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

DRUGS

MILRINONE