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An Overview of Critical Care |
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Sepsis |
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Although patients are admitted to the intensive care unit with a myriad of disease processes, the majority of patients die of multi-organ failure from sepsis. It appears that the initial insult removes the patient’s physiologic reserve, and the “second hit” (sepsis) kills them. The term “sepsis” tends to be used loosely to convey a series of symptoms and signs associated with systemic inflammation.
A series of definitions have evolved (3): systemic inflammatory response syndrome – tachycardia, tachypnea, pyrexia (or hypothermia), leucocytosis or leucopenia, all without identification of an infective organism (this response occurs due to any tissue injury – surgery and trauma included). If an organism is identified, this is sepsis. If there is evidence of hypotension or hypoperfusion, this is severe sepsis. If the blood pressure falls and stays down, this is refractory (septic) shock. What is important about these definitions is that they emphasize inflammation rather than infection. · The “second hit”
Figure 1: Interaction of Infection, Sepsis and SIRS (from ref 3) It is invariably the patient’s own inflammatory response that kills them. We are only beginning to understand this process. There are two major injuries that occur in sepsis: 1.Widespread release of cytokines and cytotoxic enzymes damages the endothelium, the lining of blood vessels, turning (more or less) water tight blood vessels into sieves – allowing large amounts of protein rich fluid to leak into the lax subcutaneous tissues, causing tissue edema and intravascular dehydration. This appears to occur predominantly due to loss of colloid oncotic pressure (capillary leak syndrome). Simultaneously: 2. Damage to the lining of blood vessels causes the activation of the coagulation cascade, and initial intravascular deposition of thrombus (before clotting factors are used up and the patient bleeds). The result of intravascular thrombosis and hypotension is ischemic injury to many of the body’s organs (4).
The predominant sign of systemic inflammation is hypotension: this occurs due to myocardial depression, loss of arteriolar tone (due to excessive production of nitric oxide), arterial to venous shunting and macrovascular damage. The key injury in sepsis is in the microcirculation, where there is extensive capillary leak and intravascular thrombosis, alongside a loss of oxygen extraction capacity. The microcirculatory injury is patchy, and individual organs have varying degrees of injury within them. This makes treatment of sepsis extremely difficult.
There is some evidence that, due to hypotension and blood distribution, sustained loss of blood flow into the splanchnic bed, along with inadequate nutrient intake, leads to degeneration and atrophy of the gut mucosa. Intestinal flora become virulent and cross through the defunct gut wall into the blood – translocating – looking for food (5;6) . The presence of microbes, endotoxin/exotoxin in the portal circulation appears to amplify the systemic inflammatory response (Gut Origin Theory).
How best then to deal with sepsis? The first step is immediate resuscitation of the patient – administration of oxygen with or without airway control and mechanical ventilation, and reestablishment of a circulation using large volume fluid resuscitation. Colloidal agents may be used to reduce the overall volume requirements, and minimize inevitable tissue edema; albumin, though, appears to have no role. Volume loading is applied until specific targets are reached – physiologic range blood pressure, urinary output/mentation, a sustained CVP rise etc. If such intervention does not restore blood pressure, then vasoactive medications are required. Norepinephrine appears to be the agent of choice (7): it is a potent vasoconstrictor, which also has beta adrenergic effects (norepinephrine should only be used if the patient has been fully volume loaded in advance). These effects increase stroke volume and splanchnic blood flow. If additional beta activity is required, dobutamine or dopamine is added (8;9) . Some units use dopamine as a preferential first line agent, this has the disadvantage of being particularly chronotrophic, and may steal intestinal mucosal blood flow (7).
Following initial resuscitative efforts, it is essential to commence empiric antimicrobial therapy and control the source of the infection: abscesses need to be drained, infected lines removed. A low serum albumin at this stage is indicative of capillary leak and negative acute phase response (10) (the liver produces cytokines rather than albumin in sepsis), and is indicative of severity of illness (11). Restoration of splanchnic blood flow and enteral feeding of the gut is essential.
There is some evidence that enteral feeds enhanced with nucleotides, glutamine and omega-3 fatty acids may enhance immune function (12).
Patients in septic shock may develop a relative deficiency of cortisol (required for activation of catecholamines) (13) and vasopressin (14;15) . Physiologic replacement of these hormones may reduce vasopressor requirements (16-18) .
The coagulopathy associated with sepsis can be treated with activated protein C (19), which appears to modulate the response, and improve outcome (20), presumably due to a reduction in the incidence of organ ischemia.
Adequacy of resuscitation is evaluated by looking at endorgan perfusion – using clinical examination and interpretation of monitored variables. There is no ideal method (21). Secondary sources of sepsis should be continuously monitored and iatrogenic and secondary injury (bed sores and deep vein thrombosis) avoided. |
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Please note: these tutorials are for personal study purposes only. They are not currently peer reviewed, and no responsibility will be taken for mistakes or inaccuracies. Reproduction of information is forbidden. All material is copyrighted by the GasWorks Group. |
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