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).
- 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.
- 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
-
Javaloyes P, Miró Ò, Gil V, Martín-Sánchez FJ, Jacob J, Herrero P, Takagi K, Alquézar-Arbé A, López Díez MP, Martín E, Bibiano C, Escoda R, Gil C, Fuentes M, Llopis García G, Álvarez Pérez JM, Jerez A, Tost J, Llauger L, Romero R, Garrido JM, Rodríguez-Adrada E, Sánchez C, Rossello X, Parissis J, Mebazaa A, Chioncel O, Llorens P; ICA-SEMES Research Group. Clinical phenotypes of acute heart failure based on signs and symptoms of perfusion and congestion at emergency department presentation and their relationship with patient management and outcomes. Eur J Heart Fail. 2019 Nov;21(11):1353-1365. Available at: https://onlinelibrary.wiley.com/doi/10.1002/ejhf.1502
Masip J, Frank Peacok W, Arrigo M, Rossello X, Platz E, Cullen L, Mebazaa A, Price S, Bueno H, Di Somma S, Tavares M, Cowie MR, Maisel A, Mueller C, Miró Ò. Acute Heart Failure in the 2021 ESC Heart Failure Guidelines: a scientific statement from the Association for Acute CardioVascular Care (ACVC) of the European Society of Cardiology. Eur Heart J Acute Cardiovasc Care. 2022 Jan 18:zuab122. Available at: https://academic.oup.com/ehjacc/advance-article-abstract/doi/10.1093/ehjacc/zuab122/6510668?redirectedFrom=fulltext
Chuzi S, Allen LA, Dunlay SM, Warraich HJ. Palliative Inotrope Therapy: A Narrative Review. JAMA Cardiol. 2019 Aug 1;4(8):815-822. Available at: https://jamanetwork.com/journals/jamacardiology/article-abstract/2737414
Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, González-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P; Authors/Task Force Members; Document Reviewers. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2016 Aug;18(8):891-975. Available at: https://onlinelibrary.wiley.com/doi/10.1002/ejhf.592
Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL; American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013 Oct 15;62(16):e147-239. Available at: https://www.sciencedirect.com/science/article/pii/S0735109713021141?via%3Dihub