Aprotinin

CLASS

  • antifibrinolytic

MECHANISM OF ACTION

  • single chain polypeptide which occurs naturally in bovine lung and other tissues
  • inhibits fibrionlysis via inactivation of free plasmin
  • also inhibits trypsin and kallikrein
    -> when given prior to bypass: prevents clotting activation, factor consumption, platelet dysfunction -> reduced blood loss and transfusion

PHARMACEUTICS

  • clear, colourless solution
  • 1.4mg/mL in 0.9% saline = 10,000 kallikrein inactivator units

DOSE

  • IV dose = 500,000 -> 1,000,000 KIU -> 200,000 KIU/hr until bleeding stops

INDICATIONS

  1. life-threatening haemorrhage from hyperplasminaemia
  2. acute pancreatitis
  3. reduction of blood loss during bypass surgery, prostatectomy & liver transplantation
  4. prevention of DVT

ADVERSE EFFECTS

  • increased mortality -> moratorium
  • renal failure
  • can have hypersensitivity on repeat exposure
  • can produce thrombophlebitis

PHARMACOKINETICS

  • Absorption – IV only
  • Distribution – highly protein bound
  • Metabolism – lysosomes of kidneys
  • Elimination – t1/2 = 1 hr

EVIDENCE

Positive

  • shown to decrease bleeding and transfusion requirements with regard to patient with platelet dysfunction post cardiac bypass (inhibition of platelet aggregation -> prevention of microaggregate formation) in multiple previous trials (Cochrane review 2001 & JTCVD 2004)
  • used to help with haemostasis and shown to decrease transfusion requirements in multiple studies including in trials recently
  • transfusion and bleeding in cardiac surgical patients produces increased morbidity and therapies to decrease this are therefore important

Negative

  • recent published meta-analysis and FDA inquiry has revealed a significant increase in morbidity associated with its use (in particular a significant increase in acute renal dysfunction) but not increase in CVA, MI or mortality. (Circulation 2007;115:2801–13)
  • NEJM January 2006 – observational study with >4000 patients -> increased risks of CVA, MI, renal failure and CCF
  • increased risk of renal dysfunction (decreased GFR) but does not increase risk for renal failure requiring dialysis
  • BART trial in (Blood conservation using antifibrinolytics; a randominsed trial) – a trial comparing Aprotinin, Tranexamic and Epsilon-aminocaproic acid in preliminary data found that aprotinin produced a trend towards increased mortality -> moratorium on aprotinin use pending BART data -> significant increase in mortality and morbidity and recommended not using aprotinin in high risk cardiac surgery (May 2008 – NEJM)

There currently needs to be more information gathered to make a final decision on whether or not aprotinin should be disallowed in cardiac surgery.


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, a Clinical Adjunct Associate Professor at Monash University, and the Chair of the Australian and New Zealand Intensive Care Society (ANZICS) Education Committee. 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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