Milrinone (Primacor) | Medication Reference

Bedside Snapshot

Inodilator: Used for acute decompensated heart failure and low-output states; increases inotropy and lusitropy while reducing afterload and pulmonary vascular resistance
β-Receptor Independent: Unlike catecholamines (dobutamine), milrinone works independently of β-receptors, so it can be useful in patients on chronic β-blockers or with downregulated β-receptors
Hemodynamic Profile: ↑ cardiac output, ↓ SVR and PVR, but often with hypotension due to vasodilation. May precipitate or worsen shock in borderline patients
Typical Adult Infusion: 0.25–0.75 mcg/kg/min IV, often without a loading dose in the ICU to avoid abrupt hypotension. Loading dose 50 mcg/kg over 10 minutes exists on-label but is frequently omitted
Renal Elimination: Eliminated renally with a relatively long half-life (~2 hours in normal function, longer in CKD) → effects linger after you turn it off, especially in renal failure
Major Risks: Ventricular arrhythmias, hypotension, and accumulation in renal impairment; avoid or use extreme caution in significant hypotension, severe aortic stenosis, or advanced CKD

Brand & Generic Names

Generic Name: Milrinone lactate
Brand Names: Primacor, generics

Medication Class

Phosphodiesterase-3 (PDE3) inhibitor; inodilator (inotrope + vasodilator)

Pharmacology

Mechanism of Action:

Selective inhibition of phosphodiesterase-3 (PDE3) in cardiac and vascular smooth muscle
In cardiac myocytes: PDE3 inhibition ↑ intracellular cAMP → ↑ calcium influx during systole → positive inotropy and improved lusitropy (relaxation)
In vascular smooth muscle: ↑ cAMP leads to vasodilation of systemic and pulmonary vasculature → ↓ SVR and PVR, ↓ ventricular afterload, ↓ filling pressures
Independence from β-adrenergic receptors allows effect even in the presence of β-blockade, but also means there is no β-receptor down-titration control of effect
Chronotropic effect is modest compared to dobutamine, but tachyarrhythmias can still occur due to increased inotropy and intracellular calcium

Pharmacokinetics:

Onset: Hemodynamic effects begin within 5–15 minutes of starting infusion (faster if a loading dose is given)
Distribution: Volume of distribution ~0.4–0.7 L/kg; minimally protein bound; distributes well into tissues
Metabolism: Minimal hepatic metabolism; drug is largely unchanged
Elimination: Primarily renal (~80–90% excreted unchanged in urine); elimination half-life ~2–2.5 hours with normal renal function, prolonged significantly in renal impairment
Special Considerations: Because of the relatively long half-life, changes in rate take time to equilibrate, and toxicity (hypotension, arrhythmias) may persist after stopping the infusion—especially in CKD

Indications

Short-term treatment of acute decompensated heart failure with low cardiac output, especially when cardiac index is low despite adequate filling pressures
Adjunct in cardiogenic shock in selected patients, typically when systemic blood pressure is adequate or supported by vasopressors, and afterload reduction is desired
Support after cardiac surgery for low-output syndrome or RV dysfunction, often in combination with vasopressors
Occasionally used in pulmonary hypertension or RV failure (off-label) due to pulmonary vasodilation, with careful attention to systemic blood pressure

Dosing & Administration

Available Forms:

Vials or ampules: typically 10 mg/10 mL (1 mg/mL) or 20 mg/20 mL
For infusion, commonly diluted in 0.9% NaCl or D5W to concentrations like 200 mcg/mL or institution-specific standard
Administered via controlled IV infusion pump; central access preferred for higher concentrations or prolonged infusions

Adult Dosing (IV):

Scenario	Dose	Route / Duration	Notes
Label loading dose (often omitted)	50 mcg/kg	IV over 10 minutes	Frequently avoided in ICU due to risk of hypotension/arrhythmia
Maintenance infusion – usual range	0.25–0.75 mcg/kg/min	Continuous IV infusion	Start low (e.g., 0.25) and titrate based on hemodynamics and side effects
Hemodynamically fragile or hypotensive	0.125–0.25 mcg/kg/min	Continuous IV infusion	Avoid loading dose; combine with vasopressor support as needed
Renal impairment (CrCl 30–50 mL/min)	Reduce rate by ~25–50%	Continuous IV infusion	Example: 0.125–0.375 mcg/kg/min; titrate to effect and adverse events
Severe renal impairment (CrCl <30 mL/min)	Consider 0.1–0.25 mcg/kg/min or avoid	Continuous IV infusion	High risk of accumulation; some centers prefer alternative inotropes
Post-cardiac surgery low-output state	0.25–0.5 mcg/kg/min	Continuous IV infusion	Used with invasive hemodynamic monitoring when possible
Maximum dose (per many protocols)	0.75–1 mcg/kg/min	Continuous IV infusion	Higher doses significantly increase risk of hypotension and arrhythmias

Contraindications

Contraindications:

Known hypersensitivity to milrinone or formulation components
Severe obstructive aortic or pulmonic valvular disease where increasing inotropy and decreasing afterload may worsen outflow obstruction
Severe hypotension or profound shock where additional vasodilation would be dangerous (unless vasopressors are in place and the risk is accepted)

Major Precautions:

Renal impairment: markedly reduced clearance and prolonged half-life; accumulation greatly increases risk of hypotension and arrhythmias
History of significant ventricular arrhythmias or severe ischemic cardiomyopathy: milrinone can precipitate or worsen ventricular ectopy and VT/VF
Electrolyte abnormalities (hypokalemia, hypomagnesemia) increase proarrhythmic risk; correct before and during therapy
In acute myocardial infarction with hypotension, use very cautiously; inodilators can worsen ischemia by lowering diastolic pressure and increasing demand
Long-term use in chronic heart failure is associated with increased mortality and is generally avoided outside of palliative or advanced HF (bridge to transplant/LVAD) settings

Hypotension Risk: Vasodilation can cause severe hypotension, especially in borderline patients. Often requires concurrent vasopressor support.

Arrhythmia Risk: Can precipitate ventricular ectopy, VT, or VF, especially with electrolyte abnormalities or ischemic cardiomyopathy. Correct K+ and Mg2+ before use.

Renal Accumulation: Prolonged half-life in CKD leads to accumulation and increased toxicity. Reduce dose significantly or consider alternative.

Adverse Effects

Common:

Hypotension (most common)
Ventricular ectopy (PVCs), non-sustained ventricular tachycardia
Headache
Tremor, nervousness
Thrombocytopenia (less common but reported)

Serious:

Sustained ventricular tachycardia or ventricular fibrillation
Severe hypotension with end-organ hypoperfusion requiring vasopressors
Atrial arrhythmias (e.g., atrial fibrillation with rapid ventricular response)
Worsening ischemia in patients with severe coronary artery disease

Special Populations

Elderly Patients:

Often have reduced renal function; adjust dose accordingly
Start at lower end of dosing range (0.125–0.25 mcg/kg/min)
Higher risk of arrhythmias

Renal Impairment:

Dose reduction essential based on CrCl (see dosing table)
CrCl 30–50: reduce by 25–50%
CrCl <30: reduce to 0.1–0.25 mcg/kg/min or avoid
Monitor closely for prolonged effects after dose changes

Hepatic Impairment:

Minimal hepatic metabolism; no specific dose adjustment for hepatic impairment alone
However, liver disease often coexists with renal dysfunction—monitor accordingly

Pregnancy:

Category C: Limited data; use only if benefit justifies potential risk
Used in peripartum cardiomyopathy in select cases

Lactation:

Unknown if excreted in breast milk; use caution

Monitoring

Clinical Monitoring:

Continuous ECG monitoring for ventricular ectopy and tachyarrhythmias
Blood pressure and heart rate continuously or very frequently during initiation and titration
Invasive hemodynamic monitoring (A-line +/- PA catheter) in high-risk patients to guide titration based on CI, SVR, and filling pressures
Renal function (serum creatinine, urine output) at baseline and regularly thereafter to adjust dosing
Electrolytes (especially potassium and magnesium) before and during therapy

Clinical Pearls

Inodilator Concept: Think of milrinone as an inodilator—great when you want more squeeze AND less afterload, but dangerous in an already vasoplegic, hypotensive septic patient.

Combination Therapy: Often used in combination with norepinephrine or other vasopressors in cardiogenic shock: one drug for flow (milrinone), one for pressure (norepi).

Skip the Load: Skip the loading dose in unstable patients; start a low infusion and up-titrate slowly while watching BP and arrhythmias.

β-Blocker Patients: In patients on chronic β-blockers with low cardiac output, milrinone may be more effective than dobutamine because it bypasses β-receptors.

Long Half-Life: Because of the long half-life, be patient when adjusting the dose and cautious when transporting—hemodynamics may continue changing after rate changes or after stopping the infusion.

Not for Chronic Use: Long-term milrinone in chronic heart failure increases mortality. Reserve for acute situations or bridge-to-transplant/LVAD scenarios.

References

1. Lexicomp. (2024). Milrinone: Drug information. Wolters Kluwer.
2. Felker, G. M., Benza, R. L., Chandler, A. B., et al. (2003). Heart failure etiology and response to milrinone in decompensated heart failure: Results from the OPTIME-CHF study. Journal of the American College of Cardiology, 41(6), 997–1003. https://doi.org/10.1016/S0735-1097(02)02968-6
3. Cuffe, M. S., Califf, R. M., Adams, K. F., et al. (2002). Short-term intravenous milrinone for acute exacerbation of chronic heart failure: A randomized controlled trial. JAMA, 287(12), 1541–1547. https://doi.org/10.1001/jama.287.12.1541
4. Tariq, S., & Aronow, W. S. (2015). Use of inotropic agents in treatment of systolic heart failure. International Journal of Molecular Sciences, 16(12), 29060–29068. https://doi.org/10.3390/ijms161226147
5. EMCrit Project. (2023). Inotropes & vasopressors in cardiogenic shock. https://emcrit.org/