Infectious Disease · PANCE / PANRE

Sepsis and Septic Shock

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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Risk factors

  • Extremes of age, immunocompromise (chemotherapy, transplant, HIV, asplenia)
  • Chronic illness (diabetes, cirrhosis, CKD, COPD, heart failure)
  • Indwelling devices (central lines, urinary catheters, prosthetic joints)
  • Recent surgery, trauma, burns
  • Healthcare exposure (MRSA, VRE, MDR gram-negatives)

Pathophysiology

Pathogen-associated molecular patterns (PAMPs) trigger massive innate immune activation via toll-like receptors, releasing inflammatory cytokines (TNF, IL-1, IL-6). Endothelial dysfunction increases capillary leak; nitric oxide drives vasodilation; coagulation activation produces microthrombi (DIC). Result: distributive shock with maldistributed blood flow, mitochondrial dysfunction, and multi-organ failure. Late phase involves immunoparalysis and secondary infections.

Clinical presentation

Symptoms

  • Source-specific: cough/dyspnea (pneumonia), dysuria/flank pain (urosepsis), abdominal pain (intra-abdominal), headache/neck stiffness (meningitis), skin erythema (SSTI)
  • Generalized: fever or hypothermia, chills, malaise, altered mental status
  • Decreased urine output, lightheadedness, syncope

Signs / physical exam

  • Tachycardia, tachypnea, hypotension, fever or hypothermia
  • Altered mentation (often subtle in elderly)
  • Warm, flushed extremities early (vasodilated 'warm shock'); cool, mottled extremities late
  • Capillary refill >3 sec, oliguria
  • Source-specific findings: dullness/crackles, costovertebral angle tenderness, peritoneal signs, indurated cellulitis, purpuric rash

Classic findings

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.

Differential diagnosis

  • Hypovolemic shock — GI/hemorrhagic losses, narrow pulse pressure, cool extremities, low CVP; responds rapidly to volume
  • Cardiogenic shock — MI, severe HF, arrhythmia; elevated JVP, pulmonary edema, low cardiac output despite normal volume
  • Obstructive shock — Tamponade, tension pneumothorax, massive PE; distended neck veins with hypotension
  • Anaphylaxis — Acute trigger, urticaria, angioedema, wheezing; epinephrine first-line
  • Adrenal crisis — Hyponatremia, hyperkalemia, hypoglycemia, refractory hypotension; give hydrocortisone empirically
  • Thyroid storm — Tachycardia out of proportion, hyperthermia, agitation, AF; TSH/free T4
  • Drug overdose/withdrawal — Hypotension with specific toxidrome; targeted history and tox screen

Diagnostic workup

Diagnostic criteria

Sepsis = suspected/documented infection + SOFA increase ≥2 from baseline. Septic shock = sepsis + vasopressors needed for MAP ≥65 + lactate >2 mmol/L despite adequate resuscitation. qSOFA (screening): RR ≥22, altered mental status, SBP ≤100 — ≥2 suggests high mortality risk.

Labs

  • Serum lactate (initial and repeat at 2-4 h)
  • Blood cultures × 2 from separate sites BEFORE antibiotics (do not delay antibiotics if cultures cannot be obtained within 45 min)
  • CBC, CMP, LFTs, coagulation (PT/PTT/INR), fibrinogen, D-dimer
  • Urinalysis, urine culture
  • Source-specific cultures: sputum/respiratory tract, wound, CSF, peritoneal fluid
  • 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

Second-line / adjunct

  • Norepinephrine first-line vasopressor (target MAP ≥65)
  • Add vasopressin 0.03 U/min (sparing norepinephrine, reduces AF risk) or epinephrine if refractory
  • Hydrocortisone 200 mg/day if refractory shock despite adequate fluids and vasopressors
  • Crystalloid preferred over colloid; balanced crystalloid (lactated Ringer's, Plasma-Lyte) over normal saline (SMART trial)
  • Lung-protective ventilation (TV 6 mL/kg IBW) if ARDS develops
  • Glycemic control: target 140-180 mg/dL (avoid hypoglycemia)
  • DVT prophylaxis, stress ulcer prophylaxis

Complications

  • Multi-organ dysfunction syndrome (MODS): ARDS, AKI, hepatic dysfunction, DIC, encephalopathy
  • 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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