A study unveiled during a late-breaking "best of the best" presentation at the American Heart Association's Resuscitation Science Symposium on Nov. 15 in Orlando evaluated the safety, feasibility and cooling efficacy of intra-nasal evaporative cooling in the prehospital setting. The study, titled "Intra-Arrest Intra-Nasal Cooling: A Randomized Prehospital Study: PRINCE (Pre-ROSC Intra Nasal Cooling Effectiveness)," was conducted in Europe and sponsored by San Diego-based BeneChill, which developed the novel RhinoChill intra-nasal device under evaluation. Lead investigator and study co-author Maaret Castren, MD, PhD, of the Karolinksa Institute in Stockholm, Sweden, presented the results.
Fifteen EMS systems in Belgium, Germany, Italy, the Czech Republic and Sweden participated, initiating intra-nasal cooling in witnessed cardiac arrest patients even before the return of spontaneous circulation (182 total). Cooling began 23 minutes following arrest, without interrupting ACLS protocols.
Patients' tympanic temperature, measured upon arrival at the emergency department, was lowered to an average of 93.6_ F in those treated with RhinoChill, versus 95.9_ without treatment. The treatment provided a significant edge over hospital-initiated cooling methods alone, achieving the target tympanic temperature of 93.2_ F three hours faster and the target core temperature two hours faster.
Thirty-seven percent of those treated with RhinoChill during resuscitation survived neurologically intact, versus 21% who received hospital cooling alone, and 47% of the RhinoChill patients survived to discharge, compared to 31% of those who didn't receive intra-nasal cooling. Patients who received CPR within 10 minutes of collapse fared even better: Approximately 59.1% survived to discharge versus 29.4% without RhinoChill treatment, and 45.5% survived neurologically intact versus 17.6% without treatment.
The most common adverse event was nasal discoloration due to the cold, which resolved spontaneously following treatment.
RhinoChill offers several advantages over currentmethods, such as surface cooling or intravascular devices, used to induce hypothermia. These methods canbe invasive, cumbersome, may interfere with the resuscitation effort and are impractical for use in the field. BeneChill is non-invasive, portable and doesn't require refrigeration or an external power source and induces very rapid cooling of the target organ, the brain. "It was specifically designed to be used by non-specialized medical personnel in the field," said BeneChill founder and CEO Denise Barbut, MD, MRCP.
How it works
A nasal catheter delivers a proprietary inert mist that evaporates in the patient's nasal cavity, taking off heat and cooling the brain. "The catheter is attached to a bottle with the liquid coolant in it, and then oxygen flows through the bottle and pushes the coolant out," Barbut said. "Once it's in the nose, the oxygen -- or any other gas for that matter -- helps the liquid mist evaporate even faster and, therefore, cool better."
This novel cooling method drew great interest at the AHA meeting and is garnering attention from the EMS community.
"There are a number of things about this method that are appealing to me right off the bat," said James Dunford, MD, FACEP, EMS medical director for San Diego Medical Services Enterprise and a professor of clinical medicine and surgery at the University of California, San Diego Medical Center Department of Emergency Medicine. "It not only cools, it cools the brain, which could have theoretical advantages, and it doesn't take rocket science to place a cannula in someone's nose and turn on a machine. Any cooling strategy in the prehospital setting is going to have to meet those kinds of parameters -- ease of use, portability, lack of interruption of other critical things that are happening during cardiac arrest. This device appears to accomplish those things."
Barbut said that it's the first treatment that's actually aimed at the brain itself and which cools from the brain down, rather than from the body up. "It can be given as close to the time of injury as is possible and hours before anything else, and it can cool the brain absent any circulation, which is obviously not the case if you're trying to cool the brain through the blood.
"The brain starts dying from the minute the heart stops beating, and then dies exponentially thereafter, from time zero on," Barbut said. "The closer to that point that you can cool it, the more brain you're likely to save. The soonest you can start it is when the ambulance actually gets there -- about eight minutes or so."
"The animal data -- and we've got to be careful about extrapolating to humans, but it's really promising -- shows that the sooner you cool patients, the better off you are," Dunford said. "Here's a study that's actually doing it in the middle of arrest. They're not waiting for the patient to be resuscitated and brought to the hospital. They're really taking it right to the living room. We know that you can resuscitate animals to a neurologically intact survivor better if you get them cooler sooner. In the middle of the arrest may be, in some animal studies, the best time to do it."
Barbut said that in their randomized human study, they gave the RhinoChill device to second-tier ambulance crews. Theoretically, the treatment could be initiated sooner, achieving even better outcomes. "We started the cooling 23 minutes from the moment the heart stopped beating. The intention now is to start earlier, and as we go forward and as people get more comfortable with the commercial use of the device, the hope is that the time interval from collapse to starting nasal cooling will go from 23 minutes all the way back to eight or, at most, 10 minutes."
Beyond cardiac arrest
Intra-nasal cooling could eventually be used to treat other conditions as well. "We have only used it in cardiac arrest to date, simply because the benefits of cooling in cardiac arrest are the best established. However, the medical community very strongly believes, and increasingly so, that all forms of cerebral ischemia like stroke and head injury will also benefit from cooling," Barbut said.
"The key message is the benefit of cooling on the brain, in whatever condition -- cardiac arrest, stroke or head injury -- has been established and embraced by the medical community, but to date, there has been no technology, no method of initiating the cooling early enough to have a real effect on outcomes."
BeneChill will be marketed commercially in Europe in 2010. Barbut said they'll eventually seek FDA approval in the U.S. It's currently an investigational device.
Dunford said he's optimistic about the BeneChill results, and would like to see large-scale studies of cooling devices performed in the U.S., ideally through a robust clinical trial network, such as the Resuscitation Outcomes Consortium (ROC).
"I applaud these guys for what they've done," he said. "I think it's going to change the whole paradigm, because if in fact it bears out that you can change the entire curve of death, then we won't be declaring people dead so often in the field. We will be moving people into reanimation centers doing cooling strategies with ongoing CPR. By cooling people you offer a new hope, and that is that cooling and other interventions at the hospital may be able to resuscitate a person. The arena of reanimation medicine is geared for precisely this kind of movement in prehospital care in the future."
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