Sepsis & Septic Shock

A dysregulated host response to infection that produces life-threatening organ dysfunction. The Sepsis-3 framework (2016) abandoned the old "SIRS-based sepsis/severe sepsis" terminology and reframed sepsis around organ dysfunction (SOFA score) and septic shock around vasopressor-dependent hypotension plus hyperlactataemia. This is a perennial high-yield NEET PG topic spanning definitions, the qSOFA screen, the Surviving Sepsis Campaign 1-hour bundle, and vasopressor pharmacology.

Definitions & classification (Sepsis-3, 2016)

The defining shift: sepsis is no longer "infection + SIRS". SIRS criteria were too sensitive and non-specific (a patient with a simple flu meets them). Sepsis-3 anchors the diagnosis to demonstrable organ dysfunction.

Term	Sepsis-3 definition
Infection	Invasion of normally sterile tissue by organisms
Sepsis	Life-threatening organ dysfunction caused by a dysregulated host response to infection = suspected/confirmed infection + acute rise in SOFA score ≥ 2 points
Septic shock	Subset of sepsis with circulatory + cellular/metabolic abnormality profound enough to substantially increase mortality. Clinically = sepsis + vasopressor requirement to keep MAP ≥ 65 mmHg AND serum lactate > 2 mmol/L (>18 mg/dL) despite adequate fluid resuscitation

High-yield: Septic shock (Sepsis-3) requires BOTH a vasopressor need (MAP ≥ 65) and lactate > 2 mmol/L after fluids. In-hospital mortality of septic shock exceeds 40%, versus ~10% for sepsis.

Terms abolished in Sepsis-3: "Severe sepsis" (now redundant — all sepsis implies organ dysfunction) and SIRS as a defining criterion.

SIRS criteria (historical / still asked)

Despite being demoted, SIRS is still examined as a "two of four" screen:

1. Temperature > 38°C or < 36°C
2. Heart rate > 90/min
3. Respiratory rate > 20/min or PaCO₂ < 32 mmHg
4. WBC > 12,000 or < 4,000/µL or > 10% immature bands (left shift)

High-yield: SIRS = ≥ 2 of 4. It is now considered too non-specific to define sepsis but remains a useful bedside alert.

qSOFA — the bedside screen

qSOFA (quick SOFA) is a rapid bedside screening tool (no labs needed) to flag patients at risk of poor outcome outside the ICU. It is NOT a diagnostic criterion for sepsis — a common MCQ trap.

qSOFA criterion	Cut-off
Respiratory rate	≥ 22/min
Altered mentation	GCS < 15
Systolic BP	≤ 100 mmHg

Mnemonic: "qSOFA = RAS" (Respiration, Altered sensorium, Systolic BP). Score ≥ 2 identifies high risk and should prompt full assessment and SOFA scoring.

High-yield: qSOFA ≥ 2 → escalate. But the 2021 Surviving Sepsis Campaign recommends AGAINST using qSOFA as the SOLE screening tool — it lacks sensitivity. NEWS/MEWS or SIRS may screen earlier; qSOFA is more prognostic than diagnostic.

SOFA score — the organ-dysfunction engine

SOFA = Sequential (Sepsis-related) Organ Failure Assessment. It scores 0–4 across six organ systems; a rise of ≥ 2 points from baseline (assume baseline 0 if unknown) defines organ dysfunction in sepsis.

System	Marker assessed
Respiration	PaO₂/FiO₂ ratio
Coagulation	Platelet count
Liver	Bilirubin
Cardiovascular	MAP / vasopressor dose
CNS	Glasgow Coma Scale
Renal	Creatinine / urine output

Mnemonic for the six systems: "Reasonable Care Leads to Careful Recovery" — Respiration, Coagulation, Liver, Cardiovascular, CNS, Renal.

High-yield: A new SOFA rise ≥ 2 carries ~10% in-hospital mortality in suspected infection. SOFA needs labs (so it is ICU-oriented); qSOFA needs none (bedside).

Etiology & microbiology

• Most common sources: respiratory (pneumonia, ~most frequent), then abdominal, genitourinary, and skin/soft tissue/line-related.
• Organisms: Gram-positive (Staph aureus, Streptococcus pneumoniae) now rival or slightly exceed Gram-negatives in many series. Gram-negatives (E. coli, Klebsiella, Pseudomonas) remain major in urinary/abdominal sources. Fungi (Candida) rising in ICU.
• High-risk hosts: extremes of age, diabetes, malignancy, immunosuppression, indwelling devices, recent surgery, cirrhosis, asplenia.

Pathophysiology — the dysregulated response

The hallmark is maladaptive, simultaneous pro- and anti-inflammatory activation:

1. PAMPs/DAMPs (e.g., LPS endotoxin) engage Toll-like receptors → NF-κB activation.
2. Cytokine storm: TNF-α, IL-1, IL-6 drive fever, capillary leak, and vasodilation.
3. Nitric oxide (iNOS) surge → profound vasodilation and vasopressor resistance → distributive shock.
4. Endothelial injury & glycocalyx degradation → capillary leak, third-spacing, relative hypovolaemia.
5. Coagulation activation via tissue factor → microthrombi → DIC; consumption of platelets and clotting factors.
6. Mitochondrial dysfunction / cytopathic hypoxia → cells cannot use oxygen even when delivered → lactate rises (also from anaerobic glycolysis and impaired clearance).

Haemodynamic phenotype: warm shock early — high cardiac output, low SVR, warm extremities, bounding pulses, wide pulse pressure. Progresses to cold shock (low output, vasoconstricted, mottled) as myocardial depression supervenes.

High-yield: Septic shock is the classic example of distributive (vasodilatory) shock — low SVR, high/normal cardiac output, warm peripheries early. Lactate rises from both tissue hypoperfusion and mitochondrial/cytopathic dysfunction, not hypoxia alone.

Clinical features

• Fever or hypothermia, rigors, tachycardia, tachypnoea.
• Altered mental status (often the earliest sign in the elderly).
• Hypotension; warm flushed skin early, mottled cold extremities late.
• Oliguria, raised creatinine (acute kidney injury).
• Signs of source: consolidation, peritonitis, dysuria/loin pain, cellulitis, line-site erythema.
• Petechiae/purpura suggest meningococcaemia or DIC.

Diagnosis & investigations

Investigation of choice for the source: two sets of blood cultures BEFORE antibiotics (do not delay antibiotics > 45 min for cultures), plus site-specific cultures (urine, sputum, CSF, wound, line tips).

Investigation	Purpose / finding
Serum lactate	Tissue hypoperfusion marker; > 2 = part of septic shock; > 4 = severe — guides resuscitation
Blood cultures ×2	Identify organism + sensitivity; before antibiotics
CBC	Leukocytosis/leukopenia, left shift, thrombocytopenia (DIC)
Procalcitonin	Adjunct — supports bacterial infection; used to de-escalate/stop antibiotics, not to start them
CRP	Non-specific inflammation marker
Coagulation (PT/aPTT, fibrinogen, D-dimer)	DIC screen
ABG	Metabolic (lactic) acidosis, P/F ratio for ARDS
RFT, LFT, electrolytes	Organ dysfunction (SOFA)
Imaging	Source localisation (CXR, USG abdomen, CT)

High-yield: Lactate is the key resuscitation/prognosis biomarker. Procalcitonin does NOT initiate antibiotics — its evidence-based role is to guide stopping/de-escalation. Persistently elevated or rising lactate after resuscitation predicts mortality; lactate clearance is a recognised target.

Management — Surviving Sepsis Campaign (SSC) bundles

The "Hour-1 Bundle" (begin immediately on recognition)

The 2018 SSC collapsed the old 3-hour and 6-hour bundles into a single 1-hour bundle to start at the moment of recognition (time zero = triage/earliest chart documentation):

Flow (Hour-1): Measure lactate → Obtain blood cultures before antibiotics → Give broad-spectrum antibiotics → Begin 30 mL/kg crystalloid for hypotension or lactate ≥ 4 → Start vasopressors if hypotensive during/after fluids to keep MAP ≥ 65 → Remeasure lactate if initially elevated.

Mnemonic for the bundle: "BUFALO" — Blood cultures, Urine output (monitor), Fluids, Antibiotics, Lactate, Oxygen.

Bundle element	Specifics
1. Measure lactate	Repeat within 2–4 h if > 2 mmol/L; target normalisation
2. Blood cultures	×2 sets before antibiotics (don't delay antibiotics)
3. Antibiotics	Broad-spectrum IV; ideally within 1 h. For shock: within 1 h is a strong recommendation
4. IV fluids	30 mL/kg balanced crystalloid within first 3 h for hypotension/lactate ≥ 4
5. Vasopressors	If MAP < 65 during/after fluids — noradrenaline first
6. Reassess	Dynamic measures (passive leg raise, pulse-pressure variation, capillary refill), repeat lactate

High-yield: Initial fluid = 30 mL/kg crystalloid within 3 hours. Resuscitation target MAP ≥ 65 mmHg. SSC 2021 recommends balanced crystalloids (Ringer lactate/Plasma-Lyte) over 0.9% saline, and against starches (HES) and against routine albumin first-line (albumin reserved for large-volume requirements).

Drug of choice — vasopressors

Agent	Role	Mechanism
Noradrenaline (norepinephrine)	First-line vasopressor	Potent α₁ (vasoconstriction) + modest β₁
Vasopressin (up to 0.03 U/min)	Add-on to raise MAP / reduce noradrenaline dose	V1 receptor vasoconstriction
Adrenaline (epinephrine)	Second add-on if target not met	α + β agonist
Dobutamine	Add if myocardial dysfunction / persistent hypoperfusion despite adequate volume + MAP	β₁ inotrope
Dopamine	Reserved; only in highly selected (bradycardic, low arrhythmia risk) — more arrhythmias	dose-dependent

High-yield: Noradrenaline is the first-choice vasopressor in septic shock. Add vasopressin second (catecholamine-sparing). Dopamine is discouraged (arrhythmogenic, no mortality benefit). Add dobutamine when there is persistent hypoperfusion with cardiac dysfunction. If hypotension is severe/refractory, vasopressors may be started peripherally and even before fluid loading is complete.

Source control

Source control = physical removal/drainage of the infectious focus. Identify and address ASAP (ideally within 6–12 hours): drain abscesses, remove infected lines/catheters/implants, debride necrotic tissue, relieve obstructed urinary/biliary systems, resect/repair perforated viscus.

High-yield: Antibiotics + fluids without source control fail. An undrained abscess or infected line keeps seeding the blood regardless of antibiotic adequacy.

Adjuncts

• Corticosteroids: IV hydrocortisone 200 mg/day only in refractory septic shock (ongoing pressor requirement). Not for sepsis without shock.
• Glucose: insulin to target ≤ 180 mg/dL (avoid tight control < 110 — hypoglycaemia risk).
• Transfusion: restrictive threshold — transfuse PRBC when Hb < 7 g/dL (haemoglobin target 7–9).
• Lung-protective ventilation if ARDS: tidal volume 6 mL/kg predicted body weight, plateau pressure < 30.
• VTE prophylaxis, stress-ulcer prophylaxis, early enteral nutrition.
• Activated protein C (drotrecogin alfa) — WITHDRAWN (no benefit, bleeding risk). Common MCQ distractor.

Complications

• Multi-organ dysfunction syndrome (MODS) — leading cause of death.
• Acute kidney injury (acute tubular necrosis) requiring renal replacement.
• ARDS (acute respiratory distress syndrome).
• Disseminated intravascular coagulation (DIC) — bleeding + microthrombi.
• Septic cardiomyopathy (reversible LV depression).
• Critical illness polyneuropathy/myopathy.
• Adrenal insufficiency / critical illness-related corticosteroid insufficiency.
• Waterhouse–Friderichsen syndrome — bilateral adrenal haemorrhage, classically with meningococcaemia (also other organisms).
• Stress hyperglycaemia, GI stress ulceration, secondary/nosocomial infection.

Key differentials

Condition	Distinguishing pointer
Cardiogenic shock	Cold, clammy, raised JVP, pulmonary oedema; low cardiac output, high SVR
Hypovolaemic/haemorrhagic shock	History of fluid/blood loss; low CVP, no infective focus
Anaphylaxis	Acute exposure, urticaria, bronchospasm, angioedema; treat with adrenaline IM
Neurogenic shock	Spinal injury; hypotension WITH bradycardia, warm dry skin
Adrenal (Addisonian) crisis	Hyponatraemia, hyperkalaemia, pigmentation; responds to steroids
Pancreatitis / severe burns	SIRS without true infection — non-infective inflammation
Thyroid storm / DKA	Metabolic derangement mimicking sepsis
Pulmonary embolism	Obstructive shock — raised JVP, clear lungs, RV strain on ECG

High-yield: Septic = warm, vasodilated, high-output, low SVR distributive shock. Cardiogenic/hypovolaemic/obstructive = cold, low-output, high SVR. This haemodynamic split is a classic single-best-answer discriminator.

Recently asked / exam angle

• "Septic shock definition (Sepsis-3)?" → vasopressor need for MAP ≥ 65 + lactate > 2 mmol/L after adequate fluids.
• "Initial fluid bolus in septic shock?" → 30 mL/kg balanced crystalloid within 3 hours.
• "First-line vasopressor?" → Noradrenaline. Second add-on → vasopressin. Avoid dopamine.
• "Target MAP?" → ≥ 65 mmHg.
• "qSOFA components?" → RR ≥ 22, altered mentation (GCS < 15), SBP ≤ 100; score ≥ 2 = high risk; not diagnostic.
• "SOFA systems / a rise of how many points?" → six systems; rise ≥ 2.
• "Which biomarker guides stopping antibiotics?" → Procalcitonin.
• "Best resuscitation/prognosis marker?" → Lactate (and lactate clearance).
• "Steroid in sepsis?" → Hydrocortisone 200 mg/day only in refractory shock.
• "Withdrawn sepsis drug?" → Activated protein C (drotrecogin alfa).
• "Type of shock in sepsis?" → Distributive (vasodilatory).
• "Waterhouse–Friderichsen association?" → Meningococcaemia → bilateral adrenal haemorrhage.
• "Transfusion threshold?" → Hb < 7 g/dL (restrictive).
• Statement/assertion-reason items often pair "SIRS defines sepsis" (FALSE post-Sepsis-3) with organ-dysfunction reasoning.

Rapid revision

1. Sepsis = infection + SOFA rise ≥ 2 (life-threatening organ dysfunction from a dysregulated host response).
2. Septic shock = sepsis + vasopressor need (MAP ≥ 65) + lactate > 2 mmol/L despite fluids; mortality > 40%.
3. qSOFA = RR ≥ 22, altered mentation, SBP ≤ 100 — bedside screen (≥ 2), not diagnostic; SSC advises against using it alone.
4. SOFA = 6 systems (Respiration, Coagulation, Liver, Cardiovascular, CNS, Renal); needs labs.
5. Hour-1 bundle (BUFALO): lactate, cultures before antibiotics, broad-spectrum antibiotics, 30 mL/kg crystalloid, vasopressors for MAP ≥ 65, recheck lactate.
6. Balanced crystalloids preferred over normal saline; avoid HES/starches.
7. Noradrenaline = first-line vasopressor; add vasopressin, then adrenaline; dobutamine for myocardial dysfunction; avoid dopamine.
8. Lactate is the resuscitation/prognosis marker; procalcitonin guides stopping antibiotics, not starting.
9. Source control within 6–12 h is mandatory — drain, remove lines, debride.
10. Hydrocortisone 200 mg/day only in refractory septic shock; transfuse at Hb < 7.
11. Septic shock is distributive — warm, high-output, low SVR early; cold/low-output late.
12. Activated protein C is withdrawn; Waterhouse–Friderichsen = meningococcaemia + adrenal haemorrhage.