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This best practice guideline has been designed for critical care units, however, it can be applied to other areas within your health service who use vasoactive infusions, such as anaesthetics, cardiology and emergency departments.

Mechanism of action/pharmacology

Milrinone is a positive inotrope and vasodilator, with little chronotropic activity. Milrinone selectively inhibits PEAK III cAMP (cyclic adenosine monophosphate) phosphodiesterase isozyme in cardiac and vascular muscle, leading to an increase in intracellular ionised calcium and contractile force in cardiac muscle.1,2 This activity results in left ventricular afterload reduction, with an increase in cardiac output and a reduction in total peripheral resistance.3

Onset of action: 5–15 minutes.4

Duration of action: 3–5 hours.1

Half-life: 2–4 hours, renal impairment prolongs half-life.4

Indications

Cardiogenic shock secondary to acute decompensated systolic heart failure.

Short-term therapy for severe heart failure refractory to other treatment

Low cardiac output states post cardiac surgery.2,5

Precautions

  • Hypersensitivity to milrinone or other bipyridines2
  • Hypotension due to uncorrected hypovolaemia
  • Severe obstructive aortic or pulmonary valvular disease or hypertrophic subaortic stenosis – milrinone may aggravate outflow tract obstruction2
  • Risk of systolic anterior motion of the mitral valve and/or dynamic left ventricular outflow tract obstruction
  • Supraventricular and ventricular arrhythmias
  • Severe renal impairment (CrCl < 30 mL/min) increases the terminal elimination half-life; consider dose reduction.2

Medication presentation

10 mg/10mL ampoule

Medication storage

Store vials below 30°C. Do not freeze.6

Infusion solutions are stable for up to 24 hours.6

Preparation

 

IV bag

Syringe driver

Prescribe

20 mg in 100 mL

10 mg in 50 mL

Make up infusion in

100 mL bag of glucose 5%*

Glucose 5%*

Volume to be removed from IV bag

20 mL

Not applicable

Draw up 40 mL in the syringe

Drug dose to be added

20 mg (20 mL)

10 mg (10 mL)

Final volume

100 mL

50 mL

Final concentration

200 microg/mL

200 microg/mL

1mL/hr =

200 microg/hr

200 microg/hr

* Glucose 5% is preferred for dilution of all inotropes and vasopressors. However, milrinone is also compatible with Hartmann’s and sodium chloride 0.9%.6

Administration - this guideline is intended for central access only

Administer continuous intravenous infusion through a central access line.6

Infusions should be administered via a syringe driver or infusion pump, preferably with medication error reduction software enabled.

Avoid administration via lines where other drugs or fluids may be bolused or flushed.7

Dosing

Starting rate: 0.1 microg/kg/min.8

In common practice the loading dose is omitted as it is associated with hypotension.

Usual rate range: 0.125 to 0.35 microg/kg/min.9

Titrate in accordance with haemodynamic and clinical response, with dose adjustments every 2–4 hours due to long half-life.

Maximum rate: 0.75 microg/kg/min.2

Dose based on actual body weight up to a maximum of 120 kg.10

Weaning: The infusion should be weaned slowly (2–4-hourly), monitoring for clinical signs of inadequate cardiac output.

Infusion rate guide: Maintenance continuous infusion rate for milrinone (mL/hr) (using 200 microg/mL solution).

Patient weight (kg)

Infusion rate (mL/hr)

0.05

microg/kg/min

Infusion rate (mL/hr)

0.1

microg/kg/min

Infusion rate (mL/hr)

0.15

microg/kg/min

Infusion rate (mL/hr)

0.2

microg/kg/min

Infusion rate (mL/hr)

0.25

microg/kg/min

Infusion rate (mL/hr)

0.3

microg/kg/min

Infusion rate (mL/hr)

0.35 microg/kg/min

40

0.6

1.2

1.8

2.4

3

3.6

4.2

50

0.75

1.5

2.25

3

3.8

4.5

5.25

60

0.9

1.8

2.7

3.6

4.5

5.4

6.3

70

1.05

2.1

3.15

4.2

5.3

6.3

7.35

80

1.2

2.4

3.6

4.8

6

7.2

8.4

90

1.35

2.7

4.05

5.4

6.8

8.1

9.45

100

1.5

3

4.5

6.0

7.5

9

10.5

110

1.65

3.3

4.95

6.6

8.3

9.9

11.55

120

1.8

3.6

5.4

7.2

9

10.8

12.6

Calculation:

Infusion rate (mL/hr) = (patient weight (kg) × dose (microg/kg/min) × 60) ÷ infusion strength (microg/mL).

Monitoring

Continuous blood pressure and cardiac monitoring for the duration of the infusion.6

Daily 12-lead ECG.

Monitor fluid balance and electrolytes at least daily.

Side effects

  • Supraventricular and ventricular arrhythmias5
  • Hypotension – concomitant vasopressor use may be required5
  • Mild thrombocytopenia.5

Compatibilties

Consult the following references, which are available online through the Clinicians Health Channel:

  • Australian injectable drugs handbook
  • Trissel’s™ in IV compatibility (Micromedex) – from the site homepage, select the ‘IV Compatibility’ tab.

Important drug interactions

Anagrelide or cilostazol are agents that also inhibit phosphodiesterase III and, in combination with milrinone, may increase the risk of adverse effects.5,11

References

  1. Micromedex [online] (accessed 29 November 2017)
  2. MIMS [online] (accessed 29 November 2017)
  3. Shipley J, Tolman D, Hastillo A, et al. Milrinone: basic and clinical pharmacology and acute and chronic management. The American Journal of the Medical Sciences 1996; 311(6):286–291
  4. Lexicomp [online] (accessed 29 November 2017)
  5. Australian medicines handbook [online] (accessed 29 November 2017)
  6. Australian injectable drugs handbook (AIDH) [online] (accessed 17 October 2017)
  7. University College London Hospitals (UCL). UCL hospitals injectable medicines administration guide: pharmacy department, 3rd edn. Wiley-Blackwell, Chichester, 2013
  8. Baruch L, Patacsil P, Hameed A, et al, Pharmacodynamic effects of milrinone with and without a bolus loading infusion. American Heart Journal, 2001;141(2):266–273
  9. Yancy C, Jessup M, Bozkurt B, et al. 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. Journal of the American College of Cardiology 2013; 62(16):e147–239
  10. Kane-Gill S, Dasta J-F (eds). High-risk IV medications in special patient populations. Springer, London, 2011
  11. Stockley’s drug interactions [online] (accessed 29 November 2017)

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Centre of Clinical Excellence - Acute
Safer Care Victoria

Acknowledgements

We would like to thank the pharmacists involved in writing the guidelines: Melissa Ankravs, Melanie Kowalski, Rachel Fyfe, Robyn Ingram, Annalie Jones, Susan Trevillian, and Lucy Sharrock.

Page last updated: 11 Nov 2020

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