## Clinical Context: Septic Shock Management This patient meets criteria for septic shock (hypotension unresponsive to fluid resuscitation, evidence of tissue hypoperfusion with elevated lactate). Vasopressor support is now indicated. ## Mechanism of Action & Selection **Key Point:** Noradrenaline (norepinephrine) is the first-line vasopressor in septic shock because it combines α₁-adrenergic vasoconstriction (restores MAP) with moderate β₁-adrenergic inotropic support, maintaining organ perfusion. **High-Yield:** Surviving Sepsis Campaign (2021) guidelines recommend noradrenaline as the initial vasopressor of choice in septic shock, with a target MAP ≥65 mmHg. ## Pharmacology of Adrenergic Agonists in Shock | Agent | α₁ | β₁ | β₂ | Clinical Use | Advantage | |-------|-----|-----|-----|---|---| | **Noradrenaline** | +++ | ++ | + | First-line septic shock | Balanced vasoconstriction + inotropy | | Adrenaline | +++ | +++ | +++ | Refractory shock, anaphylaxis | Potent but increases lactate, arrhythmia risk | | Dopamine | ++ | +++ | + | Alternative if noradrenaline unavailable | Tachycardia, arrhythmia prone | | Phenylephrine | +++ | — | — | Pure vasoconstriction only | No inotropic support; reflex bradycardia | ## Dosing & Titration **Clinical Pearl:** Noradrenaline is started at 0.01–0.05 mcg/kg/min IV and titrated upward in 0.05–0.1 mcg/kg/min increments every 5–10 minutes until target MAP is achieved. Requires central line for infusion (risk of extravasation). ## Why Fluid Resuscitation Alone Is Insufficient The patient has already received maximal fluid resuscitation (as stated). Persistent hypotension despite adequate preload indicates **distributive shock** requiring vasopressor support to restore vascular tone and peripheral resistance. **Tip:** Always ensure adequate fluid resuscitation BEFORE starting vasopressors; however, once maximal fluid is given and shock persists, vasopressors are mandatory.
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