Milrinone

CLASS

  • bipyridine

MECHANISM OF ACTION

  • non receptor mediated inhibitor of cAMP phosphodiesterase III isoenzyme -> decrease the hydrolysis of cAMP
  • increase cAMP (analogous to activating a Gs protein)
    -> increase in adenyl cyclase
    -> increase protein kinases
    -> increased phosphorylation of proteins
    -> net influx of Ca2+ into muscle

-> ‘inodilator’
-> inotropy
-> vascular and bronchial muscle relaxation

  • inotropy + decreased SVR -> increased SV -> increased Q
  • effective in patients on b-blockers and with b-adrenoceptor downregulation (as occurs in chronic CHF)
  • less increase in myocardial O2 consumption and tachycardia than b-agonists, with lower filling pressures and lower pulmonary vascular resistance (PVR)
  • titratable infusion, unlike levosimendan which has long duration of action

PHARMACEUTICS

  • 1mg/mL vials
  • dilute
  • use within 24 hrs

DOSE

  • loading dose 50mcg/kg
  • infusion 0.375-0.75mcg/kg/min

INDICATION

  • low cardiac output states (considered first line by some, rarely used by others)

ADVERSE EFFECTS

  • hypotension -> consider adding noradrenaline
  • bronchospasm (edit: really?)
  • arrhythmias (rare, less tachycardia than b-agonists)
  • thrombocytopaenia
  • hepatic dysfunction

PHARMACOKINETICS

  • Distribution – Vd 0.38L/kg, 70% protein bound
  • Metabolism – minimal
  • Elimination – t1/2 = 2.3 hrs, action ceases 8 hours post termination of infusion, renal elimination -> prolongs half life

EVIDENCE

  • more successful weaning from bypass (proven in a small (n ~50) RCT vs placebo – 100% vs 33%)

Warrilow’s ‘case for milrinone’:

  • inodilator
  • effective in patient receiving beta blockers or with down regulation of cardiac adrenoreceptors (chronic cardiac failure)
  • less tachyarrhythmias than b-agonists
  • pulmonary vasodilator
  • hypotension due to vasodilation (often needs noradrenaline, which also has some mild b-agonism)
  • relatively cheap in short term

References and Links

  • Warrillow SJ. The case for milrinone. Crit Care Resusc. 2008 Sep;10(3):180-1. PMID: 18798713. [Free fulltext]
  • Yamada T, Takeda J, Katori N, Tsuzaki K, Ochiai R. Hemodynamic effects of milrinone during weaning from cardiopulmonary bypass: comparison of patients with a low and high prebypass cardiac index. J Cardiothorac Vasc Anesth. 2000 Aug;14(4):367-73. PMID: 10972598.

CCC 700 6

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of two amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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