Intended for healthcare professionals

Rapid response to:

Endgames Case Report

Life threatening lactic acidosis

BMJ 2010; 340 doi: (Published 25 March 2010) Cite this as: BMJ 2010;340:c857

Rapid Response:

Re: Medical Mythology

Title: Mixing apples and oranges seems better than clinical
common sense…

Dear editors of the BMJ,
Dear Pr Robert Matz,

First we would like to thank Pr Matz for his interest in our article
recently published in BMJ. Referring to a recent meta-analysis, he
ironically compared metformin associated lactic acidosis (MALA) to a
medical myth that is about to die.1 We confess that we are deeply annoyed
by this disparaging comment and worried about its bad consequences on BMJ
readers. Mythology combined with a small dose of evidence based medicine
has always been a good way to support any argument though. Because one
meta-analysis mixed 347 heterogeneous trials and concluded that no case of
severe lactic acidosis was found with metformin, we should erase the
hundreds of cases of MALA described in the literature of critical care
medicine. To make such good words as those of Pr Matz, one would respond
that combining apples and oranges carries the risk of something resulting
in a fruit salad.

When no randomised clinical trial has yet proved that a dramatically high
lactate level with a fulminant multiorgan failure may be closely related
to metformin overdose, wouldn’t you start renal replacement therapy if you
knew that your patient has a metformin overdose and is going to die unless
metformin is removed? How could Pr Matz explain such metabolic disaster as
those described in previously healthy subjects after an intentional
poisoning with metformin?2 Many experimental and clinical datas support
the fact that metformin is a cause of reversible inhibition of
mitochondrial respiration.3 As highlighted by our case report, MALA is a
critical emergency that is always managed in the ICU by intensivists.4

This could explain why most diabetologists and internal medicine
practitioners have never encountered the disease and are still sceptical
about its existence. Unfortunately, we are afraid MALA is not going to RIP
but more and more patients will die, if we continue to question its

1. Salpeter SR, Greyber E, Pasternak GA, Salpeter Posthumous EE. Risk
of fatal and nonfatal lactic acidosis with metformin use in type 2
diabetes mellitus. Cochrane Database Syst Rev. 2010 20:CD002967.

2. Guo PY, Storsley LJ, Finkle SN. Severe lactic acidosis treated
with prolonged hemodialysis: recovery after massive overdoses of
metformin. Semin Dial 2006; 19:80-3.

3. Levy B, Perez P, Perny J. Where does the lactate come from? A rare
cause of reversible inhibition of mitochondrial respiration. Critical Care
2010, 14:136

4. Seidowsky A, Nseir S, Houdret N, Fourrier F. Metformin-associated
lactic acidosis: a prognostic and therapeutic study. Crit Care Med

Competing interests:
None declared

Competing interests: No competing interests

01 April 2010
Malcolm LEMYZE
Department of Critical Care Medicine, Schaffner Hospital, 62300 Lens, France