**1. Introduction**

Traumatic brain injury (TBI) is a major source of death and severe disability worldwide. In the USA alone, this type of injury causes 290,000 hospital admissions, 51,000 deaths, and 80,000 permanently disabled survivors [1,2]. Intracranial hypertension develops commonly in acute brain injury related to trauma [3,4]. Raised Intracranial pressure (ICP) is an important predictor of mortality in patients with severe TBI, and aggressive treatment of elevated ICP has been shown to reduce mortality and improve outcome [4-11]. Guidelines for the Management of Severe TBI, published in the Journal of Neurotrauma in 2007 [12] make a Level II recommendation that ICP should be monitored in all salvageable patients with a severe TBI (Glasgow Coma Scale [GCS] score of 3–8 after resuscitation) and an abnormal computed tomography (CT) scan. ICP monitoring is also recommended in patients with severe TBI and a normal CT scan if two or more of the following features are noted at admission: age over 40 years, unilateral or bilateral motor posturing, or systolic blood pressure < 90 mm Hg (Level III recommendation). Furthermore, ICP should be maintained less than 20 mmHg and cerebral perfusion pressure (CPP) between 50 and 70 mmHg (Level III).

As in ischemia –reperfusion injuries, the acute post-injury period in TBI is characterized by several pathophysiologic processes that start in the minutes to hours following injury and may last for hours to days. These result in further neuronal injury and are termed the secondary injury. Cellular mechanisms of secondary injury include all of the following: apoptosis, mitochondrial dysfunction, excitotoxicity, disruption in ATP metabolism, disruption in calcium homeostasis, increase in inflammatory mediators and cells, free radical formation, DNA damage, blood-brain barrier disruption, brain glucose utilization disruption, microcirculatory dysfunction and microvascular thrombosis [13-50]. All of these processes are temperature dependent; they are all aggravated by fever and inhibited by

© 2013 Sadaka et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 Sadaka et al., licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

hypothermia [13-50]. In addition, several studies have shown that development of fever following TBI is closely linked to intracranial hypertension and worsened outcome [51-53].

Therapeutic Hypothermia in Traumatic Brain Injury 81

GOS = Glascow Outcome Score

Traumatic Brain Injury: Randomized Controlled Trials

**Table 1.** Effects of Hypothermia on intracranial pressure and outcome in patients with severe

Clinical trials of hypothermia and temperature management for severe traumatic brain injury are divided into trials in which hypothermia is used to treat elevated intracranial pressure and those in which hypothermia is intended as a neuroprotectant, irrespective of intracranial pressure. In this article, we will review the current clinical evidence behind therapeutic hypothermia for the treatment of intracranial hypertension (ICH) in severe TBI patients, as well as therapeutic hypothermia as a neuroprotectant in severe TBI.
