Norepinephrine
- Receptors: Potent α1, some β1.
- Dose: Titrate up (1–40 mcg/min typical; no true max).
- Pearls: Default first-line in septic/distributive shock. Raises MAP via vasoconstriction with limited tachyarrhythmia. Neutral on PVR.
Epinephrine
- Receptors: β1/β2 dominant at low dose; α1 at higher doses.
- Dose: 1–20 mcg/min.
- Pearls: Use in anaphylaxis, refractory septic/cardiogenic shock, peri-arrest. Boosts HR and CO; increases lactate/glucose (confounds resuscitation markers).
Vasopressin
- Receptors: V1 (vasoconstriction), V2 (renal water retention).
- Dose: 0.03 U/min (fixed).
- Pearls: Add-on in septic shock, effective in acidemia, neutral on PVR (good in RV failure). Excess → digital/mesenteric ischemia.
Phenylephrine
- Receptors: Pure α1.
- Dose: 40–180 mcg/min.
- Pearls: Raises SVR but reflex brady may lower CO. Use in tachyarrhythmias or anesthesia hypotension. Avoid in RV failure (↑PVR).
Dopamine
- Receptors: Dose dependent (DA, β1, α1).
- Dose: 2–20 mcg/kg/min.
- Pearls: Unreliable, arrhythmogenic, worsens outcomes vs NE. Largely abandoned.
Dobutamine
- Receptors: Predominant β1, some β2, mild α1.
- Dose: 2.5-5 mcg/min.
- Pearls: Inodilator—improves contractility/output, lowers SVR. First-line in low-output cardiogenic shock. Risk of hypotension, tachyarrhythmia.
Milrinone
- Mechanism: PDE-3 inhibitor → ↑cAMP, inotropy + vasodilation independent of β-receptors.
- Dose: 0.125–0.75 mcg/kg/min (no bolus in shock).
- Pearls: Useful in RV failure, patients on β-blockers. Long half-life, renally cleared, may cause profound hypotension.
Isoproterenol
- Receptors: Pure β agonist (β1 + β2).
- Dose: 1–10 mcg/min.
- Pearls: Potent chronotrope/inotrope with vasodilation. Used for refractory bradycardia, torsades, β-blocker OD. Causes tachyarrhythmia, hypotension.
Vasopressor Comparison Table
| Drug | Receptors | Typical Dose | Key Points |
|---|---|---|---|
| Norepinephrine | α1 ↑↑, β1 ↑ | 1–40 mcg/min (0.01–3 mcg/kg/min) | Default first-line; potent vasoconstrictor; neutral on PVR |
| Epinephrine | β1 ↑↑, β2 ↑, α1 ↑ (dose-dep) | 1–20 mcg/min | Anaphylaxis, refractory shock, ↑HR/CO, ↑lactate |
| Vasopressin | V1, V2 | 0.03 U/min (fixed) | Adjunct in septic shock; neutral PVR; ischemia risk |
| Phenylephrine | Pure α1 | 40–180 mcg/min | ↑SVR, reflex brady; avoid in RV failure |
| Dopamine | DA (low), β1 (mod), α1 (high) | 2–20 mcg/kg/min | High arrhythmia/mortality; obsolete |
| Dobutamine | β1 ↑↑, β2 ↑, α1 (mild) | 2.5–5 mcg/kg/min | Inodilator; ↑CO, may ↓BP; tachyarrhythmia risk |
| Milrinone | PDE-3 inhibitor (↑cAMP) | 0.125–0.75 mcg/kg/min | Inotropy + vasodilation; RV failure/β-blocker use; renal clearance |
| Isoproterenol | Pure β (β1 + β2) | 1–10 mcg/min | Potent chronotrope; bradycardia, torsades, β-blocker OD |
Vasopressor Choice for Type of Shock
| Scenario | Preferred Agents | Avoid / Use with Caution | Rationale |
|---|---|---|---|
| Septic shock (default) | Norepinephrine ± Vasopressin | Dopamine | NE = best mortality data; add vaso for synergy & catecholamine-sparing |
| Refractory septic shock | NE + Vasopressin ± Epinephrine | Phenylephrine (unless AF w/ RVR) | Epinephrine adds inotropy; avoid excessive α-only pressors that lower CO |
| Anaphylaxis | Epinephrine | Phenylephrine, Vasopressin | β2 bronchodilation + mast cell stabilization |
| Cardiogenic shock (low CO, hypotension) | Dobutamine ± NE, Epinephrine, Milrinone (if on β-blockers or RV failure) | Phenylephrine, high-dose vasopressin | Inotropes improve contractility; NE/Epi provide perfusion pressure |
| Cardiogenic shock (low CO, normotensive) | Dobutamine or Milrinone | NE (unless hypotension develops) | Inodilators improve output; milrinone preferred if RV failure or on β-blockers |
| RV failure / Pulmonary HTN | Milrinone, Dobutamine, Epinephrine, Vasopressin | Phenylephrine, high-dose NE | Milrinone reduces PVR; vasopressin neutral on PVR; avoid α1-only pressors |
| Bradycardia / BRASH / Torsades | Isoproterenol, Epinephrine | Phenylephrine, Vasopressin | Iso = most potent chronotrope; Epi supports HR + BP; phenyl/vaso worsen brady |
| AF with RVR + hypotension | Phenylephrine, Vasopressin | Epinephrine, Dobutamine, Isoproterenol | α-only agents increase BP without worsening tachyarrhythmia |
| Profound acidosis / hypoxemia | Vasopressin, Epinephrine | NE alone (less effective) | Vaso works when catecholamine receptors fail; epi can still stimulate |
| Post-cardiotomy vasoplegia | Vasopressin, Methylene Blue, Hydroxocobalamin | Phenylephrine alone | Catecholamine-refractory vasodilation responds better to non-adrenergics |
| Peri-arrest / crashing shock | Epinephrine (push-dose or infusion) | Dobutamine, Milrinone | Rapid α + β support in near-code physiology |
| Chronic β-blocker use | Milrinone | Dobutamine | PDE-3 bypasses β-receptor blockade |
Key trials for Vasopressors
SOAP II (NEJM 2010) – Dopamine vs norepinephrine in undifferentiated shock (n=1679). Mortality overall: no difference, but more arrhythmias with dopamine and higher mortality in cardiogenic shock subgroup → dopamine largely abandoned as first-line. (PubMed)
VASST (NEJM 2008) – Vasopressin (low-dose) vs norepinephrine in septic shock already on catecholamines (n=778). No mortality benefit overall; signal of benefit only in less severe shock; modest NE-sparing. Bottom line: use vaso as an adjunct, not a replacement. (New England Journal of Medicine)
VANISH (JAMA 2016) – Early vasopressin vs norepinephrine as initial therapy in septic shock, kidney failure–free days primary outcome (n=409). No improvement in renal outcomes or mortality; permissible to start NE first and add vaso. (JAMA Network)
CENSER (AJRCCM 2019) – Early low-dose norepinephrine vs standard care in early sepsis (n=310). Improved shock control at 6 h and less fluid/vaso exposure; mortality signal not definitive. Takeaway: start NE early when hypotension is real. (PubMed)
SEPSISPAM (NEJM 2014) – MAP 65–70 vs 80–85 in septic shock (n=776). No mortality difference; in chronic HTN, higher MAP reduced need for RRT but not deaths. Practical: target ~65; consider higher only for select kidneys/HTN. (New England Journal of Medicine)
65 Trial (JAMA 2020) – ICU patients ≥65 yrs with vasodilatory hypotension: permissive hypotension MAP 60–65 vs usual care (n=2600). No increase in 90-day mortality; lower vasopressor exposure. Message: in older vasoplegia, lower targets are safe and limit catecholamine burden. (PubMed)
CAT Study / “Adrenaline vs Noradrenaline” (ICM 2008) – Epi vs NE in heterogeneous ICU shock. Similar time to target MAP and outcomes; more metabolic effects with epi. Use: epi is acceptable but usually not first-line in septic shock unless you want β-inotropy/chronotropy. (PubMed)
Annane 2007 (Lancet) – Epinephrine alone vs NE+dobutamine in septic shock. No efficacy/safety difference; supports using epi as single inopressor rather than stacking dobutamine in some phenotypes. (Annals of Translational Medicine)
OptimaCC (JACC 2018) – Cardiogenic shock post-MI: epinephrine vs norepinephrine (n=57). Similar MAP/CI, but more refractory shock with epi. Bedside: prefer NE to support MAP; add separate inotrope as needed. (PubMed)
VANCS (Anesthesiology 2017) – Post-cardiac surgery vasoplegia: vasopressin vs norepinephrine (n=300). Fewer complications (incl. AF) with vasopressin; suggests vaso first-line in postcardiotomy vasoplegic shock. (PubMed)
Vasopressors
Quick bedside guide to pressors, inotropes, receptor profiles, dosing, and shock-specific selection.
Vasopressor Comparison Table
| Drug | Receptors | Typical dose | Onset / half-life | Main effects | Best use / pearls |
|---|---|---|---|---|---|
| Norepinephrine | α1 ↑↑, β1 ↑ | 1–40 mcg/min (~0.01–3 mcg/kg/min) |
Rapid / 2–3 min | Strong vasoconstriction, modest inotropy | Default first-line for septic or undifferentiated vasodilatory shock |
| Epinephrine | β1 ↑↑, β2 ↑, α1 ↑ (dose-dependent) |
1–20 mcg/min | Rapid / 2–3 min | Inotropy, chronotropy, vasopressor effect at higher dose | Anaphylaxis, peri-arrest, refractory shock, severe bradycardia |
| Vasopressin | V1, V2 | 0.03 U/min fixed dose | Rapid / 10–20 min | Non-catecholamine vasoconstriction | Adjunct in septic shock, useful in acidemia, can help in AF with RVR |
| Phenylephrine | Pure α1 | 40–180 mcg/min | Rapid / 2–3 min | Pure vasoconstriction, reflex bradycardia | May help if hypotension with tachyarrhythmia, but can worsen CO and RV afterload |
| Dopamine | DA low dose, β1 moderate, α1 high dose | 2–20 mcg/kg/min | Rapid / 2 min | Chronotropy, inotropy, vasopressor at higher dose | Generally avoided due to arrhythmias and inferior outcome data |
| Dobutamine | β1 ↑↑, β2 ↑, mild α1 | 2.5–5 mcg/kg/min up to ~20 |
Rapid / 2 min | Inotropy with some vasodilation | Low-output cardiogenic shock, often paired with norepinephrine if hypotensive |
| Milrinone | PDE-3 inhibitor (↑ cAMP) |
0.125–0.75 mcg/kg/min | Minutes / hours | Inotropy plus vasodilation, lowers PVR | RV failure, pulmonary HTN, beta-blocker patients, watch renal function |
| Isoproterenol | Pure β (β1 + β2) |
1–10 mcg/min | Rapid / 2–5 min | Chronotropy, inotropy, vasodilation | Torsades, refractory bradycardia, some BRASH-type physiology |
- ✓Norepinephrine is the default first-line pressor for septic and most vasodilatory shock states
- ✓Vasopressin is usually an adjunct, not a replacement, and is especially nice in acidemia
- ✓Dobutamine and milrinone are for low-output states, not pure vasoplegia
- ✓Phenylephrine can be useful in tachyarrhythmia but is often a bad choice in RV failure
- ✓Dopamine is mostly out because of arrhythmias and weaker evidence
- •Septic shock norepinephrine first, then add vasopressin if escalating
- •Refractory septic shock norepinephrine plus vasopressin, then consider epinephrine
- •Anaphylaxis epinephrine is the main agent
- •Cardiogenic shock with low output dobutamine plus norepinephrine as needed for pressure
- •RV failure / pulmonary HTN milrinone, dobutamine, epinephrine, or vasopressin are generally friendlier than alpha-only agents
- •AF with RVR and hypotension phenylephrine or vasopressin can support pressure without adding more tachycardia
- •Bradycardia / torsades / BRASH isoproterenol or epinephrine
- •Post-cardiotomy vasoplegia vasopressin first, with non-adrenergic rescue options when needed
- •SOAP II dopamine had more arrhythmias and worse cardiogenic shock outcomes than norepinephrine
- •VASST vasopressin did not beat norepinephrine overall, so use it as an adjunct
- •VANISH early vasopressin was not superior to norepinephrine for renal or mortality outcomes
- •CENSER early norepinephrine improved early shock control
- •SEPSISPAM and 65 Trial lower MAP targets are usually fine unless there is a specific reason otherwise
- •OptimaCC in cardiogenic shock, norepinephrine is usually favored over epinephrine for pressure support
- •VANCS vasopressin looked favorable in postcardiotomy vasoplegia
Acidemia
Vasopressin may work better than escalating catecholamines when severe acidemia is blunting adrenergic response.
RV failure
Avoid making RV afterload worse with pure alpha agents unless you have a very specific reason.
Tachyarrhythmia
Phenylephrine or vasopressin can support MAP without driving the heart rate harder.
Low output
If the problem is low cardiac output, adding more vasoconstriction alone usually is not the answer.