A 50-year-old healthy woman was relaxing at home with her husband watching TV. She didn’t take any medications or smoke, drink, or use drugs. Suddenly, he noticed that she had stopped talking to him. Concerned, he took her pulse but she was pulseless. He called 911, and was instructed over the phone on how to perform CPR. When they arrived eight minutes later, she was in full cardiac arrest. She was shocked three times to terminate ventricular fibrillation, and was intubated in the field.
She arrived at our local community hospital and was placed in an Arctic Sun® 5000 Temperature Management System (Medivance, Inc., C.R. Bard, Inc.). What is therapeutic hypothermia for cardiac arrest, and how does it work? This article will outline the pathophysiology of this innovative protocol and look at its long-term outcomes.
There are approximately 300,000 out-of-hospital cardiac arrests each year in the United States.1 Many are due to coronary artery ischemia, although some, as in this case study, occur in patients with structurally normal hearts. The outcomes are quite poor — fewer than 10% of such patients ever leave the hospital alive, and many of the survivors are neurologically devastated.2 Even aggressive interventions such as training more bystanders to perform CPR or making AEDs more readily accessible in the community have failed to make a significant dent in these dismal statistics.
Pathophysiology of Hypothermia
Experimental data from animal studies and clinical evidence have shown that hypothermia offers neuroprotective benefits. Hypothermia slows down brain metabolism.3 It reduces the consumption of oxygen and glucose. Hypothermia also helps limit the release of the neurotransmitter glutamate and the elevation of intracellular calcium, which occur in the brain during hypoxia.3 All of these factors help diminish excitotoxic cell death and cell apoptosis in the brain during cardiac arrest.
Early Clinical Data
Two landmark studies published in 2002 in the New England Journal of Medicine paved the way for our current resuscitative hypothermia protocols. We will review both studies briefly. The Hypothermia after Cardiac Arrest Study Group was a multicenter study organized in Europe between 1996–2001.4 The authors randomized 275 patients who presented with an out-of-hospital cardiac arrest to either receive a hypothermia or normothermia protocol. Patients who were entered into the hypothermia arm of the study were cooled down to 32–34 ºC for 24 hours using an external cooling device. Subjects in the normothermia group were treated according to the usual standards of care for post-cardiac arrest.
The clinical outcomes for the therapeutic hypothermia group were remarkable.4 Roughly 55% (75/136) of the hypothermia patients were assessed at having a favorable neurologic outcome at six-month follow-up, as compared with only 39% (54/137) in the normothermia group. The death rate at six-month follow-up in the hypothermia group was also much lower than in the other group, at 41% versus 55%. Interestingly, the complication rate was no different between the two groups. This latter finding was critical, since there are theoretical concerns that hypothermia could increase the infection or bleeding rates.
Researchers in Australia also published a fascinating study in 2002 replicating the European results.5 They took 77 cardiac arrest patients between 1996–1999 and randomized them to either hypothermia or normothermia protocols. Patients were cooled to 33 ºC externally for roughly 24 hours, then rewarmed. As in the European study, subjects in the hypothermia arm had a much higher survival rate with a good outcome at discharge, 49% versus only 26% in the normothermia group. Not surprisingly, the authors found that across the board, older patients did worse than younger patients. For each two-year increment in patient age, they had a corresponding 9% reduction in the chance of a good outcome.5
Hospital Course for Current Case
The 50-year-old cardiac arrest survivor described above was entered into Woodland Clinic’s Arctic Sun therapeutic hypothermia protocol. She was cooled to 32–34 ºC for 24 hours followed by a period of gradual rewarming. Paralytic and other agents were given to prevent shivering. A cardiac catheterization and echocardiogram revealed normal coronary arteries and normal heart function. The toxicology screen was negative. No obvious cause for the cardiac arrest could be found, although she did have persistent, unexplained hypokalemia. Later work-up for that was also normal.
Unfortunately, she remained in a persistent, vegetative coma for three weeks, even off all sedation. We placed a single-chamber defibrillator as well as a tracheostomy. However, she was completely unresponsive, and things began to look hopeless for her outlook. Then, after three weeks in a coma, she suddenly woke up and began smiling. She spoke appropriately and interacted with the ICU staff. Each day she became less confused and brighter neurologically.
The patient recently came in for a four-month checkup. We have treated her persistent hypokalemia with spironolactone, and feel that the hypokalemia helped trigger the unexplained cardiac arrest. Her brain function continues to improve. She can read, make jokes, and hopes to eventually return to work as an accountant. However, she is currently not neurologically “normal.” We will likely need to wait at least a year to see how much her brain function will ultimately improve.
Recent Clinical Data
Several more recent studies have looked at outcomes in cardiac arrest survivors who undergo resuscitative hypothermia. The Minneapolis Heart Institute initiated the “Cool It” protocol in 2006.6 Over a three-year period they enrolled 140 cardiac arrest patients who underwent a standard hypothermia protocol. The authors replicated other studies with their findings that 56% of the hypothermia group survived to discharge, and 92% of those had a “positive neurologic outcome.” They observed a 20% increase in the risk of death for every hour delay to initiate cooling.
Dumas et al described their prospective study based in France of 1,145 consecutive out-of-hospital cardiac arrest survivors treated from 2000–2009.7 All received a standard hypothermia cooling protocol. Thirty percent of the patients achieved a favorable neurologic outcome at discharge. Interestingly, the neurologic outcome was much better for patients who had initially presented with ventricular fibrillation than those who had pulseless electrical activity/asystole. Patients who had an initially unshockable rhythm were almost twice as likely to have a poorer neurologic outcome.
Therapeutic hypothermia is an excellent way to treat cardiac arrest survivors. Multiple studies have shown that such protocols can be easily and safely implemented in even rural hospitals. Although long-term data are still being assembled, initial results are very promising at improving the very poor neurologic and mortality outcomes in this patient group. For my patient, this was a remarkable “brain freeze” protocol that worked.
Disclosures: Dr. Glatter has no disclosures to report.
- Lloyd-Jones D, Adams RJ, Brown TM, et al. Heart disease and stroke statistics—2010 update: A report from the American Heart Association. Circulation 2010;121:e46–e215.
- Sasson C, Rogers MAM, Dhal J, et al. Predictors of survival from out-of-hospital cardiac arrest. Circ Cardiovasc Qual Outcomes 2010;3:63–81.
- Delhaye C, Mahmoudi M, Waksman R. Hypothermia therapy: Neurogical and cardiac benefits. J Am Coll Cardiol 2012;59:197–210.
- Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002;346:549–556.
- Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346:557–563.
- Mooney MR, Unger BT, Boland LL, et al. Therapeutic hypothermia after out-of-hospital cardiac arrest. Circulation 2011;124:206–214.
- Dumas F, Grimaldi D, Zuber B, et al. Is hypothermia after cardiac arrest effective in both shockable and nonshockable patients? Circulation 2011;123:877–886.
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