Systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic shock were initially defined in 1991 by a consensus panel convened by the American College of Chest Physicians (ACCP) and Society of Critical Care Medicine (SCCM), then they were reconsidered in 2001 during an International Sepsis Definitions Conference that included representatives from the ACCP, SCCM, American Thoracic Society (ATS), European Society of Intensive Care Medicine (ESICM), and Surgical Infection Society (SIS).
(Levi, et al., 2003)
A practical modification of the definitions has since been published, which provides exact hemodynamic definitions for septic shock . (Annane , et al., 2005)
The definitions presented in a way that highlights the notion that both SIRS and sepsis exist on a continuum of severity that ends with multiple organ dysfunction syndrome (MODS).
SIRS is defined as 2 or more of the following variables: Fever of more than 38°C (100.4°F) or less than 36°C (96.8°F) , Heart rate of more than 90 beats per minute , Respiratory rate of more than 20 breaths per minute or arterial carbon dioxide tension (PaCO 2) of less than 32 mm Hg , Abnormal white blood cell count (>12,000/µL or < 4,000/µL or >10%immature [band] forms) , Increased C reactive protein, Increased cardiac output, low systemic vascular resistance , Increased oxygen consumption, Increased procalcitonine concentration, Increased interleukin 6 (IL6), IL8 , Otherwise unexplained alternation in coagulation parameter, alternation in mental status, hyperbilirubinemia , Increased insulin requirement. (Fink, et al., 2004)
There are no universally accepted criteria for individual organ dysfunction in MODS. However, progressive abnormalities of the following organ-specific parameters are commonly used to diagnose MODS and are correlated with increased ICU mortality:
PO2/FiO2 ratio, Serum creatinine, Platelet count, Glasgow coma score, Serum bilirubin, Pressure-adjusted heart rate (defined by heart rate multiplied by the ratio of central venous pressure and mean arterial pressure). ( Cook, et al., 2007)
Bacterial infections are the commonest aetiological agents of both community-acquired and hospital related sepsis, but a causative organism is confirmed in only 60% cases. Disease progression is similar regardless of organism. However, there has been a rise in multiply resistant bacteria such as Acinobacter species, Enterococci and methicillin resistant Staphylococcus aureus (MRSA) .The microbiology and primary sources of infection have undergone a remarkable transition over the past 30 years. The predominant pathogen responsible for sepsis in the 1960s and 1970s were Gram-negative bacilli; however, over the past few decades there has been a progressive increase in the incidence of sepsis caused by Gram-positive and opportunistic fungal pathogens. Although the abdomen was the major source of infection in sepsis from 1970 to 1990, in the past decade pulmonary infections have emerged as the most frequent site of infection. (Eaton, et al., 2003)
Polymicrobial diseases, caused by combinations of viruses, bacteria, fungi, and parasites, are being recognized with increasing frequency. In these infections, the presence of one micro-organism generates a niche for other pathogenic micro-organisms to colonize; one micro-organism predisposes the host to colonization by other microorganisms, or two or more non-pathogenic micro-organisms together cause disease. The medical community is recognizing the significance of Polymicrobial diseases and the major types of microbial community interactions associated with human health and disease. Many traditional therapies are just starting to take into account the polymicrobial cause of diseases and the repercussions of treatment and prevention .Polymicrobial episodes were significantly more likely to be hospital-acquired, to emanate from bowel or multiple foci, and to occur in immunocompromised patients, especially those with terminal malignancies, nonhematologic malignancies or multiple underlying diseases (Bakaletz, et .,2004)
Sepsis is one of the oldest and most elusive syndromes in medicine. Hippocrates claimed that sepsis was the process by which flesh rots, swamps generate foul airs, and wounds fester.
(Majino, et al., 1991)
Galen later considered sepsis a laudable event, necessary for wound healing (Funk, et al., 2009)
With the confirmation of germ theory by Semmelweis, Pasteur, and others, sepsis was recast as a systemic infection, often described as “blood poisoning,” and assumed to be the result of the host's invasion by pathogenic organisms that then spread in the bloodstream. However, with the advent of modern antibiotics, germ theory did not fully explain the pathogenesis of sepsis: many patients with sepsis died despite successful eradication of the inciting pathogen.Thus, researchers suggested that it was the host, not the germ, that drove the pathogenesis of sepsis.
(Cerra, et al., 1985)
In 1992, an international consensus panel defined sepsis as a systemic inflammatory response to infection, noting that sepsis could arise in response to multiple infectious causes and that septicemia was neither a necessary condition nor a helpful term. (Bone, et al., 1992)
The incidence of severe sepsis depends on how acute organ dysfunction is defined and on whether that dysfunction is attributed to an underlying infection.Organ dysfunction is often defined by the provision of supportive therapy (e.g., mechanical ventilation), and epidemiologic studies thus count the “treated incidence” rather than the actual incidence. In the United States, severe sepsis is recorded in 2% of patients admitted to the hospital. Of these patients, half are treated in the intensive care unit (ICU), representing 10% of all ICU admissions. (Lidicker , et al., 2001)
Risk factors for severe sepsis are related both to a patient's predisposition for infection and to the likelihood of acute organ dysfunction if infection develops. There are many well-known risk factors for the infections that most commonly precipitate severe sepsis and septic shock, including chronic diseases (e.g., the acquired immunodeficiency syndrome, chronic obstructive pulmonary disease, and many cancers) and the use of immunosuppressive agents.
(Pinsky, et al., 2001)
The clinical manifestations of sepsis are highly variable, depending on the initial site of infection, the causative organism, the pattern of acute organ dysfunction, the underlying health status of the patient, and the interval before initiation of treatment.The signs of both infection and organ dysfunction may be subtle, and thus the most recent international consensus guidelines provide a long list of warning signs of incipient sepsis. (Levi, et al., 2003)
Acute organ dysfunction most commonly affects the respiratory and cardiovascular systems. Respiratory compromise is classically manifested as the acute respiratory distress syndrome (ARDS), which is defined as hypoxemia with bilateral infiltrates of noncardiac origin .
(Rubenfeld, et al., 2012)
Cardiovascular compromise is manifested primarily as hypotension or an elevated serum lactate level. After adequate volume expansion, hypotension frequently persists, requiring the use of vasopressors, and myocardial dysfunction may occur.
(Dellinger, et al., 2013)
Before the introduction of modern intensive care with the ability to provide vital organ support, severe sepsis and septic shock were typically lethal. Even with intensive care, rates of in-hospital death from septic shock were often in excess of 80% as recently as 30 years ago.
(Silva,et al., 1998)
The early management of patients with severe sepsis and septic shock centers on the administration of antibiotics, IV fluids, and vasoactive agents, followed by source control. However, the specific approach to the resuscitation of patients with septic shock remains highly controversial. However, it is likely that the early detection of sepsis with the timely administration of appropriate antibiotics is the single most important factor in reducing morbidity and mortality from sepsis. It has become increasingly apparent that in many patients there is a long delay in both the recognition of sepsis and the initiation of appropriate therapy. This has been demonstrated to translate into an increased incidence of progressive organ failure and a higher mortality. (Westphal , et al., 2011)
Empirical IV antibiotic therapy should be started as soon as possible and within the first hour of recognition of severe sepsis, after appropriate cultures have been obtained. In a retrospective analysis of 2,600 patients demonstrated that the risk of dying increased progressively with an increase in the time to receipt of the first dose of antibiotic from the onset of sepsis-induced hypotension.(Kumar, et al., 2008)
Beyond the early administration of antibiotics, aggressive “supportive measures” may be harmful and the “less is more” paradigm appears applicable for the management of patients with severe sepsis. In these highly vulnerable patients, more intensive treatment may promote the chance of unwanted adverse effects and, hence, iatrogenic injury.
(Kox , et al., 2013).
In some patients, hypotension and tachycardia do resolve with limited fluid resuscitation. However, fluids alone will not reverse the hemodynamic instability of patients with more severe sepsis; in these patients, fluids alone are likely to exacerbate the vasodilatory shock and increase the capillary leak and tissue edema. Based on these data, its better limiting the initial fluid resuscitation to approximately 20 to 30 mL/kg . It is important to emphasize that this conservative approach to fluid management in patients with sepsis is based on indirect evidence and not on a randomized controlled trial specifically designed to answer this question. Furthermore, this recommendation differs somewhat from that of the most recent Surviving Sepsis Campaign guidelines, which suggest “a minimum fluid challenge of 30ml/kg” and that “greater amounts of fluid may be needed in some patients. (Levi, et al., 2013)
A large number of hemodynamic, perfusion, oxygenation, and echocardiographic targets have been proposed as resuscitation goals in patients with severe sepsis and septic shock. (Avwzedo, et al., 2010)
Most of these targets, however, are controversial and are not supported by outcome data. The Surviving Sepsis Campaign guidelines recommend a CVP of 8 to 12 mm Hg (12-15 mm Hg if mechanically ventilated), an Scvo2 > 70%, and a urine output > 0.5 mL/kg/h as targets for resuscitation. (Rhodes, et al., 2012)
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