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.
Try two board-style Sepsis and Septic Shock questions
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Question 1Infectious DiseaseMedium
A 68-year-old male presents with fever, altered mental status, and stiff neck. A non-blanching petechial rash is progressing rapidly to purpura. BP is 80/50 and he is obtunded. Blood cultures are drawn. Which of the following is the most appropriate immediate next step?
ALumbar puncture before antibiotics
BEmpiric IV acyclovir
CEmpiric IV antibiotics and dexamethasone
DCT head with contrast
Reveal answer & full explanation
Correct answer: C — Empiric IV antibiotics and dexamethasone
ALumbar puncture before antibiotics
BEmpiric IV acyclovir
CEmpiric IV antibiotics and dexamethasone✓
DCT head with contrast
Why Empiric IV antibiotics and dexamethasone is correct
Non-blanching petechial/purpuric rash with septic shock indicates Neisseria meningitidis meningococcemia — a life-threatening emergency; do not delay antibiotics for LP or CT
Give IV ceftriaxone 2 g q12h immediately plus vancomycin for MRSA and resistant pneumococcal coverage
Dexamethasone 0.15 mg/kg q6h should be given before or with the first antibiotic dose — reduces mortality and neurologic sequelae
Add IV fluids and vasopressors for septic shock; LP can follow after antibiotics if the patient stabilizes
Why the others are wrong
Lumbar puncture before antibiotics — must not delay antibiotics in suspected bacterial meningitis with septic shock (premature procedure)
Empiric IV acyclovir — is added when HSV encephalitis is suspected but never replaces or delays empiric antibacterial therapy (right-concept-wrong-pathogen)
CT head with contrast — should not delay antibiotic administration in this presentation (anchoring on imaging)
Additional high-yield points
Prior antibiotics may render cultures negative within hours, but Gram stain and antigen testing remain useful
Chemoprophylaxis for close contacts: ciprofloxacin 500 mg single dose or rifampin
Question 2Infectious DiseaseMedium
A 70-year-old male with pneumonia has BP 95/60 (baseline 130/80), respiratory rate 24, and altered mental status. Lactate is 3.2 mmol/L. Despite 30 mL/kg crystalloid resuscitation, mean arterial pressure (MAP) remains 60 mmHg. Which of the following is the most appropriate next step in management?
ANorepinephrine infusion
BDobutamine infusion
CIV hydrocortisone
DAdditional 30 mL/kg crystalloid
Reveal answer & full explanation
Correct answer: A — Norepinephrine infusion
ANorepinephrine infusion✓
BDobutamine infusion
CIV hydrocortisone
DAdditional 30 mL/kg crystalloid
Why Norepinephrine infusion is correct
This patient meets criteria for septic shock: persistent hypotension requiring vasopressors to maintain MAP >=65 mmHg plus lactate >2 mmol/L despite adequate fluid resuscitation
After the initial 30 mL/kg crystalloid fails to reach the MAP goal, a vasopressor is the appropriate next intervention
Norepinephrine is the first-line vasopressor per the Surviving Sepsis Campaign
It raises MAP predominantly through alpha-1 mediated vasoconstriction with modest inotropy, restoring perfusion pressure</parameter>
Why the others are wrong
Dobutamine infusion — right-concept-wrong-setting; dobutamine is reserved for septic cardiomyopathy with low cardiac output despite an adequate MAP, not as first-line vasopressor therapy
IV hydrocortisone — correct-drug-wrong-step; hydrocortisone is added for refractory shock requiring escalating vasopressors, not immediately after the initial fluid bolus
Additional 30 mL/kg crystalloid — anchoring on more fluid; another large bolus is not indicated once 30 mL/kg has been given without reaching the MAP goal, and it risks volume overload
Additional high-yield points
Vasopressin is a second-line add-on vasopressor in septic shock
Empiric broad-spectrum antibiotics within 1 hour and source control are also critical management priorities
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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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