Kajbaf Farshad, Lalau Jean-Daniel
BMC Pharmacol Toxicol. 2013 Apr 12;14:22. doi: 10.1186/2050-6511-14-22.
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.
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.
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).
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.
分析血液酸碱度、乳酸和血浆二甲双胍浓度在严重二甲双胍相关性乳酸性酸中毒中的预后价值，可能有助于解决以下矛盾：二甲双胍具有显著的有益作用，但也与危及生命的不良反应相关。
基于869份关于二甲双胍相关性乳酸性酸中毒（MALA）的药物警戒报告，这些报告提供了动脉血酸碱度、乳酸浓度、血浆二甲双胍浓度及预后的数据，我们选取了血pH值<7.0且乳酸浓度>10 mmol/L的病例。将这些病例的预后与严重的非二甲双胍相关性乳酸性酸中毒的情况进行比较。
56例患者符合上述标准。平均动脉血pH值和乳酸值分别为6.75±0.17和23.07±6.94 mmol/L。即便pH值低至6.5，乳酸和二甲双胍浓度分别高达35.3 mmol/L和160 mg/L（正常<1 mg/L），生存率仍为53%。幸存者和非幸存者在平均动脉血pH值和乳酸浓度方面无显著差异。随后死亡的患者平均二甲双胍浓度较高，但这种差异是由于该组中的一名患者值非常高（188 mg/L），该患者合并了多种触发因素。脓毒症、多种药物过量以及至少两种乳酸性酸中毒触发因素在非幸存者中显著更常见（p分别为0.007、0.04和0.005）。这与一项关于非二甲双胍相关性乳酸性酸中毒的研究形成对比，在该研究中没有幸存者，尽管平均酸中毒程度较轻（平均pH值：6.86）。
在56例严重二甲双胍相关性乳酸性酸中毒病例中，血液pH值和乳酸没有预后价值。可以合理排除二甲双胍蓄积程度作为预后因素。最终，二甲双胍相关性乳酸性酸中毒的决定因素似乎是触发因素的性质和数量。引人注目的是，大多数患者存活了下来——尽管平均pH值在其他情况下与良好预后不相符。
