![]() | Only 14 pages are availabe for public view |
Abstract The clinical features of all critical illnesses are similar, regardless of the type of insult sustained, be it injury, operation, or infection. Metabolic response to surgery and trauma still represent one of the most complicated phenomena by which the body react to stress conditions like surgery, trauma and infections. Critically ill patients also typically have immunologic abnormalities that may make them more susceptible to invasive infection by a variety of microorganisms, including those that are not usually pathogenic. However well adapted we are in dealing with infection and injury, these insults have the potential to demand an exteme workload from the body and thus can push metabolic responses to point of dysfunction or failure. Conceptually, the systemic response to injury can be broadly compartmentalized into two phases: (1) A pro-inflammatory phase characterized by activation of cellular processes designed to restore tissue function and eradicate invading microorganisms, and (2) An anti-inflammatory or counter-regulatory phase that is important for preventing excessive proinflammatory activities as well as restoring homeostasis in the individual. Nutrition support is indicated in surgical patients if they are significantly malnourished prior to surgery, if they are expected to remain Nil per os (NPO) for more than 5 days postoperatively, or if they are critically ill. The goal of nutrition is to minimize protein loss and to provide key nutrients to maintain immune and other critical functions during and after surgical and traumatic injury. However, depending on current understanding of many of such aspects, new therapies are emerging as well as modifications of old ones are being carried out. “Urinary nitrogen losses will diminish in individuals fed a protein-free diet but will never become zero because of the body’s inability to completely reutilize nitrogen”. Nitrogen (N) balance is the most important nutritional test in patients receiving nutrition support. “The metabolic tragedy of sepsis is that the suppression of proteolysis seen in prolonged starvation does not occur and breakdown of protein continues”. Among the different enzymes involved in the ubiquitination of the substrate protein, the activity of the ubiquitin ligases may be rate limiting for the process and is also providing substrate specificity to the system, because different ubiquitin ligases recognize specific proteins. Recent studies suggest that the ubiquitin ligases artogin-1 and MuRF1 are particularly important for the development of muscle wasting in various catabolic conditions. Although many of the new therapies are still experimental (eg: β estradiol in shocked and septic patients, pentoxyphylline in hemorrhagic and septic shock, γ interferon in sepsis, and many other drugs), such therapies present hope for better managing critically ill patients after major surgery, severe trauma and sepsis. Since pain is regarded as a potent trigger for the catabolic response to surgery, specific anesthetics and analgesic techniques have been used to influence protein catabolism. Biologic treatment of patients with sepsis and other critical illnesses can be directed at inhibiting the biologic effects of endotoxin, at altering circulating levels of endotoxin, or at reducing the levels and effects of mediators released in response to endotoxin. Strategies have included treatment with antibodies against endotoxin, TNF, or IL-6, and treatment with IL-1ra. Patients who are at particularly high risk of developing gram-negative sepsis— for example, patients undergoing elective major surgical procedures—possibly may benefit most from anticytokine treatment, because it can be given as prophylaxis to these patients. Another treatment modality that may find applications in the future is induction of heat-shock or stress-response proteins, which function as “molecular chaperones”. Recent trials regarding tumor vaccines represent future hope for possibility of management of aggressive cancers, also may replace chemo and radiotherapy in treatment and/or down-staging of inoperable cancers. |