Therapeutic Hypothermia

November 12, 2009

File:Prianishnikov 1812.jpgCatherine Lucero, MD

Faculty peer reviewed

A recent article in the New York Times highlighted the remarkable recovery of a doctor who regained essentially all his mental function just six weeks after suffering a cardiac arrest with a post -resuscitation Glasgow coma score of 4.(1) Although the ambulance had originally rushed the doctor to the nearest hospital in Nassau County, he was quickly transferred to New York Presbyterian Hospital, where the receiving team induced hypothermia for the subsequent 24 hours. Five days later, the doctor woke up. Success stories such as these have now prompted the New York City Fire Department to form plans to bypass hospitals that do not have a protocol in place for induced hypothermia following cardiac arrest.

Resumption of spontaneous circulation after prolonged ischemia due to cardiac arrest carries significant morbidity and mortality and much effort has been directed toward reducing the debilitating consequences. Data from a national registry reviewed in 2006 noted in-hospital mortality rates following cardiac arrest to be as high as 67%. Furthermore, patients who do survive rarely undergo complete recovery. The central nervous system in particular appears to be at risk for residual disease. Resumption of spontaneous circulation results in impaired cerebrovascular autoregulation, disrupted calcium homeostatis, failure of microcirculatory reperfusion despite adequate cerebral perfusion pressure, and activation of cell-death signaling pathways(2). These events occur in the hours to days following the initial resuscitation. However, investigators now believe that mild to moderate hypothermia (32-34°C) may reduce neuronal damage by reducing free radical production, decreasing oxygen demand, and inhibiting excitatory neurotransmitters(3). Several initial supporting studies in anoxic animals demonstrated neurologic improvement following induced hypothermia and prompted subsequent research in human patients.

One of the first studies to demonstrate an association between therapeutic hypothermia in post-cardiac arrest patients and improved neurologic outcomes was a small case-control study performed in Australia. Investigators compared 22 patients that underwent cooling to a goal temperature of 33˚C to a control group of 22 patients identified retrospectively. 11 of the 22 patients in the hypothermia group suffered only minimal to moderate disability compared to just 3 patients in the control group (p < 0.05). Furthermore, mortality in the hypothermia group was substantially reduced compared to the control group (45% vs. 77% respectively, p < 0.05).

In 2002, Bernard et al. randomized 77 successfully resuscitated patients initially presenting in ventricular fibrillation to receive either induced hypothermia to 33˚ C for 12 hours or standard treatment at normothermia. Unblinded assessment at discharge demonstrated a good outcome in 49% of patients in the hypothermia group compared to just 26% in the normothermia group (p = 0.046).

Another well-known study from 2002 evaluated neurologic outcomes in 273 post-cardiac arrest patients at six months following resuscitation(3). Patients presented in either ventricular fibrillation or a non-perfusing ventricular tachycardia. After randomization, 137 patients underwent sedation and cooling to a target core body temperature of 32-34˚C for 24 hours followed by passive re-warming for eight hours. 136 control patients received standard care at normothermia. Although patients in the hypothermia group had a higher incidence of coagulopathy, sepsis, and pneumonia, none of these complications reached statistical significance. Blinded neurologic assessment at six months demonstrated favorable outcomes in 55% of the hypothermia group compared to favorable outcomes in only 39% of the control group. Furthermore, investigators calculated a risk reduction of 16% with a number needed to treat of just six in order to prevent one unfavorable neurologic outcome in these patients who otherwise had a poor prognosis.

Limited data exists concerning the effect of hypothermia on the neurologic outcome of patients not presenting in ventricular fibrillation (VF). In a recent review article highlighting several clinical trials, Bernard(6) describes a notable study done in Scotland, which retrospectively evaluated 139 patients with witnessed out-of-hospital cardiac arrest and treated with therapeutic hypothermia. Although 41% of patients presenting in VF had a subsequent favorable outcome, only 7% of patients not presenting in VF had a similarly favorable outcome. The two other small studies in the review article did not demonstrate a significant difference between the outcomes of patients presenting in VF compared to those patients in non-VF rhythms. In the end, Bernard concludes that only a small amount of data supports the benefit of hypothermia in non-VF patients. However, hypothermia does appear to improve the neurologic recovery in patients presenting in ventricular fibrillation.

Despite the retrospective methods and small sample sizes of the clinical trials conducted to date, the American Heart Association felt strongly enough about the long-term improvement in neurologic function to release a consensus statement in 2008, which states that induced hypothermia should now be standard of care for patients resuscitated after witnessed cardiac arrest.(2) The Fire Department of New York City has already sent letters to the hospital executives in Manhattan informing them of their plan to take cardiac arrest patients directly to centers with therapeutic hypothermia treatment available. Both Bellevue Hospital and Langone Medical Center have a therapeutic hypothermia protocol in place. Given the results of the studies described above and the consensus statement by the AHA, I appreciate these efforts. As a resident in the intensive care unit, I personally treated post-cardiac arrest patients with therapeutic hypothermia, and though it is labor intensive, I believe that witnessing the neurologic return in patients makes the cooling process worth the effort.

Dr. Lucero is a 3rd year internal medicine resident at NYU Medical Center.

Peer reviewed by Laura Evans MD, NYU Division of Pulmonary and Critical Care Medicine

References:
1. Hartocollis, A. City Pushes Cooling Therapy for Cardiac Arrest. NY Times. 2008 Dec 3. http://www.nytimes.com/2008/12/04/nyregion/04cool.html?_r=1&emc=eta1
2. Neumar, R. W., Nolan, J. P., Adrie, C., Aibiki, M., Berg, R. A., Bottiger, B. W., Callaway, C., Clark, R. S.B., Geocadin, R. G., Jauch, E. C., Kern, K. B., Laurent, I., Longstreth, W.T. Jr, Merchant, R. M., Morley, P., Morrison, L. J., Nadkarni, V., Peberdy, M. A., Rivers, E. P., Rodriguez-Nunez, A., Sellke, F. W., Spaulding, C., Sunde, K., Vanden Hoek, T. (2008). Post-Cardiac Arrest Syndrome: Epidemiology, Pathophysiology, Treatment, and Prognostication A Consensus Statement From the International Liaison Committee on Resuscitation (American Heart Association, Australian and New Zealand Council on Resuscitation, European Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Asia, and the Resuscitation Council of Southern Africa); the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council Clinical Cardiology; and the Stroke Council. Circulation 2008;118(23): 2452-2483
3. The Hypothermia after Cardiac Arrest Study Group. Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac Arrest. N Engl J Med 2002;346(8):549-56.
4. Bernard SA, Jones BM, Horne MK. Clinical trial of induced hypothermia in comatose survivors of out-of-hospital cardiac arrest. Ann Emerg Med 1997;30:146-15
5. Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, Smith K. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002;346:557-563.
6. Bernard, SA. Hypothermia after cardiac arrest: expanding the therapeutic scope. Crit Care Med 2009;37(7 Suppl):S227-33.

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