Vasopressors

Background

• Goal is to reach critical organ perfusion pressure
  • Brain: MAP of 50 mmHg
  • Heart: MAP of 65 mmHg
  • Kidneys: MAP 65-75 mmHg
• IV Vasopressor have not been shown to be unsafe when used peripherally If running peripherally perform frequent site check via institutional protocol.
  • Ideally use proximal (antecubital fossa) large-bore IV (at least 18-gauge)

Types

Vasopressors

Vasopressors may be initiated peripherally while central access is being obtained — do not delay for central line placement (SSC 2021).

Pressor	Initial Dose	Max Dose	Cardiac Effect	BP Effect	Arrhythmias	Special Notes
Dobutamine	2-5 mcg/kg/min	20 mcg/kg/min (up to 40 in refractory cases)	Strong β₁ agonist (+inotrope, +chronotrope); weak β₂ agonist (+vasodilation)	Minimal α effect; may decrease BP due to β₂ vasodilation	Variable HR effects; can cause tachycardia	Indicated in decompensated systolic CHF and cardiogenic shock with adequate BP. Not a vasopressor — it is an inotrope. Must be used with a vasopressor if hypotensive.
Dopamine	2-5 mcg/kg/min	20 mcg/kg/min	β₁ and endogenous norepinephrine release	Mixed α and β effects at all doses; α effects predominate at higher doses	Arrhythmogenic from β₁ effects	More adverse events (especially arrhythmia) when used in shock compared to norepinephrine. SSC 2021 suggests against dopamine as first-line except in select patients with bradycardia and low risk of tachyarrhythmia.
Epinephrine	1-10 mcg/min (0.01-0.1 mcg/kg/min)	0.5 mcg/kg/min	+Inotropy, +chronotropy (β₁)	Low dose: β₂ vasodilation may predominate; high dose: α₁ vasoconstriction predominates	Significant — tachycardia, SVT, VT. Increases myocardial O₂ demand.	2nd or 3rd line for septic shock (SSC 2021: add after norepinephrine ± vasopressin). 1st line for anaphylaxis (0.3-0.5 mg IM) and cardiac arrest. May cause splanchnic vasoconstriction, lactic acidosis, and hyperglycemia.
Norepinephrine	2-5 mcg/min (0.01-0.03 mcg/kg/min)	0.5-1 mcg/kg/min (some sources up to 3.3 mcg/kg/min)	Mild β₁ direct effect (+inotropy)	Strong α₁ and α₂ vasoconstriction; β₁ effect	Less arrhythmogenic than dopamine	1st line for septic shock (SSC 2021). Increases MAP primarily via vasoconstriction. Increases coronary perfusion pressure. Minimal β₂ effect.
Milrinone	50 mcg/kg IV over 10 min (loading dose often omitted in acute illness due to hypotension risk)	0.375-0.75 mcg/kg/min	PDE-3 inhibitor → ↑intracellular cAMP → ↑Ca²⁺ influx → +inotropy	Arteriolar and venous vasodilator (reduces preload AND afterload)	Less arrhythmogenic than dobutamine	Inodilator — useful in decompensated HF with elevated afterload, RV failure, or pulmonary hypertension. Causes hypotension — not a vasopressor; use with a vasopressor if MAP is low. Renally cleared — dose-reduce in CKD.
Phenylephrine	100-180 mcg/min, then 40-60 mcg/min	0.4-9.1 mcg/kg/min	No direct cardiac effect	Pure α₁ agonist → vasoconstriction	May cause reflex bradycardia	Short duration of action (5-20 min IV). Use in septic shock only if: NE causes arrhythmias, cardiac output is high with persistent hypotension, or as salvage when NE + vasopressin have failed.
Vasopressin	0.03 U/min (fixed dose)	0.04 U/min	No direct inotropic or chronotropic effect; possible reflex bradycardia	V₁ receptor agonist → vascular smooth muscle constriction	Minimal	2nd line in septic shock — add to NE rather than escalating NE (SSC 2021 suggests adding before epinephrine). Fixed dose — generally not titrated. May reduce the risk of atrial fibrillation vs. catecholamine-only regimens. Avoid dose >0.04 U/min → risk of cardiac and mesenteric ischemia.
Methylene blue	IV bolus 1-2 mg/kg over 15 min	1-2 mg/kg/hour (limited data on max duration)	Possible increased inotropy; improves cardiac ATP utilization	Inhibits NO-mediated peripheral vasodilation → increases SVR	Minimal reported	Salvage therapy for refractory vasodilatory shock unresponsive to catecholamines. Contraindicated in G6PD deficiency (hemolytic anemia), ARDS, severe pulmonary hypertension. Interferes with pulse oximetry readings (falsely low SpO₂). Avoid with serotonergic drugs (risk of serotonin syndrome).
Angiotensin II (Giapreza)	20 ng/kg/min	40-80 ng/kg/min (max 200 ng/kg/min per label)	No direct cardiac effect	AT₁ receptor agonist → potent arteriolar vasoconstriction; also stimulates aldosterone secretion	Minimal	Salvage therapy for refractory vasodilatory shock (ATHOS-3 trial). May be particularly useful in patients on ACEi/ARB or with high renin states. Monitor for thrombosis (increased risk reported).

Medication	IV Dose (mcg/kg/min)	Standard Concentration	Final Concentration
Norepinephrine (Levophed)	0.01-2 mcg/kg/min	8 mg in 500 mL D5W	16 mcg/mL
Dopamine	2-20 mcg/kg/min	400 mg in 250 mL D5W	1,600 mcg/mL
Dobutamine	2-20 mcg/kg/min	250 mg in 250 mL D5W	1,000 mcg/mL
Epinephrine	0.01-1 mcg/kg/min	1 mg in 250 mL D5W	4 mcg/mL

Norepinephrine 2-5 mcg/min (0.01-0.03 mcg/kg/min), max 0.5-1 mcg/kg/min IV drip — 1st line for septic shock (SSC 2021) Epinephrine 1-10 mcg/min (0.01-0.1 mcg/kg/min), max 0.5 mcg/kg/min IV drip — 1st line for anaphylaxis and cardiac arrest Vasopressin 0.03 U/min (fixed dose), max 0.04 U/min IV drip — Add to NE rather than escalating NE (SSC 2021) Dopamine 2-5 mcg/kg/min, max 20 mcg/kg/min IV drip — SSC 2021 suggests against as 1st line; more arrhythmogenic than NE Dobutamine 2-5 mcg/kg/min, max 20 mcg/kg/min IV drip — Inotrope, not a vasopressor; use with vasopressor if hypotensive Phenylephrine 100-180 mcg/min, then 40-60 mcg/min IV drip — Pure alpha-1 agonist; short duration 5-20 min Milrinone 0.375-0.75 mcg/kg/min (loading often omitted) IV drip — Inodilator; causes hypotension; useful in RV failure/pulmonary HTN Methylene blue 1-2 mg/kg IV bolus over 15 min IV — Salvage for refractory vasodilatory shock; contraindicated in G6PD deficiency Angiotensin II (Giapreza) 20 ng/kg/min, max 40-80 ng/kg/min IV drip — Salvage for refractory vasodilatory shock (ATHOS-3 trial)

Causes of non-response to vasopressors

• Acidosis
  • Dx: Blood gas, BMP
  • Tx: treat underlying cause, consider bicarbonate gtt
  • Note: Vasopressin (in contrast to catecholamine vasopressors) does not show decreased efficacy in setting of acidosis
• Hypothyroidism
  • Dx: Clinical, TSH
  • Tx: levothyroxine
• Anaphylaxis
  • Dx: History
  • Tx: Epinephrine, methylene blue, ECMO
• Adrenal insufficiency
  • Dx: Clinical, cortisol level, hyperkalemia + hyponatremia
  • Tx: Hydrocortisone 100-200mg
• Hypocalcemia
  • Dx: ionized calcium, prolonged QTc
  • Tx: Calcium chloride or calcium gluconate
• Occult bleeding
  • Dx: Clinical (consider GI bleed and retroperitoneal hematoma)
  • Tx: Transfusion, treat coagulopathy, surgery/IR interventions
• Toxicologic
  • Dx: Clinical (consider beta blocker toxicity, calcium channel blocker toxicity, TCA overdose, etc)
  • Tx: Depends on etiology (glucagon, hyperinsulin euglycemia therapy, sodium bicarbonate, ECMO, etc)
• 2nd cause of shock
  • Dx: Clinical, consider RUSH exam
  • Tx: Address underlying cause

Push (Bolus) Dose Pressors

• Use for temporary BP or CO boost with no evidence for improved patient outcome
  • Post-intubation hypotension
  • Propofol-induced hypotension
  • A-fib with hypotension
    • Easier to convert well-perfused heart
• Retrospective review of push-dose phenylephrine showed improved early hemodynamic stability but increased ICU mortality
• While epinephrine and phenylephrine are most commonly used, push dose vasopressin and norepinephrine are reasonable alternatives

Epinephrine

• α₁, α₂, β₁, β₂ effects
• Inopressor
• Increases heart rate and inotropy and vasoconstricts
• 10 cc syringe with 9 cc of NS and draw up 1 mL of 1:10,000 epi (cardiac epinephrine with 10mL of 100 mcg/mL which is 1 mg of epinephrine)
  • Now have 10mL of 10mcg/mL (1:100,000)
    • Use 0.5-2mL (5-20 mcg) every 1-5min (similar to epinephrine drip)
    • Can give peripherally since similar concentrations are give subcutaneously with lidocaine with epinephrine (1:100,000)
• Onset - 1min
• Duration - 10min
• Effects are usually gone within 5 minutes

Phenylephrine

• Pure α (no effect on heart) potent vasoconstrictor
• Useful in tachycardic patient since no effect on HR and might even decrease from reflex parasympathetic response
• Increase in heart perfusion can improve cardiac output

• Place 1mL of 10mg/mL vial in 100mL NS
  • Now have 100mcg/mL with total bag containing 10 mg of phenylephrine
  • Draw up 10mL from bag with syringe
  • Use 0.5-2mL (50-200mcg) every 1-5 minutes
    • Can give peripherally since drug is approved for IM or SQ use
• Onset - 1min
• Duration - 20min
• Effects are usually gone within 5 minutes

Extravasation Injury

• Classically norepinephrine drips
• Avoid hand/wrist and ensure peripheral IV quality before starting vasopressors
• May occur with IO placements as well
• Push dose epinephrine and phenylephrine have low chance of causing extravasation injury
• Dermal necrosis:
  • Prevention - phentolamine mesylate 10mg into each liter of norepinephrine solution (pressor effect is not changed)
• Treatment ()

1. If the pt is relying on the agent for their hemodynamics, switch the pressor to another IV or place an immediate IO or central line
2. Do not discontinue the IV
3. Aspirate as much residual as you can
4. Administer subcutaneous phentolamine mesylate (Regitine) using 25 G or smaller needle
   • Place 5 mg (1 ml) in 9 ml of NS
   • A dose of 0.1 to 0.2 mg/kg (up to a maximum of 10 mg) should then be injected through the catheter and subcutaneously around the site
   • Administered as soon as the extravasation is detected, even if the area initially looks just a little white or OK
   • Should see near-immediate effects; otherwise consider an additional dose
   • Discontinue the IV/catheter
   • May cause systemic hypotension (but they should be on pressors at another site)
5. Consult plastic surgery

Medication Dosing

Norepinephrine 0.05-0.4mcg/kg/min (start 5-15mcg/min) IV Epinephrine 0.01-0.5mcg/kg/min IV Vasopressin 0.03-0.04 units/min (fixed dose, do not titrate) IV Dopamine 2-20mcg/kg/min IV Phenylephrine 100-180mcg/min (0.4-9.1mcg/kg/min) IV Dobutamine 2-20mcg/kg/min IV

See Also

• Critical care quick reference
• Undifferentiated shock
• Undifferentiated shock (peds)

External Links

• EMCrit Podcast - Vasopressor Basics
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5052865/pdf/ceem-15-010.pdf
• EMCrit Podcast - Push Dose Pressors