Therapeutic Hypothermia for Traumatic Brain Injury

Abstract

Experimental evidence demonstrates that therapeutic temperature modulation with the use of mild induced hypothermia (MIH, defined as the maintenance of body temperature at 32-35 °C) exerts significant neuroprotection and attenuates secondary cerebral insults after traumatic brain injury (TBI). In adult TBI patients, MIH has been used during the acute "early" phase as prophylactic neuroprotectant and in the sub-acute "late" phase to control brain edema. When used to control brain edema, MIH is effective in reducing elevated intracranial pressure (ICP), and is a valid therapy of refractory intracranial hypertension in TBI patients. Based on the available evidence, we recommend: applying standardized algorithms for the management of induced cooling; paying attention to limit potential side effects (shivering, infections, electrolyte disorders, arrhythmias, reduced cardiac output); and using controlled, slow (0.1-0.2 °C/h) rewarming, to avoid rebound ICP. The optimal temperature target should be titrated to maintain ICP <20 mmHg and to avoid temperatures <35 °C. The duration of cooling should be individualized until the resolution of brain edema, and may be longer than 48 h. Patients with refractory elevated ICP following focal TBI (e.g. hemorrhagic contusions) may respond better to MIH than those with diffuse injury. Randomized controlled trials are underway to evaluate the impact of MIH on neurological outcome in adult TBI patients with elevated ICP. The use of MIH as prophylactic neuroprotectant in the early phase of adult TBI is not supported by clinical evidence and is not recommended.

Effects of Mild Hypothermia Treatment on Rat Hippocampal β-Amyloid Expression Following Traumatic Brain Injury

“…MIH involves the rapid application of mild hypothermia regimens, as suggested and confirmed by several recent studies (Brain Trauma Foundation et al, 2007;van der Worp et al, 2007;Song and Lyden, 2012;Urbano and Oddo, 2012). In a study of 1626 patients with severe TBI, suggested that hyperthermia following TBI was a key detrimental factor to patient prognosis, accentuating delayed mechanisms that follow initial physical disruption during the primary injury and causing injury to hippocampal tissues.…”

“…More recently, mild induced hypothermia (MIH) has also been shown to significantly reduce the incidence of SBI (van der Worp et al, 2007). In fact, therapeutic temperature modulation using MIH has been reported to attenuate SBI following TBI in a variety of clinical settings when applied on an individual patient basis with consideration for the rate of edema progression (Urbano and Oddo, 2012). As a result, the American Association of Neurological Surgeons recommended MIH treatment in its Guidelines for the Management of Severe Traumatic Brain Injury (2008) (Brain Trauma Foundation et al, 2007).…”

Moderate Hypothermia Significantly Decreases Hippocampal Cell Death Involving Autophagy Pathway after Moderate Traumatic Brain Injury

“…Earlier work showed that moderate hypothermia after brain injury is associated with various pathological mechanisms, including reduction of cerebral metabolic rate, limitation of apoptosis, mitochondrial dysfunction and disruptions to calcium homeostasis, attenuation of inflammatory and immune response, suppression of free radicals, reduction of blood-brain barrier disruption, vascular permeability, and epileptic activity. [29][30][31] But the accurate mechanisms of cerebral protection provided by hypothermia after brain injury have not been fully addressed.…”

Specific intensive care management of patients with traumatic brain injury: Present and future

“…[3940] However, the literature suggests that therapeutic hypothermia should be instituted as soon as practical (in the emergency room) and beneficial effect usually seen when it has been continued for at least 72 h.[40] In a RCT ( n = 82), role of moderate hypothermia (32-33°C) in closed head injury (GCS 5-7) patients was found to hasten the neurologic recovery and improved the outcome. [41] A Cochrane review in 2009 analyzed 23 trials with a total of 1614 patients and found no evidence supporting the use of hypothermia during the treatment of TBI, but did find a statistically significant increased risk of pneumonia and other potentially harmful side-effects.…”