title: The prognostic value of blood pH and lactate and metformin concentrations in severe metformin-associated lactic acidosis.
abstract: OBJECTIVE
  Analysis of the prognostic values of blood pH and lactate and plasma metformin concentrations in severe metformin-associated lactic acidosis may help to resolve the following paradox: metformin provides impressive, beneficial effects but is also associated with life-threatening adverse effects.
  
  
  METHODS
  On the basis of 869 pharmacovigilance reports on MALA with available data on arterial pH and lactate concentration, plasma metformin concentration and outcome, we selected cases with a pH < 7.0 and a lactate concentration >10 mmol/L. Outcomes were compared with those described for severe metformin-independent lactic acidosis.
  
  
  RESULTS
  Fifty-six patients met the above-mentioned criteria. The mean arterial pH and lactate values were 6.75 ± 0.17 and 23.07 ± 6.94 mmol/L, respectively. The survival rate was 53%, even with pH values as low as 6.5 and lactate and metformin concentrations as high as 35.3 mmol/L and 160 mg/L (normal < 1 mg/L), respectively. Survivors and non-survivors did not differ significantly in terms of the mean arterial pH and lactate concentration. The mean metformin concentration was higher in patients who subsequently died but this difference was due to a very high value (188 mg/L) in one patient in this group, in whom several triggering factors were combined. Sepsis, multidrug overdoses and the presence of at least two triggering factors for lactic acidosis were observed significantly more frequently in non-survivors (p = 0.007, 0.04, and 0.005, respectively). This contrasts with a study of metformin-independent lactic acidosis in which there were no survivors, despite less severe acidosis on average (mean pH: 6.86).
  
  
  CONCLUSIONS
  In 56 cases of severe metformin-associated lactic acidosis, blood pH and lactate did not have prognostic value. One can reasonably rule out the extent of metformin accumulation as a prognostic factor. Ultimately, the determinants of metformin-associated lactic acidosis appear to be the nature and number of triggering factors. Strikingly, most patients survived - despite a mean pH that is incompatible with a favorable outcome under other circumstances.
authors.forename: Farshad
authors.initials: F
authors.lastname: Kajbaf
authors.forename: Jean-Daniel
authors.initials: JD
authors.lastname: Lalau
mesh_terms: D000140:Acidosis, Lactic / Q000097:blood* / Q000139:chemically induced / Q000175:diagnosis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016903:Drug Monitoring / Q000379:methods* / Q000706:statistics & numerical data; D062787:Drug Overdose / Q000097:blood / Q000175:diagnosis; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000097:blood; D007773:Lactates / Q000097:blood*; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000097:blood*; D008875:Middle Aged; D060735:Pharmacovigilance; D011379:Prognosis; D018805:Sepsis / Q000097:blood / Q000175:diagnosis; D012720:Severity of Illness Index; D016019:Survival Analysis
chemical_list: D007004:Hypoglycemic Agents; D007773:Lactates; D008687:Metformin