الفهرس 
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Abstract
The protocol of EGDT refers to the administration of intravenous fluids within the first 6 hours of patients presentation with the use of physiologic targets to guide this fluid management.
Early goal directed therapy targets:
MAP ≥65 mmHg (MAP = [(2 x diastolic) + systolic] /3).
Urine output: ≥ 0.5 ml / kg / hour.
CVP 8 to 12 mmHg.
ScvO2 ≥ 70 % percent (when central access is available) or SvO2 ≥ 65 % percent.
It Began in the early 1990s, the EGDT Collaborative group challenged the paradigm of sepsis care as an “ICU disease” by applying similar urgent early diagnostic and therapeutic principles as that used in acute myocardial infarction, stroke, and trauma at the point of presentation in the ED.
The early hemodynamic and physiologic response to severe sepsis and septic shock results from hemodynamic changes that create an imbalance between systemic oxygen delivery and demands. These changes can include decreased vasomotor tone, hypovolemia, decrease in arterial oxygen content, myocardial depression, increase in metabolic demands, and impairment in systemic oxygen utilization.
Sepsis is a life-threatening inflammatory disorder and also represents the immune systems response to infection.Now defined as desregulated host response to infection The pathophysiology of process of sepsis involving a complex interaction of proinflammatory and anti-inflammatory mediators in response to pathogen invasion. These mechanisms lead to endothelium damage, vascular permeability, micro vascular dysfunction, coagulation pathway activation, and impairment in tissue oxygenation resulting in the cascade of sepsis.
The systems most commonly affected are the respiratory system, genitourinary system, and gastrointestinal system, as well as the skin and soft tissue. These sites involved in more than 80% of all cases of sepsis.
Persons in the extremes of age are at higher risk of developing sepsis. Patients older than 65 years are 13 times more risky to develop sepsis and have a two fold higher risk of death from sepsis independent of sex, race, co morbid associated conditions, and severity of illness.
Sepsis affect cardiac functions in the form of dysfunction of LV and RV systolic and diastolic functions but was not absolutely recognized until the wide spread use of echocardiography in the ICU.
EGDT relies partly on a measure of fluid responsiveness, CVP that inaccurately measures preload dependence and lactate level and ScVO2 may be indirect indicators of the effects of limited contractility, but they also reflect tissue dysoxia and microcirculatory perfusion abnormalities.
Early management of sepsis requires stabilization of respiration. Hypotension whenoccur, this signify inadequate tissue perfusion. After the initial respiratory stabilization, treatment of severe sepsis and septic shock consists of fluid resuscitation, vasopressor therapy, infection identification and control the source, proper antibiotic administration, and the removal or drainage of the source of infection.
The recommended investigations to be done include: basic metabolic profile,complete blood count with differential, measurement of liver enzyme levels and lactate , coagulation profile , and urinalysis. Suspected pulmonary infections should be evaluated using arterial blood gas testing to assess hypoxemia and acid-base abnormalities and chest radiography. If suspect disseminated intravascular coagulation fibrin degradation products d-dimer levels, and fibrinogen levels should be measured. Several biologic markers of sepsis such as procalcitonin, C-reactive protein, activated partial thromboplastine time, and interleukin-6 may have diagnostic and prognostic implications. Pan cultures include: blood cultures ,urine culture, stool culture , sputum culture, and skin and soft tissue culture should be obtained. Cerebrospinal fluid (CSF), joint, pleural, and peritoneal fluid should be examined as clinically indicated.
Echocardiography is very recommended to diagnose endocarditis as a source of sepsis, especially performed in patients with a heart murmur or suspected intravenous drug use
Intravascular hypovolemia in patients with sepsis, is typical and may be severe, require rapid fluid resuscitation.The adequate optimal volume of resuscitative fluid is unknown. multiple studies of EGDT reported intravenous fluid infusions targeted to physiologic endpoints and resulted in range of volume from 3 to 5 liters.No actual difference between using crystalloids (eg, normal saline, Ringer’s lactate) and albumin solutions in the treatment of severe sepsis or septic shock, but they have identified reported potential harm from the use of pentastarch or hydroxyethyl starch rather than a crystalloid solution.
Most of the physicians use the measurements of CVP to guide initial fluid therapy. After the first 12 hours of sepsis, CVP is poor to predict hemodynamic response to fluid challenge. Thereafter, use of cardiac output monitoring systems to assess changes in arterial waveform is more accurate in predicting if fluid responsive or not . Survival rate increase with a positive fluid balance (i.e., intravenous fluid input minus urine output) of 3 to 4 L at 12 hours.
Vasopressors are the second line agents in the treatment of sepsis and septic shock; we prefer intravenous fluids as long as they increase perfusion without seriously impairing gas exchange. However, intravenous vasopressor mostly norepinephrine is useful in patients who remain hypotensive despite adequate fluid resuscitation or who develop cardiogenic pulmonary edema.
Early perfect choice of antibiotic therapy is associated with better outcome. Consensus guidelines recommend antibiotic therapy within one hour of suspected sepsis. In septic shock, the initiation of antibiotic therapy within one hour increases survival; with each hour antibiotic therapy is delayed, survival decreases by about 8%.Combination therapy demonstrated survival benefit and improved clinical response in patients who had septic shock. However; combination antibiotic therapy did not improve sepsis survival compared with monotherapy in hemodynamicaly stable patients. When there is a risk of Pseudomonas aeruginosa bacteremia, antipseudomonal combination therapy is recommended.
Additional therapies in treatment of septic shock:
Inotropic therapy should not be used to increase the cardiac index to supernormal levels. Inotropic drugs include dobutamine, milrinone and dopamine. Dobutamine is the usual Inotropic agent.
Corticosteroids as Adrenal dysfunction has been found to be present in up to 19 % of vasopressor-dependent patients following adequate volume resuscitation in the ED.
Mechanical ventilation alters the hemodynamic phenotype in severe sepsis and septic shock compared to a spontaneously breathing patient. While ScvO2 generally increases upon the introduction of mechanical ventilation, hemodynamic perturbations resulting from adverse heart–lung interactions may trigger more therapeutic interventions. These can range from modifying the fraction of inspired oxygen, positive end-expiratory pressure, fluid administration, vasoactive agents, and decreasing the work of breathing after intubation. Low tidal volume is preferred in ventilated patients.
Metabolic control:Glycemic control (i.e., serum bloodglucose levels less than 180 mg per dL [10 mmol per L]).
Blood transfusion:Blood product therapy with packed red blood cells is recommended in patients with a hemoglobin level less than 7 g per dL (70 g per L) for a target level of 7 to 9 g per dL (70 to 90 g per L), although the early goal-directed therapy protocol uses a target hematocrit level of 30% or greater in patients with low central venous oxygen saturation (less than 70%).
EGDT effects on inflammation: Pathogenic, diagnostic, therapeutic, and prognostic Implications In addition to the primary stimulus of the systemic inflammatory response syndrome, global tissue hypoxia independently contributes to endothelial activation, the disruption of the homeostatic balance of coagulation, vascular permeability, and vascular tone. One of the possible explanations of why EGDT patients required less mechanical ventilation despite receiving more liberal fluid therapy during the first 6 h may be deduced from a reduction in IL-8 levels, which is associated with ALI . While equal at baseline,IL-8 was significantly reduced over the period of 12 to 72 h in the EGDT.