Septic Shock

Definition (Sepsis-3 Criteria)

Septic shock is defined as sepsis (suspected infection + acute organ dysfunction with SOFA score increase ≥2 from baseline) plus:

(Harrison's, p. 8257)

The core mechanism is a dysregulated host response to infection leading to:

Massive cytokine release (TNF-α, IL-1, IL-6) → systemic inflammation
Vasodilation + capillary leak → distributive shock physiology (low SVR, high CO early)
Endothelial dysfunction → impaired microvascular perfusion
Mitochondrial dysfunction → cellular oxygen utilization failure despite adequate delivery
Coagulopathy → disseminated intravascular coagulation (DIC) in severe cases
Multi-organ dysfunction → renal, hepatic, pulmonary, cardiac failure

The result is tissue hypoperfusion despite often-normal or elevated cardiac output — distinguishing it from cardiogenic or hypovolemic shock.

Source	Common Pathogens
Pneumonia (most common)	S. pneumoniae, Klebsiella, Staph aureus
Urinary tract / urosepsis	E. coli, Klebsiella, Pseudomonas
Intra-abdominal	E. coli, Bacteroides, Enterococcus
Skin/soft tissue	S. aureus (MRSA), Streptococcus
Bacteremia / line-related	S. aureus, coagulase-negative Staph, gram-negatives
Fungal	Candida spp. (immunocompromised)

Hemodynamic: Hypotension, tachycardia, warm/flushed skin early (cold/clammy late)
Respiratory: Tachypnea, hypoxia (ARDS in ~30%)
Neurological: Altered mental status, confusion
Renal: Oliguria, rising creatinine
Metabolic: Elevated lactate, metabolic acidosis (high anion gap)
Skin: Mottling, purpura (meningococcemia), petechiae

No single diagnostic test — clinical diagnosis based on Sepsis-3 criteria.

Key investigations:

Blood cultures ×2 (before antibiotics if possible, do not delay >45 min)
Serum lactate (>2 mmol/L = high-risk; >4 mmol/L = severe)
CBC, CMP, coagulation studies (PT/PTT, fibrinogen, D-dimer)
Procalcitonin (supports bacterial infection; guides antibiotic de-escalation)
ABG (assess oxygenation, acid-base)
Cultures from suspected source (urine, sputum, wound)
Chest X-ray / CT as clinically indicated

Bedside SOFA / qSOFA (quick screen: RR ≥22, altered mentation, SBP ≤100 — score ≥2 prompts full evaluation)

Septic shock is a time-sensitive emergency. Management follows the Surviving Sepsis Campaign (SSC) Hour-1 Bundle:

Action	Detail
Measure lactate	Remeasure if initial >2 mmol/L
Blood cultures	Before antibiotics
Broad-spectrum antibiotics	Within 1 hour of recognition
IV fluid bolus	30 mL/kg crystalloid
Vasopressors	If hypotension persists despite fluids; target MAP ≥65 mmHg

(Harrison's, p. 8273)

30 mL/kg IV crystalloid within first 3 hours
Balanced crystalloids (e.g., lactated Ringer's) preferred over normal saline (reduces AKI/mortality)
Guide ongoing resuscitation by lactate clearance, dynamic fluid responsiveness (pulse pressure variation, straight leg raise), or focused cardiac ultrasound
Avoid hydroxyethyl starches and gelatins

Agent	Role
Norepinephrine	First-line vasopressor; target MAP ≥65 mmHg
Vasopressin	Add to reduce norepinephrine dose (up to 0.03 units/min)
Epinephrine	Second-line if MAP target not achieved
Dopamine	Avoid except in bradycardia or low tachyarrhythmia risk
Dobutamine	Add for myocardial dysfunction / low cardiac output

Administer within 1 hour of septic shock recognition
Broad-spectrum empiric coverage based on likely source and local resistance patterns
De-escalate based on culture results and clinical improvement (typically at 48–72 hours)
Procalcitonin-guided de-escalation reduces antibiotic duration

Common empiric regimens:

Source	Typical Regimen
Unknown/community	Pip-tazo or carbapenems ± vancomycin (if MRSA risk)
Pneumonia (CAP)	β-lactam + macrolide or fluoroquinolone
Urosepsis	Ceftriaxone or fluoroquinolone (adjust for local resistance)
Intra-abdominal	Pip-tazo or carbapenem
MRSA/line infection	Add vancomycin or daptomycin
Candida risk	Add echinocandin (anidulafungin/micafungin)

Identify and control the infectious source within 6–12 hours: drain abscess, remove infected catheter/device, debride necrotic tissue

Hydrocortisone 200 mg/day (continuous infusion or 50 mg q6h) for refractory septic shock (MAP not maintained despite adequate fluids + vasopressors)
Reduces vasopressor duration; no clear mortality benefit in unselected patients
Consider fludrocortisone 50 mcg/day if using hydrocortisone (APROCCHSS trial)

Lung-protective ventilation: tidal volume 6 mL/kg IBW, plateau pressure <30 cmH₂O
FiO₂ titration to SpO₂ 92–96%
Prone positioning for P/F ratio <150

Intervention	Target/Detail
Glucose control	140–180 mg/dL (avoid hypoglycemia)
DVT prophylaxis	LMWH preferred
Stress ulcer prophylaxis	PPI or H2 blocker in high-risk patients
Renal replacement therapy	For refractory AKI, acidosis, or fluid overload
Blood transfusion	Hgb <7 g/dL (restrictive strategy); <9 g/dL with active MI/severe hypoxia
Nutrition	Early enteral nutrition if hemodynamically stable

Key Sources: Harrison's Principles of Internal Medicine, 21st Ed. (pp. 8257, 8273); Surviving Sepsis Campaign International Guidelines 2021

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