Can an early diagnostic procedure of metformin-associated lactic acidosis in an emergency unit reduce mortality?

Damien Sémely; Emily Bennett; Christine Vallejo; Franck Saint-Marcoux; Louis Merle; Yves Nouaille; Gérard Lachâtre; Marie-Laure Laroche

doi:10.1016/j.therap.2016.05.006

Can an early diagnostic procedure of metformin-associated lactic acidosis in an emergency unit reduce mortality?

Therapie. 2016 Dec;71(6):605-612. doi: 10.1016/j.therap.2016.05.006. Epub 2016 Jun 16.

Authors

Damien Sémely¹, Emily Bennett², Christine Vallejo², Franck Saint-Marcoux³, Louis Merle¹, Yves Nouaille¹, Gérard Lachâtre³, Marie-Laure Laroche⁴

Affiliations

¹ Centre régional de pharmacovigilance, de pharmaco-épidémiologie et d'information sur les médicaments, CHU de Limoges, 87042 Limoges, France; Service de pharmacologie, toxicologie et pharmacovigilance, CHU de Limoges, 87042 Limoges, France.
² Département des urgences, CHU de Limoges, 87042 Limoges, France.
³ Service de pharmacologie, toxicologie et pharmacovigilance, CHU de Limoges, 87042 Limoges, France.
⁴ Centre régional de pharmacovigilance, de pharmaco-épidémiologie et d'information sur les médicaments, CHU de Limoges, 87042 Limoges, France; Service de pharmacologie, toxicologie et pharmacovigilance, CHU de Limoges, 87042 Limoges, France. Electronic address: marie-laure.laroche@chu-limoges.fr.

PMID: 27425264
DOI: 10.1016/j.therap.2016.05.006

Abstract

Objective: Metformin-associated lactic acidosis (MALA) is a rare but serious adverse reaction with a mortality rate of up to 50%. Unfortunately, diagnosis and care management are often delayed. The objective was to assess the impact on the mortality rate and length of hospital stay of a MALA early diagnosis procedure in diabetic patients with metformin at emergency department (ED) admission.

Method: From 1/7/2012, a new MALA diagnosis procedure (pH, lactate, metformin) was implemented in all diabetic patients with metformin just after their admission to the ED. The pharmacovigilance staff confirmed the MALA cases (defined as pH≤7.35, lactate concentration>5mmol/L) in patients exposed to metformin and after a causality assessment to eliminate other common causes of lactic acidosis. To assess the impact of this new diagnosis procedure, a before-after study was conducted between two groups: a series of cases with intervention (IG; 1/7/2012-30/6/2013) and a control series of past cases without intervention (CG; 1/1/2011-30/6/2012). The main outcome was the relative reduction of mortality rate and length of hospital stay between the two groups.

Results: Thirty-four MALA cases were confirmed in 745 subjects admitted with lactic acidosis, (IG: 12; CG: 22). A higher illness severity score in the IG vs. CG was observed: respectively arterial lactate (14.2±6.9 vs. 8.8±5.8mmol/L, P<0.05), arterial bicarbonate (7.8±4.3 vs. 14.3±6.3mmol/L, P<0.05). The median time up to MALA diagnosis was 20.5 (Q1-Q3: 11.3-38.5) minutes for IG and 55.0 (Q1-Q3: 33.0-132.0) minutes for CG. After procedure implementation, the mortality relative risk reduction was 26.7% (95% CI: -84.3%, 70.8%), and especially 54.2% (95% CI: -265.2%, 94.2%) in the ED. There was no difference in the hospital stay duration between the two groups.

Conclusion: While the results were not significant, the study suggests that the implementation of a MALA early diagnosis procedure in all patients with metformin admitted to an ED tends to decrease mortality, especially for serious MALA cases detected earlier.

Keywords: Acidose lactique; Critical care; Diagnosis; Diagnostic; Lactic acidosis; Metformin; Metformine; Pharmacovigilance; Soins intensifs.