Targeted temperature management (TTM), previously known as therapeutic hypothermia or protective hypothermia, is an active treatment that tries to achieve and maintain a specific body temperature in a person for a specific duration of time in an effort to improve health outcomes during recovery after a period of stopped blood flow to the brain.
[2] Periods of poor blood flow may be due to cardiac arrest or the blockage of an artery by a clot as in the case of a stroke.
[1][7] These recommendations were largely based on two trials from 2002 which showed improved survival and brain function when cooled to 32–34 °C (90–93 °F) after cardiac arrest.
[11] A recent Cochrane Review summarized available evidence on the topic and found that targeted temperature management around 33 °C may increase the chance to prevent brain damage after cardiac arrest by 40%.
[19] The earliest rationale for the effects of hypothermia as a neuroprotectant focused on the slowing of cellular metabolism resulting from a drop in body temperature.
[20] Accordingly, most early hypotheses suggested that hypothermia reduces the harmful effects of ischemia by decreasing the body's need for oxygen.
[22] In the special case of infants with perinatal asphyxia, it appears that apoptosis is a prominent cause of cell death and that hypothermia therapy for neonatal encephalopathy interrupts the apoptotic pathway.
In general, cell death is not directly caused by oxygen deprivation, but occurs indirectly as a result of the cascade of subsequent events.
By making the cell membrane more impermeable, hypothermia helps prevent the cascade of reactions set off by oxygen deprivation.
[21] Targeted temperature management may also help to reduce reperfusion injury, damage caused by oxidative stress when the blood supply is restored to a tissue after a period of ischemia.
Hypothermia has been shown to help moderate intracranial pressure and therefore to minimize the harmful effects of a patient's inflammatory immune responses during reperfusion.
[21] Overt activation of N-methyl-D-aspartate (NMDA) receptors following brain injuries can lead to calcium entry which triggers neuronal death via the mechanisms of excitotoxicity.
[16] Core body temperature must be measured (either via the esophagus, rectum, bladder in those who are producing urine, or within the pulmonary artery) to guide cooling.
[29][30][31][32][33] Adverse events associated with this invasive technique include bleeding, infection, vascular puncture, and deep vein thrombosis (DVT).
Unlike non-invasive methods which can be administered by nurses, the insertion of cooling catheters must be performed by a physician fully trained and familiar with the procedure.
This technique uses two cannulae, inserted into a person's nasal cavity, to deliver a spray of coolant mist that evaporates directly underneath the brain and base of the skull.
[citation needed] The method is compact enough to be used at the point of cardiac arrest, during ambulance transport, or within the hospital proper.
[38] The Food and Drug Administration also has reported several cases of external cooling blankets causing significant burns to the skin of person.
The frozen iteration involves continuous application of caps filled with Crylon gel cooled to −30 °C (−22 °F) to the scalp before, during and after intravenous chemotherapy.
[21] Napoleonic surgeon Baron Dominique Jean Larrey recorded that officers who were kept closer to the fire survived less often than the minimally pampered infantrymen.
Such an extreme drop in body temperature brings with it a whole host of side effects, which made the use of deep hypothermia impractical in most clinical situations.
[21] In the 1980s further animal studies indicated the ability of mild hypothermia to act as a general neuroprotectant following a blockage of blood flow to the brain.
[43] Both studies, one occurring in Europe and the other in Australia, demonstrated the positive effects of mild hypothermia applied following cardiac arrest.
[8] Responding to this research, in 2003 the American Heart Association (AHA) and the International Liaison Committee on Resuscitation (ILCOR) endorsed the use of targeted temperature management following cardiac arrest.
[44] Currently, a growing percentage of hospitals around the world incorporate the AHA/ILCOR guidelines and include hypothermic therapies in their standard package of care for patients with cardiac arrest.
[27] Over this same period a particularly successful research effort showed that hypothermia is a highly effective treatment when applied to newborn infants following birth asphyxia.
[49] Animal studies have shown the benefit of targeted temperature management in traumatic central nervous system (CNS) injuries.
[50] A systematic review of randomised controlled trials in traumatic brain injury (TBI) suggests there is no evidence that hypothermia is beneficial.
[51] A clinical trial in cardiac arrest patients showed that hypothermia improved neurological outcome and reduced mortality.
[8] A retrospective study of the use of hypothermia for cardiac arrest patients showed favorable neurological outcome and survival.