Cooling the body, in a general sense, has been recognised for hundreds of years as a potentially useful therapy. Since the 1950s, cardiac surgeons have used moderate hypothermia, or cooling, to protect the brain against the global ischemia that can occur during some open-heart surgeries¹.
Only recently has therapeutic hypothermia been recognised as a way to prevent ongoing damage to the neurological system that occurs hours after cardiac arrest. Two prospective randomised trials published in the New England Journal of Medicine in 2002, comparing mild hypothermia with normothermia in comatose survivors of out-of-hospital cardiac arrest, prompted health organisations around the world to take a closer look at recommending the therapy.
One of the landmark studies tracked the success of therapeutic hypothermia in five European countries: Germany, Austria, Finland, Belgium and Italy².Another study followed trials at four Australian hospitals³. Both studies showed significantly improved neurologic outcomes among patients managed with induced hypothermia at 32–34°C.
"Therapeutic hypothermia after cardiac arrest has been shown to improve survival and good neurological function by as much as 16%," says Lance Becker, emergency medicine specialist at the Center for Resuscitation Science, an interdisciplinary research group focused on creating and developing new therapies for sudden death and cardiac arrest, at the University of Pennsylvania Health System.
According to the American Heart Association, only about 6% of Americans survive to hospital discharge when a cardiac arrest happens outside the hospital.
"What therapeutic hypothermia does is not only improve the overall survival after someone has initially survived a cardiac arrest, but improves the neurologic outcomes as well," says cardiologist Mary Ann Peberdy, professor of internal medicine and emergency medicine at Virginia Commonwealth University.
Today, the International Liaison Committee on Resuscitation (ILCOR) and the American Heart Association recommend therapeutic hypothermia for comatose patients who have suffered out-of-hospital cardiac arrest from ventricular fibrillation and have been resuscitated.
The American Heart Association recommends these patients be mildly cooled for 12–24 hours from a normal body temperature of 37°C to 32–24°C. In its 2005 guidelines, the association stated that similar therapeutic hypothermia therapy may be beneficial for patients with non-ventricular fibrillation arrest out-of-hospital or for in-hospital arrest.
The Canadian Association for Emergency Physicians Critical Care Committee also advocates the use of an algorithm for the induction of hypothermia in the emergency department, according to a paper by J Kennedy et al in the March 2008 Canadian Journal of Emergency Medicine4.
How cooling works
Lowering the body temperature lowers the metabolic rate and, therefore, the demand for oxygen and other nutrients that the tissue needs. David G Beiser, assistant professor of medicine at University of Chicago and a practising emergency physician, has researched the molecular underpinnings of hypothermia. He believes that the therapy does far more.
"It is not just lowering the energy demands, but actually changing the way things are done at a molecular level and initiating protective pathways," he says. "So, it is increasing activity at certain levels to protect the cells."
While Beiser admits this thinking needs more research scrutiny, he and colleagues have published studies showing that, in cellular models, cooling actually upregulates certain metabolic pathways.
"Everybody has always assumed that, with hypothermia, we would turn down everything, including gene transcription and metabolic pathways," he says. "Now, we are concentrating on those pathways to figure out why they are turned up and whether these pathways have a protective effect."
"There are very specific conditions – a patient with sepsis, for example – that would warrant consideration to withhold the therapy," Becker says. "But, for the most part, if you are trying to restore that person to life, there is almost no reason you would withhold the therapy."
Doctors and other cooling champions within institutions need to keep in mind, however, certain nuances of providing the therapy. For example, these patients may need to be paralysed to prevent shivering.
"The population is prone to seizures, and, when you paralyse them, you cannot detect if they are seizing," Peberdy says. "We have implemented continuous EEG monitoring, so we can detect seizures when they are happening – not 24 hours later when we stop the paralytic agent."
Many practitioners believe that true candidates for cooling go beyond those described in the guidelines and position statements.
"Some people, including me, say if cooling works in one subset of patients, it should work in everybody who has a cardiac arrest, who is comatose following resuscitation," Beiser says.
"We really do not have any other therapies that work and have been studied to the degree that cooling has. Cooling needs to be the standard of care right now. Unless we are going to just give up on these patients, we should cool them."
Widespread adoption takes time
It has been more than five years since the American Heart Association and ILCOR issued an advisory statement recommending therapeutic hypothermia for some cardiac arrest patients. While most emergency departments in the UK and other European countries are on board with using the therapy, emergency departments in the US and Canada are just starting to offer it.
"What is unfortunate is that many American doctors who should know about it do not know about it and do not do it," says Becker. "So, there are many American patients who do not get the therapy, even though they would probably benefit from it."
A 2006 survey published in Critical Care Medicine found that 74% of US respondents and 64% of non-US respondents had never used therapeutic hypothermia. US experts estimate that less than half of emergency departments use therapeutic hypothermia today. Half of Canadian emergency physicians claim they have used therapeutic hypothermia in practice.
Barriers to cooling
Expense should not be an obstacle to practising the therapy. The equipment necessary for cooling is relatively inexpensive and, in its basic form, already exists in hospital emergency departments.
"You do not have to use the really expensive technologies out there," Beiser says. "In fact, we do not use them. We induce cooling using chilled saline and we have an inexpensive cooling blanket system."
The systematic approach for cooling often puts nurses at the frontline of care for administering the therapy, after a doctor has given his or her orders. Some hospitals are hesitant to dedicate the nursing staff needed to cool patients and monitor the process.
"When we first started our programme, we used to have to have two nurses for every patient that we had for the first several hours," Peberdy says. "We initially packed people in ice and wrapped them in cooling blankets, and nurses would have to change the icepacks and the beds. Patients would be unstable. It would take a lot of their attention."
Since then, she says they have moved to a cooling technology. "[It] has made the nursing input much less demanding, in terms of the cooling process."
There is a learning curve for successful cooling and no universal protocol for implementing the practice. That lack of standardisation has been a hurdle in Canada, according to Steven Brooks, assistant professor in the department of medicine, division of emergency medicine at the University of Toronto.
"I certainly think that people are more aware of therapeutic hypothermia and are more enthusiastic about it, and increasingly interested in trying to find better ways of doing it," he says. "I think we are beyond asking, 'Should we do this?' and now it is more, 'How do we do this best?'."
Despite a lack of standardised protocols within and across hospitals, Beiser says there are examples of protocols that experienced cooling champions are willing to share. He maintains that adding cooling to their therapeutic repertoires is one of the easier, less expensive and most impactful things that hospitals can do.
The American Heart Association's 2005 Guidelines for CPR and Emergency Cardiovascular Care explain the positive aspects of inducing hypothermia in suffering patients.
Both permissive hypothermia (allowing a mild degree of hypothermia >33°C [91.5°F] that often develops spontaneously after arrest) and active induction of hypothermia may play a role in postresuscitation care. In two randomised clinical trials (LOE 1; LOE 2) induced hypothermia (cooling within minutes to hours after ROSC) resulted in improved outcome in adults who remained comatose after initial resuscitation from out-of-hospital ventricular fibrillation (VF) cardiac arrest. Patients in the study were cooled to 33°C (91.5°F) or to the range of 32−34°C (89.6−93.2°F) for 12−24 hours. The Hypothermia After Cardiac Arrest (HACA) study included a small subset of patients with in-hospital cardiac arrest.
A third study (LOE 2) documented improvement in metabolic end points (lactate and O2 extraction) when comatose adult patients were cooled after ROSC from out-of-hospital cardiac arrest in which the initial rhythm was pulseless electrical activity (PEA)/asystole.
In the HACA and Bernard studies, only about 8% of patients with cardiac arrest were selected for induced hypothermia. Patients were haemodynamically stable but comatose after a witnessed arrest of presumed cardiac etiology. This highlights the importance of identifying the subset of patients who may most benefit. Although the number of patients who may benefit from hypothermia induction is limited at present, it is possible that with more rapid and controlled cooling and better insights into optimal target temperature, timing, duration, and mechanism of action, such cooling may prove more widely beneficial in the future. A recent multicentre study in asphyxiated neonates showed that hypothermia can be beneficial in another select population.
Complications associated with cooling can include coagulopathy and arrhythmias, particularly with an unintentional drop below target temperature. Although not significantly higher, cases of pneumonia and sepsis increased in the hypothermia-induction group. Cooling may also increase hyperglycemia.
Most clinical studies of cooling have used external cooling techniques (cooling blankets and frequent applications of ice bags) that may require a number of hours to attain target temperature. More recent studies suggest that internal cooling techniques (cold saline, endovascular cooling catheter) can also be used to induce hypothermia. Providers should continuously monitor the patient"s temperature during cooling.
In summary, providers should not actively rewarm hemodynamically stable patients who spontaneously develop a mild degree of hypothermia (>33°C [91.5°F]) after resuscitation from cardiac arrest. Mild hypothermia may be beneficial to neurologic outcome and is likely to be well tolerated without significant risk of complications.
In a select subset of patients who were initially comatose but hemodynamically stable after a witnessed VF arrest of presumed cardiac etiology, active induction of hypothermia was beneficial. Thus, unconscious adult patients with ROSC after out-of-hospital cardiac arrest should be cooled to 32−34°C (89.6−93.2°F) for 12−24 hours when the initial rhythm was VF (Class IIa). Similar therapy may be beneficial for patients with non-VF arrest out of hospital or for in-hospital arrest (Class IIb).
While experts suggest that the earlier cooling begins, the better for cardiac arrest patients, ambulances do not have the equipment for cooling.
Several institutions are working on developing technology that would allow healthcare personnel to provide the therapy in the field, but that technology is about a year from being widely available. Experts agree that more research needs to be done on how widespread cooling is and why so many institutions have yet to establish cooling practice.
Message to doctors
Cooling experts say that doctors need to take the initiative and educate themselves on how to cool patients. They also should be advocates for patients and voice their concerns at facilities that do not offer the therapy.
American states are beginning to divert out-of-hospital cardiac arrest patients to facilities that do offer cooling. Peberdy's facility was the first centre in Richmond practising hypothermia. She and her team have seen significant results: they've doubled their neurologically intact survival rate.
"I do not know anybody that argues the data," she says. "I think the reality is that many institutions just bury their heads in the sand because it is often very difficult to care for these complex patients." The pressure is definitely on for more US hospitals to offer cooling.
1. "Therapeutic hypothermia after Cardiac Arrest." Circulation. 2003, 108; p118.
2. The Hypothermia after Cardiac Arrest Study Group. "Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest." New England Journal of Medicine. 2002, 346; pp549–556.
3. Bernard SA, Gray TW, Buist MD et al. "Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia". New England Journal of Medicine. 2002, 346; pp557–563.
4. "The use of induced hypothermia after cardiac arrest: a survey of Canadian emergency physicians." Canadian Journal of Emergency Medicine 2008, 10(2); pp125-30.