الفهرس 
Hala Salah El-Din Elozairy
Hala Salah El-Din ElozairyOnly 14 pages are availabe for public view
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Abstract
Sepsis is a clinical syndrome characterized by systemic inflammation and widespread tissue injury due to infection. There is a continuum of illness severity ranging from sepsis to severe sepsis and septic shock. When infection is absent, the clinical syndrome is termed Systemic Inflammatory Response Syndrome (SIRS).
A review of studies evaluating the epidemiology of sepsis shows a very high prevalence, both among all hospitalized patients (one third) and among those admitted to ICUs (over 50%). More than half of all septic patients develop severe sepsis and a quarter develop septic shock; thus, 10-15% of all patients admitted to ICUs develop septic shock. This shows how valuable to assess the medical and economical burden of such a problem. Standardized diagnostic criteria for sepsis, severe sepsis, septic shock, and organ dysfunction and failure associated to infection have enabled the epidemiological evaluation of septic syndromes, as well as of their progression in recent years and of the efficacy of new treatment measures.
Sepsis is the culmination of complex interactions between the infecting microorganism and the host immune, inflammatory, and coagulation responses. Both the host responses and the characteristics of the infecting organism influence the outcome of sepsis.
During sepsis, a wide array of endogenous humoral and cellular mediator systems are activated, including complement, coagulation and fibrinolytic systems, with the release of cytokines and lipid mediators such as eicosanoids, platelet-activating factor, and endothelin-1. The inflammatory response involves the activation of endothelial cells, platelets, macrophages, monocytes and neutrophils generating oxygen and nitrogen radicals. Also, the activation of sympathoadrenal axis (with increased level of norepinephine), the activation of rennin-angiotensin-aldosterone system (with increased level of angiotensin II), and increase in the vasopressin levels are often part of host response. These mechanisms largely responsible for the clinical manifestations of sepsis, finally lead to tissue hypoxia, which represents the common pathway of organ dysfunction.
In septic shock, there is a disturbance of procoagulant-anticoagulant balance with increase in procoagulant factors & decrease of anticoagulant factors which is a key feature in pathogenesis of septic shock.
Nitric Oxide (NO) appears to be an important mediator of impaired vascular responsiveness to vasoconstrictor agents in sepsis. Inhibition of NO synthesis improves vasopressor-responsiveness and increases Blood Pressure (BP) in most septic animal models and in humans; however, animal studies reveal numerous adverse effects of NO Synthase (NOS) inhibition.
In shock, there is an imbalance between oxygen supply and demand, which results in a systemic clinical syndrome characterized by hypotension and hypoperfusion leading to cellular dysfunction. Sepsis is a systemic response to infection, and septic shock is sepsis with hypotension and abnormalities in perfusion.
Septic shock is associated with 3 major pathophysiological effects within the cardiovascular system which are vasodilatation, maldistribution of blood flow and myocardial depression.
Monitoring outcomes of therapy, recognition of the early signs and symptoms of septic shock is pivotal in improving patients’ outcomes. Appropriate monitoring of patients with septic shock is imperative, with specific consideration given to detecting changes in perfusion and tissue oxygenation. Basic monitoring should include pulse oximetry, electrocardiography, and invasive blood pressure monitoring. Central venous pressure monitoring or pulmonary artery catheterization, along with measurements of venous oxygen saturation (mixed “SvO2” or central venous “ScVO2”), may be useful in evaluating cardiovascular status if a patient is refractory to initial volume resuscitation or if oxygenation indices will be used as the end point of resuscitation.
Initial management is aimed at securing the airway and correcting hypoxemia. Intubation and mechanical ventilation may be required. Once the patient’s respiratory status has been stabilized, the adequacy of perfusion should be assessed. Hypotension is the most common indicator that perfusion is inadequate. However, critical hypoperfusion can also occur in the absence of hypotension, especially during early sepsis. Common signs of hypoperfusion include cool, vasoconstricted skin due to redirection of blood flow to core organs (although warm, flushed skin may be present in the early phases of sepsis), restlessness, oliguria or anuria, and lactic acidosis.
Once it has been established that hypoperfusion exists, early restoration of perfusion is necessary to prevent or limit multiple organ dysfunction, as well as reduce mortality. Tissue perfusion should be promptly restored using intravenous fluids, vasopressors, red blood cell transfusions, and inotropes. It is recommended for patients to be managed with therapy aimed at achieving a central (or mixed) venous oxygen saturation ≥70 percent within six hours of presentation. It is reasonable to simultaneously aim for a central venous pressure 8 to 12 mmHg, Mean Arterial Pressure (MAP) ≥ 65 mmHg, and urine output ≥ 0.5 ml per kg per hour.
Start boluses of intravenous fluids as first-line therapy in patients who demonstrate impaired perfusion. Fluid boluses are repeated until blood pressure and tissue perfusion are acceptable, pulmonary edema ensues, or there is no further response. These parameters should be assessed before and after each fluid bolus. There is no data to support preferential administration of crystalloid or colloid.
Start vasopressors for patients who remain hypotensive following intravascular volume repletion. Although there is no definitive evidence of the superiority of one vasopressor over another, it is suggested to begin with norepinephrine.
For patients whose ScVO2 remains < 70 percent after intravenous fluid and vasopressor therapy, it is reasonable to administer additional therapies, including blood transfusions or inotropic therapy.
Prompt identification and treatment of the culprit site of infection are essential. Sputum and urine should be collected for gram stain and culture. Intra-abdominal fluid collections should be percutaneously sampled. Blood should be taken from two distinct venipuncture sites and from indwelling vascular access devices and cultured aerobically and anaerobically.