5 Neuroprotective Strategies to Reduce Brain Injury

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NEUROLOGY UPDATE

Welcome to Neurology Times. I’m Dr. Andrew Wilner, and today on Neurology Update I’d like to discuss neuroprotective strategies to reduce brain injury after cardiopulmonary resuscitation (CPR) for cardiac arrest.

Out of hospital CPR for cardiac arrest rarely leads to a successful recovery. Less than 10% of patients with an out of hospital cardiac arrest survive.¹ Approximately half of those survivors suffer some neurologic deficit at discharge.²

These grim statistics have fueled clinical trials of a variety of neuroprotective strategies to improve neurological prognosis after cardiac arrest.

The American Academy of Neurology recently published evidence-based guidelines to reduce brain injury in adults who are comatose after cardiac resuscitation.³ The Academy assessed clinical trials of diazepam, hemofiltration, lidoflazine, magnesium, nimodipine, selenium, steroids, thiopental, 100% oxygen, xenon gas, and lowering body temperature pre-hospital or in-hospital.

Of these potential therapies for out of hospital cardiac arrest, only in-hospital hypothermia has proven successful. (Pre-hospital cooling has been evaluated, and has not been proven effective.)

Therapeutic hypothermia after cardiac arrest was initially recommended by the International Liaison Committee on Resuscitation in 2002 and has become standard of care.⁴

The Academy recommends one of two different protocols for in-hospital hypothermia:

1) For patients who are comatose after out of hospital cardiac arrest due to pulseless tachycardia or ventricular fibrillation, the current protocol for therapeutic hypothermia is reduction of body temperature to 32-34 degrees Centigrade for 24 hours. Based on 2 Class I studies, this carries a Level A recommendation.

2) Alternatively, for patients whose initial rhythm was ventricular tachycardia, ventricular fibrillation, or asystole/pulseless electrical activity, “targeted temperature management” aims for a body temperature of 36 degrees for 24 hours followed by 8 hours of rewarming to 37 degrees and temperature maintenance below 37.5 degrees until 72 hours. Based on 1 Class 1 study, this carries a Level B recommendation.

Both of these strategies are for patients who are comatose after cardiac resuscitation. They are not suitable for awake patients. The optimal temperature and duration of hypothermia for best survival and neurological outcomes have not been determined.⁵

To achieve therapeutic hypothermia, patients are cooled to 32 to 34 degrees for 24 hours using cooling blankets or pads, ice packs, or chilled intravenous fluids. Sedation and neuromuscular blockade to decrease shivering are routine.

Potential mechanisms of action of neuroprotection by hypothermia include slowed cerebral metabolic rate, reduced intracellular accumulation of calcium, and decreased inflammation.⁵

Adverse events secondary to therapeutic hypothermia may include cardiac arrhythmia, bleeding, hyperglycemia and infection.

To summarize, here are 5 facts about neuroprotective strategies for cardiac arrest.

1. In order to reduce brain injury after cardiac arrest in adults who are comatose after successful out of hospital CPR, the American Academy of Neurology recommends therapeutic hypothermia or targeted temperature management.

2. Therapeutic hypothermia for 24 hours is recommended for adults who are comatose after cardiac arrest due to pulseless ventricular tachycardia or ventricular fibrillation that occurs out of hospital (Level A recommendation).

3. Targeted temperature management for adults who are comatose after out of hospital cardiac arrest due to ventricular tachycardia, ventricular fibrillation, or asystole/pulseless electrical activity is a reasonable alternative (Level B recommendation).

4. No neuroprotective drug has proved effective in the setting of coma after cardiac resuscitation.

5. Cooling prior to arrival at the hospital is not helpful and should not be offered.

Research continues regarding the ideal temperature for cooling as well as its duration.⁶ The importance of fever prevention has also been recognized.

Thank you for listening to today’s Neurology Update on neuroprotective strategies to reduce brain injury after successful cardiopulmonary resuscitation for out of hospital cardiac arrest. I’m Dr. Andrew Wilner, reporting for Neurology Times.

References:

1. Donnino MW, Andersen LW, Berg KM et al. Temperature management after cardiac arrest. Circulation. 2015;132:2448-2456.

2. Laver S, Farrow C, Turner D, Nolan J. Mode of death after admission to an intensive care unit following cardiac arrest. Intensive Care Med. 2004;30:2126-2128.

3. Geocadin RG, Wijdicks E, Armstrong MJ, et al. Practice guideline summary: Reducing brain injury following cardiopulmonary resuscitation. Neurology. 2017;88:1-9.

4. Nolan JP, Morley PT, Vanden Hoek TL, et al. Therapeutic hypothermia after cardiac arrest. An advisory statement by the Advancement Life support Task Force of the International Liaison committee on Resuscitation. Resuscitation. 2003;57:231-235.

5. Aneman A, Cariou A, Nolan JP. Understanding temperature goals after cardiac arrest. Intensive Care Med. 2017; DOI 10.1007/s00134-017-4753-9.

5. Kirkegaard H, Soreide E, de Haas I, et al. Targeted temperature management for 48 vs 24 hours and neurologic outcome after out-of-hospital cardiac arrest. A randomized clinical trial. JAMA. 2017;318:341-350.