See KC. Metformin-associated lactic acidosis: A mini review of pathophysiology, diagnosis and management in critically ill patients. World J Diabetes 2024; 15(6): 1178-1186 [PMID: 38983827 DOI: 10.4239/wjd.v15.i6.1178]
Corresponding Author of This Article
Kay Choong See, FCCP, FRCP, MBBS, MRCP, Adjunct Associate Professor, Department of Medicine, National University Hospital, Level 10, NUHS Tower Block, 1E Kent Ridge Road, Singapore 119228, Singapore. kaychoongsee@nus.edu.sg
Research Domain of This Article
Critical Care Medicine
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Diabetes. Jun 15, 2024; 15(6): 1178-1186 Published online Jun 15, 2024. doi: 10.4239/wjd.v15.i6.1178
Metformin-associated lactic acidosis: A mini review of pathophysiology, diagnosis and management in critically ill patients
Kay Choong See
Kay Choong See, Department of Medicine, National University Hospital, Singapore 119228, Singapore
Author contributions: See KC is responsible for all elements of the manuscript.
Conflict-of-interest statement: Dr. See reports personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from GSK, personal fees from Novartis, outside the submitted work.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Kay Choong See, FCCP, FRCP, MBBS, MRCP, Adjunct Associate Professor, Department of Medicine, National University Hospital, Level 10, NUHS Tower Block, 1E Kent Ridge Road, Singapore 119228, Singapore. kaychoongsee@nus.edu.sg
Received: December 24, 2023 Revised: April 4, 2024 Accepted: April 23, 2024 Published online: June 15, 2024 Processing time: 170 Days and 1.6 Hours
Abstract
Metformin is a common diabetes drug that may reduce lactate clearance by inhibiting mitochondrial oxidative phosphorylation, leading to metformin-associated lactic acidosis (MALA). As diabetes mellitus is a common chronic metabolic condition found in critically ill patients, pre-existing metformin use can often be found in critically ill patients admitted to the intensive care unit or the high dependency unit. The aim of this narrative mini review is therefore to update clinicians about MALA, and to provide a practical approach to its diagnosis and treatment. MALA in critically ill patients may be suspected in a patient who has received metformin and who has a high anion gap metabolic acidosis, and confirmed when lactate exceeds 5 mmol/L. Risk factors include those that reduce renal elimination of metformin (renal impairment from any cause, histamine-2 receptor antagonists, ribociclib) and excessive alcohol consumption (as ethanol oxidation consumes nicotinamide adenine dinucleotides that are also required for lactate metabolism). Treatment of MALA involves immediate cessation of metformin, supportive management, treating other concurrent causes of lactic acidosis like sepsis, and treating any coexisting diabetic ketoacidosis. Severe MALA requires extracorporeal removal of metformin with either intermittent hemodialysis or continuous kidney replacement therapy. The optimal time to restart metformin has not been well-studied. It is nonetheless reasonable to first ensure that lactic acidosis has resolved, and then recheck the kidney function post-recovery from critical illness, ensuring that the estimated glomerular filtration rate is 30 mL/min/1.73 m2 or better before restarting metformin.
Core Tip: Metformin-associated lactic acidosis (MALA) in critically ill patients may be suspected in a patient who has received metformin and who has a high anion gap metabolic acidosis, and confirmed when lactate exceeds 5 mmol/L. Risk factors include those that reduce renal elimination of metformin and excessive alcohol consumption. Treatment of MALA involves immediate cessation of metformin, supportive management, treating other concurrent causes of lactic acidosis like sepsis, and treating any coexisting diabetic ketoacidosis. Severe MALA requires extracorporeal removal of metformin with either intermittent hemodialysis or continuous kidney replacement therapy.
