Metformin-associated Lactic Acidosis

OVERVIEW

  • metformin use is associated with lactic acidosis, but it remains controversial as a disease entity

MECHANISM

  • the mechanism of lactic acidosis is uncertain

Metabolic effects of metformin include:

  • decreased gluconeogenesis
  • increased peripheral glucose uptake
  • decreased fatty acid oxidation

CLINICAL FEATURES

  • presence of risk factors
  • abdominal pain
  • nausea and vomiting
  • fatigue
  • myalgias
  • altered mental status
  • myocardial insufficiency
  • multi-organ failure

RISK FACTORS

  • advanced age
  • high dose
  • renal failure (metformin is excreted unchanged in the urine)
  • hypoxia
  • active alcohol intake
  • sepsis
  • dehydration
  • shock
  • acidosis

INVESTIGATIONS

  • high anion gap metabolic acidosis (HAGMA)
  • high lactate

MANAGEMENT

  • rule out other causes of lactic acidosis (sepsis, cardiogenic shock, hypoperfusion, ischaemic bowel)
  • withdrawal of metformin
  • RRT

RRT

  • remove metformin and correct acidosis
  • best performed early due to large volume of distribution of metformin
  • use hemodialysis
  • use HCO3 buffer

CONTROVERSY

  • Some argue that metformin itself does not cause lactic acidosis, that it is actually due to the underlying conditions such as renal failure and diabetes mellitus.
  • However, there are definite cases of lactic acidosis from acute metformin overdose with no other underlying risk factors.

References and Links

Journal articles

  • Orban JC, Fontaine E, Ichai C. Metformin overdose: time to move on. Crit Care. 2012 Oct 25;16(5):164. PMC3682282.
  • Salpeter SR, Greyber E, Pasternak GA, Salpeter EE. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev. 2010 Apr 14;(4):CD002967. PMID: 20393934.

FOAM and web resources


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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