Chill pill: How new methods in therapeutic hypothermia can save lives

Therapeutic hypothermia  is currently one of the hottest trends in medicine. It's mainly being used to reduce injury to the brain following a disruption of blood flow. The rapid cooling down of core body temperature followed by a slow warming back to normal has been shown to greatly improve outcomes following heart attacks and strokes. Invasive protocols (cooling catheters placed in the inferior vena cava via the femoral artery) and non-invasive protocols (chilled water blankets against the skin) can be used to induce hypothermia. The benefits of therapeutic hypothermia decrease with time between injury and induction of cooling. This means that in emergency situations, the best outcome occurs when emergency personnel start the cooling process in route to the hospital. Out of hospital induction of hypothermia, however, has been limited by technical difficulties with cooling patients. Advances in modulating thermoregulation and quickly cooling immobilization collars could provide solutions to inducing hypothermia in emergency situations.

Thermoregulation is an extremely important process that allows the body to maintain a certain range of core body temperature regardless of the environmental temperature. Under normal circumstances thermoregulatory processes are extremely advantageous.It's clearly in one’s best interest not to freeze or overheat. In emergency situations, however, the body's thermoregulatory processes can act as a barrier to inducing hypothermia. Investigations have begun to create pharmacological interventions that could block these thermoregulatory processes.

Andrej Romanovsky, who heads the fever lab at Saint Joseph's Hospital and Medical Center, found that the experimental drug M8-B attenuates the cold response. This drug acts by blocking the activation of the thermal sensing receptors TRPM8. Disruption of TRPM8 resulted in the absence of thermoregulatory processes set to warm the body up.

M8B, however, is not the only drug under investigation for altering thermoregulatory processes. Cheng Chi Lee at the University of Texas at Austin has showed that 5’-adenosine monophosphate (5'-AMP) suppresses cold defenses. The resulting therapeutic hypothermia was shown to reduce injury in an early cardiac arrest model. While M8-B mechanistically works through altering cold perception, 5'-AMP suppresses metabolism. Suppression of metabolism reduces the thermoregulatory defense.

These pharmacological manipulations do not reduce temperature per se, but they allow for easier manipulation of core body temperature via the surrounding environment. This means that even with these drugs, a source of cooling must be available. Life Core Technologies’ neck immobilization collar induces hypothermia by cooling blood to the brain. Unlike normal immobilization collars, this collar contains a cooling element that automatically activates on positioning of the collar around the neck. Within seconds the non-hazardous cooling agent can reach -5° C. This patented collar  meets the American Heart Association's guidelines and can already be found in select emergency vehicles.

Although the effectiveness of therapeutic hypothermia decreases with time between injury and cooling, inducing hypothermia consistently and effectively outside of the hospital can be difficult. Recent innovative advances make inducing hypothermia at site possible.