SHOCK

Definition

Classification / Types of Shock

1. Hypovolemic Shock

• Cause: Reduction in circulating blood or plasma volume
• Examples: Hemorrhage, severe burns, vomiting, diarrhea, dehydration, trauma
• Mechanism: Reduced venous return → decreased cardiac output (CO) → tissue hypoperfusion
• Most studied form; hemorrhagic shock has been known since battlefield medicine of the 18th century

2. Cardiogenic Shock

• Cause: Failure of the cardiac pump
• Examples: Myocardial infarction (most common), ventricular arrhythmias, cardiac tamponade, pulmonary embolism, ventricular rupture
• Mechanism: Intrinsic myocardial damage or extrinsic compression/outflow obstruction → low CO → hypoperfusion
• Prognosis is poor; mortality remains high

3. Septic Shock

• Cause: Overwhelming microbial infections (gram-positive bacteria most common, then gram-negative, then fungi)
• Mechanism: Dysregulated host immune response → massive inflammatory mediator release (TNF, IL-1, IL-6, NO) → peripheral vasodilation, endothelial activation, vascular leakage, DIC → tissue hypoperfusion
• Defined as sepsis + hemodynamic compromise despite adequate fluid resuscitation
• US incidence exceeds 750,000 cases/year; mortality 20-40%

4. Neurogenic / Distributive Shock

• Cause: Spinal cord injury, spinal anesthesia, anaphylaxis (IgE-mediated)
• Mechanism: Loss of sympathetic vasomotor tone → acute vasodilation → hypotension and tissue hypoperfusion
• In anaphylactic shock: IgE-mediated release of histamine and other mediators causes systemic vasodilation + increased vascular permeability

Pathophysiology

General Mechanism

1. Trigger (hemorrhage, MI, sepsis, etc.) → ↓ cardiac output or ↓ effective circulating volume
2. ↓ Arterial blood pressure → detected by baroreceptors
3. Sympathetic activation (main compensatory response):
   • Arteriolar constriction → ↑ total peripheral resistance (TPR)
   • Venous constriction → maintains venous return
   • ↑ Heart rate (up to 160-180 bpm) and contractility
4. Neurohormonal responses: release of epinephrine, norepinephrine, ADH (vasopressin), RAAS activation → Na+ and water retention
5. If uncorrected: progressive cellular hypoxia → anaerobic metabolism → lactic acidosis → organ failure

Septic Shock - Additional Mechanisms

• Toll-like receptors (TLRs) - recognizing PAMPs
• G-protein coupled receptors - detecting bacterial peptides
• C-type lectin receptors - recognizing fungal cell wall components

Stages of Shock

Morphological / Organ Changes in Shock (Pathology)

• Brain: Hypoxic encephalopathy, ischemic neuronal injury
• Heart: Subendocardial hemorrhage/necrosis (contraction band necrosis); ischemic changes
• Kidneys: Acute tubular necrosis (ATN) - most common; "shock kidney" with pale cortex; ischemic injury to proximal tubule and thick ascending limb
• Lungs: Diffuse alveolar damage → Adult Respiratory Distress Syndrome (ARDS) - "shock lung"
• GI Tract: Mucosal ulceration (stress ulcers - "stress gastritis"), ischemic colitis
• Liver: Centrilobular necrosis (zone 3) - most vulnerable to ischemia; fatty change
• Adrenals: Lipid depletion (adrenal medulla activation)

Clinical Features

Treatment of Shock

A. General / Non-specific Measures (Basic Life Support)

1. Airway and breathing - ensure oxygenation (high-flow O2, intubation if needed)
2. IV access and hemodynamic monitoring - central venous pressure, arterial line
3. Fluid resuscitation - crystalloids (normal saline, Ringer's lactate) or colloids; blood transfusion in hemorrhagic shock
4. Treat the underlying cause - antibiotics for sepsis, revascularization for MI, surgery for bleeding, epinephrine for anaphylaxis

B. Pharmacological Treatment (Vasoactive/Inotropic Drugs)

1. Dopamine (DA)

• Mechanism: Acts on DA1, beta-1, and (at high doses) alpha-1 receptors
• Dose-dependent effects:
  • Low dose (1-5 mcg/kg/min): DA1 agonism → renal and splanchnic vasodilation → increased urine output (renoprotective)
  • Moderate dose (5-10 mcg/kg/min): Beta-1 → positive inotropic effect, increased CO
  • High dose (>10-20 mcg/kg/min): Alpha-1 → peripheral and renal vasoconstriction
• Use: Cardiogenic and septic shock; preserves renal function
• Causes less increase in heart rate than isoprenaline; preferred inotrope

2. Dobutamine

• Mechanism: Primarily beta-1 agonist (also partial beta-2 and alpha effects from stereoisomers)
• Effect: Increases myocardial contractility and cardiac output with minimal increase in heart rate or peripheral resistance
• Use: Cardiogenic shock; when increased contractility is needed without excessive tachycardia
• Preferred when DO2 (oxygen delivery) needs optimization without elevating BP too much

3. Norepinephrine (NE)

• Mechanism: Predominantly alpha-1 agonist; some beta-1 activity
• Effect: Potent vasoconstriction → increased TPR and BP; also modest increase in contractility
• Use: Septic shock (first-line vasopressor per Surviving Sepsis Campaign); neurogenic shock
• Caution: Can intensify peripheral vasoconstriction → organ ischemia (kidneys, gut)

4. Epinephrine (EPI)

• Mechanism: Agonist at alpha-1, beta-1, and beta-2 receptors
• Effects: Increases heart rate, force of contraction, BP; bronchodilation (beta-2)
• Use:
  • Anaphylactic shock - drug of choice (IM 0.5 mg, 1:1000 solution)
  • Septic shock refractory to NE
• Caution: Can predispose to dangerous arrhythmias; increases myocardial O2 demand

5. Vasopressin (ADH)

• Mechanism: V1 receptor agonist → direct vasoconstriction (independent of adrenergic system)
• Use: Septic shock refractory to catecholamines; as adjunct to NE to reduce catecholamine dose
• Low-dose vasopressin (0.03-0.04 units/min) is commonly added in refractory septic shock

6. Phenylephrine

• Mechanism: Pure alpha-1 agonist
• Effect: Peripheral vasoconstriction, increased BP, reflex bradycardia
• Use: Neurogenic shock, vasodilatory shock; spinal anesthesia-induced hypotension

7. Isoprenaline (INE)

• Mechanism: Non-selective beta agonist (beta-1 + beta-2)
• Effect: Powerful chronotropic and inotropic agent; lowers TPR (beta-2 vasodilation)
• Use: Cardiogenic shock with bradycardia; rarely used because it greatly increases myocardial O2 demand

8. Corticosteroids

• Use: Refractory septic shock (relative adrenal insufficiency)
• Drug: Hydrocortisone 200-300 mg/day IV in divided doses
• Mechanism: restores vascular responsiveness to catecholamines; anti-inflammatory

9. Vasodilators (e.g., Nitroprusside)

• Use: Cardiogenic shock - where reflex vasoconstriction is already intense
• Rationale: Decreasing afterload can improve cardiac output and reduce cardiac work
• Only used if minimally adequate BP can be maintained

Summary Table: Drugs in Shock

Specific Management by Type

Complications

• ARDS (Adult Respiratory Distress Syndrome) - "shock lung"
• Acute Tubular Necrosis (ATN) - "shock kidney" - leading cause of acute kidney injury
• Disseminated Intravascular Coagulation (DIC) - especially in septic shock
• MODS (Multi-Organ Dysfunction Syndrome) - the ultimate complication
• Ischemic hepatitis (shock liver)

Conclusion

• Goodman & Gilman's Pharmacological Basis of Therapeutics, Ch. 12 (Adrenergic Agonists and Antagonists)
• Robbins, Cotran & Kumar - Pathologic Basis of Disease, Ch. 4 (Hemodynamic Disorders, Shock)
• Guyton and Hall Textbook of Medical Physiology, Ch. 24 (Stages of Shock)
• Sabiston Textbook of Surgery, Ch. 6 (Shock)