Systemic inflammatory response syndrome (SIRS)—Two or more of the following, due to either an infectious or a noninfectious etiology:
- Temperature >380C or >360C
- Respiratory rate >24 breaths/ min
- Heart rate >90 beats/ min
- WBC count >12,000/uL or <4000/uL, or >10% bands
Sepsis—SIRS witha proven or suspected microbial etiology
Severe sepsis—Sepsis withone or more signs of organ dysfunction
Septic shock—Sepsis witharterial blood pressure<90 mmHg or 40 mmHg below pt’s normal blood pressure for at least 1 hdespite fluid resuscitation
• Blood cultures are positive in 20–40% of sepsis cases and in 40–70% of septic shock cases. Of cases with positive blood cultures,-40% are due to gram-positive bacteria, 35% to gram-negative bacteria, and 7% to fungi.
• Any class of microorganism can cause severe sepsis.
• A significant proportion of cases have negative microbiologic data.
Epidemiology and Risk Factors
The incidence of severe sepsis and septic shock is increasing in the United States, with >300,000 cases each year. Two-thirds of cases occur in pts hospitalized for other reasons. Sepsis is a contributing factor in >200,000 deaths eachyear in the United States.
The higher incidence of sepsis is due to the aging of the population, longer survival of pts withch ronic diseases, medical treatments (e.g., with steroids or antibiotics), and invasive procedures (e.g., catheter placement). Gram-negative sepsis is associated withunderlying diabetes mellitus, lymphoproliferative disorders, cirrhosis of the liver, burns, neutropenia, and indwelling urinary cathe ters. Gram-positive sepsis is associated withindwelling mechanical devices and intravascular catheters, IV drug use, and burns. Fungal sepsis is associated with neutropenia and broad-spectrum antimicrobial therapy.
Pathogenesis and Pathology
Local and Systemic Host Responses
• Recognition of microbial molecules by tissue phagocytes triggers production and release of cytokines and other mediators that increase blood flow to the infected site, enhance the permeability of local blood vessels, attract neutrophils to the infected site, and elicit pain.
• Through intravascular thrombosis (the hallmark of the local immune response), the body attempts to wall off invading microbes and prevent the spread of infection and inflammation. Key features of the systemic immune response include intravascular fibrin deposition, thrombosis, and DIC; the underlying mechanisms are the activation of intrinsic and extrinsic clotting pathways, impaired function of the protein C–protein S inhibitory pathway, depletion of antithrombin and protein C, and prevention of fibrinolysis by increased plasma levels of plasminogen activator inhibitor 1.
Organ Dysfunction and Shock
• Endothelial injury: Widespread endothelial injury is believed to be the major mechanism for multiorgan dysfunction.
• Septic shock: The hallmark is a decrease in peripheral vascular resistance despite increased levels of vasopressor catecholamines. Cardiac output and blood flow to peripheral tissues increase, and oxygen utilization by these tissues is greatly impaired.
- Encephalopathy (disorientation, confusion)
- DIC, acrocyanosis, ischemic necrosis of peripheral tissues (e.g., digits)
- Skin: hemorrhagic lesions, bullae, cellulitis. Skin lesions may suggest specific pathogens—e.g., petechiae and purpura with Neisseria meningitidis, ecthyma gangrenosum in neutropenic pts with Pseudomonas aeruginosa.
- Gastrointestinal: nausea, vomiting, diarrhea, ileus, cholestatic jaundice
- Hypoxemia: ventilation-perfusion mismatchand increased alveolar capillary permeability withincreased pulmonary water content
• Cardiopulmonary manifestations:
Acute respiratory distress syndrome (progressive diffuse pulmonary infiltrates and arterial hypoxemia) develops in -50% of pts withsevere sepsis or septic shock.
Hypotension: Normal or increased cardiac output and decreased systemic vascular resistance distinguish septic shock from cardiogenic or hypovolemic shock.
Myocardial function is depressed withdecreased ejection fraction.
• Renal manifestations: oliguria, azotemia, proteinuria, renal failure due to acute tubular necrosis
• Coagulation: thrombocytopenia in 10–30% of pts. With DIC, platelet counts usually fall below 50,000/uL.
• Neurologic manifestations: polyneuropathy with distal motor weakness in prolonged sepsis
• Leukocytosis with a left shift, thrombocytopenia
• Prolonged thrombin time, decreased fibrinogen, presence of D-dimers, suggestive of DIC
• Hyperbilirubinemia, increase in hepatic aminotransferases, azotemia, proteinuria
• Metabolic acidosis, elevated anion gap, elevated lactate levels, hypoxemia
Definitive diagnosis requires isolation of the microorganism from blood or a local site of infection. Culture of infected cutaneous lesions may help establish the diagnosis. Lacking a microbiologic diagnosis, the diagnosis is made on clinical grounds.
1. Antibiotic treatment
2. Removal or drainage of a focal source of infection
· Remove indwelling intravascular catheters and send tips for quantitative culture; replace Foley and other drainage catheters.
· Rule out sinusitis in pts withnasal intubation.
· Perform CT or MRI to rule out occult disease or abscess.
3. Hemodynamic, respiratory, and metabolic support
a. Maintain intravascular volume withIV fluids. Initiate treatment with 1–2 L of normal saline administered over 1–2 h, keeping pulmonary capillary wedge pressure at 12–16 mmHg or central venous pressure at 8–12 cmH2O, urine output at >0.5 mL/kg per hour, mean arterial blood pressure at >65 mmHg, and cardiac index at >4 (L/min)/m2. Add inotropic and vasopressor therapy if needed. Maintain central venous O2 saturation at _70%, using dobutamine if necessary.
b. Maintain oxygenation withventilator support as indicated.
c. Monitor for adrenal insufficiency or reduced adrenal reserve. Pts witha plasma cortisol response of <9 ug/dL to an ACTH challenge may have improved survival if hydrocortisone (50 mg q6h IV) and 9-alpha fludrocortisone (50 ug/d via nasogastric tube) are administered for 7 days.
4. Other treatments (investigational): Antiendotoxin, anti-inflammatory, and anticoagulant drugs are being studied in severe sepsis treatment. The anticoagulant recombinant activated protein C (aPC), given as a constant infusion of 24 ug/kg per hour for 96 h, has been approved for treatment of severe sepsis or septic shock in pts with APACHE II scores of >25 preceding aPC infusion and low risk of hemorrhagic complications. The long-term impact of aPC is uncertain, and long-term survival data are not yet available. Other agents have not improved outcome in clinical trials.
Shock Algorithm Guidelines
In all, 20–35% of pts withsevere sepsis and 40–60% of pts with septic shock die within 30 days, and further deaths occur within the first 6 months. The severity of underlying disease most strongly influences the risk of dying.
In the United States, most episodes of severe sepsis and septic shock are complications of nosocomial infections. Thus the incidence of sepsis would be affected by measures to reduce those infections (e.g., limiting the use and duration