Life-threatening organ dysfunction from dysregulated host response to infection; septic shock is sepsis plus pressor-requiring hypotension with lactate >2.
Also known as: sepsis, septic shock, severe sepsis, SIRS, sepsis-3
Overview
Sepsis-3 (2016): life-threatening organ dysfunction caused by a dysregulated host response to infection, operationalized as a SOFA score increase ≥2 attributable to infection. Septic shock: sepsis with persistent hypotension requiring vasopressors to maintain MAP ≥65 mmHg AND serum lactate >2 mmol/L despite adequate volume resuscitation.
Epidemiology
Estimated 1.7 million US adult sepsis cases annually with ~270,000 deaths. Leading cause of hospital mortality and the most expensive condition in US healthcare. Highest incidence in elderly and immunocompromised.
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Patient with fever, tachycardia, hypotension, and altered mental status with an identifiable infectious source — qSOFA ≥2 (RR ≥22, altered mentation, SBP ≤100) on the ward warns of high mortality risk.
Procalcitonin and CRP — may help with antibiotic stewardship and de-escalation
ABG/VBG, ScvO2 if central access
Imaging
Chest X-ray (often first), CT chest/abdomen/pelvis if source unclear
Bedside ultrasound (RUSH or FALLS protocol) for shock characterization
Echocardiography to assess cardiac function and volume status
Diagnostic algorithm
flowchart TD
A[Suspected infection<br/>+ acute organ dysfunction] --> B[Hour-1 Bundle]
B --> C[Lactate measured]
B --> D[Blood cultures<br/>before antibiotics]
B --> E[Broad-spectrum<br/>antibiotics ≤1 h]
B --> F[30 mL/kg crystalloid<br/>if hypotension or lactate ≥4]
F --> G{MAP <65 after fluids?}
G -->|Yes| H[Septic shock — norepinephrine<br/>target MAP ≥65]
H --> I{Refractory?}
I -->|Yes| J[Add vasopressin ± hydrocortisone]
G -->|No| K[Sepsis without shock<br/>continue source control, narrow Abx]
Surviving Sepsis Campaign Hour-1 Bundle and escalation pathway for septic shock.
Treatment
First-line
Hour-1 bundle (Surviving Sepsis Campaign 2021):
1. Measure lactate; remeasure if initial >2
2. Obtain blood cultures before antibiotics
3. Administer broad-spectrum antibiotics within 1 hour (within 3 hours for sepsis without shock if diagnosis uncertain)
4. Begin 30 mL/kg crystalloid IV for hypotension or lactate ≥4 mmol/L (within 3 hours)
5. Vasopressors to maintain MAP ≥65 if hypotensive during/after fluids
Empiric antibiotics — broad-spectrum guided by suspected source:
• Community pneumonia: ceftriaxone + azithromycin or respiratory fluoroquinolone (levofloxacin, moxifloxacin)
• Healthcare-associated pneumonia/VAP: cefepime or piperacillin-tazobactam + vancomycin
• Intra-abdominal: piperacillin-tazobactam or meropenem; add vancomycin if MRSA risk
• Urosepsis: ceftriaxone (community) or piperacillin-tazobactam (catheter/healthcare)
• Skin/soft tissue with concern for MRSA: vancomycin, linezolid, or daptomycin
• Febrile neutropenia: cefepime, meropenem, or piperacillin-tazobactam; add vancomycin if line, hypotension, or MRSA risk
Source control: drain abscess, remove infected line/catheter, debride necrotizing infection — as soon as feasible
Post-sepsis syndrome: long-term cognitive impairment, ICU-acquired weakness, increased mortality for years
Secondary infections (line sepsis, VAP, C. difficile)
Sepsis-induced cardiomyopathy
Ischemic complications: digital gangrene, bowel ischemia
PANCE pearls
Antibiotic delay matters: each hour of delay increases mortality ~7% (Kumar Crit Care Med 2006).
Lactate is a marker of tissue hypoperfusion AND adrenergic stress — trend it, but use a serial decrease as a resuscitation target.
Balanced crystalloids over 0.9% saline reduce major adverse kidney events (SMART trial).
qSOFA is a screening tool, not a diagnostic standard — do not delay treatment in a sick-looking patient who falls short of qSOFA criteria.
Source control is sometimes more important than antibiotics: drain pus, remove the line, debride the wound.
References
Surviving Sepsis 2021 — Evans et al., Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021 (Crit Care Med 2021)
Sepsis-3 — Singer et al., The Third International Consensus Definitions for Sepsis and Septic Shock (JAMA 2016)
SMART Trial — Semler et al., Balanced Crystalloids versus Saline in Critically Ill Adults (NEJM 2018)
VANISH/VASST — Vasopressin trials informing modern shock management
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