Sepsis and Septic Shock¶
Chapter 315 | Part 8: Critical Care Medicine
KEY CLINICAL POINTS¶
- Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection; septic shock is a subset with profound circulatory, cellular, and metabolic abnormalities.
- Global sepsis incidence is ~48.9 million cases/year, with ~1.7 million in the U.S. Mortality rates are 15% for sepsis and up to 40% for septic shock.
- Common pathogens include gram-positive (Staphylococcus, Streptococcus, Enterococcus) and gram-negative (E. coli, Klebsiella, Pseudomonas) organisms.
- Early recognition with qSOFA score ( ≥ 2) and prompt antibiotics (within 1 hour of shock recognition) are critical for improved survival.
- Management includes fluid resuscitation (30 mL/kg crystalloid), vasopressors (norepinephrine), source control, and antimicrobial stewardship.
1. DEFINITION & OVERVIEW¶
Sepsis is life-threatening organ dysfunction from a dysregulated host response to infection. Septic shock is sepsis with profound circulatory, cellular, and metabolic abnormalities. Sepsis-3 redefined sepsis as meeting SOFA score ≥ 2 with infection, abandoning SIRS criteria.
1.1 Sepsis and Septic Shock Definitions¶
Sepsis: Life-threatening organ dysfunction from a dysregulated host response to infection. Septic shock: Sepsis with profound circulatory, cellular, and metabolic abnormalities increasing mortality risk beyond sepsis alone.
1.2 Historical Context¶
Originally termed 'severe sepsis' in 1992, redefined in 2016 as sepsis with hypotension unresponsive to fluid resuscitation. SIRS criteria were abandoned in Sepsis-3 due to poor specificity for sepsis.
2. EPIDEMIOLOGY¶
Global sepsis incidence: 48.9 million cases/year (1.7 million in U.S.). Mortality: 11 million globally/year (85% in low/middle-income countries). U.S. mortality: 15% for sepsis, 40% for septic shock. Incidence in hospitalized adults: ~6% (stable over time).
2.1 Incidence and Mortality¶
Global sepsis incidence: 48.9 million/year (1.7 million in U.S.). Mortality: 11 million globally/year (85% in low/middle-income countries). U.S. mortality: 15% for sepsis, 4,000,000 sepsis deaths/year.
2.2 Risk Factors¶
Age ≥ 65 years, male sex, comorbidities (diabetes, obesity, renal/hepatic insufficiency, cancer), recent hospitalization, and immunosuppression increase risk.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Sepsis arises from bacterial, viral, fungal, or parasitic infections. Pathogenesis involves immune activation, endothelial dysfunction, coagulopathy, and organ failure. Key mechanisms include cytokine storm, NET formation, and microvascular thrombosis.
3.1 Pathogens and Sites¶
88% community-onset (detected within 48h of hospitalization), 12% hospital-onset. Common sites: urinary tract (48.9%), respiratory tract (32.9%), intraabdominal (13.6%), skin (10.3%).
3.2 Immune and Coagulation Pathways¶
PAMPs/DAMPs activate PRRs, triggering cytokine release. Endothelial activation leads to microvascular thrombosis, disseminated intravascular coagulation (DIC), and organ hypoperfusion.
4. CLINICAL FEATURES¶
Nonspecific signs: fever, tachycardia, altered mental status. Organ-specific manifestations include ARDS, AKI, hepatic dysfunction, and coagulopathy. Neurologic complications: sepsis-associated encephalopathy in 54% of patients.
4.1 Systemic Manifestations¶
Fever, tachycardia, tachypnea, hypotension, altered mental status, and organ dysfunction (e.g., oliguria, respiratory distress).
4.2 Organ-Specific Complications¶
ARDS (7%), AKI (67%), hepatic dysfunction (50%), coagulopathy (35%), and neurologic encephalopathy (54%).
5. DIFFERENTIAL DIAGNOSIS¶
Sepsis mimics include noninfectious causes: heart failure, pulmonary embolism, connective tissue disease, and noninfectious abdominal syndromes. 25% of ICU sepsis patients have mimics (e.g., cardiovascular or respiratory causes).
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnostic criteria: qSOFA score ( ≥ 2) for sepsis, SOFA score ≥ 2 with infection for sepsis. Investigations include CBC, lactate, blood cultures, imaging, and microbiologic testing. qSOFA is more specific than SIRS for end-organ dysfunction.
6.1 Diagnostic Criteria¶
qSOFA score ( ≥ 2): respiratory rate ≥ 22, SBP ≤ 100 mmHg, or GCS ≤ 15. SOFA score ≥ 2 with infection indicates sepsis.
6.2 Laboratory and Imaging¶
CBC, lactate, blood cultures, urinalysis, chest/abdominal imaging. Point-of-care testing for pathogens.
7. MANAGEMENT & TREATMENT¶
Early antibiotics (within 1 hour of shock recognition), fluid resuscitation (30 mL/kg crystalloid), vasopressors (norepinephrine), source control, and ICU admission within 6 hours. Antibiotic selection based on infection site and resistance patterns.
Table 315-1: Site-Specific Empiric Antibiotic Recommendations¶
| SITE OF INFECTION | INITIAL EMPIRIC THERAPY | OTHER CONSIDERATIONS |
|---|---|---|
| Pulmonary (CAP) | Multidrug therapy with b-lactam + macrolide or fluoroquinolone | Add vancomycin/linezolid for MRSA risk |
| Pulmonary (HAP/VAP) | Vancomycin + antipseudomonal agents (piperacillin-tazobactam, ceftazidime, etc.) | Consider carbapenems for resistant organisms |
| Central Nervous System (Meningitis) | Vancomycin + ceftriaxone | Add ampicillin for >50 years or immunocompromised |
| Skin and Soft Tissue (Necrotizing Fasciitis) | Vancomycin + piperacillin-tazobactam/carbapenem | Surgical consultation required |
| Intraabdominal (Severe) | Imipenem-cilastatin + metronidazole | Consider carbapenems for ESBL-resistant organisms |
| Genitourinary (Pyelonephritis) | Ceftriaxone + trimethoprim-sulfamethoxazole | Avoid fluoroquinolones in high-resistance areas |
7.1 Initial Management¶
IV access, fluid resuscitation (30 mL/kg), vasopressors, source control, and ICU admission within 6 hours. Empiric antibiotics within 1 hour of shock recognition.
7.2 Antibiotic Therapy¶
Site-specific empiric regimens (Table 315-1). Broad-spectrum coverage for gram-negative and MRSA. Avoid unnecessary antifungals unless risk factors are present.
8. PROGNOSIS & COMPLICATIONS¶
Mortality: 15% for sepsis, 40% for septic shock. Long-term sequelae include chronic kidney disease, cognitive impairment, and organ dysfunction. Complications include ARDS, AKI, DIC, and multiorgan failure.
8.1 Mortality Rates¶
15% mortality for sepsis, 40% for septic shock. 25% of ICU sepsis patients have sepsis mimics (e.g., heart failure, respiratory disease).
8.2 Long-Term Outcomes¶
Chronic kidney disease, cognitive impairment, and organ dysfunction in survivors. Neurologic sequelae include delirium, seizures, and coma.
9. SPECIAL CONSIDERATIONS¶
Pregnancy: Risk of maternal and fetal mortality; sepsis in pregnancy is associated with higher mortality. Pediatrics: Higher mortality due to underdeveloped immune systems. Elderly: Increased risk due to comorbidities and frailty.
9.1 Pregnancy¶
Sepsis in pregnancy has higher maternal and fetal mortality. Risk factors include preterm labor and placental infection.
9.2 Pediatrics¶
Children have higher mortality due to underdeveloped immune systems and limited clinical presentation.
10. KEY POINTS & CLINICAL PEARLS¶
Early recognition with qSOFA, prompt antibiotics (within 1 hour of shock), fluid resuscitation (30 mL/kg), and source control are critical. Avoid overuse of broad-spectrum antibiotics. Monitor for coagulopathy and renal function.