Friday, April 17, 2020

Sepsis and Septic Shock Essay Example

Sepsis and Septic Shock Essay Sepsis refers to the uncontrolled systemic immune response to infection. It describes the condition known as systemic inflammatory response syndrome in which as infectious etiology is identified or suspected (Munford, 2001). The key element in sepsis is the overwhelming systemic inflammation as a result of the host’s reaction to microbial invasion. It involves augmented inflammatory signals in response to an infectious insult that is not controlled by local inflammatory processes. Bacteremia, which is the presence of bacteria and in blood or septicemia, which is the presence of any microbial agent in the blood can lead to sepsis. When the regulatory controls that put the inflammatory response in check are unable to contain the overwhelming reaction, unaffected organs are involved and severe sepsis ensues which is characterized by multiorgan dysfunction. As the homeostatic counterregulatory mechanism fails, sepsis progresses to septic shock, which is the presence of hypotension along with along with organ dysfunction. The hypotension, which is defined as systolic blood pressure of less than 90 mmHg or 40 mmHg less than the patient’s usual blood pressure, is unresponsive to fluid resuscitation. Unlike sepsis which is reversible, patients in septic shock have unfavorable prognosis and usually succumb despite aggressive treatment (Munford, 2001).EpidemiologyOver 10 million cases of sepsis have been reported in the United States based on a 22-year period study of discharge data from 750 million hospitalizations (Martin, Mannino, Eaton, Moss, 2003). Annually, approximately 750,000 people develop sepsis and more than 210,000 cases are fatal (Bernard, Vincent, Laterre, Larosa, Dhainaut, Lopez-Rodriguez et al 2001; Hotchkiss Karl, 2003). Despite advances in critical care management, sepsis has a mortality rate of 30 to 50 percent and is among the primary causes of death in intensive care units (Bernard et 2003; Mitchell, Cotran, 1999). It is believed th at the increasing incidence of severe sepsis is due to the growing population among the elderly as a result of increasing longevity among people with chronic diseases and the high prevalence of sepsis developing among patients with acquired immune deficiency syndrome (Munford, p.798 2001).PathophysiologyThere are a lot of factors attributable to the development of sepsis. Several studies have conflicting results on the pathologic basis of the disease and the exact mechanism involved has not been elucidated. The pathogenesis of sepsis is a series of complex interactions between offending microorganism and the host inflammatory, immune and coagulation responses. The accepted theory is that sepsis results from an uncontrolled inflammatory response in which our own defense system becomes so powerful that it causes more damage to our organs than the etiologic agent of the initial infection Hotchkiss Karl, 2003). This is based on the overstimulated immune response seen in studies of anim al models of sepsis which does not seem to correlate which the clinical picture in humans. Clinical trials involving anti-inflammatory agents have not been successful in patients with sepsis which led investigators to question if sepsis is indeed the result of uncontrolled inflammation (Hotchkiss Karl, 2003). In fact, sepsis with organ dysfunction is attributed to an inadequate immune response to primary local infection which allowed it to spill into the bloodstream and the ensuing tissue injury is primarily caused by superantigens and other virulence factors from the infecting microorganism (Russel, J.A., 2006).Approximately 70 percent of cases of septic shock are caused by gram-negative bacilli which produce endotoxin, hence the term endotoxic shock (Mitchell, Cotran, 1999). The endotoxins are the lipopolysaccharides(LPS) from the bacterial cell wall that are released after the wall is degraded during an inflammatory response. The reproduction of the hemodynamic picture of septi c shock through the injection of LPS alone shows that LPS is one of the main culprits of septic shock. The complex inflammatory cascade caused by LPS eventually leads to hypoxic injury and the multi organ failure is mostly evident in the brain, heart, kidneys, lungs, and gastrointestinal tract. The widespread hypoxia during septic shock causes the brain to develop ischemic encephalopathy while in the heart, cardiac muscles undergo coagulation necrosis and subendocardial hemorrhages. The kidneys undergo acute tubular necrosis as a result of extensive ischemic injury. This results into electrolyte disorders, oliguria and anuria which are severe complications of sepsis. Despite the high resistance of lungs tissues to hypoxic injury, diffuse alveolar damage can be seen in severe bacterial sepsis. In the gastrointestinal tract, hemorrhagic enteropathy develops which appears as patchy mucosal hemorrhages and necrosis. The liver undergoes fatty change and in severe ischemic injury, central hemorrhagic necrosis can be seen (Mitchell, Cotran, 1999).Clinical FeaturesThe clinical manifestations of sepsis are usually superimposed with the signs and symptoms of the primary infection and other underlying medical condition of the patient.However, in the course of the disease, an increasing intensity of inflammatory response to infection becomes evident although the rate varies among patients. Hyperventilation is usually one of the early signs. Manifestations of ischemic encephalopathy such as disorientation and confusion may also occur early in sepsis. They are usually seen among the elderly and in patients with preexisting neurocognitive deficits (Munford, 2001). Patients with hypotension usually presents with weak but rapid pulse accompanied by tachypnea and cold, clammy skin. However, patients in septic shock may be initially warm due to peripheral vasodilation in the skin (Mitchell, Cotran, 1999). It should be noted that some patients with sepsis are normothermic and e ven in the presence of infection, fever can be absent especially in neonates, elderly, and patients with uremia or suffering from alcoholism (Munford, p.801 2001).The occurrence of disseminated intravascular coagulation or DIC, which results from the widespread activation of the coagulation system, can predispose patients to ischemic necrosis especially to those with hypotension. This leads to skin lesions seen as pustules, cellulites, bullae or hemorrhagic lesions. Gastrointestinal involvement manifests as nausea, vomiting, diarrhea and ileus. Patients with stress ulcers may present with upper gastrointestinal bleeding. In cases of prolonged and severe hypotension, ischemic bowel necrosis may occur as well as acute hepatic injury. Elevation of serum levels of conjugated bilirubin often leads to cholestatic sepsis. Liver function test may reveal elevated blood levels of alkaline phosphatase which along with the elevated bilirubin represent an underlying hepatocellular or canalicular dysfunction (Munford, 2001).Treatment and PrognosisPatients with sepsis requires urgent management which is best accomplished in an intensive care setting by medical specialist experienced in the care of critically ill patients. The management entails immediate treatment of the focus of infection while providing adequate hemodynamic and ventilatory support.The appropriate antimicrobial therapy should be given immediately based on blood culture and sensitivity although an empiric initial treatment should be started based on known pathogens at identified sites of infection. An adequate antibiotic cover should include therapy against gram-positive and gram-negative microorganism. Pending results from blood cultures, empiric antimicrobial therapy can be based on several factors, especially in patients with no obvious source of infection. In immunocompetent adults, acceptable regimens include ceftriaxone or ticarcillin-clavulanate or piperacillin-tazobactam and imipenem-cilastin or mero penem. Gentamycin or tobramycin may be added to these regimens. If the causative agent is suspected to be methicillin-resistant staphylococcous areus, vancomycin should be added to these regimens (Munford, 2001). In patients with AIDS, ceftazidime, tircacillin-clavilanate or piperacillin-tazobactam plus tobramycin should be used. In patients with drug allergy to beta lactams, ciprofloxacin plus vancomycin and tobramycin should be used (Munford, 2001). Other factors to be considered are the presence of neutropenia or neutrophil count of less than 500 per microliter, splenectomy and history of intravenous drug abuse. These patients require appropriate antimicrobial cover based on their higher susceptibility to certain microorganisms.The immediate removal of the focus of infection is also important in the successful management of patients with sepsis. Sites of infection should be identified immediately and appropriate drainage should be done when possible. In patients with indwelling i ntravenous catheters, microbial cultures should be done and a new catheter should be placed in another site. Adequate hemodynamic and respiratory support should also be provided especially in patients with septic shock to prevent tissue injury secondary to ischemia. The pulmonary wedge pressure and central venous pressure should be monitored constantly. Metabolic support should also be provided. The urine output should be watched closely for oliguria and anuria. Diuretic therapy with furosemide may be used (Munford, 2001).Despite aggressive treatment, many patients with severe sepsis and septic shock succumb to the disease. Several new agents have been developed which should promising outcome in averting death. These are drugs that neutralize the bacterial endotoxin such as monoclonal antibodies to endotoxins and drugs that interfere with the mediators of inflammatory response such as monoclonal antibodies to tumor necrosis factor alpha. Another promising drug for severe sepsis is d rotrecogin alfa or recombinant human activated protein C which has shown antithrombotic, antiinflammatory, and profibrinolytic properties. A clinical study has shown that the drug significantly reduced the mortality in severe sepsis although due to its antithrombotic properties, the patients are at a higher risk of bleeding (Bernard, et al 2001).Further studies are necessary to better understand the pathogenesis leading to sepsis. The knowledge gained in these studies which further enhance the development of newer drugs with better safety profile. In addition, more clinical trials are important to assess the drug efficacy of existing drugs so that better management of sepsis can be formulated to improve the morbidity and mortality of the disease.

Worn Path By Eudora Welty Essays - Eudora Welty,

Worn Path By Eudora Welty In ?A Worn Path? Eudora Welty's plot is not all that clear in the beginning of her short story, but progresses as her character carries on against all of the overwhelming forces against her. In this short story a black elderly woman, Phoenix Jackson, must overcome the odds against her as she valiantly travels through many obstacles in order to contribute to the wellness of her grandson, for whom she is making this trip down ?a worn path.? It is at this point that all of Welty's readers' hearts open up to this poor, elderly woman as she makes an attempt to carry on her love for her grandson by taking a long journey down a familiar path in order to get medication that seems to help ease his sickness pains. However, there are many forces against Phoenix that Welty includes in her story in order to make Phoenix's adventure end in a victory. Poverty, old age, and her journey through the woods are all of the odds which Phoenix must overcome. Poverty is a major hardship that most of us will never have to face, but in Phoenix's case, poverty is present everyday in her and her grandson's life. Since she is in this state of poverty, Phoenix is not able to enjoy life's luxuries as others do and must make do with what she can. As she begins her journey, it becomes clear that she lacks the money to pay for transportation to and from town; therefore, she starts down her path carrying a ?thin, small cane made from an umbrella? (132). Although Welty never really emphasizes what this is used for the reader can assume that she uses it because she does not have the money to buy the actual cane needed to help her walk properly. Another conflict dealing with poverty arouses when she feels it necessary to steal from a hunter she encounters in the woods. While the hunter walks away her sneaky ?fingers slid down and along the ground under the piece of money with grace and care they would have in lifting an egg from under a setting hen? (134). Here Welty shows that Phoenix must do what she has to in order to survive. Even though it may not appear right, her poverty forces her to act in a way that she only knows best. For instance, when people have a barrier separating them between something they want, they are going to do what they can to achieve their goal no matter what stands in their way. In this case Phoenix is a poor woman and the money catches her eye. Acting on her instinct, she takes what is not hers and hopes that she can get away with it. However, because of her perseverance and determination to better the health of her grandson, Phoenix journeys into town to receive charity that the doctor's office provides her. This ?soothing medicine? they give her is the reason why she makes this trip in the first place (136). However, she is looked upon as a charity case since she has no money to pay for the medication he needs and is given the medicine for free. All of these examples that Welty has described in ?A Worn Path? allow her story to develop by making readers think about what she writes. Poverty is an important issue in today's society and it makes one think of all the fortunes they have. In this sense, Welty also makes one fear poverty by the way she addresses it. The images allow one to feel Phoenix's pain that comes along with poverty. Joyce Carol Oates backs up this statement by adding that by ?disciplining her [Welty's] vision in order to gain deeper penetration into the dark and lovely realities of the lonely human spirit and shaping her fiction so that each story should be something achieved...? (362). Oates simply means that Welty goes beyond normal realities in order to grab the reader's attention. Through poverty, Welty takes a worldwide problem and stretches it to a level in which the person reading her story feels saddened by the power she displays. To be old, poor, and a surrogate mother is a hard job, and Welty does a wonderful job of portraying this through the underlying problem of poverty. Another overpowering element in ?A Worn Path? is Phoenix's age. Welty writes that she has ?numberless branching wrinkles? which illustrates that she has many years behind her (132). It is here