## Clinical Context In refractory septic shock unresponsive to noradrenaline (first-line vasopressor), the next agent of choice is **epinephrine**, which combines both α and β-adrenergic effects. ## Why Epinephrine is Preferred **Key Point:** Epinephrine is the second-line vasopressor in septic shock when noradrenaline fails, as per Surviving Sepsis Campaign guidelines. | Feature | Epinephrine | Dopamine | Phenylephrine | Isoproterenol | |---------|-------------|----------|---------------|---------------| | α-effect | Strong | Dose-dependent | Very strong | Weak/None | | β1-effect | Strong | Moderate | None | Very strong | | β2-effect | Moderate | Weak | None | Very strong | | Inotropy | Excellent | Moderate | None | Excellent | | Vasodilation | Moderate | Dose-dependent | None | Marked | | Tachycardia | Marked | Moderate | Minimal | Severe | | **Use in sepsis** | **2nd-line** | **3rd-line** | **Avoid** | **Contraindicated** | ## Mechanism of Action in Septic Shock 1. **α-adrenergic effect** → Vasoconstriction → ↑ SVR and BP 2. **β1-adrenergic effect** → ↑ Contractility and CO → Improved tissue perfusion 3. **β2-adrenergic effect** → Mild vasodilation in skeletal muscle **High-Yield:** Epinephrine restores both perfusion pressure (via α-effect) and cardiac output (via β1-effect), making it superior to pure α-agonists in sepsis. ## Dosing in Septic Shock - Start: 0.05–0.1 mcg/kg/min IV infusion - Titrate to target MAP ≥65 mmHg - Maximum: 0.5–1.0 mcg/kg/min **Clinical Pearl:** Epinephrine may cause tachycardia and arrhythmias; monitor ECG and heart rate closely. It is preferred over dopamine in septic shock because dopamine increases the risk of tachyarrhythmias and may worsen splanchnic perfusion at higher doses. ## Guideline Reference [cite:Surviving Sepsis Campaign 2021] recommends noradrenaline as first-line; epinephrine as second-line when noradrenaline is inadequate.
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