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Critical illness in adults is often followed by acute lung injury (ALI). The most severe form of ALI, termed Acute Respiratory Distress Syndrome (ARDS), has a mortality rate of about 50% in most series and higher than 90% when it is associated with severe sepsis and multiple system organ failure (). Among the clinical conditions associated with the development of ARDS, sepsis is the most common and lethal. Despite recent advances in critical care medicine, the current therapeutic approach for ALI and ARDS is just supportive, not curative. Significant improvements in supportive treatment in the intensive care unit (e.g., more specific antibiotic treatment, improved mechanical ventilation, improved monitoring of circulation, better nursing care, etc.) are mainly responsible for improvements in survival in ARDS and sepsis. However, the incidence of sepsis is rising while a third of septic patients will succumb to this devastating syndrome (). The septic insult results in a complex cascade of inflammatory mediators, such as cytokines, that is initiated by the organisms themselves or by their soluble products. Although cytokine production is not unique to systemic infection, measurement of circulating inflammatory mediators can confirm the presence of host inflammation, but may not distinguish crucial pathways involved in disease progression and outcome ().

Brain edema and encephalopathy are severe central nervous system complications of acute liver failure (ALF). Brain edema frequently results in an increase in intracranial pressure (ICP) which consequently leads to brain stem herniation: the major cause of mortality in patients with ALF. ICP is a critical measure which defines the prognosis in patients with ALF (–). Orthotopic liver transplantation (OLT) results in survival rates in excess of 70%, however 30–40% of patients with ALF die (primarily due to the deadly effects of raised ICP) while on the liver transplantation list waiting for a donor organ to become available. When uncontrolled intracranial hypertension develops, death occurs in over 90% of patients with ALF. Therefore, there is an urgent need for new therapeutic approaches to the prevention of brain edema and increased ICP in ALF. The potential targets for therapy and the currently used agents to treat increased ICP in ALF are illustrated in Figure 12-1.

Atherosclerotic heart disease is the leading cause of death in developed nations. Manifestations include myocardial ischemia or infarction. In addition, some patients develop cardiovascular insufficiency, with the additional risk of systemic ischemia. Hypothermia has been shown to protect tissues during ischemia and thus may have clinical benefit in patients with cardiovascular disorders. This chapter will explore the potential therapeutic role for hypothermia in regional and global myocardial ischemia, as well as systemic ischemia secondary to heart failure.

Laboratory studies of therapeutic hypothermia have utilized animals that are much smaller than the average-sized human, making rapid cooling feasible. Cooling techniques can be very invasive without concern about the long-term risks. In addition, cooling is often started either before or early during the insult. For therapeutic hypothermia to be taken to clinical trials and, further, to become part of standard clinical practice, novel cooling techniques will be needed. The optimal technique for total body cooling should be easily applied, should cool the entire organism rapidly, and should carry little risk. Ideally, the technique should be applicable by lay people or physician extenders, preferably even in the field. In addition, techniques for selective brain cooling may provide the same benefits without the possible systemic side effects.

Hypothermia in humans is defined as a core temperature below 35°C. Primary accidental hypothermia occurs as a result of overwhelming cold stress, such as cold water immersion or exposure. Secondary accidental hypothermia is a result of alterations in thermoregulation and heat production. Secondary hypothermia occurs more frequently, and injuries are the common etiologic factor. Mild hypothermia frequently occurs in the operating room. This chapter will review the organ-specific effects of hypothermia and potentially detrimental effects of hypothermia on trauma and postoperative patients.

Hypothermia research has come a long way over the past 50 years. We have asked many questions about how hypothermia works and in which situations is it beneficial. From a mechanistic standpoint, our understanding of the effects of hypothermia, both beneficial and detrimental, are much more complex than just direct effects on oxygen metabolism, as was first thought.