free collaborative open access anaesthesia education

MILRINONE

CLASS

Sympathomimetic, inodilator

PRESENTATION

Clear, colourless solution in clear glass vial

Formulations

  • 10ml vial; 10mg, 1mg/ml (1:1000)

INDICATIONS & DOSING

Acute pulmonary hypertension with cardiogenic shock, post-cardiopulmonary bypass cardiac dysfunction

  • Adult/paediatric neb: 5mg/5ml, nebulised
  • Adult/paediatric bolus; 50mcg/kg IV over 10 minutes
  • Adult/paediatric infusion; 0.375 – 0.75mcg/kg/min, max 1.13 mg/kg/day

PRACTICALITIES

Administration

  • Mixed with N/saline or 5% dextrose, using a dilution of 10mg in 50ml (200mcg/ml)
  • Boluses; avoid unless clinically peri-arrest, if necessary then slow bolus over 10/60 to avoid hypotension
Incompatabilities
  • Frusemide, sodium bicarbonate
Practice tips
  • May be given via peripheral venous access
  • Do not administer undiluted unless via nebuliser
  • May still be clinically efficacious in maximally sympathetically driven states or in the context of maximal inotropic support as clinical effect is independent of adrenoreceptors
  • Not subject to tachyphylaxis

PHARMACOKINETICS

Onset

  •  IV; 5-15 minutes

Duration of action

  • Cessation of effect approximately 8 hours after ceasing IV infusion

Metabolism

15% hepatically conjugated, to an inactive O-glucorinide metabolite

Elimination

85% excreted renally unchanged, 15% excreted renally as conjugated metabolite

MECHANISM

Selective phosphodiesterase III inhibition prevents the degradation of intracellular cAMP in target tissues.

Cardiac myocytes; increased cAMP stimulates protein kinases, enhancing the uptake, storage, and release of calcium from the sarcoplasmic reticulum during excitation-coupling, leading to inotropy and augmentation of adrenergic receptor stimulation.

Vascular smooth muscle; increased cAMP results in vasodilation of both systemic and pulmonary vascular beds.

DESIRED CLINICAL EFFECTS

Cardiovascular

  • Increases cardiac output (CO) via increased inotropy, lusitropy and chronotropy (mild) as well as reduced dromotropy and afterload (systemic and pulmonary)

Respiratory

  • Decreases pulmonary vascular resistance (PVR), pulmonary artery pressures and reduced right ventricular afterload
Neurological
  • Preserves cerebral blood flow and cerebral autoregulation
Renal 
  • Increases renal blood flow, GFR and urine output secondary to effects on cardiac output
Gastrointestinal
  • Increases splanchnic blood flow secondary to effects on cardiac output

OTHER CLINICAL EFFECTS, ADVERSE EFFECTS & TOXICITIES

Respiratory

  • Bronchoconstriction (rare)

Cardiovascular

  • Tachycardia, dysrhythmias including Torsades De Pointes
  • Increases myocardial oxygen demand
  • Hypotension

Neurological

  • Headache, dizziness, tremor

Gastrointestinal

  • Elevation in LFTs

Haematological

  • Antiplatelet effect; reversible thrombocytopenia, platelet dysfunction (rare)

CONSIDERATIONS

Precautions

  • Hypotension
  • Hypovolaemia, distributive shock states
  • Ischaemic heart disease/myocardial ischaemia
  • Fixed cardiac output states; aortic/mitral valve stenosis, LVOT obstruction
  • Renal failure; reduced drug elimination

Obstetric

ADEC category B3

Drug interactions

  • Inotropes, sympathomimetics; additive inotropic action
  • Vasodilators; additive vasodilator action 

REFERENCES

Drug information has been compiled from multiple sources including

  • Drugs in Anaesthesia and Intensive Care (Scarth & Smith)
  • Micromedex (IBM)
  • BJA Education (Oxford Academic)
  • Pharmacology for Anaesthesia and Intensive Care (Cambridge)
  • Australian Prescriber (NPS MedicineWise)
  • Clinical experience of authors

Leave a Reply

Close Menu