The prognostic value of blood pH and lactate and metformin concentrations in severe metformin-associated lactic acidosis

BMC Clinical Pharmacology

Jean-Daniel Lalau²  Farshad Kajbaf¹ 

[1] Service d’Endocrinologie-Nutrition, Hôpital Sud, Amiens cedex 1, F-80054, France;Université de Picardie Jules Verne, Amiens, France

关键词: Prognosis;    Metformin;    Lactic acidosis;    Lactate;    Type 2 diabetes;   

Others  :  860616
DOI  :  10.1186/2050-6511-14-22

 received in 2012-07-13, accepted in 2013-03-20,  发布年份 2013

【 摘 要 】

Aims

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.

Research design and 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.

【 授权许可】

   
2013 Kajbaf and Lalau; licensee BioMed Central Ltd.

【 图 表 】

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