title: Can an early diagnostic procedure of metformin-associated lactic acidosis in an emergency unit reduce mortality?
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Damien
authors.initials: D
authors.lastname: Sémely
authors.affiliation: Département des urgences, CHU de Limoges, 87042 Limoges, France.
authors.forename: Emily
authors.initials: E
authors.lastname: Bennett
authors.affiliation: Département des urgences, CHU de Limoges, 87042 Limoges, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Vallejo
authors.affiliation: Service de pharmacologie, toxicologie et pharmacovigilance, CHU de Limoges, 87042 Limoges, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Saint-Marcoux
authors.affiliation: 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.
authors.forename: Louis
authors.initials: L
authors.lastname: Merle
authors.affiliation: 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.
authors.forename: Yves
authors.initials: Y
authors.lastname: Nouaille
authors.affiliation: Service de pharmacologie, toxicologie et pharmacovigilance, CHU de Limoges, 87042 Limoges, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Lachâtre
authors.affiliation: 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.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Laroche
keywords: Acidose lactique; Critical care; Diagnosis; Diagnostic; Lactic acidosis; Metformin; Metformine; Pharmacovigilance; Soins intensifs