Methods and clinical applications of targeted temperature management

Hypoxic/ischemic brain damage is well-known catastrophic injury. The specific treatment, socalled neuroprotective therapy, aims to prevent or diminish this havoc damage. However, approved neuroprotective therapy in clinical practice is limited. Targeted temperature management (TTM) shows the most promising neuroprotective therapy. Moreover, TTM is also useful for intracranial pressure (ICP) control. Many methods of TTM have been reported. TTM can apply to several clinical conditions associated with hypoxic/ischemic brain injury or elevated intracranial pressure. Neurology Asia 2015; 20(4) : 325 – 333 Address correspondence to: Dr.Sombat Muengtaweepongsa, Division of Neurology, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand 12120. INTRODUCTION Targeted temperature management (TTM) has substituted therapeutic hypothermia in the various recommendations from the major medical professional societies.TTM is a kind of therapy that lowers a patient’s core temperature with the intention to help reduce the risk of brain injury from impairment of cerebral blood flow. Neuroprotection is a well-known indication of TTM. Almost all of neuroprotective therapies for ischemic brain insult do not show any benefit in human.TTM is the only one neuroprotective treatment that shows benefit in clinical trials. Standard guidelines recommend TTM as a neuroprotective treatment in patients after cardiac arrest. TTM is also an effective option for treatment of elevated intracranial pressure. MECHANISM OF HYPOXIC/ISCHEMIC CASCADE Hypoxic/ischemic brain injury is a damage that results from the cessation of cerebral blood flow. Interruption of cerebral blood flow results in multiple neurologic injuries, the socalled hypoxic/ischemic cascade. Lack of oxygen and blood supply leads to adenosine triphosphate (ATP) producing failure. Neurons and glial cells switch to anaerobic process, result in lactic acidosis. Na−K ATPase pumps fail, causing cells to become depolarized, allowing ions, especially calcium (Ca) to influx the cells. Intracellular calcium levels rises, then stimulate the release of the excitatory amino acid neurotransmitter glutamate. Glutamate allows more calcium influx by trigger opening of Ca-permeable NMDA receptors and AMPA receptors. The generation of dangerous chemicals including free radicals, reactive oxygen species, endonucleases, ATPases, and phospholipases, the so-called excitotoxicity, begins after excess calcium influx. Cell membrane and mitochondria break down causing necrotic cells and apoptosis. Glutamate and other toxic chemicals are released into the environment by these necrotic cells. These toxins damage surrounding cells. Further damage, the so-called reperfusion injury, begins when the brain is reperfused. Inflammatory cells accumulate to swallow up damaged tissue and release many cytokines. Harmful chemicals destroy the blood–brain barrier (BBB). Damaged BBB leads to leakage of large molecules especially albumins causing cerebral edema. Cerebral edema causes compression of and further damage to brain tissue. A summary of the ischemic cascade is shown in Figure 1.