ICU Pharmacotherapy MasterclassReceptors • MAP • CO • SVR • PVR • Shock phenotype

Vasopressors & Inotropes

Choose vasoactive therapy by pressure, flow, vascular tone, ventricular phenotype and rhythm. This masterclass separates “raise the MAP” from “restore perfusion,” then links to each medication monograph for exact dosing and safety details.

1. Think in pressure + flow + phenotype

A normal MAP does not guarantee adequate cardiac output, and a low MAP does not tell you which receptor to stimulate.

Is MAP inadequate?

If perfusion pressure is below the patient-specific target, choose a vasopressor rather than an inotrope alone.

Is flow inadequate?

Use echo, capillary refill, urine output, lactate trajectory and other hemodynamics to identify low output.

What is the vascular tone?

Warm vasoplegia, cold vasoconstriction and mixed states require different receptor strategies.

Which ventricle is failing?

LV failure, RV failure and biventricular failure respond differently to afterload and inodilators.

Reassess after every change

Trend MAP plus perfusion and flow. Do not keep escalating an agent that worsens rhythm, ischemia or output.

2026 Surviving Sepsis Campaign: norepinephrine remains first-line in septic shock; add vasopressin as norepinephrine requirements escalate, then add epinephrine if MAP remains inadequate despite norepinephrine + vasopressin. Persistent hypoperfusion with cardiac dysfunction is a separate problem that may require inotropic support.

2. Receptor / hemodynamic comparison

These arrows are qualitative—not exact dose-response equations. Patient physiology can reverse the expected net effect.

Agent	α1	β1	β2	V1	PDE3	MAP	HR	CO	SVR	Bedside pearl
Norepinephrine	+++	+	0/+	0	0	↑↑	↔ / slight ↑	↔ / ↑ if preload/contractile reserve	↑↑	Default first-line vasopressor in septic shock; strong vasoconstriction with modest β1 support.
Vasopressin	0	0	0	+++	0	↑	↔ / ↓	↔ / ↓ if excessive afterload	↑	Catecholamine-sparing adjunct for vasoplegia; often used as a fixed low-dose infusion rather than titrated like norepinephrine.
Epinephrine	++	+++	++	0	0	↑↑	↑↑	↑↑	variable / ↑ at higher effect	Powerful combined pressor + inotrope; useful when severe vasoplegia and low output coexist, but tachyarrhythmia and lactate rise can complicate interpretation.
Phenylephrine	+++	0	0	0	0	↑	↓ / ↔	↓ / ↔	↑↑	Pure α1 vasoconstrictor. Niche agent when tachyarrhythmia limits β stimulation; can reduce stroke volume when afterload is already high.
Dopamine	+/++	++	+	0	0	↑	↑↑	↑	variable / ↑	Receptor effects overlap rather than switching cleanly by dose. Arrhythmia risk and worse outcomes versus norepinephrine make it a non-routine septic-shock pressor.
Dobutamine	+	+++	++	0	0	↔ / ↓	↑	↑↑	↓ / ↔	β-dominant inotrope for low-output states when pressure is adequate or supported. Can worsen hypotension and tachyarrhythmia.
Milrinone	0	indirect	indirect	0	+++	↓ / ↔	↔ / ↑	↑	↓	PDE3 inodilator; useful in selected low-output/RV states and may retain effect during β-blockade, but renal accumulation and hypotension are major limitations.

Dopamine caveat: avoid teaching “renal dose → β dose → α dose” as if receptors switch on at precise cutoffs. Dopamine’s receptor effects overlap, and the clinically important point is that tachyarrhythmias and variable hemodynamics limit routine use.

3. Shock phenotype → medication strategy

The first question is not “which pressor is strongest?” It is “what is failing now?”

Septic vasoplegia, preserved cardiac output

Start / pressure strategy

Norepinephrine

Next if phenotype persists

Add vasopressin as norepinephrine requirements escalate; add epinephrine if MAP remains inadequate despite norepinephrine + vasopressin.

Avoid the reflex

Dopamine as routine first-line therapy; reflex inotrope use without evidence of cardiac dysfunction/hypoperfusion.

Septic shock + cardiac dysfunction + persistent hypoperfusion

Start / pressure strategy

Maintain an adequate vasopressor (usually norepinephrine; epinephrine is an alternative in selected patients).

Next if phenotype persists

Add dobutamine to norepinephrine or use epinephrine alone when persistent low-output hypoperfusion remains after adequate volume status and pressure.

Avoid the reflex

Using an inotrope instead of a vasopressor when MAP is still below target.

Cardiogenic shock with hypotension

Start / pressure strategy

Restore perfusion pressure—norepinephrine is commonly favored when a vasopressor is required.

Next if phenotype persists

If cardiac output remains inadequate despite pressure, add an inotrope chosen by rhythm, renal function, β-blockade, RV/LV phenotype and blood pressure.

Avoid the reflex

Escalating pure vasoconstriction indefinitely without reassessing output, congestion and mechanical causes.

RV failure / pulmonary hypertension + systemic hypotension

Start / pressure strategy

Protect systemic pressure and RV coronary perfusion; norepinephrine and/or carefully selected vasopressin may be useful depending on phenotype.

Next if phenotype persists

If low output persists, consider dobutamine or milrinone while preventing systemic hypotension; add inhaled pulmonary vasodilator when appropriate.

Avoid the reflex

Large uncontrolled fluid loading or systemic vasodilation that worsens RV perfusion pressure.

Tachyarrhythmia + vasodilatory hypotension

Start / pressure strategy

Norepinephrine often remains preferable because it produces less tachycardia than epinephrine/dopamine.

Next if phenotype persists

Phenylephrine is a niche option when β stimulation is clearly harmful and cardiac output can tolerate pure vasoconstriction.

Avoid the reflex

Treating the monitor number while ignoring stroke volume, afterload and the arrhythmia itself.

Bradycardia + hypotension + low output

Start / pressure strategy

Treat the rhythm/cause and support pressure. Epinephrine may be useful when chronotropy and inotropy are simultaneously needed.

Next if phenotype persists

Consider pacing or other rhythm-specific therapy when indicated rather than relying indefinitely on catecholamine chronotropy.

Avoid the reflex

Assuming dopamine is automatically the best agent simply because the patient is bradycardic.

4. Advanced phenotypes: cardiogenic shock and RV failure

LV-predominant low-output shock

If pressure is inadequate, secure coronary/systemic perfusion pressure with a vasopressor before or alongside an inotrope.
Dobutamine raises contractility but can lower SVR; it is easier to titrate rapidly because of its short half-life.
Milrinone is an inodilator and may retain effect during β-blockade, but hypotension and renal accumulation can be major problems.
Serial echo and congestion/perfusion assessment should determine whether you need more flow, less afterload, decongestion, revascularization or mechanical circulatory support.

RV-predominant shock / pulmonary hypertension

Maintain systemic pressure to protect RV coronary perfusion while avoiding excessive increases in PVR.
Norepinephrine often supports systemic pressure; vasopressin can be a catecholamine-sparing adjunct in vasodilatory states.
Dobutamine or milrinone may improve RV contractility/forward flow but can worsen systemic hypotension.
Consider inhaled nitric oxide or inhaled epoprostenol as pulmonary vasodilator adjuncts when appropriate; treat the precipitating cause and optimize ventilation/oxygenation.

Inhaled NO monograph →Epoprostenol monograph →

Advanced vasoplegia adjuncts

Angiotensin II is an alternative adjunctive vasopressor in selected refractory vasodilatory shock, but the 2026 sepsis guideline still prefers norepinephrine first-line and does not elevate angiotensin II above the standard norepinephrine → vasopressin → epinephrine sequence. Methylene blue and hydroxocobalamin are rescue strategies with context-specific evidence—not routine substitutes for source control, adequate resuscitation and standard pressors.

Methylene blue →Hydroxocobalamin →

5. Safety and titration traps

Peripheral start

Do not delay urgently needed vasopressor support solely while waiting for central access. Use an appropriate, well-functioning peripheral IV with frequent site checks and a local extravasation protocol; the 2026 sepsis guideline does not prescribe one universal catheter size, site or duration.

Extravasation

Stop the infusion at the affected site, aspirate if appropriate, elevate/assess the limb and use the institution's antidote/extravasation pathway. Re-site the infusion promptly.

Arrhythmia

Epinephrine, dopamine and dobutamine can increase tachyarrhythmia burden. Treat rhythm and ischemia risk as part of titration, not as an afterthought.

Lactate

Epinephrine can increase lactate through β2-mediated glycolysis. A rising lactate after epinephrine does not automatically mean worsening tissue hypoxia; interpret it with perfusion and flow.

Ischemia

Excessive vasoconstriction can cause digital, mesenteric or other ischemia. More MAP is not always more perfusion.

Weaning

There is no universal evidence-based rule that one pressor must always be stopped before another. Wean according to the residual shock phenotype and the patient's response.

Milrinone + renal failure

Renal clearance means accumulation can prolong hypotension/arrhythmia risk. Dose adjustment and repeated reassessment are essential.

Phenylephrine

A pure α1 agent can raise MAP while lowering stroke volume. Reserve it for a physiology where that tradeoff makes sense.

Dopamine

Avoid 'renal-dose dopamine' for kidney protection; it does not provide a renal-protective strategy and is not a routine septic-shock pressor.

6. Core vasoactive monographs — dosing + bedside pearl

Expand a card for the current dosing framework, then open the full page for organ-failure adjustments, monitoring and citations.

Norepinephrine

Potent Alpha-1 & Beta-1 Inotrope / Vasopressor

Dose + pearl ▼

Dose framework: Septic shock: titrate norepinephrine promptly to the perfusion/MAP target (SSC uses an initial MAP target around 65 mmHg for most adults), using the institution’s standardized concentration and weight-based or non-weight-based protocol. Do not equate 0.02–0.05 mcg/kg/min with a fixed 2–5 mcg/min across body weights. Current U.S. norepinephrine labeling for acute hypotension starts 8–12 mcg/min and lists a typical maintenance dose of 2–4 mcg/min; ICU sepsis protocols commonly use different weight-based starting schemes. There is no universal evidence-based maximum in refractory shock.

Bedside pearl: Norepinephrine is the first-line vasopressor for septic shock. When the norepinephrine requirement is escalating, SSC 2026 suggests adding vasopressin rather than relying on a universal numeric trigger; follow the local fixed-dose vasopressin protocol and reassess shock phenotype.

Open complete monograph →

Vasopressin

V1a & V2 Receptor Agonist / Non-Adrenergic Vasopressor

Dose + pearl ▼

Dose framework: Septic shock/vasodilatory shock: follow the local sepsis protocol or current product label. Many ICU protocols use a low fixed dose around 0.03 units/min as a norepinephrine adjunct. Current U.S. Vasostrict labeling starts septic shock at 0.01 units/min and allows titration by 0.005 units/min every 10–15 minutes up to 0.07 units/min. Do not mix this shock regimen with vasopressin regimens for other indications.

Bedside pearl: In septic shock, vasopressin is commonly given as a low fixed-dose infusion according to the local protocol (often 0.03 U/min, sometimes 0.04 U/min). SSC 2026 suggests adding it when norepinephrine requirements are escalating rather than at one universal norepinephrine cutoff.

Open complete monograph →

Epinephrine

Potent Alpha-1, Beta-1, and Beta-2 Adrenergic Agonist

Dose + pearl ▼

Dose framework: Septic-shock hypotension (current U.S. label): 0.05–2 mcg/kg/min IV infusion, titrated to the desired MAP and weaned gradually. Adult anaphylaxis: 0.3–0.5 mg IM in the anterolateral thigh; may repeat every 5–10 minutes as needed. Adult cardiac arrest: epinephrine 1 mg IV/IO every 3–5 minutes per AHA ALS guidance.

Bedside pearl: Epinephrine stimulates hepatic beta-2 receptors causing glycogenolysis and transient hyperlactatemia — do not confuse epinephrine-induced Type B hyperlactatemia with worsening tissue hypoperfusion!

Open complete monograph →

Phenylephrine

Pure Selective Alpha-1 Adrenergic Agonist

Dose + pearl ▼

Dose framework: Use the product- and indication-specific regimen. Current U.S. labeling for perioperative vasodilatory hypotension includes bolus dosing around 40–100 mcg and infusion 10–35 mcg/min; some newer labeled products also include weight-based vasodilatory-shock regimens. Do not merge these formulations into one universal ICU dose range.

Bedside pearl: Phenylephrine increases MAP at the expense of cardiac output — avoid in septic shock with cardiac dysfunction.

Open complete monograph →

Dopamine

Dopaminergic & Adrenergic Agonist

Dose + pearl ▼

Dose framework: Current U.S. label: start 2–5 mcg/kg/min IV continuous infusion and titrate in 5–10 mcg/kg/min increments to hemodynamic response and tolerability; do not exceed 50 mcg/kg/min.

Bedside pearl: Dopamine is no longer first-line for septic shock due to higher arrhythmia risk.

Open complete monograph →

Dobutamine

Synthetic Inotrope / Beta-1 & Beta-2 Agonist

Dose + pearl ▼

Dose framework: Current U.S. labeling: the infusion rate needed to increase cardiac output usually ranges from 2.5–15 mcg/kg/min; rare patients have required rates up to 40 mcg/kg/min. Titrate to clinical/hemodynamic response rather than a universal CI or ScvO2 target.

Bedside pearl: Dobutamine is an INODILATOR — in septic shock with myocardial dysfunction and persistent hypoperfusion, dobutamine may be added to norepinephrine when blood pressure requires vasopressor support; it is not mandatory to pair norepinephrine in every patient if adequate arterial pressure is otherwise maintained.

Open complete monograph →

Milrinone

Phosphodiesterase-3 (PDE-3) Inhibitor Inodilator

Dose + pearl ▼

Dose framework: Current U.S. labeling: loading dose 50 mcg/kg IV over 10 minutes, followed by 0.375–0.75 mcg/kg/min (standard 0.5 mcg/kg/min), titrated to clinical/hemodynamic response. In ICU shock practice the loading dose is often omitted when hypotension risk is high; that omission is practice-based rather than the labeled regimen.

Bedside pearl: Milrinone elimination is strongly affected by renal function. In renal impairment, reduce the maintenance infusion according to current labeling/local protocol and monitor closely for hypotension and arrhythmias; dobutamine is an alternative, not an automatic replacement.

Open complete monograph →

7. Resident progression — R1 to R5

Commit to pressure/flow reasoning before opening the answer.

First-line septic shock

A patient remains hypotensive after appropriate initial fluid resuscitation. MAP is 54 mmHg with warm extremities and no obvious low-output phenotype.

Show reasoning →

Reasoning: Start norepinephrine promptly and titrate to the perfusion/MAP target. Current 2026 Surviving Sepsis Campaign guidance recommends norepinephrine first-line over dopamine or epinephrine.

Escalating norepinephrine

Septic shock requires steadily rising norepinephrine. MAP is barely at target, rhythm is sinus tachycardia and perfusion remains marginal.

Show reasoning →

Reasoning: Add vasopressin rather than simply continuing catecholamine escalation. Reassess source control, volume responsiveness, cardiac function and perfusion at the same time.

Pressure fixed, perfusion not fixed

MAP is 70 on norepinephrine, but lactate rises, capillary refill is prolonged, urine output falls and echo shows new LV systolic dysfunction with low forward flow.

Show reasoning →

Reasoning: This is a low-output phenotype despite adequate pressure. After confirming adequate volume status and excluding mechanical causes, add inotropic support—dobutamine with norepinephrine or epinephrine alone are guideline-supported options in septic shock with persistent hypoperfusion and cardiac dysfunction.

RV failure under pressure

Severe pulmonary hypertension with a dilated RV, septal flattening, low LV filling, systemic hypotension and rising lactate. The patient is already on norepinephrine.

Show reasoning →

Reasoning: The goals are systemic pressure/RV coronary perfusion plus forward flow while avoiding further RV afterload. Consider carefully selected vasopressin and/or an inotrope such as dobutamine or milrinone depending on BP, renal function and rhythm; inhaled pulmonary vasodilator may be useful. Avoid indiscriminate fluids or systemic vasodilation.

Mixed vasoplegic + cardiogenic shock

Post-resuscitation shock: MAP 58 on norepinephrine, sinus tachycardia 135, cool extremities, VTI is low, LV EF is depressed, RV is moderately impaired, lactate is rising and creatinine is worsening.

Show reasoning →

Reasoning: Treat the phenotype rather than selecting one 'strongest' pressor. Restore MAP with norepinephrine ± vasopressin, evaluate whether epinephrine or a separate inotrope best balances flow versus tachyarrhythmia, and recognize that milrinone may worsen hypotension and accumulate as renal function falls. Serial echo/perfusion response should determine the next move.

Evidence anchors

Surviving Sepsis Campaign 2026 ↗Shock physiology topic →