الفهرس 
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Abstract
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection and results in self-tissue injury. Organ dysfunctions can be assessed by acute change in total SOFA score ≥ 2 points.
Septic shock is a subset of sepsis in which underlying circulatory, cellular and metabolic disorders are profound enough to substantially increase mortality. It characterized by persistent hypotension (that requires vasopressors to maintain mean arterial pressure ≥ 65mmHg) and high serum lactate level >2 mmol/L despite adequate volume resuscitation.
The pathogenesis of septic shock is not precisely understood, but it involves a complex interaction between the pathogen and the host immune system. The normal physiologic response to localized infection includes the activation of host defense mechanisms that result in the influx of activated neutrophils and monocytes, the release of inflammatory mediators, local vasodilatation, increased endothelial permeability and activation of coagulation pathways.
When sepsis extends to other tissues, this results in multiple organ dysfunction syndrome that may be the first clinical sign of sepsis. No organ is immune to the consequences of sepsis.
The heart is the main victim in sepsis, hypotension developed due to release of vasoactive mediators and intravascular volume depletion. Tachycardia occurs as a response to cardiac underfilling, adrenergic stimulation and fever. Sepsis-related tachycardia has several adverse effects on the heart, including restricted diastolic ventricular filling, increased oxygen requirements and tachycardia-induced cardiomyopathy.
Other organ disorders include acute respiratory distress syndrome, bacterial translocation through the broken mucosal barrier, disturbed conscious level and oliguria.
Early diagnosis of septic shock is necessary for proper management; initiation of early goal directed therapy is the key to reduce the mortality rate. The traditional lines of treatment are: 1- Intravenous fluid resuscitation.
2- Infusion of catecholamines.
3- Methylene blue.
4- Corticosteroids.
5- Antimicrobial therapy.
6- Source control.
7- Red blood cell, plasma and platelets transfusion.
Catecholamine infusion is a life-saving therapy in septic shock; they are subdivided into vasopressor and inotropes. Vasopressors are acting mainly on α receptors; they are required when fluid administration fails to restore adequate arterial pressure and organ perfusion. Inotrops are acting mainly on β receptors and best used in case of cardiac dysfunction to maintain adequate cardiac index, urine output and mixed venous oxygen saturation.
However; prolonged catecholamines infusion can maximize the cardiac work with high risk of cardiotoxicity, arrhythmias and myocardial infarction. Other disorders are pulmonary edema, hyperglycemia, lipolysis, hypokalemia, negative immunomodulating effects, stimulation of intestinal bacterial growth, myocyte apoptosis and inhibition of erythropoiesis.
Availability of different β blockers drugs with different characters (elimination half-time, elimination process, receptor binding affinities), allows β blockers to be used in septic shock. They have different effects on many systems:
Cardiac effects: β blockers are used after fluid resuscitation in order to brake the adrenergic system, so protect the heart from excessive adrenergic stimulation, attenuate excessive tachycardia and suppress cardiac dysrhythmias and so decrease oxygen demand. β blockers may be used in combination with catecholamines with no contrast, even may help to decrease its infusion dose. However; decrement in MAP and macrocirculation were reported in some studies. Other β blockers effects:
Anti-inflammatory and immunoregulatory effects: β1 receptor blocking is equal to β2 receptor activation, both have anti-inflammatory effects i.e. reducing serum TNF-α, IL-1β, IL-6 levels and increasing serum IL-10 level.
Metabolic effects: β1 receptors blockade may reduce arterial lactate level, while β2 receptors blockade decrease muscular lactate production, decrease blood glucose level, attenuate resting energy expenditure and reverse muscle protein catabolism.
GIT effects: improving gut microcirculation, maintaining intact healthy mucosa, facilitating gut motility and preventing bacterial translocation.
Effects on overall mortality: β blockers therapy either selective or non-selective can decrease mortality and improve outcome. In addition, previous β blockers users ”chronic users” are associated with high survival rate if they developed septic shock later. However some believe no change in mortaliy.