What is the pathophysiology of targeted temperature management (TTM)?

Updated: Jul 26, 2019
  • Author: Alex Koyfman, MD; Chief Editor: Karlheinz Peter, MD, PhD  more...
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Answer

Answer

Cardiac arrest and return of spontaneous circulation (ROSC) is a case of whole-body ischemia and subsequent reperfusion injury. This injury mechanism along with pre-arrest comorbidities cause enormous biochemical, structural, and functional insults, which in a complex interrelated process leads to progressive cell destruction, multiorgan dysfunction, neuronal apoptosis, and death. [37] Many of these processes are temperature sensitive. Hypothermia has been shown to attenuate or ameliorate many deleterious temperature-sensitive mechanisms, thereby contributing to protection of the brain and heart.

The pathophysiologic mechanisms involved in hypothermia are incompletely understood but have been studied in cellular, animal, and human models.

The following actions are associated with hypothermia:

  • Reducing cerebral metabolism (approximately 6-8% per 1ºC) and demand

  • Reducing excitatory amino acids (glutamate release)

  • Attenuation and/or reversibility of ischemic depolarization of the central nervous system (CNS), leading to membrane stabilization, electrolyte redistribution, and normalization of intracellular water concentration and intracellular pH (stabilization of the blood-brain barrier)

  • Attenuation of oxygen free radical production and lipid peroxidation

  • Restoration of normal intracellular signaling mechanisms (including calcium modulation) and inhibition of deleterious signaling mechanisms, such as apoptotic signaling

  • Restoration of protein synthesis and gene expression

  • Inhibition of deleterious inflammatory products (ie, cytokines, interleukins, arachidonic acid cascade end products)

  • Attenuation of cerebrospinal fluid (CSF) platelet-activating factor (PAF)

  • Inhibition of cytoskeletal breakdown

In the heart, hypothermia may decrease the area of injury, promote epicardial reflow, decrease myocardial metabolic demand, and preserve intracellular high-energy phosphate stores. [38, 39, 40]


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