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. Sepsis-3 retired the term 'severe sepsis' and replaced the SIRS-based definition (≥2 of abnormal temperature, heart rate, respiratory rate, or WBC) with infection-related organ dysfunction.
Epidemiology
About 1.7 million US adults develop sepsis annually, and at least 350,000 die during hospitalization or are discharged to hospice (CDC). 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 1CardiovascularMedium
A 68-year-old man is brought to the ED with confusion and fever after three days of dysuria and flank pain. He is lethargic with temperature 39.3 C, HR 122, BP 78/44, RR 24, and SpO2 95% on room air. Exam shows warm, flushed extremities with bounding pulses and brisk capillary refill. Lungs are clear and jugular venous pressure is flat. Lactate is 4.6 mmol/L and urinalysis shows pyuria with bacteriuria. Which of the following is the most likely diagnosis?
ANeurogenic shock
BCardiogenic shock
CObstructive shock
DHypovolemic shock
ESeptic shock
Reveal answer & full explanation
Correct answer: E — Septic shock
ANeurogenic shock
BCardiogenic shock
CObstructive shock
DHypovolemic shock
ESeptic shock✓
Why Septic shock is correct
This patient has distributive (septic) shock from urosepsis, with fever, pyuria, and bacteriuria localizing the source to the urinary tract
The classic distributive profile is warm, well-perfused extremities with bounding pulses, brisk capillary refill, low systemic vascular resistance, and a wide pulse pressure
Lactic acidosis and end-organ dysfunction (confusion) confirm shock with tissue hypoperfusion
Why the others are wrong
Cardiogenic shock — Produces cool, mottled extremities, elevated JVP, pulmonary congestion, and a narrow pulse pressure from pump failure, none of which are present (confused-with cool-shock)
Hypovolemic shock — Produces cool, clamped-down extremities with delayed capillary refill following obvious volume loss such as hemorrhage or diarrhea (confused-with cool-shock)
Obstructive shock — Tamponade, tension pneumothorax, or massive PE produces elevated JVP, muffled or unilateral absent breath sounds, and impaired venous return, not warm flushed skin (anchoring)
Neurogenic shock — it is also a warm distributive shock, but loss of sympathetic tone after a cervical or high thoracic spinal cord injury typically causes hypotension with relative bradycardia; nothing here suggests spinal cord injury, and a heart rate of 122 with fever, pyuria and bacteriuria after days of dysuria and flank pain points to a urinary source of septic shock (confused-with warm-shock)
Additional high-yield points
Recognition of the warm, hyperdynamic distributive phenotype directs early fluid resuscitation, broad-spectrum antibiotics within one hour, and source control
Question 2Infectious DiseaseMedium
A 70-year-old male with pneumonia has BP 82/48 (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
BDopamine infusion
CDobutamine infusion
DIV hydrocortisone
EAdditional 30 mL/kg crystalloid
Reveal answer & full explanation
Correct answer: A — Norepinephrine infusion
ANorepinephrine infusion✓
BDopamine infusion
CDobutamine infusion
DIV hydrocortisone
EAdditional 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
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
Dopamine infusion — superseded-guideline trap; dopamine was once offered as an alternative first-line vasopressor, but compared with norepinephrine it causes more tachyarrhythmias without improving survival, so the Surviving Sepsis Campaign recommends norepinephrine as the first-line agent
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.
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 (RR ≥22, altered mental status, SBP ≤100) is a bedside prognostic prompt: ≥2 suggests high mortality risk, but the Surviving Sepsis Campaign (2021, 2026) recommends against using it as a single screening tool because of poor sensitivity — screen with SIRS, NEWS/NEWS2, or MEWS plus clinical judgment.
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)
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["Norepinephrine, target MAP ≥65<br/>(septic shock if lactate >2)"]
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 2018 bundle update; antibiotic timing per current SSC guidelines):
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 ceftriaxone + a respiratory fluoroquinolone (levofloxacin, moxifloxacin)
• Hospital-acquired 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) — alpha-1 vasoconstriction raises SVR, with modest beta-1 inotropy; dopamine is not recommended first-line (more arrhythmias)
Add vasopressin 0.03 U/min (acts on V1 vascular receptors to vasoconstrict, unlike renal V2 water reabsorption; spares 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
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 prognostic prompt, not a diagnostic criterion or a stand-alone screen (Surviving Sepsis Campaign 2021 and 2026 favor SIRS, NEWS, or MEWS for screening) — 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)
VASST 2008 — Russell JA et al., Vasopressin versus Norepinephrine Infusion in Patients with Septic Shock (N Engl J Med 2008;358:877-87)
VANISH 2016 — Gordon AC et al., Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock: The VANISH Randomized Clinical Trial (JAMA 2016;316:509-18)
SSC Bundle 2018 — Levy MM, Evans LE, Rhodes A, The Surviving Sepsis Campaign Bundle: 2018 Update (Crit Care Med 2018;46:997-1000)
Surviving Sepsis 2026 — Prescott HC, Antonelli M, et al., Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2026 (Crit Care Med 2026;54:725-812)
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