Sarah Perman and colleagues’ study on the positive effects of chilling particular cardiac arrest patients after their hearts restart helps to confirm the anecdotal experience of resuscitation experts and demonstrates the ethos of academic medicine at University of Colorado Hospital.
Perman, MD, MS, an assistant professor in the University of Colorado School of Medicine’s Department of Emergency Medicine, is an advocate of using therapeutic hypothermia on nearly all cardiac arrest patients lucky enough to have been resuscitated. It’s standard practice in the UCH Emergency Department, where Perman is the go-to faculty member for all things resuscitation-related (among other examples, she was the driving force in the ED’s acquisition of its LUCAS 2 automatic CPR machine).
The number of emergency patients arriving at UCH without a pulse has been growing, to about 120 in 2015. Perman and her ED colleagues manage to restart the hearts of about half of them, she said. Therapeutic hypothermia has long been considered a vital tool in ensuring the long-term well-being of those who make it. Perman’s work has bolstered the evidence to support the clinical practice.
Perman’s study came about because cardiac arrest can have different immediate causes, and medical practice has been ahead of medical research with respect to a certain class of patients who suffer the attacks. Therapeutic hypothermia (TH) has been proven to work with pulseless ventricular tachycardia (a heart rate so fast that blood stops pumping) and ventricular fibrillation (rapid, erratic beats that stop effective pumping). But for other types of cardiac arrest, there’s a lot less data.
One of these, called asystole, means there’s no electrical activity in the heart – the dreaded electrocardiogram flatline. Another, called pulseless electrical activity (PEA), shows the heart has electrical activity, but, as the name suggests, no pulsing at all. In either of these cases, one can’t shock the heart back into action with a defibrillator. Rather, they require administering CPR and pumping the patient with epinephrine. Fewer than 10 percent of patients with nonshockable cardiac arrest survive, Perman said.
But given that there are some 530,000 cardiac arrests each year in the United States alone, improving the prospects of even a small percentage of them can mean many lives saved.
Therapeutic hypothermia has been used in the ED and the Medical and Cardiac intensive care units at UCH since the American Heart Association began recommending it in 2005. It has been central to preserving the brains of those whose hearts restart. Patients are cooled with liquid-infused pads and blankets to 33 degrees Celsius (91.4 degrees Fahrenheit), kept at that temperature for 24 hours, and gradually rewarmed to the standard 37 C/98.6 F over the course of eight hours.
The protocol reduces cerebral metabolism by 6 percent to 10 percent for each degree Celsius of cooling. The cooling cuts back on the cascade of destructive brain effects that happen when a brain starved of blood gets big drinks of it again. For example, lower metabolism cuts the need for oxygen and glucose; it lowers lactate – an acid – levels in the brain, blocks the release of free radicals, decreases inflammation and edema (brain swelling), reduces disruption to the blood-brain barrier, and limits damage to blood-vessel linings, among other benefits.
The missing piece
But the seminal studies on therapeutic hypothermia (HACA and Bernard) both published in the same edition of the New England Journal of Medicine in February 2002, focused only on ventricular tachycardia and ventricular fibrillation patients. Those with nonshockable rhythms were, from the evidence-based medicine perspective, left out of the cold.
And so, Perman said, despite physicians around the world prescribing TH to patients who had nonshockable rhythms, there remained lingering doubt as to whether it was in fact effective. The most straightforward path to an answer would be a randomized, controlled trial with nonshockable cardiac arrest patients, some who receive TH, others who stay warm.
That’s happening now in France, in fact, where multiple hospitals have been participating in the HYPERION study since 2014. But attempting such a study in the United States would be “very challenging,” as Perman put it. For one thing, there’s the prospect of getting informed consent from patients who typically arrive unconscious. For another, there’s now a lot of peer-reviewed as well as anecdotal evidence of the benefits of TH for cardiac arrest patients. That makes forming a control group difficult.
“Because of the state of clinical science, a lot of very advanced centers are cooling all cardiac arrest patients,” Perman said – the exceptions being cases where injuries prevent it, and also those who arrive with serious cognitive impairment already. “So in terms of doing a randomized, controlled, placebo-based study, it could be ethically challenging.”
Perman, who arrived at UCH in mid-2013, was still in her fellowship at the University of Pennsylvania when a good alternative struck her and PhD epidemiology student Anne Grossestreuer. They had met while Perman earned her master’s degree in epidemiology at Penn. Penn’s Center for Resuscitation Science had been keeping a registry of cardiac arrest patients treated for therapeutic hypothermia since 2000. Why not retrospectively compare statistics on similar patients who received – and didn’t receive – TH and see how the outcomes differed?
They identified 519 patients with nonshockable rhythms and assigned them a likelihood of receiving TH based on age, sex, location of cardiac arrest, whether the arrest was witnessed, and duration of the arrest. They found that survival to discharge after TH was 60 percent higher than that of those who didn’t receive it (29 percent survived, versus 18 percent without TH). In addition, TH was associated with a 3.5-fold higher likelihood of a better neurological outcome, among other findings.
The feedback on the study has been good, Perman said.
“I think people are excited to read about the outcomes,” she said. “A lot of people have said they’re happy to have data to support their practice.”
As it turned out, the American Heart Association provided an additional boost to TH for nonshockable patients right around the same time Perman’s work hit the Web: It updated its guidelines to strongly recommend the practice for such patients in November.
Perman’s work to advance resuscitation care at UCH continues. She launched a registry of UCH cardiac arrest patients early this year. She was also a player in the updating of a post-arrest care pathway in the Epic electronic health record, to help ensure that resuscitation and post-resuscitation care is consistent and to the highest standards. Richard Zane, MD, chairman of CU’s Department of Emergency Medicine and UCHealth’s executive director of Emergency Services, said Perman’s work is “squarely within the academic and clinical sweet spot” of the department.
“Her work will inform emergency physicians and critical care specialists how best to care for patients in the most dire circumstances and in ways that will positively affect their outcomes,” Zane said. “As an emergency physician scientist specifically trained in resuscitation research, Sarah is doing exactly what we hoped she would do: expanding our research agenda, creating new knowledge, collaborating across disciplines and bringing national attention to the department.”