In the last 30 years, there have been immense advances in the treatment and prevention of sudden cardiac arrest, including beta-blocker therapy and automatic implantable cardiac defibrillators.
In addition, communities have organized emergency medical systems (EMS) designed to provide early cardiac care for the prevention and treatment of cardiac arrest occurring outside the hospital (OHCA). One of the great frustrations of physicians working in the EMS environment is the successful cardiac resuscitation for the patient who is left with severe neurological impairment or brain death. It is clear that resuscitation of the brain is very time dependent. Complete interruption of blood flow to the brain leads to the loss of consciousness within seconds and death of vulnerable neurons in several brain regions occurs within minutes, whereas 20-40 minutes of ischemia is required to kill cardiac myocytes.
To improve survival and prevent the neurological sequelae of OHCA, total body hypothermia is advised based on animal laboratory experiments and a few small clinical studies carried out in a total of 179 OHCA patients (N. Engl. J. Med. 2002;346:557-63 and 549-56).
Both studies show both a neurological and survival benefit – particularly in patients resuscitated from ventricular fibrillation – in comatose patients in whom resuscitation was achieved within 5-10 minutes after witnessed cardiac arrest when cooled to 32-34 degrees Celsius within 60 minutes of collapse. These studies led to the recommendation by the International Liaison Committee on Resuscitation (Circulation 2004;110;3385-97) that cooling to 32-34 degrees Celsius for 12-24 hours should be used in unconscious patients with OHCA with VF and possibly non-VF arrests.
These recommendations were supported by the AHA Guideline Committee (Circulation 2010;122:S768-86) As a result, cooling comatose OHCA patients after resuscitation is widely used in emergency departments in the United States and Europe with the use of a variety of devices and techniques including large volume saline, external cooling devices, intravenous catheter devices, and intranasal devices. When hypothermia was initially recommended, a number of questions were unanswered and remain unanswered despite multiple publications and wide clinical experience in the succeeding 12 years. Some of those questions include the timing, duration, and intensity of cooling, the preferable technique of cooling, and risk and benefits of the different cooling techniques.
In the United States, pressure infusion of 2 liters of ice cold saline is the usual initial method of cooling to 32-34 degrees Celsius followed by 12-36 hours with surface cooling.
Investigators in Seattle randomized OHCA patients prior to hypothermia or standard therapy with both VF and non-VF rhythms before hospitalization to improve the previous reported benefit when initiated in hospital (JAMA 2014;311;45-52).
The initiation of prehospital therapy achieved cooling 1 hour earlier than in previous hospitalization studies. The result in 1,359 OHCAs over a 5-year period raises important questions about the benefit of hypothermia. The researchers failed to find any benefit in regard to neurological outcomes or mortality. In VF OHCA, they observed a survival rate to hospital discharge of 62.7 % (intervention group) and 64.3% (controls). In the patients without VF, those rates were 19.2 and 16.3, respectively.
Neurological outcomes were also similar for patients with VF at 57.5% (intervention group) and 61.9% (controls), respectively. The non-VF rates were 14.4% (intervention) and 13.4 % (controls). Hypothermia was associated with significant adverse events, including pulmonary edema and increased use of diuretics.
These observations are contrary to previous observations and should provide an opportunity to reevaluate hypothermia for OHCA. These patients represent a series of complex metabolic issues that deserve careful research to provide answers to some of the outstanding issues. The recent studies provide an environment of equipoise where we can step back and revaluate this complex procedure in randomized control trials.
Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.