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Milrinone - paediatrics

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For use in Ward 23B Intensive observation area (IOA)

Purpose of guideline

  • This guideline covers the use of a milrinone infusion in the cardiac ward.
  • Use of milrinone and the appropriate dose is to be determined by the consultant cardiologist and/or cardiac surgeon only.

Action of medication

Milrinone is a positive inotrope and vasodilator, with little chronotropic activity. It is a phosphodiesterase inhibitor and acts by selectively inhibiting phosphodiesterase III in cardiac and vascular muscle resulting in increased levels of cAMP. The increased cAMP levels cause cAMP mediated increases in intracellular ionised calcium and contractile force in the myocardium and cAMP dependent contractile protein phosphorylation and relaxation in the vascular muscle.   This combined effect increases myocardial contractility and causes vasodilatation, thus milrinone is known as an inodilator.  It also lowers preload by increasing diastolic myocardial relaxation, lusitropy relaxant properties, this improves coronary perfusion1.

Indications

  • Low output states following cardiac surgery including weaning from cardiopulmonary bypass pump.
  • Short-term therapy in severe congestive heart failure.

Dose and prescription

Dose

  • Loading dose: to be administered in theatres and PICU only
  • Maintenance dose:  0.25 - 0.75 micrograms/kg/minute via continuous IV infusion.
  • Renal impairment:reduce dose by 50 to 75% of normal dose. (1)

Prescription

  • To be charted on the Fluid balance chart with a cross-reference on the drug chart stating "Milrinone as per fluid balance chart".
  • Prescription on the Fluid balance chart must include:
    • Amount of drug to be added, in milligrams.
    • Diluent and final volume of infusion.
    • Dose in micrograms/kg/minute
    • Rate in mLs/hour
    • Target blood pressure (systolic and diastolic) and heart rate.

Administration

  • Give as continuous infusion

Infusion preparation for child UNDER 30kg

  • Dilute 0.75mg/kg milrinone with glucose 5% or sodium  chloride 0.9% to make up a total volume of 50mls.
  • Check your preparation using the example below:
Example for child weighing 5Kg
Dose (micrograms/kg/min) 0.25 micrograms/kg/minute
Amount of milrinone to be  added 0.75mg x 5 Kg = 3.75 mg
Diluent (type and final  volume) Glucose 5% to make up to 50 mL
Rate (in mls/hour) 1 mL /hour =  0.25 micrograms/Kg/minute

Refer to  PICU Cardiovascular Drug Infusion chart for children under 30 kg

Infusion preparation for child 30kg AND OVER

Administration (continued)

  1. Administer by IV infusion via a syringe driver only.
  2. Central line administration is preferred but can give peripherally.
  3. Correct hypovolaemia before commencing administration.
  4. Do not use a milrinone line to co-administer other infusions.
  5. Do not flush the line containing milrinone.
  6. Prepare a fresh solution for administration every 24 hours.
  7. Drug incompatibility: Do NOT administer with frusemide infusion/injection as precipitation will occur

Observation and documentation

  1. Continuous ECG monitoring for supraventricular and ventricular arrhythmias.
  2. Monitor and document the following at least hourly, or as specified by the prescriber:
    1. Heart rate (HR)
    2. Blood pressure (BP)
    3. Oxygen saturations (Sp02).
    4. IV site, when used peripherally. Avoid extravasation.
    5. Adverse reactions
  3. Monitor
    1. Fluid and electrolyte status (especially potassium and magnesium). Adjust diuretics and electrolytes if necessary.
    2. Renal function
    3. Platelet count - regularly throughout infusion
  4. The dose in micrograms/kg/minute is recorded on the patients observation chart hourly
  5. The volume of the infusion administered is recorded on the fluid balance chart hourly.
  6. Weaning and cessation of milrinone is done with ongoing assessment of the patient's haemodynamic status
  7. Milrinone infusion at a low dose (i.e 0.25 mcg/kg/min) does not require weaning as changes in haemodynamics usually take 4-6 hours.

Special considerations

  • The time for milrinone to reach steady state will vary and would normally be 4-5 half lives of milrinone. As the half life varies with patient age there will also be a variation in the time to reach steady state with neonates potentially taking up to 24 hours.

  • When milrinone is discontinued the time for loss of therapeutic effect will correspondingly vary with half life, with neonates potentially taking a longer time. Therefore be observant for signs of cardiovascular instability / poor perfusion following   discontinuation of Milrinone infusion and seek medical review if clinical deterioration observed.

  • Continuous cardiovascular monitoring for a minimum of 24 hours after the Milrinone infusion has been discontinued. Neonates may require longer monitoring.

  • An increase in diuresis may occur with milrinone therapy; (due to improvement in cardiac output) therefore concomitant diuretic doses may need to be reduced.

  • Handover between staff is important: discussion with medical staff needs to take place at both morning and evening handover and also between nursing staff at each shift change:

    • To confirm that the infusion is to continue.

    • To check the current rate

    • To independently double check the infusion dose calculation by both nursing staff members

Contraindications and Precautions

Contraindications

  • Severe obstructive aortic or pulmonary valve disease, or hypertrophic subaortic stenosis.
  • Severe hypovolaemia.
  • Hypersensitivity to milrinone or any of the injection ingredients.

Precautions

  • Hypotension should be resolved prior to milrinone treatment.
  • Excessive decrease in blood pressure during administration may require the milrinone infusion to be stopped and the hypotension resolved. If needed the milrinone could be restarted at a lower rate.
  • Hypokalaemia should be corrected.
  • Unknown safety or efficacy in heart failure if used for periods longer than 48 hours.
  • Atrial flutter and fibrillation when not controlled with agent to prolong A -V node conduction time.
  • Monitor digoxin levels if appropriate.
  • Severe renal impairment; Renal impairment: reduce dose by 50 - 75% of normal dose.

Possible Adverse effects

  • Arrhythmia: Ectopic beats, ventricular tachycardia, supraventricular tachycardia.
  • Hypotension.
  • Hypokalaemia.
  • Thrombocytopenia - risk increases with increasing duration of therapy.
  • Headache.
  • Tremor.
  • Extravasation

Drug interactions

  • Drug incompatibility: DO NOT administer with frusemide infusion/injection as precipitation will occur.
  • Do not co-infuse other infusions into the milrinone line

Presentation

  • Injection ampoules (single-dose) 1mg/mL, 10mL

For detailed information about dopamine hydrochloride, including clinical pharmacology, go to the New Zealand Medsafe Data Sheet. Information is also available on the NZFC.

References

  1. Primacor (milrinone) data sheet. Auckland: Sanofi-Aventis, 2011.
  2. Phelps S, Hak E, Crill C (eds.). Pediatric Injectable Drugs(9th ed.). Maryland: American Society of Health-Systems Pharmacists, 2011.
  3. Woods, DJ (editor), New Zealand Formulary for Children [Internet]. 2016 [updated 2016 March 1; 2015 Sept 1; cited 2016, March 18]. Available from: www.nzfchildren.org.nz

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Document Control

  • Date last published: 30 March 2016
  • Document type: Drug Dosage Guideline
  • Services responsible: Paediatric Cardiology
  • Intended users: Ward 23B Intensive Observation Area (IOA)
  • Author(s): John Stirling, Marion Hamer, Brenda Hughes
  • Editor: Marion Hamer
  • Review frequency: 2 years