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Erschienen in: Critical Care 1/2020

Open Access 01.12.2020 | Letter

Association between metformin use prior to admission and lower mortality in septic adult patients with diabetes mellitus: beware of potential confounders

verfasst von: Patrick M. Honore, Aude Mugisha, Luc Kugener, Sebastien Redant, Rachid Attou, Andrea Gallerani, David De Bels

Erschienen in: Critical Care | Ausgabe 1/2020

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Abkürzungen
MET
Metformin
AKI
Acute kidney injury
RRT
Renal replacement therapy
IHD
Intermittent hemodialysis
CRRT
Continuous renal replacement therapy
We read with great interest the recent paper by Liang et al. who conclude that their meta-analysis indicated an association between metformin (MET) use prior to admission and lower mortality in septic adult patients with diabetes mellitus [1]. We would like to make some comments. Nearly half of critically ill patients, especially those with septic shock, have or develop acute kidney injury (AKI), and 20–25% need renal replacement therapy (RRT) within the first week of their admission [2]. Because of its low molecular weight and minimal protein binding, metformin is equally (highly) eliminated by ultrafiltration (convection) and dialysis (diffusion). Furthermore, its large volume of distribution within a two-compartment pharmacokinetic model implies that metformin may be more effectively cleared by prolonged RRT. This was corroborated by Keller et al., who showed a dramatic reduction of metabolic acidosis and metformin plasma concentrations within the first 24 h after initiating CRRT in patients with MET-induced lactic acidosis, followed by normalization on the second day in all subjects [3]. Although we do not know the exact rate of CRRT in both arms [1], it may well be that one group had more CRRT than the other, particularly the metformin group. For instance, in the study of Doenyas-Barak et al., which had a huge impact on the conclusions of this meta-analysis, the use of RRT was higher in the MET-treated population (38.6 vs. 21.2%, p = 0.13) [1, 4]. Accordingly, we suspect that the observed difference in mortality rate may be due to the more frequent use of RRT in the MET-treated population. A protective effect of RRT has already been suggested by Peters et al., who found that despite higher illness severity, the mortality rate in patients with MET-associated lactic acidosis treated with intermittent hemodialysis (IHD) was no different to that of non-dialyzed subjects [5].

Acknowledgements

We would like to thank Dr. Melissa Jackson for critical review of the manuscript.
Not applicable.
Not applicable.

Competing interests

The authors declare to have no competing interests.
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Literatur
2.
Zurück zum Zitat Peters E, Antonelli M, Wittebole X, Nanchal R, François B, Sakr Y, et al. A worldwide multicentre evaluation of the influence of deterioration or improvement of acute kidney injury on clinical outcome in critically ill patients with and without sepsis at ICU admission: results from The Intensive Care Over Nations audit. Crit Care. 2018;22(1):188. https://doi.org/10.1186/s13054-018-2112-z..CrossRefPubMedPubMedCentral Peters E, Antonelli M, Wittebole X, Nanchal R, François B, Sakr Y, et al. A worldwide multicentre evaluation of the influence of deterioration or improvement of acute kidney injury on clinical outcome in critically ill patients with and without sepsis at ICU admission: results from The Intensive Care Over Nations audit. Crit Care. 2018;22(1):188. https://​doi.​org/​10.​1186/​s13054-018-2112-z.​.CrossRefPubMedPubMedCentral
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Zurück zum Zitat Keller G, Cour M, Hernu R, Illinger J, Robert D, Argaud L. Management of metformin-associated lactic acidosis by continuous renal replacement therapy. PLoS One. 2011;6:e23200.CrossRef Keller G, Cour M, Hernu R, Illinger J, Robert D, Argaud L. Management of metformin-associated lactic acidosis by continuous renal replacement therapy. PLoS One. 2011;6:e23200.CrossRef
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Zurück zum Zitat Doenyas-Barak K, Beberashvili I, Marcus R, Efrati S. Lactic acidosis and severe septic shock in metformin users: a cohort study. Crit Care. 2016;20:10.CrossRef Doenyas-Barak K, Beberashvili I, Marcus R, Efrati S. Lactic acidosis and severe septic shock in metformin users: a cohort study. Crit Care. 2016;20:10.CrossRef
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Zurück zum Zitat Peters N, Jay N, Barraud D, Cravoisy A, Nace L, Bollaert PE, et al. Metformin-associated lactic acidosis in an intensive care unit. Crit Care. 2008;12:R149.CrossRef Peters N, Jay N, Barraud D, Cravoisy A, Nace L, Bollaert PE, et al. Metformin-associated lactic acidosis in an intensive care unit. Crit Care. 2008;12:R149.CrossRef
Metadaten
Titel
Association between metformin use prior to admission and lower mortality in septic adult patients with diabetes mellitus: beware of potential confounders
verfasst von
Patrick M. Honore
Aude Mugisha
Luc Kugener
Sebastien Redant
Rachid Attou
Andrea Gallerani
David De Bels
Publikationsdatum
01.12.2020
Verlag
BioMed Central
Erschienen in
Critical Care / Ausgabe 1/2020
Elektronische ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-020-02909-3

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