الفهرس 
Physiological Implication for Therapeutic HypothermiaOnly 14 pages are availabe for public view
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Abstract
Cardiac arrest leads to sudden termination of blood flow, leading to a rapid exhaustion of cerebral oxygen and adenosine triphosphate stores and depressed cerebral function. Neuronal damage occurs in the CNS during cardiac arrest (Phase I, ”No Flow”) and following the return of spontaneous circulation (ROSC) (Phase II, ”Low Flow”). The survival of neurons differs, depending on the type, site and period of global anoxia. In general, neurons in the cerebral cortex, hippocampus, and basal ganglia are the most susceptible.
Therapeutic hypothermia (also called targeted temperature management) refers to deliberate reduction of the core body temperature, typically to a range of about 32° to 34° C in patients who don’t regain consciousness after return of spontaneous circulation following a cardiac arrest.
Following are the benefits of therapeutic hypothermia (TH) which are associated with slowing down of cellular cascade after cardiac arrest by slowing down the cerebral metabolism (approximately 6-8% per 1°C) reducing excitatory amino acids (glutamate) release attenuation and/or reversibility of ischemic depolarization of the CNS leading to membrane stabilization, electrolyte redistribution and normalization of intracellular water concentration and intracellular pH (stabilization of the blood-brain barrier), reduction 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 (i.e., cytokines, interleukins, arachidonic acid cascade end products), attenuation of CSF platelet-activating factor (PAF) and inhibition of cytoskeletal breakdown.
Many hypothermia-induced metabolic changes occur relatively quickly, within the first few hours. These include changes in energy metabolism and decreases in adenosine tri-phosphate (ATP) demand. Other changes, such as a rise in lactate level, occur over a longer period of time (>3 h). Induction of hypothermia also leads to an increase in membrane stability, with decreased permeability of cellular membranes, the blood-brain barrier and blood vessel walls.
There are numerous strategies to cool patients, based on the four basic mechanisms for heat loss: convection, conduction, evaporation and radiation. In addition, heat generation in patients with hyperthermia can sometimes be reduced by antipyretic agents. However, in patients with elevated temperature caused by impaired thermoregulation (such as central fever or heat stroke) these agents are often ineffective. Various cooling techniques have been used in in vitro and clinical studies, including ice-water circulating blankets, ice bags, air mattresses, cooling catheters, intravenous infusion of cooled fluids (4°C) followed by cooling through other methods, the infusion of extra corporeally cooled blood via the carotid artery, helmets and cooling caps with cold fluids or chemical cooling capabilities, ice-water nasal lavage, cold peritoneal lavage and cardiopulmonary bypass.
There are few true contraindications for TH. Medical conditions in which the risk may be excessive include documented intracranial hemorrhage, severe hemorrhage leading to exsanguination, hypotension refractory to multiple vasopressors, severe sepsis, and pregnancy. Given that most patients from CA die of neurological consequences for which TH is the only proven beneficial therapy, the decision to withhold TH must be weighed carefully.
The best time to initiate hypothermia after CA is not completely understood till date. It is logical to conclude that the benefits may be maximized if hypothermia is initiated as soon as possible after successful resuscitation.
The hypothermia comprises of three phases-induction, maintenance, and rewarming.
Several methods may be used to induce and maintain hypothermia. The methods may be classified as noninvasive and invasive.
We searched for trials where therapeutic hypothermia (any target temperature less than 35) was applied during resuscitation, after ROSC or later after stabilization of the patient. We included randomized controlled trials and cohort studies in adult survivors of cardiac arrest. We excluded animal studies.
Our systematic search of databases of medical literature resulted in 94 hits. After we excluded hits referring to other treatment modalities than hypothermia or other diseases than resuscitation from cardiac arrest and articles not containing original data, 10 studies remained.
One study searched for predictors of outcome after cardiopulmonary resuscitation in TH patients and nine studies searched for survival and neurological out come after application of TH.
Current evidence suggests that mild TH improves survival and neurologic out come in patients resuscitated from CA of presumed cardiac origin.