Vasopressors & Inotropes
at the bedside
persistent hypotension, mean arterial pressure (MAP) <65 mmHg, or clinical hypoperfusion (mottling, cool extremities, rising lactate, falling urine output) during ongoing fluid resuscitation = vasopressor now, not another reflex bolus.
- reassess volume status → quickly: passive leg raise or a POCUS look at the IVC; do not keep giving fluid on reflex if not fluid responsive.
- start early → once hypotension or hypoperfusion persists and fluid responsiveness looks unlikely: vasopressor alongside ongoing fluid, not after a fixed volume finishes.
- start norepinephrine → while access is sorted; a peripheral line is fine short term, do not wait for a central line.
- target MAP → ≥65 mmHg by default; invasive arterial monitoring as soon as available; individualize lower in older adults or chronic hypertensives (below).
early warning signs
- norepinephrine already needed at moderate dose within the first hour of resuscitation
- lactate rising rather than clearing despite an adequate MAP
- new mottling, altered mentation, or UOP <0.5 mL/kg/hr
escalate now if
- norepinephrine-equivalent dose above 1 mcg/kg/min → refractory shock, ICU
- a second or third vasoactive agent needed to hold MAP ≥65 mmHg → second agent, ICU
- lactate not clearing despite an adequate MAP and volume status → reassess
- a new arrhythmia limiting further titration → troubleshooting
- a suspected cardiogenic component needing inotrope titration → inotrope, then cardiogenic shock
- any patient being considered for invasive hemodynamic monitoring or mechanical circulatory support → ICU
define & classify
a vasopressor raises blood pressure mainly by increasing systemic vascular resistance (SVR); an inotrope raises cardiac output mainly by increasing myocardial contractility.
- vasodilation → vasopressor
- low cardiac output → inotrope
- mixed shock → targeted combination
| agent | class | receptor / action | best fit |
|---|---|---|---|
| norepinephrine | mixed | α1 +++, β1 ++ | vasodilatory shock, first line (1) |
| epinephrine | mixed | α1 ++, β1 +++, β2 ++ | anaphylaxis; add-on when norepinephrine + vasopressin aren’t enough |
| vasopressin | vasopressor | V1 (vascular smooth muscle) | fixed-dose, catecholamine-sparing add-on (2)(3) |
| dopamine | mixed | dose-dependent: D1 → β1 → α1 | now mostly bradycardia-associated hypotension only (4) |
| phenylephrine | vasopressor | α1 only, pure | narrow: tachyarrhythmia-limited states, salvage |
| dobutamine | inotrope | β1 +++, β2 + | low cardiac output, inotrope not pressor |
| milrinone | inotrope | PDE-3 inhibitor (↑ cAMP) | low cardiac output, renally cleared |
initial management
starting norepinephrine
- norepinephrine 0.01–0.5 mcg/kg/min IV, titrate to MAP ≥65 mmHg; consider 60–65 mmHg in elderly or chronic hypertensives (SSC 2026, individualized targets in older adults (1)).
- peripheral infusion via a large proximal vein is acceptable for up to 24 hr while central access is obtained; extravasation is uncommon with close monitoring (5). Do not delay the drug for the line.
- norepinephrine, not dopamine, is first line even in cardiogenic-predominant shock (4).
second agent
- before any second vasopressor, reassess volume and cardiac function on POCUS: an under-filled or failing heart needs fluid or an inotrope, not more vasoconstriction.
- add vasopressin, fixed 0.03 units/min, once norepinephrine is around 0.25–0.5 mcg/kg/min; not titratable, it stays fixed and spares catecholamine dose.
- hydrocortisone 50 mg IV q6h (200 mg/day) for septic shock with ongoing vasopressor need despite adequate fluids: an ICU-level therapy, not for transient hypotension; current guidance sets no vasopressor dose or duration threshold before starting (6).
refractory, third agent
- add epinephrine 0.01–0.5 mcg/kg/min if MAP still inadequate on norepinephrine + vasopressin; lactate and glucose rise as a drug effect, not necessarily worsening shock.
- angiotensin II or methylene blue are specialist-directed rescue options for true refractory vasodilatory shock, not a ward-level order.
methylene blue: mechanism & cautions
methylene blue inhibits soluble guanylate cyclase, blocking the nitric oxide-cGMP pathway behind pathologic vasodilation in vasoplegic shock (septic, post-cardiopulmonary bypass, drug-induced) (7). Adjunctive rescue only, for shock refractory to norepinephrine, vasopressin and epinephrine; never routine or first-line; ICU / specialist discussion first. Contraindicated in G6PD deficiency (hemolysis, methemoglobinemia). Caution with serotonergic drugs (SSRIs, SNRIs, MAOIs, linezolid): MAO-A inhibition, serotonin syndrome risk. Caution in pulmonary hypertension: blunts pulmonary as well as systemic nitric oxide-mediated vasodilation.
low cardiac output, cold shock
- dobutamine 2.5–10 mcg/kg/min (up to 20) if there’s myocardial dysfunction despite an adequate MAP, cold extremities, or oliguria with a normal-to-full ventricle on POCUS, not an empty, underfilled one.
- milrinone 0.375–0.75 mcg/kg/min is an alternative inotrope, the loading dose is usually skipped in shock since it worsens hypotension. renally cleared, reduce the dose or avoid in acute kidney injury (AKI) or chronic kidney disease (CKD). No clear outcome difference against dobutamine (10): renal function is the practical tiebreaker.
reassess
- recheck MAP, lactate trend, capillary refill, and UOP every 30–60 min while titrating.
- a falling lactate and improving mentation matter more than the number on the monitor alone.
- re-image with POCUS if the dose keeps climbing, don’t just add another agent blind.
advanced management
- norepinephrine-equivalent above 1 mcg/kg/min, or 2 or more vasoactive agents = refractory shock: look for a missed cause (undrained source, adrenal insufficiency, occult cardiogenic component), not just a higher dose.
- phenylephrine (peripheral bolus 50–200 mcg (8) or infusion up to 180 mcg/min): reserve for a tachyarrhythmia limiting norepinephrine / epinephrine, or salvage when norepinephrine + low-dose vasopressin fails
- pure α1: drops cardiac output in preload-dependent patients
- a push around norepinephrine initiation was independently associated with higher ICU mortality in a matched cohort (9): use briefly, reassess, do not repeat
- weaning: once MAP is stable off escalating support, taper the most recently added or highest-risk agent first, one at a time; reassess after each step.
troubleshooting
- escalating norepinephrine with a full IVC and B-lines on POCUS → reassess for an occult cardiogenic component, add dobutamine rather than another vasopressor.
- digital mottling or cyanosis on vasopressin → reduce or stop it, do not push past 0.04 units/min.
- new tachyarrhythmia limiting epinephrine or norepinephrine titration → correct K+ and Mg2+, consider phenylephrine as a bridge.
- persistent hypotension despite 3 agents → reassess adrenal axis, source control, and volume status. this is an escalation trigger, not a fourth drug.
- extravasation or a line concern on a peripheral pressor → stop the infusion, aspirate, escalate access urgently.
evidence
| source | type |
|---|---|
| 1. Surviving Sepsis Campaign 2026 (SCCM/ESICM) | guideline |
| 2. VASST trial, N Engl J Med 2008 | RCT |
| 3. VANISH trial, JAMA 2016 | RCT |
| 4. SOAP-II trial, N Engl J Med 2010 | RCT |
| 5. Tian et al., safety of peripheral vasopressors, Emerg Med Australas 2020 | review |
| 6. SCCM/ESICM 2024 focused update, corticosteroids in sepsis / ARDS / CAP | guideline |
| 7. Management of vasoplegic shock, BJA Education | review |
| 8. Phenylephrine and epinephrine push-dose vasopressors, ACEP Now | review |
| 9. phenylephrine push before continuous norepinephrine in septic shock, CHEST 2020 | cohort |
| 10. DOREMI trial, N Engl J Med 2021 | RCT |
| Oxford Handbook of Critical Care Medicine, 4th ed | textbook |
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Last updated · October 2026