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Chapter 46: Sepsis and Septic Shock

INTRODUCTION

  • The older and more recent definitions of terms related to sepsis are given in Table 46-1. Sepsis-3 redefined sepsis by combining sepsis and severe sepsis from the Sepsis-2 guideline.

TABLE 46-1Comparison of Definitions from Sepsis-2 and Sepsis-3 Guidelines
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TABLE 46-1 Comparison of Definitions from Sepsis-2 and Sepsis-3 Guidelines

Sepsis-2 Guideline (2012)

Sepsis-3 Guideline (2016)

Systemic inflammatory response syndrome (SIRS) to infectious or noninfectious insults: Two or more of the following:

  • Temperature >38°C or <36°C

  • Heart rate >90 beats/minute

  • Respiratory rate >20 breaths/minute

  • WBC >12,000/mm3 (12 × 109/L) or <4000 cells/mm3 (4 × 109/L) or >10% (0.10) immature bands

Sepsis: SIRS + probable or documented infection

Severe sepsis: Sepsis + one or more organ dysfunction or hypoperfusion

Septic shock: Sepsis + refractory hypotension despite fluid resuscitation (30 mL/kg) or serum lactate >1 mmol/L

Sepsis: Life-threatening organ dysfunction caused by a dysregulated host response to infection

  • Acute change in total SOFA score ≥2 points

Septic shock: Sepsis + persistent hypotension requiring vasopressor use and serum lactate >2 mmol/L despite adequate fluid resuscitation

SOFA, sequential organ failure assessment; WBC, white blood cell.

ETIOLOGY AND PATHOPHYSIOLOGY

  • Patients at risk for infection who are predisposed to sepsis include advanced or very young age; preexisting conditions including heart failure, diabetes, chronic obstructive pulmonary disease, cirrhosis, alcohol dependence, and end-stage renal disease; and other immunosuppressive diseases such as neoplasm and human immunodeficiency virus (HIV) disease.

  • The most common anatomic source of infection that leads to sepsis is the lung (40%–42%), followed by intra-abdominal space (31%–34%) and genitourinary tract (11%–15%). The microorganisms isolated from blood cultures of patients with sepsis or septic shock include gram-negative organisms in 44%–59% of patients, gram-positive bacteria in 37%–52%, anaerobic organisms in 5%, and fungi in 4%–10%.

  • Escherichia coli is by far the most commonly isolated gram-negative microorganism in sepsis (55%–60%), followed by Klebsiella species, Proteus species, Enterobacter species, and Pseudomonas aeruginosa. Mortality increases significantly with increasing severity of sepsis (3.5% for sepsis, 9.9% in severe sepsis, and 29% in septic shock), especially in presence of P. aeruginosa. The most common gram-positive organisms are Staphylococcus aureus, followed by coagulase-negative Staphylococci, Enterococcus species, and Streptococcus pneumoniae.

  • Candida species (particularly Candida albicans) are common fungal etiologic agents of bloodstream infections. The 30-day mortality rate for sepsis due to candidemia is 54%.

  • The pathophysiologic focus of gram-negative sepsis has been on the lipopolysaccharide (endotoxin) component of the gram-negative cell wall membrane. Lipid A is a part of the endotoxin molecule from the gram-negative bacterial cell wall that is highly immunoreactive and is responsible for most of the toxic effects. In gram-positive sepsis, the exotoxin peptidoglycan on the cell wall surface appears to exhibit proinflammatory activity.

  • Sepsis involves a complex interaction of proinflammatory (eg, tumor necrosis factor-α [TNF-α]; interleukin [IL]-1, IL-6, IL-12) and anti-inflammatory mediators (eg, ...

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