A major point of any traumatic brain injury (TBI) treatment is to inhibit a secondary brain injury due to space-occupying lesions or cerebral blood-flow abnormalities. Research has shown that these situations can be prevented during TBI through therapeutic hypothermia and temperature monitoring and management.
Thermoregulation, which is regulation of core and brain temperature, can cause many physiological effects in human brain and body, including: decreased brain metabolic rate, cerebral blood flow, critical oxygen delivery threshold, excitotoxic mechanisms, brain thermopooling, and edema formation. Furthermore, it can lead to the modulation of inflammatory response, white matter neuroprotection, apoptosis, neurotoxicity and protein synthesis.
The first report of the therapeutic effects of hypothermia on TBI was published in 1956, and many different groups of researchers have reported the cerebroprotective effects of TBI since 1993. Multiple protective mechanisms for TBI that function by inhibiting the secondary brain injury have been reported for hypothermia. Some of these mechanisms include: inhibition of glutamic acid release, cerebral metabolism, calcium-dependent cascade reactive oxygen species, nitric oxide (NO) production, apoptosis, along with blood-brain-barrier disturbance.
On the other hand, hypothermia could induce many complications, including electrolyte imbalance, infection and thrombocytopenia. Circulatory system complications might occur, including cardiac output reduction, arrhythmia and metabolic acidosis. Also, there is a possibility for liver, renal and gastrointestinal dysfunctions, which could lead to hyperglycemia.
An appropriate centralized management of hypothermia would minimize these complications. Early hypothermia introduction is the major factor responsible for the hypothermia cerebroprotective effects, and can best be achieved with the use of air ambulance and temperature-lowering devices. Cooling should be initiated in less than 2.5 hours following the injury, to be continued down to 33 degrees C within four hours.
The routine methodology is to decrease the temperature to 32 degrees C for an hour, maintain it for 3-6 hours (short term), 24-48 hours (medium term), or up to 14 days (long term). When the outcome of hypothermia therapy was compared among different time points, six months after the injury, significant improvement was observed by long-term hypothermia.
However, the key is to come up with the optimum hypothermia in order to get the maximum cerebroprotective effect while avoiding the potential complications, by monitoring intracerebral condition via intracranial pressure (ICP) sensors. As an example, a continued hypothermia was applied for 28 days until a normal ICP was achieved in the most severe state of the disease (Glasgow coma scale of 3) with bilateral pupil dilated upon arrival. Conversation and gait were recovered with this treatment regimen, along with controlled rewarming.
It has been shown that a mild hypothermia at 35 degrees C was accompanied with a lower complication and mortality rates as compared to those of 33 degrees C. Therefore, an induced normothermia (36 degrees C) under whole-body management is currently preferred. However, age, GCS, pupil abnormality and hypothermia were recognized as independent factors that can affect a favorable outcome.
In summary, early introduction and a long-term maintenance of normothermia or hypothermia along with a controlled, slow rewarming could warrant an increase success rate in the treatment of TBI.
