Hypothermia in Comatose Survivors From Out-of-Hospital Cardiac Arrest - Hypothermia in OHCA

Description:

Therapeutic hypothermia has been shown to be associated with better neurological outcomes in patients who experience out-of-hospital cardiac arrest (OHCA). The recommended core temperature is 32-34°C. The current trial sought to study if colder temperatures would be associated with superior neurological outcomes in these patients.

Hypothesis:

Cooling to 32°C would be superior to cooling to 34°C in patients who experience OHCA.

Study Design

  • Randomized
  • Blinded
  • Parallel
  • Stratified

Patient Populations:

  • Witnessed OHCA apparently related to heart disease
  • Interval <60 minutes from collapse to ROSC
  • Age older than 18 years
  • Initial registered rhythm of a shockable rhythm (ventricular fibrillation or pulseless ventricular tachycardia) or asystole

    Number of enrollees: 36
    Duration of follow-up: 6 months
    Mean patient age: 64 years
    Percentage female: 11%

Exclusions:

  • Known pregnancy
  • GCS after ROSC >8
  • Cardiogenic shock
  • Other nonshockable rhythms (pulseless electrical activity)
  • Known terminal illness present before the OHCA
  • Possible causes of coma other than cardiac arrest

Primary Endpoints:

  • Survival free of severe dependence at 6 months

Secondary Endpoints:

  • All-cause mortality at 6 months
  • Best neurological outcome in 6 months

Drug/Procedures Used:

Patients who presented with OHCA and initial rhythm, either shockable or asystole, were randomized in a 1:1 fashion to either therapeutic hypothermia to 32°C or 34°C.

Principal Findings:

A total of 36 patients were randomized, 18-32°C and 18-34°C. Baseline characteristics were fairly similar between the three arms. Approximately 21% had diabetes, 28% had prior myocardial infarction (MI), and 27% presented with ST-segment elevation MI. About two thirds underwent bystander cardiopulmonary resuscitation (CPR), with initial rhythm being shockable in 72% of the patients. The mean time to advanced life support was 9.7 minutes, with a mean to return of spontaneous circulation (ROSC) of 26 minutes. The mean Glasgow coma scale (GCS) on admission was 3. Primary percutaneous coronary intervention was performed in 26% of patients; the median time from ROSC to initiation of hypothermia protocol was 120 minutes.

The primary endpoint of survival free of severe dependence at 6 months was similar between the 32°C and 34°C arms (44.4% vs. 11.1%, p = 0.12). When separated based on initial rhythm, there appeared to be a benefit if the initial rhythm was shockable (61.5% vs. 15.4%, p = 0.029); no difference was noted in asystolic patients (0% vs. 0%, p = 0.24). All-cause mortality was also lower in the 32°C arm (55.6% vs. 88.9%, p = 0.03). Adverse effects including bradycardia (38.9% vs. 11.1%, p = 0.054), hypokalemia (50% vs. 27.8%, p = 0.2), and bleeding (33.3% vs. 16.7%, p = 0.2) were numerically higher in the 32°C arm. The incidence of clinical seizures was significantly lower in the 32°C arm (5.6% vs. 61.1%).

Interpretation:

The results of this small trial indicate that therapeutic hypothermia to 32°C may be associated with better neurological recovery in patients with OHCA as compared with hypothermia to 34°C, especially in patients with shockable rhythms. There was also a significant reduction in clinical seizures with hypothermia to 32°C, although other adverse effects including bleeding and bradycardia were numerically higher. These results are hypothesis generating, but need further study. The sample size was very small (n = 36). The mechanism of benefit also needs to be carefully elucidated in further studies.

References:

Lopez-de-Sa E, Rey JR, Armada E, et al. Hypothermia in Comatose Survivors From Out-of-Hospital Cardiac Arrest: Pilot Trial Comparing 2 Levels of Target Temperature. Circulation 2012;Nov 6: [Epub ahead of print].

Presented by Dr. Esteban Lopez-de-Sa at the American Heart Association Scientific Sessions, Los Angeles, CA, November 6, 2012.

Clinical Topics: Arrhythmias and Clinical EP, Invasive Cardiovascular Angiography and Intervention, Implantable Devices, SCD/Ventricular Arrhythmias

Keywords: Seizures, Myocardial Infarction, Follow-Up Studies, Cardiopulmonary Resuscitation, Ventricular Fibrillation, Heart Arrest, Percutaneous Coronary Intervention, Coma, Temperature, Tachycardia, Ventricular, Out-of-Hospital Cardiac Arrest, Hypothermia, Hypokalemia, Glasgow Coma Scale, Bradycardia, Diabetes Mellitus


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