Use Inotropes for select cases of acute or end-stage heart failure

Inotrope options include dopamine, dobutamine, and milrinone. Dobutamine is usually preferred.
Abdelwahab Ward, BS Pharm, PharmD

Do the IV inotropes dobutamine (Dobutrex, Dobuject) AND MILRINONE (Primacor, Milicor) still have a role in treating heart failure with reduced ejection fraction (HFrEF)? Yes, but only in a small subset of patients. Both medications increase arrhythmias. And widespread use fell out of favor years ago, due to concerns about increased mortality, especially in patients withOUT low cardiac output and hypotension. But inotropes may still be needed for some patients with low cardiac output. Help guide appropriate use...

When should inotropes be considered?

In acute HFrEF, reserve inotropes for patients with poor perfusion, such as cool extremities or poor urine output, PLUS systolic blood pressure less than 90 mmHg. If these patients aren't hypotensive, first consider an IV vasodilator like sodium nitroprusside (Niprid, Nipruss) or nitroglycerin (Nitronal). And be ready to optimize diuretics alongside vasodilators or inotropes. In chronic HFrEF, expect to save inotropes as a palliative option, or as a "bridge" until heart transplant or left ventricular assist device (LVAD).

  • Note (1): Inotropes are options for patients with severely reduced cardiac output (i.e., SBP < 90 mmHg and/or end organ hypoperfusion; dry and cold or wet and cold)...
    • If the patient is hypotensive due to hypovolemia (dry and cold), this should be corrected before an inotrope is used.
    • If the patient is wet and cold and SBP < 90 mmHg, an inotrope is first-line.
    • If the patient is wet and cold and SBP ≥ 90 mmHg, consider an inotrope if the patient is refractory to a diuretic and vasodilator.

Which inotrope is preferred?

Lean toward dobutamine (Dobutrex) over milrinone (Milicor) for patients with hypotension or renal dysfunction. Milrinone (Milicor) is more vasodilating and renally cleared. Plus dobutamine's shorter half-life makes it easier to titrate. But consider milrinone if vasodilation is preferred, such as with pulmonary hypertension. Ensure safe use of inotropes during transitions of care. For example, verify doses in mcg/kg/min as inotrope concentrations may vary between facilities or home-infusion pharmacies.

  • NOTE (2): Inotrope options include dopamine, dobutamine, and milrinone. Dobutamine is usually preferred. Choice depends on the patient’s hemodynamics and clinical scenario. Consider the following choices...
    • Recent beta-blocker use (and NOT responding to initial dobutamine titration): milrinone (action not affected by beta-blockers).
    • Hypotension: dobutamine (if not in shock) or dopamine (to increase blood pressure).
    • Pulmonary hypertension: milrinone (reduces pulmonary vascular resistance).
    • Cardiorenal syndrome: dopamine or dobutamine are easier to titrate than milrinone (milrinone has long half-life so delay to steady-state; renally cleared).
    • Ischemic heart disease: dobutamine (minimal effect on heart rate vs dopamine; less arrhythmogenic than dopamine; increases cardiac output at least as much as dopamine with lower oxygen consumption; milrinone may increase mortality).
    • Tolerance to dobutamine: milrinone (tolerance to dobutamine begins within 48 to 72 hours).

Table (1). Commonly Used Inotropes
INOTROPE MECHANISM DOSING SIDE-EFFECTS
Beta-agonists
Dobutamine Beta-1 > beta-2 > alpha 2–20 μg/kg/min
(−) bolus dose		 Tachyarrhythmias
Hypotension
Headache
Eosinophilic myocarditis (rare)
Peripheral blood eosinophilia
Dopamine Dopa > beta, alpha in high doses Renal effect <3 μg/kg/min
Inotropic effect 3–5 μg/kg/min
Vasoconstriction
>5 μg/kg/min
(−) bolus dose		 Tachyarrhythmias
Hypertension
Myocardial ischaemia
Norepinephrine Beta-1 > alpha > beta-2 0.2–10.0 μg/kg/min
(−) bolus dose		 Tachyarrhythmias
Hypertension
Headache
Epinephrine Beta-1 > beta-2 > alpha 0.05–0.50 μg/kg/min
(+) bolus dose: 1 mg IV every 3–5 min during resuscitation		 Tachyarrhythmias
Headache
Anxiety
Cold extremities
Pulmonary oedema
Cerebral haemorrhage
Phosphodiesterase III inhibitors
Milrinone PDE3 inhibition 0.375–0.750 μg/kg/min
(+) bolus dose: 25–75 μg/kg over 10–20 min (optional)		 Tachyarrhythmias
Hypotension
Headache

References

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Abdelwahab Ward, BS Pharm, PharmD