A 68-year-old woman with sepsis secondary to urosepsis presents with hypotension (SBP 78 mmHg), tachycardia (120/min), warm peripheries, and normal mental status. After fluid resuscitation (30 mL/kg crystalloid) and broad-spectrum antibiotics, BP remains 80 mmHg and lactate is 4.2 mmol/L. Which vasopressor is the drug of choice for this patient?

Explanation

## Vasopressor Choice in Septic Shock **Key Point:** Noradrenaline (levophed) is the first-line vasopressor for septic shock refractory to fluid resuscitation, as recommended by the Surviving Sepsis Campaign guidelines. ### Pathophysiology of Septic Shock Septic shock is characterized by: - Distributive shock (peripheral vasodilation due to inflammatory mediators: TNF-α, IL-1, nitric oxide) - Relative hypovolemia (third-spacing, capillary leak) - Myocardial dysfunction (cytokine-induced) - Microvascular dysfunction and impaired oxygen extraction ### Why Noradrenaline is First-Line | Agent | α-Effect | β-Effect | Mechanism | Role in Septic Shock | |-------|----------|----------|-----------|---------------------| | **Noradrenaline** | ✓✓ (strong) | ✓ (moderate) | Restores SVR + maintains CO | **First-line** | | **Dopamine** | ✓ (dose-dependent) | ✓ (dose-dependent) | Inotropy + vasoconstriction | Second-line; less predictable | | **Phenylephrine** | ✓✓✓ (pure) | ✗ | Pure vasoconstriction | Only if CO maintained; risk of reflex bradycardia | | **Dobutamine** | ✗ | ✓✓ (strong) | Inotropy + vasodilation | Contraindicated as monotherapy; worsens hypotension | **High-Yield:** Noradrenaline combines: 1. **α-adrenergic effect** → restores systemic vascular resistance (SVR) and mean arterial pressure (MAP) 2. **β₁-adrenergic effect** → maintains cardiac output and organ perfusion This dual action makes it superior to pure vasoconstrictors (phenylephrine) or pure inotropes (dobutamine) in septic shock. ### Clinical Pearl **Target MAP ≥65 mmHg** is the goal in septic shock. Noradrenaline is titrated to achieve this target while maintaining urine output and lactate clearance. **Mnemonic:** **SSCG** = Surviving Sepsis Campaign Guidelines recommend **Noradrenaline** as first-line vasopressor in septic shock (not dopamine). **Warning:** Dopamine, while once considered equivalent to noradrenaline, has a higher risk of tachyarrhythmias and is no longer recommended as first-line in septic shock per 2016 Surviving Sepsis guidelines. ### Sequencing in Septic Shock 1. **Fluid resuscitation** (30 mL/kg crystalloid in first 3 hours) 2. **Antibiotics** (within 1 hour) 3. **Noradrenaline** if SBP <90 mmHg or MAP <65 mmHg after fluids 4. **Vasopressin or epinephrine** if inadequate response to noradrenaline [cite:Harrison 21e Ch 297; Surviving Sepsis Campaign 2016]