Cold Could Save Your Life: Therapeutic Hypothermia

        The use of therapeutic hypothermia (TH) is becoming more widespread in the treatment of nontraumatic cardiac arrest and traumatic brain injury. Patients sustaining one of these two conditions may benefit from a controlled state of mild hypothermia, in which healthcare providers lower body temperature in an effort to help recovery. This new treatment, which is still being fully explored, is starting to be implemented by ambulance services and Emergency Departments across the country. This paper seeks to outline the use of TH in cardiac arrest and traumatic brain injury, discussing the benefits, costs, and possible directions for further research.
    
Therapeutic Hypothermia in Cardiac Arrest
        Nontraumatic cardiac arrest is the medical term used to describe a stopping of the heart caused by something other than trauma (such as a heart attack). Even after successful initial treatment of cardiac arrest and return of circulation, 90% of patients end up dying in the hospital and more than 10% of survivors sustain permanent neurological damage (Wenner, 2009). Healthcare providers are hoping to cut down on that number. Therapeutic hypothermia has been used successfully in certain highly invasive surgeries for nearly 60 years, helping to reduce brain oxygen demand in procedures such as open-heart surgery (Nolan et al., 2003). More recently, healthcare providers are beginning to use therapeutic hypothermia in the pre-hospital and hospital setting to hopefully reduce neurological damage and improve survival rates frequently associated with cardiac arrest.
        Initial recommendations for implementation of TH in cardiac arrest treatment came from the International Liaison Committee on Resuscitation (ILCOR), stemming from a series of clinical trials in Europe and Australia (Upchurch, 2007). Much of the research needed to fully understand long-term complications is currently underway, hence we do not know if this is going to become a standardized component of all resuscitation care. As of now, TH seems to show most promise in the treatment of comatose patients showing a Return of Spontaneous Circulation (ROSC) (Nolan et al., 2003). Because TH itself does not “restart the heart,” it is an adjunct to the normal treatment of nontraumatic cardiac arrest; the patient still needs CPR and Advanced Cardiac Life Support (ACLS) treatment according to the national standard resuscitation protocol. Once the patient has regained a pulse (that is, they have achieved ROSC), they are then a candidate for mild hypothermic treatment.
       The treatment plan appears to vary across healthcare systems. The most widely adapted version of therapeutic hypothermic involves cooling the patient externally (with cold packs in armpits and groin), while administering cold fluids via IV (Goodloe & Reginald, 2010). Core body temperature is carefully monitored so as to not drop below 32oC (89.6oF). Because shivering would generate heat, consume valuable energy, and increase metabolic demand, healthcare providers employ sedatives and neuromuscular blockers to prevent this normal bodily response (Nolan et al., 2003).

Therapeutic Hypothermia in Traumatic Brain Injury (TBI)
        Frequently cited mechanisms for traumatic brain injury include falls and car accidents. When a patient sustains a traumatic brain injury, the initial trauma is confounded by subsequent swelling and an increase in intracranial pressure (ICP). The increasing ICP may result in further neurological damage, in addition to suppressing the apoptotic biochemical response triggered by oxygen deprivation (Finnigan, 2005). This deleterious response is referred to as secondary brain injury.
        Therapeutic hypothermia is employed in traumatic brain injury (TBI) in a similar fashion to that outlined for cardiac arrest. However in this situation, the patient never technically died, but rather just sustained a significant bodily trauma. Each year there are 1.5 million traumatic brain injuries, leading to 50,000 deaths and 80,000 cases of permanent neurological disability (Centre for Neuro Skills, 2010). Candidates for TH include patients presenting with a Glascow Coma Scale (GCS) of 3-7, a significant decline from the norm of 15. Patients in the 3-7 range traditionally demonstrate unresponsiveness and motor function indicative of significant brain damage (such as decorticate or decerebrate posturing). Cooling may be done primarily through external methods, with a gradual rewarming back to normal temperature over the 24 hours following the injury (Marion et al., 1997).

Benefits
        There appears to be two primary benefits of TH. Firstly, by cooling the body core temperature, providers can lower cellular metabolic demand. Specifically, there is a 6% reduction in the brain’s Cerebral Metabolic Rate for Oxygen (CRMO2) for each 1oC decrease in temperature, down to a lower limit of 28oC (Nolan et al., 2003). By lowering metabolic demand, the brain is less likely to experience ischemia, the cellular deprivation of oxygen. Ischemia may lead to cell death and can cause widespread neurological damage (including memory loss, motor function loss, and personality/cognitive ability changes). Hence, TH may be invaluable in reducing long-term neurological injury.
        Secondly, decreasing the body temperature stunts the inflammatory response that can propagate further damage (Goodloe & Reginald, 2010). When cells are sufficiently deprived of oxygen and then circulation is re-established, (as would normally be the case in cardiac arrest resuscitation), the body is prone to reperfusion injury. Specifically, free radicals are produced and a chemical release stimulates mitochondrial death and apoptosis (akin to “cellular suicide”). By preventing the intracellular accumulation of these free radicals and calcium buildup, providers stop the immune system from triggering the apoptotic response when circulation is restored (Wenner, 2009). In this manor, inducing a state of hypothermia appears to curb the extent of reperfusion injury and limits the neurological damage to just that of the initial trauma (Nolan et al., 2003).

Costs
        The major negative aspect of TH appears to be cost. If initiated in the pre-hospital setting, costs would include the equipment stocked on the ambulance. Additionally, ambulances must be staffed by Emergency Medical Services (EMS) providers at a high skill level. Furthermore, training and revamping resuscitation protocols is associated with extensive human time costs.
        A second negative aspect of TH is the difficulty of provider coordination. Current research suggests that TH is only effective if continued for 12 hours after it is initiated (Goodloe & Reginald, 2010). This means that a treatment initiated in an ambulance must be continued at an Emergency Department, and then subsequently in the ICU. This has presented a barrier to innovational EMS systems, such as that in Oklahoma City or Tulsa. In these cities, at least one hospital had to commit to 24-hour TH ability before it could be initiated in the pre-hospital setting (Goodloe & Reginald, 2010).
Age also appears to be a complicating factor in the use of therapeutic hypothermia. Relative to the adult population, there is less conclusive evidence supporting TH for pediatric patients (Nolan et al., 2003), and some research has suggested it may even increase mortality rates in the treatment of nontraumatic cardiac arrest (Hutchison et at., 2008). Although animal trials and adult clinical trials have showed great promise for TH, the few studies aimed at the pediatric population have demonstrated inconclusive results. Due to the relatively low incidence of nontraumatic pediatric cardiac arrest, this field of research is plagued by low sample availability. As of now, TH may hold more promise for the pediatric population in the treatment of traumatic brain injury. Compared to that of cardiac arrest, a more significant body of research suggests that children do indeed benefit from TH after sustaining TBI (Finnigan, 2005). Furthermore, as TBI is the leading cause of pediatric death in the United States, pediatric TH research is rightfully more focused on brain injury than sudden cardiac arrest treatment.

Directions for Further Research
        Therapeutic hypothermia appears to be of benefit in the treatment of nontraumatic cardiac arrest and traumatic brain injury. By lowering body temperatures, healthcare providers can decrease metabolic oxygen demand and stunt chemical releases that trigger an apoptotic response. While further research in this field will be more forthcoming, it currently appears that this treatment is largely effective, especially in the adult population. Future studies should be aimed at its use in the treatment of other severe medical emergencies. If a patient dies in a car accident, should they be a candidate for TH? Additionally, the detailed aspects of TH need to be fine-tuned. Variables such as time of treatment initiation, duration of hypothermic state, and degree of cooling need to be [and are being] investigated (Nolan et al., 2003). As costs permit, TH is likely to be introduced in more healthcare systems nationwide.



Works Referenced

Centre for Neuro Skills. (2010). “Hypothermia Treatment for Traumatic Brain Injury.” Available online at: http://www.neuroskills.com/pr-experimental.shtml

Finnigan, M. (Apr 2005). “Moderate Hypothermia a Safe Treatment for Traumatic Brain Injury in Kids.” Medical News Today. Available online at: http://www.medicalnewstoday.com/articles/23508.php

Goodloe, J.M. and Reginald, T.J. (Feb 2010). “Chill Factor.” Journal of Emergency Medical Services, 35 (2). Available online at:
http://www.jems.com/news_and_articles/articles/jems/3502/chill_factor.html

Hutchison, J.S., and colleagues for the Hypothermia Pediatric Head Injury Trial Investigators and the Canadian Critical Care Trials Group. (Jun 2008). “Hypothermia Therapy after Traumatic Brain Injury in Children.” The New England Journal of Medicine, 358 (23), pp. 2447-2456. Available online at:
http://content.nejm.org/cgi/content/full/358/23/2447

Merion et al. (Feb 1997). “Treatment of Traumatic Brain Injury with Moderate Hypothermia.” The New England Journal of Medicine, 336, pp. 540-546. Available online at: http://content.nejm.org/cgi/content/full/336/8/540

Nolan, J.P., Morley, P.T., Vanden Joek, T.L., & Hickey, R.W. (2003). “Therapeutic Hypothermia After Cardiac Arrest.” Circulation, 108, pp. 118-121. Available online at:
http://circ.ahajournals.org/cgi/content/full/108/1/118

Upchurch, J. (Jun 2007). “Human Refrigeration.” Journal of Emergency Medical Services. Available online at: http://www.jems.com:80/news_and_articles/news/Human_Refrigeration.html

Wenner, M. (Feb 2009). “Cold Relief.” Popular Science, 274 (2), pp. 54-59.