A 30-year-old man experienced an episode of syncope while at work. He fully recovered consciousness within 2 minutes, but the emergency services team was called. As he was being loaded into the ambulance he again lost consciousness, and he was noted to be in ventricular fibrillation. Advanced cardiac life support was immediately started and continued for 50 minutes before a hemodynamically stable spontaneous rhythm was obtained.
On arrival at the emergency department of the local hospital, he was intubated to protect his airway, as he was comatose. A 12-lead electrocardiogram showed ST-segment elevations in leads V1, V2, and V3 and a wide QRS complex with an rSR′ pattern, consistent with right bundle branch block.
Mild therapeutic hypothermia was initiated by infusing intravenous saline solution chilled to 4°C and by applying cooling blankets, and he was transferred to our hospital on an emergency basis for further management. Here, hypothermia was maintained using an intravenous cooling catheter.
HYPOTHERMIA: BENEFICIAL, BUT SLOW TO BE ADOPTED
Mild therapeutic hypothermia is a recommended therapeutic intervention for out-of-hospital cardiac arrest due to ventricular fibrillation. Nonetheless, first-responders, emergency-room staff, and intensive-care teams have been slow to adopt and integrate it into a comprehensive postresuscitation strategy. This article summarizes the evidence supporting this therapy and how it is performed.
PROPOSED MECHANISMS OF BENEFIT
Mild therapeutic hypothermia is thought to protect against anoxic brain injury in survivors of cardiac arrest via several mechanisms:
- Decreasing neuronal metabolism in the early stage of ischemic injury
- Decreasing glucose and oxygen consumption by the brain,1 which reduces supply-demand mismatch
- Decreasing the release of excitatory amino acids (eg, glutamate) that normally trigger cytotoxic cascades in the intermediate phase of injury2
- Reducing the production of harmful reactive oxygen species3
- Maintaining cellular pH4
- Reducing cell death5
- Slowing the breakdown of the blood-brain barrier that worsens cerebral edema.6
CLINICAL DATA SUPPORTING HYPOTHERMIA
There has been an interest in therapeutic hypothermia for several decades. In the 1950s, it was used in small numbers of cases in a variety of cardiac arrest situations.7,8 Interest was rekindled in the mid-1990s after a number of animal studies suggested it might be beneficial in prolonged cerebral ischemia and anoxia,9,10 and reports of case-series described its use in adults with out-of-hospital cardiac arrest.11,12
In October 2002, the International Liaison Committee on Resuscitation (ILCOR), made up of executive members of several organizations including the American Heart Association, recommended that “unconscious adult patients with spontaneous circulation after out-of-hospital cardiac arrest” should be cooled to 32°C to 34°C [89.6°F–93.2°F] for 12 to 24 hours “when the initial rhythm was ventricular fibrillation.”13
Two large randomized trials
This position statement was based largely on the results of two randomized clinical trials published simultaneously earlier in 2002.14,15 These two trials were important not only because they were the largest randomized trials of this therapy to that point, but also because they used meaningful, prospectively defined clinical end points: all-cause mortality and degree of cognitive preservation as assessed using the Glasgow-Pittsburgh Cerebral Performance Category (CPC) scale.
Bernard et al14 performed a randomized trial in four centers in Australia, assigning 77 patients either to a goal temperature of 32°C to 34°C or to normothermia for 12 hours, with all other resuscitative measures being the same in both groups. The primary outcome measured was survival to hospital discharge with sufficient neurologic function to be discharged to home or to a rehabilitation facility, ie, a CPC score of 1 or 2.
In the hypothermia group, 21 (49%) of the 43 patients survived and had an outcome that was considered “good” (ie, they were discharged home or to a rehabilitation facility), compared with 9 (26%) of the 34 patients in the normothermia group (unadjusted odds ratio 2.65, 95% confidence interval [CI] 1.02–6.88, P = .046). Proportionally fewer patients in the hypothermia group died—22 (51%) of 43 vs 23 (68%) of 34; however, the difference was not statistically significant (P = .145).
The Hypothermia After Cardiac Arrest Study Group15 screened 3,551 European patients who suffered out-of-hospital cardiac arrest15; 275 patients were randomized to mild therapeutic hypothermia or normothermia for 24 hours. The primary outcome was the percentage of patients who had a CPC score of 1 or 2 (vs 3 to 5) at 6 months, and the secondary outcome was the rate of death at 6 months.
At 6 months, 75 (55%) of the 136 patients in the hypothermia group had a CPC score of 1 or 2, compared with 54 (39%) of the 137 patients in the normothermia group (P = .009). The rate of death was also lower with hypothermia: 55% vs 41% (P = .02).
In both trials, patients were included only if their cardiac arrest was witnessed, if their initial cardiac rhythm was ventricular fibrillation or pulseless ventricular tachycardia, if circulation spontaneously returned within 60 minutes with standard basic and advanced cardiac life support protocols, and if they were still comatose on arrival at the hospital. They were excluded if they were over age 75, if they had suffered a cerebrovascular accident at the time of cardiac arrest, or if the arrest was caused by trauma or drug overdose. In addition, the European trial excluded patients who suffered another cardiac arrest after the initial return of spontaneous circulation but before cooling was started.