Sepsis is life-threatening organ dysfunction due to dysregulated host response to infection.

Septic shock occurs in a subset of patients with sepsis and comprises of an underlying circulatory and cellular/metabolic abnormality that is associated with increased mortality. Septic shock is defined by persisting hypotension requiring vasopressors to maintain a mean arterial pressure of 65 mm Hg or higher and a serum lactate level greater than 2 mmol/L (18 mg/dL) despite adequate volume resuscitation. [1] This new 2016 definition, also called Sepsis-3, eliminates the requirement for the presence of  systemic inflammatory response syndrome (SIRS) to define sepsis, and it removed the severe sepsis definition. What was previously called severe sepsis is now the new definition of sepsis.

 

Sepsis is defined as  systemic inflammatory response syndrome(SIRS) with a documented infection, with the identification of microorganisms from a normally sterile fluid or visual inspection of a focus of infection.

Severe sepsis consists of sepsis with evidence of end-organ hypoperfusion or dysfunction (eg, prolonged capillary refill, acute respiratory distress syndrome (ARDS), mental status changes, or elevated lactate).

Septic shock is severe sepsis with persistent hypotension despite adequate fluid resuscitation, with refractory septic shock defined as septic shock requiring high doses of vasopressors.

 

 

 

[The reliability of SIRS has increasingly been questioned, and patients meeting the definition of sepsis using SIRS criteria must be further clarified because a patient with SIRS may have a mild, self-limiting infection or may have a more severe infection with the potential to progress to severe sepsis. Patients with severe sepsis or septic shock require aggressive management, including intravenous fluid administration and prompt antibiotic therapy.]

Patients with evidence of respiratory failure from shock or pneumonia require ventilatory support. Soft tissue infections of the head and neck may compromise the airway because of mechanical obstruction. These may require acute intervention to provide a secure airway.

In many cases, early empirical antibiotic therapy is appropriate. The choice of antibiotics is based on the likely cause of the fever as well as concomitant conditions, such as absolute neutropenia and end-stage renal disease. If a specific infection is subsequently identified, antibiotic therapy should be specific to that infection. With clinically severe illness in the absence of a clear source of infection, broad-spectrum coverage of gram-positive and gram-negative aerobic and anaerobic bacteria is indicated. In acutely ill febrile patients, especially those who are immunocompromised, antiviral and antifungal treatment are also frequently indicated.

 

 

1Reprinted, with permission, from Levy MM, Fink MP, Marshall JC, et al: 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003;31:1250.

2WBC, white blood cell; SBP, systolic blood pressure; MAP, mean arterial blood pressure; Image not available., mixed venous oxygen saturation; INR, international normalized ratio; aPTT, activated partial thromboplastin time.

3Diagnostic criteria for sepsis in the pediatric population are signs and symptoms of inflammation plus infection with hyper- or hypothermia (rectal temperature >38.4°C or <35°C), tachycardia (may be absent in hypothermia patients), and at least one of the following indications of altered organ function: altered mental status, hypoxemia, increased serum lactate level, or bounding pulses.

 

5 Image not available. >70% (normally, 75-80%) and cardiac index 3.5-5.5 are normal in children; therefore, neither should be used as a sign of sepsis in newborns or children.

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Diagnostic Criteria for Sepsis.1-3
  • Infection,4 documented or suspected, and some of the following:
  • General variables
    • Fever (core temperature >38.3°C)
    • Hypothermia (core temperature <36°C)
    • Heart rate >90/min or >2 SD above the normal value for age
    • Tachypnea
    • Altered mental status
    • Significant edema or positive fluid balance (>20 mL/kg over 24 h)
    • Hyperglycemia (plasma glucose >120 mg/dL or 7.7 mmol/L) in the absence of diabetes
  • Inflammatory variables
    • Leukocytosis (WBC count >12,000/μL)
    • Leukopenia (WBC count <4000/μL)
    • Normal WBC count with >10% immature forms
    • Plasma C-reactive protein >2 SD above the normal value
    • Plasma procalcitonin >2 SD above the normal value
  • Hemodynamic variables
    • Arterial hypotension5 (SBP <90 mm Hg, MAP <70, or an SBP decrease >40 mm Hg in adults or <2 SD below normal value for age)
    • Image not available. > 70%5
    • Cardiac index5 >3.5 L/min per m2
  • Organ dysfunction variables
    • Arterial hypoxemia (Pao2/Fio2 < 300)
    • Acute oliguria (urine output <0.5 mL/kg/h or 45 mmol/L for at least 2 h)
    • Creatinine increase > 0.5 mg/dL
    • Coagulation abnormalities (INR > 1.5 or aPTT > 60 s)
    • Ileus (absent bowel sounds)
    • Thrombocytopenia (platelet count < 100,000/μL)
    • Hyperbilirubinemia (plasma total bilirubin > 4 mg/dL or 70 mmol/L)
  • Tissue perfusion variables
    • Hyperlactatemia (>1 mmol/L)
    • Decreased capillary refill or mottling

1Reprinted, with permission, from Levy MM, Fink MP, Marshall JC, et al: 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003;31:1250.

2WBC, white blood cell; SBP, systolic blood pressure; MAP, mean arterial blood pressure; Image not available., mixed venous oxygen saturation; INR, international normalized ratio; aPTT, activated partial thromboplastin time.

3Diagnostic criteria for sepsis in the pediatric population are signs and symptoms of inflammation plus infection with hyper- or hypothermia (rectal temperature >38.4°C or <35°C), tachycardia (may be absent in hypothermia patients), and at least one of the following indications of altered organ function: altered mental status, hypoxemia, increased serum lactate level, or bounding pulses.

4Infection defined as a pathological process induced by a microorganism.

5 Image not available. >70% (normally, 75-80%) and cardiac index 3.5-5.5 are normal in children; therefore, neither should be used as a sign of sepsis in newborns or children.

A combined conference of the preceding long list of societies classified sepsis based on predisposition, insult, infection, response, and organ dysfunction. Severe sepsis exists when these features are associated with organ dysfunction. The term multiple organ dysfunction syndrome (MODS) has been suggested to describe dysfunction of two or more organs associated with sepsis. Septic shock is defined as acute circulatory failure in a patient with sepsis or, more specifically, systolic blood pressure less than 90 mm Hg that is not responsive to volume resuscitation and requiring vasopressors for life support.

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Septic shock is a subset of sepsis in which the underlying circulatory and cellular/metabolic abnormalities are significant enough to substantially worsen mortality. Patients who, after adequate volume resuscitation, have persistent hypotension requiring vasopressors to maintain MAP greater than or equal to 65 mm Hg and also have a lactate greater than or equal to 2 mmol/L are categorized as having septic shock.

 

 

 

 

Sepsis occurs when a generalized proinflammatory response results from an infectious trigger.

Typically, a bacterial pathogen enters a sterile site and initiates a localized host response.

Immune cells, particularly macrophages, recognize and bind microbial components, setting off a series of reactions that result in bacterial lysis with phagocytosis of bacterial components and injured cells/tissue. This process can be associated with the production and release of a range of proinflammatory cytokines (eg, tumor necrosis factor-alpha, interleukin-1) resulting in additional inflammatory cell recruitment. When the response becomes generalized, a systemic inflammatory response and sepsis can be recognized.

Continued cellular injury leads to tissue ischemia, cytopathic injury, and alteration in apoptosis. The mechanism of organ failure may relate to decreased oxygen delivery and utilization, imbalance in the coagulation and fibrinolytic system, and cytopathic injury.

 

1. Treat the infection

Start empirical antimicrobial chemotherapy as soon as samples of blood and other relevant sites have been obtained for culture.

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Initial Antimicrobial Therapy for Severe Sepsis with No Obvious Source in Adults with Normal Renal Function1

Clinical Condition Antimicrobial Regimens (Intravenous Therapy)
Immunocompetent adult

The many acceptable regimens include:

(1) piperacillin-tazobactam (3.375 g q4–6h);

(2) imipenem-cilastatin (0.5 g q6h), ertapenem (1 g q24h), or meropenem (1 g q8h); or

(3) cefepime (2 g q12h).

If the patient is allergic to β-lactam agents, use ciprofloxacin (400 mg q12h) or levofloxacin (500–750 mg q12h) plus clindamycin (600 mg q8h). Vancomycin (15 mg/kg q12h) should be added to each of the above regimens.

Neutropenia (<500 neutrophils/μL) Regimens include (1) imipenem-cilastatin (0.5 g q6h) or meropenem (1 g q8h) or cefepime (2 g q8h) or (2) piperacillin-tazobactam (3.375 g q4h) plus tobramycin (5–7 mg/kg q24h). Vancomycin (15 mg/kg q12h) should be added if the patient has an indwelling vascular catheter, has received quinolone prophylaxis, or has received intensive chemotherapy that produces mucosal damage; if staphylococci are suspected; if the institution has a high incidence of MRSA infections; or if there is a high prevalence of MRSA isolates in the community. Empirical antifungal therapy with an echinocandin (for caspofungin: a 70-mg loading dose, then 50 mg daily), voriconazole(6 mg/kg q12h for 2 doses, then 3 mg/kg q12h), or a lipid formulation of amphotericin B should be added if the patient is hypotensive, has been receiving broad-spectrum antibacterial drugs, or remains febrile 5 days after initiation of empirical antibacterial therapy.
Splenectomy Cefotaxime (2 g q6–8h) or ceftriaxone (2 g q12h) should be used. If the local prevalence of cephalosporin-resistant pneumococci is high, add vancomycin. If the patient is allergic to β-lactam drugs, vancomycin (15 mg/kg q12h) plus either moxifloxacin (400 mg q24h) or levofloxacin (750 mg q24h) should be used.
IV drug user Vancomycin (15 mg/kg q12h) is essential.
AIDS Cefepime alone (2 g q8h) or piperacillin-tazobactam (3.375 g q4h) plus tobramycin (5–7 mg/kg q24h) should be used. If the patient is allergic to β-lactam drugs, ciprofloxacin (400 mg q12h) or levofloxacin (750 mg q12h) plus vancomycin (15 mg/kg q12h) plus tobramycin should be used.

Abbreviation: MRSA, methicillin-resistant Staphylococcus aureus.

Source: Adapted in part from DN Gilbert et al: The Sanford Guide to Antimicrobial Therapy, 43rd ed, 2013.

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2. Provide hemodynamic support

3. Provide respiratory support

4. Remove or drain infected tissues

Content 9

 

Complications of Injecting Drug Use

  • Local problems—Abscess (Figures 240-2 
    Image not available.

    A 32-year-old woman with type 1 diabetes developed large abscesses all over her body secondary to injection of cocaine and heroin. Her back shows the large scars remaining after the healing of these abscesses. (Courtesy of ­Richard P. Usatine, MD.)

    and 240-3; Abscess), cellulitis, septic thrombophlebitis, local induration, necrotizing fasciitis, gas gangrene, pyomyositis, mycotic aneurysm, compartmental syndromes, and foreign bodies (e.g., broken needle parts) in local areas.2
    • IDUs are at higher risk of getting methicillin-resistant Staphylococcus aureus(MRSA) skin infections that the patient may think are spider bites (Figure 240-4).
    • Some IDUs give up trying to inject into their veins and put the cocaine directly into the skin. This causes local skin necrosis that produces round atrophic scars (Figure 240-5).
  • IDUs are at risk for contracting systemic infections, including HIV and hepatitis B or hepatitis C.
    • Injecting drug users are at risk of endocarditis, osteomyelitis (Figures 240-6and 240-7), and an abscess of the epidural region. These infections can lead to long hospitalizations for intravenous antibiotics. The endocarditis that occurs in IDUs involves the right-sided heart valves (see Chapter 50, Bacterial Endocarditis).2 They are also at risk of septic emboli to the lungs, group A β-hemolytic streptococcal septicemia, septic arthritis, and candidal and other fungal infections.

 

Content 3

Content 11

 

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