Metformin accumulation: Lactic acidosis and high plasmatic metformin levels in a retrospective case series of 66 patients on chronic therapy

  title={Metformin accumulation: Lactic acidosis and high plasmatic metformin levels in a retrospective case series of 66 patients on chronic therapy},
  author={Sarah Vecchio and Andrea Giampreti and Valeria Margherita Petrolini and Davide Lonati and Alessandro Protti and Pietro Papa and Carla Rognoni and Antonella Valli and Loretta Rocchi and Laura Rolandi and Luigi Manzo and Carlo Alessandro Locatelli},
  journal={Clinical Toxicology},
  pages={129 - 135}
Abstract Objective. The relationship between metformin accumulation and lactate increase is still debated. This observational case series aims to evaluate the correlation of metformin plasma levels with the pH, lactate and creatinine levels, and with the mortality rate in selected patients with metformin accumulation confirmed through metformin plasma concentration detection at hospital admission. Material and methods. All cases of lactic acidosis (pH, ≤ 7.35; arterial lactate, ≥ 5 mmol/L… 

A Study of Associations Between Plasma Metformin Concentration, Lactic Acidosis, and Mortality in an Emergency Hospitalization Context.

In metformin-treated patients admitted in an emergency context, a plasma met formin concentration greater than or equal to 9.9 mg/L was strongly associated with the presence of lactic acidosis, and this threshold may assist with the delicate decision of whether or not to initiate renal replacement therapy.

Relationship Between Plasmatic Metformin Concentration and Renal Replacement Therapy: A Multicenter Cohort Study

The retrospective study design, lack of clinical data, and selection bias were major limitations, resulting in only preliminary findings, but this study could serve as a basis for future prospective clinical studies to evaluate the use of these clinical threshold values as therapeutic guides.

Identifying patients with metformin associated lactic acidosis in the emergency department

When managing lactic acidosis in the ED the diagnosis MALA should be considered in patients with a creatinine concentration of 256 μmol/l and lactate concentration of 8.4 mmol/l.

Lactate Levels with Chronic Metformin Use: A Narrative Review

Whether regular monitoring of the plasma lactate level would be beneficial in avoiding lactate accumulation and, ultimately, minimising the incidence of lactic acidosis in metformin-treated patients is investigated.

Extracorporeal treatment of metforminassociated lactic acidosis in clinical practice: a retrospective cohort study

ECTR might be lifesaving in MALA, considering the ECTR-group was significantly sicker than the non-ECTR-group, and the majority of patients were treated in line with the EXTRIP criteria.

Metformin-related lactic acidosis with acute kidney injury: results of a French observational multicenter study

MILA is associated with DD and death is due to severe refractory acidosis leading to cardiovascular collapse attributed to metformin accumulation mainly via AKI, and MALA patients are more frequently shocked andDeath is related to their underlying condition, metformIn accumulation increasing LA.

Metformin-associated lactic acidosis and factors associated with 30-day mortality

Early dialysis treatment within 6 hours after admission and haemodialysis were independently associated with lower 30-day mortality, and large scale, well-designed studies need to confirm these encouraging results.

Metformin-related lactic acidosis: is it a myth or an underestimated reality?

Routine assessment of metformin plasma concentration is not easily available in all laboratories, but plasma meetingformin concentrations measured in the emergency room could ensure the correct diagnosis, eliminating met formin as the cause of lactic acidosis if low plasma levels occurred.

Clinical presentations and prognosis of metformin-associated lactic acidosis patients in the intensive care unit: A 20-year survey

Higher levels of APACHE II score and PLL show a greater likelihood of mortality in MALA patients, and it is necessary to evaluate its clinical characteristics, especially the associated PLL and mortality.

Metformin associated lactic acidosis (MALA): clinical profiling and management

It is suggested that aged, hemodynamically frail patients, with several comorbidities and CKD, are at greater risk of MALA, despite MF dosage adjustment, and renal replacement therapy rather than simple acidosis correction by administration of alkali seems the treatment of choice, based on eventual renal recovery and overall outcome.



Lactic Acidosis in Metformin-Treated Patients

Observations suggest that accumulation of metformin may not be as significant with respect to high arterial levels of lactate and their effects as has been traditionally thought.

Role of Metformin Accumulation in Metformin-Associated Lactic Acidosis

Metformin-associated lactic acidosis is not necessarily due to metformin accumulation; true type B (aerobic) lactic Acidosis, i.e., without an apparent associated hypoxic factor, seems exceptional.

The Role of Metformin in Metformin-Associated Lactic Acidosis (MALA): Case Series and Formulation of a Model of Pathogenesis

It is suggested that the development of MALA is due to a positive feedback system involving one or more of these factors: vomiting and diarrhoea, acute kidney injury, high doses or excessive accumulation of metformin, and acute disease states leading to tissue hypoxia.

Metformin-associated lactic acidosis (MALA): clinical profile and outcomes in patients admitted to the intensive care unit.

Gastrointestinal symptoms predominate in metforminassociated lactic acidosis (MALA), and the condition is associated with significant morbidity and mortality.

Metformin-associated lactic acidosis: A prognostic and therapeutic study*

In this study, the outcome of MALA was uniformly favorable after intentional metformin overdose and the vital prognosis was mainly influenced by the occurrence of multiple organ dysfunctions, the best predictive factor of death being an acute liver dysfunction as assessed by PT activity.

Outcome of severe lactic acidosis associated with metformin accumulation

Compared to similarly severe lactic Acidosis of other origin, the prognosis of MALA is significantly better and should be considered in metformin-treated patients presenting with lactic acidosis.

Reality of severe metformin-induced lactic acidosis in the absence of chronic renal impairment.

Patients with extreme (lactic) metabolic acidosis caused by metformin can survive when CVVH treatment is initiated rapidly, andMetformin-induced lactic acidosis does occur in patients with previously normal renal function, even in young patients.

Lactic Acidosis in Metformin Therapy

Overall, it appears that mortality in patients receiving met formin who develop lactic acidosis is linked to underlying disease rather than to metformin accumulation, and that metform in can no longer be considered a toxic drug in this respect.

Metformin-associated lactic acidosis in an intensive care unit

MALA can be encountered in the ICU several times a year and still remains a life-threatening condition, although haemodialysis may possess a protective effect.

Lactic Acidosis Induced by Metformin

It is suggested that haemodialysis should systematically be performed in severe forms of lactic acidosis, since it provides both symptomatic and aetiological treatment (by eliminating lactate and metformin) and the list of contraindications to meetformin is examined.