Inotrope · PDE-3 inhibitor · Vasodilator
Milrinone (Primacor)
Also called Primacor
Indications
- Acute decompensated heart failure with low output, short term (label)
- Cardiogenic shock once MAP is supported; outcomes similar to dobutamine (DOREMI)
- Low output after cardiac surgery (off-label)
- RV failure or pulmonary hypertension, including after LVAD implantation or transplant (off-label)
- Low output in patients on β-blockers, since it acts beyond the receptor
- Bridge to transplant or palliative home infusion (off-label)
Dosing
Milrinone drip card and mL/h converterStart: 0.125–0.375 mcg/kg/min; the 50 mcg/kg load is often skipped (hypotension)
Mechanism of action
Milrinone selectively inhibits phosphodiesterase 3, the enzyme that breaks down cAMP in cardiac and vascular smooth muscle. In myocytes the higher cAMP activates protein kinase A, which phosphorylates L-type calcium channels and phospholamban, strengthening contraction and speeding relaxation. In vascular smooth muscle cAMP inhibits myosin light-chain kinase, dilating systemic and pulmonary arteries and veins. Because it acts beyond the β receptor, it works when receptors are blocked or downregulated.
Pharmacology
- Cardiovascular: an inodilator: raises cardiac output 25–42% and lowers wedge pressure 20–36% and SVR 17–37% (label), with little rise in heart rate
- Cardiovascular: lowers PVR more than dobutamine, helping the RV; BP often falls, needing a vasopressor
- Cardiovascular: improves diastolic relaxation; raises O₂ demand less than catecholamines because afterload falls
- Cardiovascular: ventricular arrhythmias in 12.1% and supraventricular in 3.8% of trial patients (label)
- Hematologic: thrombocytopenia in 0.4% (label)
- Renal: no direct effect, but AKI causes accumulation
Pharmacokinetics
| Onset | Hemodynamic effect within 5–15 min IV (label) |
|---|---|
| Peak | About 10 h to near steady state without a load (4–5 half-lives) |
| Duration | Hours; longer in kidney impairment |
| Half-life | 2.3–2.4 h in heart failure (label) |
| Distribution | Vd 0.38–0.45 L/kg (label) |
| Protein binding | About 70% (label) |
| Metabolism | Minor: 12% as an O-glucuronide (label) |
| Clearance | 0.13–0.14 L/kg/h, with active tubular secretion (label) |
| Elimination | Urine, 83% unchanged; about 90% within 8 h (label) |
| Organ failure | Kidney impairment markedly lengthens the half-life; the label lowers the rate by creatinine clearance |
Chemistry
- A bipyridine (1,6-dihydro-2-methyl-6-oxo-[3,4'-bipyridine]-5-carbonitrile), a more potent relative of amrinone; neither catecholamine nor glycoside, and achiral
- Poorly water-soluble at neutral pH (logP about 0.4), so it comes as the lactate: 1 mg/mL vials with lactic acid and dextrose, pH 3.2–4.0, and premixed 200 mcg/mL in D5W
- Furosemide precipitates at once in a milrinone line (label); dilute in 0.45% or 0.9% saline or D5W
Adverse effects and cautions
In the one-pagers
- Vasopressors and InotropesReceptors and effects: Milrinone: PDE3 inhibitor (no receptor): ↔ / ↑↑ / ↓
- Heart FailureDecompensated HF and shock: Milrinone (a PDE3 inhibitor) works despite beta-blockers. It vasodilates (watch BP) and needs a lower rate in renal impairment.
- Right Heart Failure and Pulmonary HypertensionManagement priorities: Contractility: dobutamine or milrinone, usually with a pressor.
- After Cardiac SurgeryHemodynamics, low output and vasoplegia: Contractility: epinephrine, dobutamine or milrinone (a vasodilator that often needs norepinephrine alongside). Levosimendan did not improve outcomes as prophylaxis (LEVO-CTS 2017) or rescue (CHEETAH 2017).
- LVAD BasicsSelection, implant and the early postoperative course: The first week is about the right ventricle. Unloading pulls the septum leftward and removes its help to RV contraction while pump flow raises venous return to an RV still facing high pulmonary pressures; it dilates, the LV under-fills, and flow and PI fall with a high CVP. INTERMACS counts right heart failure as needing an RVAD, prolonged inh
- Obstetric EmergenciesAmniotic fluid embolism: Right heart failure: echo, 500 mL boluses with reassessment, norepinephrine, adding dobutamine 2.5–5 or milrinone 0.25–0.75 mcg/kg/min
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Sources
- FDA label: milrinone lactate (2026)
- PROMISE (Packer, NEJM 1991)
- DOREMI (Mathew, NEJM 2021)
For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow the order, the label and your institution's protocols.