Keeping a cool Head: Hypothermia for Neuroprotection after Cardiac Arrest

Induced hypothermia (lowering the body temperature to ≤35°C) attenuates neuronal damage and provides neuroprotection mainly through lowering the rate of metabolism. It thus finds applications in ameliorating the secondary damage associated with traumatic brain injury, cardiac arrest, and stroke. This article will focus on therapeutic hypothermia after cardiac arrest.

Advantages of Hypothermia
For each degree centigrade decrease in body temperature, cellular metabolism is reduced by 5-7%, but the observed neuroprotective effect of hypothermia is much greater than can be explained by reduced metabolism alone [1].
During hypothermia the brain is exposed to fewer excitatory neurotransmitters and has more time to clear free radicals. It also reduces the average kinetic energy and hence the velocities at which free radicals travel, effectively lowering the likelihood that a free radical can damage vital cell parts before it gets neutralized by the endogenous antioxidative system.
Altogether, hypothermia induces a favorable shift in intracellular concentrations of ions and metabolites such as inorganic phosphate, lactic acid, Ca²⁺ and H⁺, hence slowing brain acidosis [1].

Hypothermia Studies
Animal studies of therapeutic hypothermia have shown profound neuroprotective effects [1]. Despite being the most used model, the small rodent brain is structurally, dimensionally, and metabolically different from the proportionally bigger and complex human brain. Therefore, it probably shows a greater response to neuroprotective efforts. Unlike with rodent models human studies must take into consideration different temperatures, duration of therapy, therapy onset/ending, cooling methods, and factors such as age, gender, and pre-existing illness [1,2]. Clinical studies of hypothermia after cardiac arrest have therefore produced strongly inconsistent results.
The two largest recent controlled studies on humans have shown significant improvements in patients’ neurological outcome and survival. The European study on “Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest” showed a reduction in mortality by 14% and a 16% increase in patients with a good neurological outcome (able to live independently ½ year after cardiac arrest) in the hypothermia group. The 2002 Australian study on “Treatment of Comatose Survivors of Out-of-Hospital Cardiac Arrest with Induced Hypothermia” demonstrated a 26% increase in patients with a good neurological outcome [1,3].

Cooling Methods
Cooling must be accompanied by the use of sedatives and neuromuscular blockers, otherwise treatment will cause shivering and hence re-warming of the body with a counterproductive increase in energy/oxygen consumption. A good treatment protocol and adequate monitoring is required to successfully apply hypothermia.
Many adequate cooling methods are available and, with advancing medical technology, even more have become available. One such new device is an intravascular heat exchanger [3], which allows for rapid cooling and exact monitoring of blood flow and temperature. Another new internal cooling method is the intravenous infusion of iced isotonic fluid, such as saline solution [2,3]. Because saline solution is readily available even in a pre-hospital setting and safe to use regardless of age or gender, this is a suitable candidate for the early initiation of hypothermia. It is nevertheless necessary to maintain the cooled state with other methods later [2,3].
External methods include the application of ice packs to areas with a high heat exchange capability like the armpits, neck, groin or the head in the form of a cooling helmet [3,4]. However, proper placing of these devices requires a breach of privacy, especially when carried out in a pre-hospital setting. In addition the rate of cooling is relatively slow. Alternative methods include the use of cooling blankets or wet-evaporative cooling [4].
Hypothermia should be initiated as soon as safely possible but homeostatic imbalances induced by ischemia and the physical insult of reperfusion will persist for days. Hence there is a long time window (48-72h) to initiate and maintain hypothermia. Any one cooling method alone has shown lower efficacy than two or more methods combined. That and the rapid invention and inclusion of new cooling methods is one reason why an optimal therapy has not been developed and should therefore be researched and compared across qualified hospitals around the world.

[1] Poldermann, Intensive Care Med, 2004
[2] Peberdy et al, Circulation, 2010
[3] Nolan et al, Circulation, 2003
[4] http://bit.ly/13SyEz4


By Rick Cornell Hellmann, Alumni Medical Neurosciences, AG Spinal Cord Injury