Pharmacology Deep Dive: Pressors and Inotropes—When to Choose Levo vs. Vaso vs. Epi
You're titrating norepinephrine at 0.3 mcg/kg/min and the MAP is still 58. Do you go higher? Add vasopressin? Switch to epinephrine? The answer depends on understanding what each drug actually does.
Receptor Pharmacology Basics
Alpha-1 Receptors
- Location: Vascular smooth muscle
- Effect: Vasoconstriction
- Clinical result: Increased SVR, increased MAP
Beta-1 Receptors
- Location: Heart (primarily)
- Effect: Increased contractility (inotropy), increased heart rate (chronotropy)
- Clinical result: Increased cardiac output
Beta-2 Receptors
- Location: Vascular smooth muscle, bronchial smooth muscle
- Effect: Vasodilation, bronchodilation
- Clinical result: Decreased SVR (at low doses), bronchodilation
Dopamine Receptors
- Location: Renal, mesenteric, coronary vasculature
- Effect: Vasodilation (at low doses)
- Clinical result: Historical "renal dose dopamine" (now debunked)
V1 Receptors (Vasopressin)
- Location: Vascular smooth muscle
- Effect: Vasoconstriction (non-catecholamine pathway)
- Clinical result: Increased SVR without direct cardiac effects
Drug-by-Drug Breakdown
Norepinephrine (Levophed)
Receptor Profile:
- Strong alpha-1
- Moderate beta-1
- Minimal beta-2
Hemodynamic Effects:
- ↑↑ SVR (vasoconstriction)
- ↑ Contractility (mild)
- ↔ or ↓ Heart rate (reflex bradycardia common)
Starting Dose: 0.05-0.1 mcg/kg/min Typical Range: 0.1-0.5 mcg/kg/min High Dose: >0.5 mcg/kg/min (consider adding second agent)
When to Use:
- First-line for septic shock (Surviving Sepsis Campaign recommendation)
- Distributive shock (vasodilation is the primary problem)
- Most shock states as initial vasopressor
Cautions:
- Peripheral ischemia at high doses
- Arrhythmias (less than dopamine/epinephrine)
- Tissue necrosis with extravasation
Vasopressin (ADH)
Receptor Profile:
- V1 (vascular)
- V2 (renal—not clinically significant at these doses)
Hemodynamic Effects:
- ↑ SVR (via non-catecholamine pathway)
- ↔ Heart rate
- ↔ Contractility
Fixed Dose: 0.03-0.04 units/min (typically 0.04) Note: Unlike catecholamines, vasopressin is not titrated to effect
When to Use:
- Second-line in septic shock (add to norepinephrine at 0.25-0.5 mcg/kg/min)
- Catecholamine-sparing (may allow lower norepinephrine dose)
- Vasoplegia post-cardiac surgery
- Relative vasopressin deficiency in sepsis
Cautions:
- Splanchnic vasoconstriction (gut ischemia risk)
- Skin necrosis (rare)
- Hyponatremia (V2 effects)
Why 0.04 units/min? Higher doses don't improve outcomes and increase ischemic complications.
Epinephrine
Receptor Profile:
- Alpha-1 (especially at higher doses)
- Strong beta-1
- Strong beta-2
Hemodynamic Effects:
- ↑ Contractility (strongest inotrope)
- ↑ Heart rate
- ↑ SVR at higher doses
- ↓ SVR at very low doses (beta-2 predominates)
Starting Dose: 0.01-0.05 mcg/kg/min Typical Range: 0.05-0.3 mcg/kg/min Code Dose: 1 mg IV push (cardiac arrest)
When to Use:
- Cardiogenic shock with hypotension (inotropy + vasoconstriction)
- Anaphylaxis (bronchodilation + vasoconstriction + inotropy)
- Cardiac arrest (ACLS protocol)
- Septic shock with myocardial dysfunction
- Severe bradycardia unresponsive to atropine
Cautions:
- Tachyarrhythmias (most arrhythmogenic pressor)
- Increased myocardial oxygen demand
- Hyperglycemia
- Lactic acidosis (beta-2 mediated—can confuse lactate trends)
Dopamine
Receptor Profile:
- Dose-dependent:
- Low dose (1-3 mcg/kg/min): Dopaminergic (renal vasodilation)
- Medium dose (3-10 mcg/kg/min): Beta-1 (inotropy)
- High dose (>10 mcg/kg/min): Alpha-1 (vasoconstriction)
When to Use (Limited):
- Symptomatic bradycardia unresponsive to atropine (ACLS)
- Rarely as first-line pressor (more arrhythmias than norepinephrine)
Why It's Fallen Out of Favor:
- Higher arrhythmia risk than norepinephrine
- "Renal dose dopamine" doesn't protect kidneys
- No survival benefit over norepinephrine in septic shock
Phenylephrine (Neo-Synephrine)
Receptor Profile:
- Pure alpha-1
Hemodynamic Effects:
- ↑↑ SVR
- ↔ or ↓ Contractility
- ↓ Heart rate (reflex bradycardia)
When to Use:
- Hypotension with tachyarrhythmias (when you can't tolerate beta effects)
- Neurogenic shock (may be preferred)
- Procedural hypotension (brief use)
Cautions:
- Reflexive bradycardia can worsen cardiac output
- Not ideal for cardiogenic shock (pure vasoconstriction without inotropy)
Dobutamine
Receptor Profile:
- Strong beta-1
- Moderate beta-2
- Minimal alpha
Hemodynamic Effects:
- ↑↑ Contractility
- ↑ Heart rate
- ↓ SVR (beta-2 vasodilation)
Starting Dose: 2.5 mcg/kg/min Typical Range: 5-20 mcg/kg/min
When to Use:
- Cardiogenic shock with adequate blood pressure (pure inotropy needed)
- Low cardiac output states
- Often combined with norepinephrine (norepi for pressure, dobutamine for output)
Cautions:
- Hypotension (vasodilation)
- Tachyarrhythmias
- Increased myocardial oxygen demand
Clinical Decision-Making by Shock Type
Septic Shock (Warm, Vasodilated)
- Norepinephrine first (vasoconstriction needed)
- Add vasopressin at 0.04 units/min when norepi 0.25-0.5 mcg/kg/min
- Consider epinephrine if echo shows poor cardiac function
Cardiogenic Shock (Cold, Vasoconstricted)
- Hypotensive: Norepinephrine or epinephrine (need pressure and inotropy)
- Normotensive: Dobutamine (pure inotropy without raising afterload)
- Consider mechanical support (IABP, Impella) early
Anaphylaxis
- Epinephrine IM (0.3-0.5 mg) first-line
- Epinephrine infusion if persistent hypotension
- Volume resuscitation critical
Neurogenic Shock (Spinal Cord Injury)
- Loss of sympathetic tone → vasodilation + bradycardia
- Norepinephrine or phenylephrine for SVR
- May need atropine or chronotropic agents for bradycardia
Post-Cardiac Surgery Vasoplegia
- Norepinephrine first
- Vasopressin often effective
- Methylene blue considered in refractory cases
Practical Tips
When to Add vs. Switch
- Add vasopressin when norepi is working but you need more without escalating catecholamines
- Add dobutamine when pressure is okay but cardiac output is low
- Switch to epinephrine when you need strong inotropy AND vasoconstriction
Monitoring Response
- MAP is not enough—assess perfusion (lactate, urine output, mental status)
- Rising lactate on epinephrine may be drug-induced, not worsening shock
Weaning Pressors
- General principle: Wean the most recently added agent first
- Vasopressin is often weaned last (non-titrating, supports catecholamine weaning)
- Wean slowly (10-20% decrements) with frequent reassessment
The Bottom Line
Pressor selection isn't one-size-fits-all. Understand the receptor pharmacology, assess the type of shock, and choose agents that address the underlying pathophysiology. Norepinephrine is first-line for most shock, but knowing when to add or switch makes you a more effective critical care provider.
Master the receptors, master the drugs, master the shock.