Advanced Pharmacology · Topic 3 of 13

Vasopressors & Inotropes

Pharmacology · vasoactive drugs

Vasopressors & Inotropes

Norepinephrine first, titrated to MAP 65; add fixed-dose vasopressin as norepinephrine climbs; add an inotrope only for low output — never instead of a vasopressor.

Key numbers

Norepinephrine first-line, titrate to MAP 65MAP 65 mmHg

Add vasopressin 0.03 units/min, not titrated0.03 units/min

Extravasation: infiltrate phentolamine 5–10 mgphentolamine 5–10 mg

01 · GiveNorepinephrine first-line, titrate to MAP 65

Norepinephrine is the first-line vasopressor in septic shock (strong recommendation over dopamine): titrate to an initial MAP of 65 mmHg (within about 5 mmHg) and start it peripherally rather than wait for central access.

02 · GiveAdd vasopressin 0.03 units/min, not titrated

When norepinephrine doses are escalating (usually about 0.25–0.5 mcg/kg/min), add vasopressin at a fixed 0.03 units/min rather than pushing norepinephrine higher; vasopressin is not titrated to response.

03 · GiveInotropes add to vasopressors, never replace

For persistent hypoperfusion from cardiac dysfunction despite adequate volume and MAP, add an inotrope — dobutamine (β1) or milrinone (PDE-3 inhibitor) — to, never instead of, the vasopressor; both cause arrhythmias and vasodilatory hypotension.

What it is

Core idea

Norepinephrine: α1 and β1, little heart-rate changeNorepinephrine is a potent α1 and β1 agonist: it raises MAP while reflex vagal slowing offsets β1 chronotropy, so heart rate changes little and cardiac output is generally maintained; fewer arrhythmias than dopamine.

Diagnosis & monitoring

Work-up

Arterial line for escalating or multiple pressorsPlace an arterial catheter for patients on intermediate-to-high, escalating or multiple vasopressors, those needing frequent blood gases, or when noninvasive pressures are inconsistent.

Do right now

In this order

First moves

Norepinephrine first-line, titrate to MAP 65MAP 65 mmHg

→

Peripheral pressors: proximal vein, short duration

→

Add vasopressin 0.03 units/min, not titrated0.03 units/min

→

Third agent: add epinephrine

Why each step

Norepinephrine first-line, titrate to MAP 65Norepinephrine is the first-line vasopressor in septic shock (strong recommendation over dopamine): titrate to an initial MAP of 65 mmHg (within about 5 mmHg) and start it peripherally rather than wait for central access.

Peripheral pressors: proximal vein, short durationRun peripheral vasopressors through a well-placed catheter proximal to the antecubital fossa for a short time (under about 6 hours is unlikely to injure tissue); most extravasations occur with catheters distal to the antecubital fossa.

Add vasopressin 0.03 units/min, not titratedWhen norepinephrine doses are escalating (usually about 0.25–0.5 mcg/kg/min), add vasopressin at a fixed 0.03 units/min rather than pushing norepinephrine higher; vasopressin is not titrated to response.

Third agent: add epinephrineIf MAP stays inadequate despite norepinephrine and vasopressin, add epinephrine; where vasopressin is unavailable, epinephrine can be added to norepinephrine alone.

Management

Orders

Extravasation: infiltrate phentolamine 5–10 mg must knowIf a vasopressor extravasates, infiltrate the area as soon as possible with phentolamine 5–10 mg in 10–15 mL of saline to prevent necrosis and sloughing.

Avoid dopamine: more arrhythmias than norepinephrineDopamine acts on D1, β1 and α1 receptors by dose; compared with norepinephrine it causes more arrhythmias and higher mortality in septic shock, so use it only when norepinephrine is unavailable.

Phenylephrine: pure α1, reflex bradycardiaPhenylephrine is a pure α1 agonist that can cause severe bradycardia and lower cardiac output; it is discouraged as the single first-line agent in cardiogenic shock.

Epinephrine: β1 at low dose, raises lactateEpinephrine has potent β1 and moderate β2 and α1 effects: low doses mainly raise cardiac output, and β2 stimulation raises lactate aerobically, which confounds lactate-guided resuscitation.

Milrinone: inodilator, renally clearedMilrinone, a PDE-3 inhibitor, raises cardiac output and lowers wedge pressure and systemic resistance without β-receptors; it is renally cleared, so reduce the dose in renal impairment and watch for hypotension and ventricular arrhythmias.

Cardiac dysfunction in sepsis: norepinephrine or epinephrineFor septic shock with cardiac dysfunction, either norepinephrine or epinephrine is a reasonable first vasopressor — norepinephrine with tachyarrhythmia, epinephrine with bradycardia.

The rules

Know these

Choose the agent by shock type must knowSeptic and other vasodilatory shock: norepinephrine. Hypotensive cardiogenic shock: norepinephrine, plus an inotrope for low output. Anaphylaxis: epinephrine. Hemorrhage: blood and bleeding control first — vasopressors never substitute.

Titrate to perfusion, not pressure aloneTitrate vasoactive drugs to MAP plus perfusion — mentation, urine output, capillary refill and lactate trend; for septic shock at 65 or older, SSC 2026 suggests an initial MAP range of 60–65 mmHg.

Norepinephrine or phenylephrine?

Commonly confused

Receptors	α1 and β1
Heart rate	Little change
Cardiac output	Generally maintained
Role	First-line in septic and cardiogenic shock

More detail

Reference

Show 6 reference facts

Angiotensin II for refractory vasodilatory shock starts at 20 ng/kg/min (maximum 80 in the first 3 hours, 40 for maintenance) and causes arterial and venous thrombosis — give VTE prophylaxis. SSC prefers norepinephrine first-line.

Vasopressin is a non-catecholamine acting on V1 receptors of vascular smooth muscle, useful when high norepinephrine doses have saturated or downregulated α1 receptors.

SSC 2026 found insufficient evidence to recommend IV methylene blue for refractory septic shock and suggests against terlipressin (digital ischemia).

Dobutamine is started at 0.5–1 mcg/kg/min and titrated; effective rates are usually 2–20 mcg/kg/min. It can cause tachyarrhythmias, ischemia and hypotension from vasodilation.

Septic shock with an ongoing vasopressor requirement also gets IV hydrocortisone 200 mg/day (see Sepsis & Septic Shock).

Avoid infusing norepinephrine into leg veins in older adults or in patients with occlusive vascular disease of the legs; check the site often for free flow.

Pearl

Pressors fix the tone, inotropes fix the pump — and neither replaces stopping the bleeding.

Sources · Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2026 — SCCM recommendations page · Evans L et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Intensive Care Med 2021;47:1181–1247 · Norepinephrine bitartrate injection prescribing information — DailyMed (§5.1 tissue ischemia; extravasation treatment) · Phenylephrine hydrochloride injection prescribing information — DailyMed (§5.2 bradycardia) · Giapreza (angiotensin II) prescribing information — DailyMed · Merck Manual Professional — Shock (table: inotropic and vasoactive catecholamines) · Sinha SS et al. 2025 Concise Clinical Guidance: ACC Expert Consensus Statement on the Evaluation and Management of Cardiogenic Shock. J Am Coll Cardiol 2025;85:1618–1641 (claims as verified on the Cardiogenic Shock sheet) · Dobutamine injection prescribing information — DailyMed · Milrinone lactate injection prescribing information — DailyMed · Starter sheet built from the verified AGACNP fact map (facts reviewed 2026-10-15).