given after defibrillation and airway management, but before any drugs.

With the new protocol, FDNY collected data to answer three questions about the cooling: whether it was working, whether it was harming, and whether it was helping. To the first it found the cooling effective; the average patient was cooled by 1.6ºC, from 35.6 to 34.

The second was based on concerns about giving big amounts of fluid to patients without cardiac function. Some literature raised concerns about pulmonary edema. In its first 17 months of cooling, FDNY found that 8.7% of protocol patients developed it.

“That was an enormous concern up front,” says Freese. “Baseline, we didn’t know what percent of patients developed pulmonary edema as a result of standard resuscitation protocols. Certainly, in giving large volumes to a less-than-functional heart, there was concern of fluid overload. We continue to see around 7%–8% of our patients develop pulmonary edema. But having followed those patients at least in the short term, and knowing they’re more likely than other patients to achieve ROSC, right now our concern of doing harm in those patients is fairly little.”

Therein, the answer to question #3: At least in the short term, there could be some benefit to this. During the department’s intra-arrest cooling study period, its ROSC rate was 32.57%. Across a comparable non-protocol control population, it was 27.9%.

The difference was even more pronounced with higher volumes: Among those who received more than 150 ccs of saline, ROSC exceeded 38%—a 10% absolute increase associated with intra-arrest cooling.

“As far as impact on short-term survival, it translates into one of the more significant changes we’ve made,” says Freese. “With implementation of the 2005 guidelines, we saw roughly a 5% increase in ROSC—all arrests, all comers, all rhythms. We’ve seen essentially the same additional benefit with intra-arrest hypothermia. It’s potentially one of the most important changes we’ve made for resuscitation care in the past 10 years in New York.”

Elsewhere, the evidence for earlier cooling isn’t entirely positive; in particular, an observational prospective study published last year by an Italian group found ICU mortality rates of 47.4% for those with early-initiated cooling vs. 23.8% for those whose cooling started later, and six-month mortality rates of 60.8% vs. 40.5% respectively.¹ But that study had important differences with prehospital cooling as Big Apple medics do it. It started with data on patients admitted, post-ROSC, to ICUs who then experienced standard care, including hypothermia. Those receiving hypothermia were classified arbitrarily into early- (less than two hours post-arrest) and late- (more than two hours) initiation groups.

“I think the big difference is that they were looking at the initiation of cooling early after resuscitation,” says Freese. “That comes back to those physiologic mechanisms we think we’re able to capture by inducing hypothermia during the arrest. There are some significant differences. You could compare it to patients who are in arrest routinely getting epinephrine; then we get a patient who is profoundly hypotensive post arrest, and we’d never consider administering epinephrine, because we’re looking to capture a different physiology, different pharmacologic goals. So we look to other drugs. I think we need to look at hypothermia in somewhat the same way: When we look at pre-ROSC and post-ROSC cooling of patients, we may be comparing apples and oranges.”

Reference

1. Italian Cooling Experience (ICE) Study Group. Early- versus late-initiation of therapeutic hypothermia after cardiac arrest: Preliminary observations from the experience of 17 Italian intensive care units. Resuscitation 2011 Dec 8.