Background    Some patients with end-stage heart failure causing symptoms at rest are placed on continuous infusions of cardiac inotropes in an attempt to improve symptoms and avoid hospitalizations. Among end-stage heart failure patients who are ineligible for advanced cardiac therapies (such as heart transplant of a ventricular assist device), mean life expectancy with inotrope-dependent medical therapy is estimated at 9.4 months, with 26% surviving to 1 year.  Hence, the home use of continuous inotrope therapy may be commonly encountered by clinicians who care for the seriously ill.

Pharmacology     Both major classes of inotropic agents, adrenergic agonists (i.e. dopamine and dobutamine) and phosphodiesterase inhibitors (i.e. milrinone), increase contractility by increasing available calcium levels within myocardial tissue via cAMP regulation (2).

Patient Selection      Patients on maximal medical therapy who continue to have refractory symptoms at rest (New York Heart Association Class IV) may benefit from home IV inotrope therapy. Eligible patients must have either failed a trial of weaning inotropic support in the inpatient setting or been too ill to attempt weaning (3,4). Patients should not receive home inotropic therapy if they are not maximized on their oral medications, unable or unwilling to utilize an infusion pump and central line, unwilling to undergo appropriate monitoring, or have refractory ventricular tachycardia or life threatening arrhythmias (5).

Outcomes and Risks  Available data assess the number of hospitalizations, symptom control, mortality, and quality of life (6-13). Unfortunately, the strength of the data is relatively weak and the outcomes are mixed as very few studies utilize the same methods or measure the same outcomes. The prevailing literature suggests trends of hastened death with dobutamine and milrinone administration largely due to arrhythmias (10,11, 14-18). However, the majority of this data is based on data from small trials on oral and intermittent IV inotropes (not continuous therapy), and, importantly, are from an era in which prophylactic ICD implantation was not the standard of care. The most recent guidelines advocate against the use of intermittent therapy altogether. Despite these risks, if the patient’s goal is to be at home, there is evidence that continuous outpatient inotrope infusion may shift the remaining survival time to a home setting through marked improvements in symptom control and therefore may be an excellent treatment for the well selected patient (9).

Practical Concerns   Inotropes are started during an inpatient hospitalization. This typically occurs in the setting of the intensive care unit where doses can be titrated to allow for a weaning trial if the patient is clinically stable enough to do so. Patients will require a PICC line or Hickman catheter for infusion with regular, high quality line care to prevent infections. Patients on home inotropes require ongoing care by an adequately trained home care team and an experienced physician (typically a cardiologist) so that their medications can be adjusted as needed. The most common side effects are hypotension and arrhythmias. For this reason electrolytes should be regularly followed, as well as renal function through regular serum creatinine monitoring in order to anticipate dosing changes that may be necessary if changes in creatinine clearance should occur.

Medicare Coverage Requirements: Medicare has strict coverage guidelines for home inotropes, which greatly affect how they are used in the US. Below are the criteria that need to be met in order for inotrope therapy to be covered (5).

• Symptoms must be uncontrolled; specifically, dyspnea at rest must be present despite maximum tolerated doses of digoxin, loop diuretics, ACEIs, or other vasodilators.
• Hemodynamic studies must be performed within six months prior to initiation of home inotropic therapy that show both:
  • Cardiac index of 2.2 L/min/m2 (maximum) and/or pulmonary capillary wedge pressure of 20 mmHg before infusions while on maximum tolerated oral medications.
  • A 20% increase in cardiac index, and/or at least a 20% decrease in pulmonary capillary wedge pressure during inotrope infusion.
• Improvement in patient “well-being” (i.e., decreased dyspnea, increased diuresis, improved renal function, or reduction in weight) must be shown with the absence of dyspnea at rest at the time of discharge and with outpatient follow up.
• There must be documented deterioration with attempts to discontinue/wean the patient from inotropes while in the hospital.
• Any life-threatening arrhythmia must be controlled and addressed prior to discharge. Some evidence suggests that oral amiodarone may benefit these patients who experience ectopy but are still benefiting from inotrope therapy (17,19).
• Covered inotrope dosing must be within the following ranges:
  • Dobutamine 2.5-10 mcg/kg/min.
  • Milrinone 0.375-0.75 mcg/kg/min.
  • Dopamine may also be used at a rate of 2 mcg/kg/min.
• Efforts to maintain the patient on the lowest practical dose must be made and documented during the first three months of therapy.

Cost     Cost of these therapies varies significantly depending on choice of drug and insurance type. Milrinone cost per month ranges between $4500-$21,000 and dobutamine between $1140-$2790 (estimates are based on a 75 kg patient with infusions of 0.5 mcg/kg/min and 5mcg/kg/min for milrinone and dobutamine respectively) (20). Medicare will reimburse for these therapies and for associated equipment such as infusion pumps, however nursing visits are not included in these estimates.

Home Care and Hospice   Many hospices will not accept inotrope-dependent patients given the cost and need for advanced training (12). Some communities have specialized home-care agencies or programs for patients on home inotropes, which may or may not be part of a hospice program.

References

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3. Lewis EF. End of life care in advanced heart failure. Curr Treat Options Cardiovasc Med. 2011; 13(1):79–89.
4. Young JB, Moen EK. Outpatient parenteral inotropic therapy for advanced heart failure. J Heart Lung Transplant. 2000; 19(8 Suppl):S49–57.
5. Gorski LA. Positive inotropic drug infusions for patients with heart failure: current controversies and best practice. Hom Healthc Nurs. 2002; 20:244-53.
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15. Amsallem E, Kasparian C, Haddour G, Boissel JP, Nony P. Phosphodiesterase III inhibitors for heart failure. Cochrane Database of Systematic Reviews. 2005, Issue 1. Art. No.: CD002230. DOI: 10.1002/14651858.CD002230.pub2.
16. Thackray S, Easthaugh J, Freemantle N, Cleland JGF. The effectiveness and relative effectiveness of intravenous inotropic drugs acting through the adrenergic pathway in patients with heart failure—a meta-regression analysis. Eur J Heart Fail. 2002; 4(4):515–29.
17. Toma M, Starling RC. Inotropic therapy for end-stage heart failure patients. Curr Treat Options Cardiovasc Med. 2010; 12(5):409–19.
18. Ewy GA. Inotropic infusions for chronic congestive heart failure: medical miracles or misguided medicinals? J Am Coll Cardiol. 1999; 33(2):572–5.
19. Nanas JN, Kontoyannis DA, Alexopoulos GP, et al. Long-term intermittent dobutamine infusion combined with oral amiodarone improves the survival of patients with severe congestive heart failure. Chest. 2001; 119(4):1173–8.
20. Vantage Home Infusion Therapy Services. prepared by Dr. Robert Buzas. http://www.vhcn.com/vantage-home-infusion-services/ 

Authors’ Affiliations: Allegheny Health Network, Pittsburgh, PA

Conflicts of Interest Statement: The authors have disclosed no relevant conflicts of interest.

Version History:  First published August 2014. References updated and copy-edited in September 2015 by Sean Marks MD.