Chapter 25-9: Septic Shock

TEXTBOOK PRESENTATION

Patients with septic shock typically have fever, tachypnea, tachycardia, and hypotension. Whereas patients with cardiogenic or hemorrhagic shock often have cold extremities, patients with septic shock often have warm extremities and bounding pulses after fluid resuscitation. (Pulses are bounding due to a widened pulse pressure.) Mentation may be impaired and urinary output decreased.

DISEASE HIGHLIGHTS

1. Epidemiology

   1. The annual incidence of sepsis exceeds 1,000,000 cases per year in the United States.

   2. Most common sources of infection are the lung, abdomen, urinary tract, and IV catheters. Commonly overlooked sources include sinusitis (associated with nasogastric tubes), acalculous cholecystitis, and Clostridium difficile colitis.

2. Pathophysiology

   1. Sepsis

      1. Occurs when an infection (bacterial, fungal, mycobacterial, or viral) causes a non-homeostatic host response to infection.

      2. There is significant biologic and clinical heterogeneity due to factors associated with both the pathogen and the host (eg, age, comorbid conditions, medications, genetics).

      3. A noninfectious process (eg, acute pancreatitis) may also trigger a similarly dysregulated immune response.

   2. In early stages of sepsis, hyperimmune responses may play a role in the organ dysfunction and cause multiple organ dysfunction syndrome, hypotension, disseminated intravascular coagulation, and death.

   3. In later stages of sepsis, patients may be hypoimmune. Hypoimmunity may also contribute to infection and death.

   4. Mechanisms of hypotension include

      1. Vasodilation (decreased systemic vascular resistance) mediated by elevated nitrous oxide levels, increased prostacyclin levels, and low vasopressin levels, lowers BP.

      2. Cardiac output can be increased or decreased in sepsis.

         1. The drop in systemic vascular resistance decreases afterload, which often results in an increase in CO.

         2. On the other hand, leakage of fluid out of intravascular space can decrease venous return and thereby decrease CO.

         3. In addition, myocardial function can be reduced and also decrease CO.

      3. Typically, the initial hemodynamic response is decreased systemic vascular resistance and increased CO (particularly after fluid resuscitation).

   5. Multiple organ dysfunction is often seen.

      1. Lung involvement: acute respiratory distress syndrome secondary to increased permeability with subsequent noncardiogenic pulmonary edema.

      2. Acute kidney injury secondary to

         1. Hypotension

         2. Renal vasoconstriction

         3. Increased tumor necrosis factor

      3. Disseminated intravascular coagulation: Multiple mediators are involved, including decreased protein C (see Chapter 8-4: Disseminated Intravascular Coagulation, for details).

   6. Lactic acidosis is common in sepsis and has many causes.

      1. Microcirculatory lesions impair oxygen delivery.

         1. Dysregulation of supply and demand

         2. Microvascular occlusion

      2. Hypotension impairs oxygen delivery.

      3. Mitochondrial injury impairs oxygen utilization.

      4. Decreased hepatic clearance of lactate contributes to lactic acidosis.

3. The current accepted definitions for sepsis and septic shock incorporate the Sequential [Sepsis-Related] Organ Failure Assessment Score (SOFA) (Table 25-2).

   1. Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection and is diagnosed when there is suspected or documented infection and an acute increase of ≥ 2 SOFA points (a proxy for organ dysfunction).

   2. Septic shock is a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality, and is diagnosed when there is sepsis and lactate > 2 mmol/L ...