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
- TPR — Metformin Overdose Quiz (2012)
Critical Care
Compendium
Chris is an Intensivist and ECMO specialist at The Alfred ICU, where he is Deputy Director (Education). He is a Clinical Adjunct Associate Professor at Monash University, the Lead for the Clinician Educator Incubator programme, and a CICM First Part Examiner.
He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives. He was one of the founders of the FOAM movement (Free Open-Access Medical education) has been recognised for his contributions to education with awards from ANZICS, ANZAHPE, and ACEM.
His one great achievement is being the father of three amazing children.
On Bluesky, he is @precordialthump.bsky.social and on the site that Elon has screwed up, he is @precordialthump.
| INTENSIVE | RAGE | Resuscitology | SMACC