الفهرس 
SepsisOnly 14 pages are availabe for public view
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Abstract
Introduction
Sepsis, sepsis syndrome, and septic shock are commonly used terms. Although these terms frequently predicted the development of end organ dysfunction or death, unfortunately they were frequently employed interchangeably, with consequent confusion between those with signs and symptoms of infection plus a positive culture and those without a positive culture.
More than 80 biological markers of sepsis (eg, C-reactive protein, interleukin 6, procalcitonin, protein C) have been investigated both for their diagnostic and prognostic capabilities. In general, presence of these markers has been associated with increasing morbidity and mortality. However, lack of availability, long result turnaround times, and nonstandardized assays and cutoff values limit their practical use.
Microalbuminuria in Sepsis
Microalbuminuria has been shown to be a non specific but sensitive marker of systemic inflammation with more rapid onse than other markers, and its importance relies on a fact that a very early feature of inflammation is increased capillary permeability to plasma proteins, which occurs within a few minutes of injury and usually returns to normal within 6 to 12 hours 1.
Capillary leak is amplified by the kidney and can be monitored by measurement of urine albumin. The degree of albuminuria is variable and in most instances may not be clinically detectable using routine urine dipstick testing. Such low rates of albumin excretion (<300 mg/ day) are termed microalbuminuria. The degree of microalbuminuria can be reliably indexed with a spot urine microalbumin-creatinine ratio (MACR) 2.
Recent studies have suggested that measurement of the urine ACR may have some predictive value for organ failure in intensive care unit (ICU) patients 1.
Treatment of Sepsis
A goal-directed hemodynamic resuscitation of severe sepsis/ septic shock includes a systematic approach to restoration of systemic oxygen delivery through a manipulation of preload (volume), afterload (blood pressure), and contractility (stroke volume) to preserve effective tissue perfusion while avoiding excessive increases in myocardial oxygen consumption (ie, tachycardia) and maintaining coronary perfusion pressure.
Early goal-directed therapy is an algorithmic approach to hemodynamic optimization and resolution of global tissue hypoxia within the first 6 hours of disease presentation . The strategy targets normal oxygen delivery by optimizing preload, afterload, oxygen content, and contractility to achieve a balance between tissue oxygen delivery and consumption (guided by central venous pressure, mean arterial pressure, and ScvO2 monitoring)3. Specifically, patients are treated by ;
Fluid resuscitation with either crystalloid or colloid to achieve a central venous pressure goal of 8 to 12 mm Hg,
Vasoactive agents to achieve a mean arterial pressure goal of 65 to 90 mm Hg,
Blood transfusion to a hematocrit level greater than 30%,
Inotrope therapy, and
Intubation, sedation, and paralysis as necessary to achieve a ScvO2 of greater than 70%.
Role of Corticosteroids in Sepsis
Because an intense inflammatory response is a component of the pathogenesis of sepsis, corticosteroids have been explored as a possible therapeutic agent. However, the use of corticosteroids in sepsis remains controversial.
The SCCM (Society of Critical Care Medicine Consensus Conference) guidelines recommend intravenous low-dose corticosteroids (hydrocortisone 200–300 mg/day) only in patients with vasopressor-dependent septic shock 4.
Administration of higher doses of corticosteroids in septic shock has been shown to be harmful 5. from another point of view, the host response to the stress of critical illness includes increased serum cortisol levels, but an inappropriate cortisol response is common in patients with septic shock6. The term relative adrenal insufficiency was introduced to describe this state which can be tested by the adrenal function test as an approach to determine the patients’ benefit from corticosteroid therapy7. The use of corticosteroids in the treatment of acute respiratory distress syndrome (ARDS) also remains controversial. Some earlier trials showed a mortality benefit among patients treated with methylprednisolone compared with those given placebo 5.
Microalbuminuria and Hydrocortisone
A severe and sustained inflammatory reaction induces rapid and profound changes in the endothelium resulting in loss of barrier integrity leading to systemic capillary leak. In the kidneys this manifests as altered glomerular permeability culminating in increased renal albumin excretion in the urine8. Microalbuminuria is found to occur in several acute inflammatory states such as burns, pancreatitis, meningitis, ischemia reperfusion injury, acute myocardial infarction, and cerebral ischemia9.
Microalbuminuria may thus reflect the evolution of systemic capillary leakage and could therefore be a useful parameter to assess the efficacy of therapies aiming to reduce endothelial damage. Recently it was demonstrated thatcorticosteroids reduce the increase in microvascular permeability induced by N-formylmethionine leucyl-phenylalanine in the rabbit 10 and that they attenuate plasma exudation by suppressing the production of nitric oxide in neutrophils, thus suggesting another level of corticosteroid action 11.