A 57-year-old man with a history of diabetes mellitus and Helicobacter pylori infection is admitted to the intensive care unit after exploratory laparotomy for perforated duodenal ulcer. Vital signs are heart rate of 113 beats per minute, blood pressure of 83/40 mm Hg, respiratory rate of 18 breaths per minute, temperature of 38.9° C, and oxygen saturation by pulse oximetry (SpO 2 ) of 98%. He subsequently remains hypotensive despite fluid resuscitation and develops oliguria and coagulopathy.
Distinguish among systemic inflammatory response syndrome, sepsis, severe sepsis, septic shock, and multisystem organ dysfunction syndrome.
Sepsis has been recognized as a clinical syndrome for many years. Systemic inflammatory response syndrome (SIRS) is a more recent development, defined by the American College of Chest Physicians in 1992. Both conditions are recognized as part of a continuum of disease processes that involve similar pathophysiologic mechanisms. SIRS is defined by four cardinal criteria that are indicators of inflammation ( Table 89-1 ).
|>90 bpm||RR >20 bpm or||>38° C or||>12,000 or|
|pCO 2 <30 mm Hg||<36° C||<4000 or|
Although SIRS is frequently associated with infection, it can be caused by many noninfectious etiologies, such as pancreatitis, trauma, surgery, cardiopulmonary bypass, burns, anaphylaxis, drugs, or aortic dissection. If SIRS is associated with positive blood cultures or other conclusive indicators of infection, it is referred to as sepsis. Severe sepsis indicates that the patient has developed organ dysfunction secondary to sepsis. In septic shock, a closely related entity, sepsis results in hypoperfusion or arterial hypotension or both. Multisystem organ dysfunction syndrome (MODS) indicates the dysfunction of two or more systems such that intervention is needed to maintain homeostasis. MODS can result from sepsis but can also be due to other conditions, such as noninfectious SIRS or cardiogenic shock. Although these conditions share many features, recent years have seen an effort to standardize and clarify their nomenclature.
What are the pathophysiology and manifestations of sepsis-related organ dysfunction?
Numerous theories have been proposed to explain the cascade of events that results in sepsis. Most of these theories share the general concept that sepsis is the result of an initial infectious insult. The infection results in immune activation, with subsequent detrimental hyperactivity of the immune system. The initial insult is most commonly a localized or blood-borne bacterial infection. The cell membranes of gram-negative bacteria contain various elements that may initiate strong immune responses, such as lipopolysaccharide, thought to be the main factor in gram-negative sepsis. Gram-positive bacteria do not contain lipopolysaccharides, and much of their pathogenicity is thought to be due to exotoxins, which are immunogenic toxins secreted by bacteria.
Numerous proinflammatory cytokines are released in response to these stimuli, such as interleukin (IL)-1, IL-2, IL-6, and IL-10; interferon-γ, and tumor necrosis factor (TNF)-α. TNF-α creates a positive feedback loop, in which it acts to increase its own production and the production of other inflammatory mediators. This process is initially beneficial as a response to bacterial invasion but can become deleterious. Cytokine production results in activation of immune cells as well as complement, which can cause apoptosis and endothelial cell dysfunction. Activated endothelial cells express molecules, such as tissue factor, that are prothrombotic. The result is microvascular thrombosis and ischemia that is thought to underlie the development of organ dysfunction. In addition, endothelial cells produce increased levels of nitric oxide (NO), which functions as a vasodilator, resulting in hypotension.
Almost any infection can result in a septic state. In some cases, it is thought that if a patient’s gastrointestinal mucosa is disrupted via hypoperfusion or other trauma, endogenous gut flora may cross the mucosal barrier and cause bacteremia and sepsis. This is known as the gut translocation theory of sepsis. It may be a particular problem in patients who are already immunocompromised, as well as patients who are hypotensive from shock and patients with gastrointestinal pathology, such as intestinal obstruction or cancer. Although the process of translocation occurs in many situations outside critical illness and may be part of normal immune surveillance, it has been suggested by numerous studies that such translocation increases septic mortality. It is likely that after an initial infection or other injury that causes decreased visceral perfusion, bacteria from the gut may cause a second insult, which then results in worse outcomes. Enteral nutrition has been advocated as a way of maintaining mucosal integrity and preventing translocation; however, this has not been conclusively proven.
Organ dysfunction can take many forms. Myocardial dysfunction is common, especially after the initial cytokine storm. It appears to be due to circulating myocardial depressant factors rather than ischemia. In the initial septic period, decreased systemic vascular resistance (SVR) and venodilation produce a hyperdynamic, high-output state. During the first few days of a septic episode, this hyperdynamic state may transition to both systolic and diastolic dysfunction. Pulmonary hypertension secondary to lung injury may exacerbate right heart failure.
Most septic states are characterized by vasodilatation and lack of appropriate response to vasoconstrictors owing to multiple factors, including activation of adenosine triphosphate–sensitive potassium channels in smooth muscle, increased production of NO, and deficiency of arginine vasopressin (AVP). This deficiency is part of the rationale for administration of exogenous AVP in septic shock. Acidosis can decrease the responsiveness of vasculature to vasopressors, exacerbating the problem.
The lung is one of the most frequently injured organs in sepsis. Under the influence of cytokines, endothelial cells in the lung upregulate adhesion molecules and chemoattractants, resulting in infiltration of lung parenchyma and alveolar spaces by activated neutrophils. These neutrophils release various inflammatory mediators that damage pneumocytes and allow leakage of fluid and proteinaceous debris into alveolar spaces. This series of events inactivates residual surfactant, causing impaired gas diffusion, atelectasis, and ventilation-perfusion mismatch. The process is termed acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) when more severe ( Table 89-2 ). High inspired oxygen concentrations and ventilator pressures necessary to maintain oxygenation may perpetuate inflammation. This injury can affect the pulmonary vasculature and cause pulmonary hypertension, which may persist after hypoxia has resolved.
|Pulmonary infiltrates||Bilateral and heterogeneous||Bilateral and heterogeneous|
|PAOP||<18 mm Hg||<18 mm Hg|
|PaO 2 :FiO 2 ratio||<300||<200|
Renal injury secondary to sepsis is also quite common. Systemic vasodilatation and hypotension can result in direct renal ischemia. In the presence of volume depletion owing to vasodilation, the kidney tries to maintain the glomerular filtration rate (GFR) by releasing substances that stimulate intrarenal vasoconstriction, particularly constriction of the efferent arteriole. Eventually, these compensatory mechanisms may fail, resulting in decreased GFR. Endothelial injury can also cause intrarenal microvascular dysfunction and thrombosis. Patients with renal dysfunction of sepsis can exhibit normal urine output, oliguria, or anuria and may have different degrees of impaired solute filtration. One well-validated framework for quantifying acute kidney injury in sepsis comprises the RIFLE criteria ( Table 89-3 ).