A Fatal Case of Metformin-associated Lactic Acidosis

Abstract

A 72-year-old woman with a history of type 2 diabetes mellitus was brought to the ER with metforminassociated lactic acidosis. She received continuous hemofiltration and hemodialysis, but the laboratory analyses showed no improvement. She died 11 hours after admission. Metformin is minimally bound to proteins and is readily dialyzable, but a prolonged period of dialysis is required, because metformin has a very large distribution volume and is distributed to multiple compartments. The peak blood metformin level was 432 mg/L in this case, which is one of the highest metformin concentrations ever reported, and eight hours of hemodialysis were not sufficient to reduce the serum level.

Metformin‐associated lactic acidosis: Moving towards a new paradigm?

“…Thus, even if metformin concentrations are low at the time of assessment (possibly many hours after LA ensued), a contributing role of metformin cannot be excluded. This is consistent with reports of MALA that are refractory to the commonly employed treatment haemodialysis …”

“…This is consistent with reports of MALA that are refractory to the commonly employed treatment haemodialysis. 4,5 Thus, for reasons stated we believe that, in the vast majority of cases, we do not have the ability to exclude the known ability of metformin to increase LA risk. Our concern is that, while attempting to add more precision to the terms used to define LA in the presence of metformin use, a binary classification system that would discount the contribution of metformin based on a cross-sectional assessment of the patient would be inappropriate from a pharmacovigilance perspective as it will probably lead to underreporting of metformin's association with LA.…”

Metformin‐associated lactic acidosis (MALA): Moving towards a new paradigm

“…Awareness of metformin blood concentrations in normal vs emergency situations is a prerequisite for analysing the relationship between the drug and lactic acidosis; trough plasma metformin concentrations are <5 mg/L under therapeutic conditions (FDA), and the highest value ever reported, in a case of voluntary metformin intoxication, is 432 mg/L …”

メトホルミン中毒による重篤な乳酸アシドーシスに対して血液浄化療法を行い救命に成功した1例(Metformin associated lactic acidosis treated with renal replacement therapy)

“…メトホルミンにより乳酸が蓄積する機序としては，ピルビン酸カルボキシラーゼを阻害することで細胞内での乳酸からピルビン酸への変換を阻害すること，肝臓での乳酸を用いた糖新生を阻害することなどが挙げられる 6), 7)。メトホルミンは大部分が腎臓で排泄されるため腎機能障害はMALAのリスクである。加えて血圧低下，脱水，敗血症，虚血，肝機能障害などの合併する病態により乳酸の産生増大と排泄低下が助長され乳酸アシドーシスが遷延すると考えられる。…”