Metformin-Associated Lactic Acidosis: Which Elimination Therapy to Use in Case of Haemodynamic Instability? A Retrospective Cohort Study
Round 1
Reviewer 1 Report
Comments and Suggestions for Authors The manuscript "Metformin-Associated Lactic Acidosis: Which Elimination Therapy to Use in Case of Haemodynamic Instability? A Retrospective Cohort Study" provides a detailed exploration into the treatment of metformin-associated lactic acidosis (MALA), particularly focusing on the effectiveness of intermittent hemodialysis versus continuous venovenous haemofiltration in patients with severe MALA and hemodynamic instability. This retrospective cohort study conducted at Leuven University Hospital over a span of six years aims to fill the knowledge gap left by the EXTRIP group's recommendations, which favored IHD based on very low-quality evidence. This manuscript contributes important findings on the management of MALA, particularly in the context of hemodynamic instability. While it suggests a clinical preference for CVVH in more severely ill patients, the retrospective design and inherent biases limit the ability to recommend one therapy over the other definitively. Addressing these gaps through future research is essential for optimizing MALA treatment and improving patient outcomes. Moreover, there is no mention of SLEDD, which has been previously described with some success (e.g., Angioi A. et al, BMC Nephr 2018).Author Response
Thank you for taking the time to review our manuscript. Your feedback is greatly valued.
We are considering conducting a prospective study on this topic in the future and will explore the possibility of analyzing low efficency dialysis methods.
Reviewer 2 Report
Comments and Suggestions for AuthorsI read with great interest the manuscript on the therapeutic management of metformin-induced lactic acidosis. The retrospective study was well thought out. Available data were taken into account and two therapeutic methods were compared - intermittent hemodialysis (IHD) as the basic elimination therapy in the case of severe metformin poisoning and, in hemodynamically unstable patients, continuous venovenous hemofiltration (CVVH). The authors also skillfully presented the limitations of the study and indicated the need for further research on this topic. The presented results are helpful to all specialists who deal with patients with lactic acidosis after using metformin.
Author Response
Thank you for taking the time to review our manuscript. Your feedback is greatly valued.
We hope to conduct a prospective study on this topic in the future.
Reviewer 3 Report
Comments and Suggestions for AuthorsThank you for giving me the opportunity to review this article called: “Metformin-Associated Lactic Acidosis: Which Elimination Therapy to Use in Case of Haemodynamic Instability? A Retrospective Cohort Study “. It is a monocentric retrospective study achieved, reporting the description of the management of 35 patients admitted for MALA in ICU and trying to compare the performances of intermittent hemodialysis versus continuous veno-venus hemofiltration. Because of the retrospective design and related bias, no conclusion can be drawn for that study. Anyway, the study is well presented, all the limits are underlined, and the reporting of this specific cohort deserved publication.
I have however some more remarks that could improve the manuscript.
Introduction: Aim of the study: “was to contribute additional evidence insights to the EXTRIP study group’s recommendation to prioritize IHD over CVVH”: --> I would only say that the main objective is to report the main practice of your center in terms of RRT for the management of MALA and compare the patients having IHD versus CVVH first in that context.
Methods: “Patients who did not achieve metabolic correction or lactate clearance were excluded from the calculation of the corresponding mean values.” à I don’t understand why you exclude those patients. It is a major issue. First, in the table, you should precise the number of patients considered for that end point. Then, maybe, you could introduce an endpoint with: timing of resolution of acidemia (or clearance of lactate) at 48h00 and put 48h00 for the non survivors (or just give the number of patients alive and with correction of their lactate at 24h (or 48h00)). It would take into account the competing risk of dying before normalisation of lactate.
Not all the patients had AKI, but all the patients benefited from RRT on ICU admission. Perhaps, you could classify the patients as follow: with 1) AKI, 2) AKI on CKD, 3) patients with CKD under dialyses.
It is really strange that not all the patients had monitorage of the correction of their lactate levels.
Furthermore, “Metabolic correction could not be demonstrated in 10 patients due to persistent hyperventilation (PaCO2 < 35 mmHg)” à I am not sure it should be specified: maybe just focus on the correction of lactate and increased of HCO3-.
Table 1 à maybe this table in supplemental and just a table with summary statistics would be easier to read.
Do you have dose of vasopressors in µg/kg/min on admission?
Author Response
Thank you for taking the time to review our manuscript. Your feedback is greatly valued.
Please see the attachment for the answers to your comments.
Author Response File: 
Author Response.docx
