Stades A M E, Heikens J T, Erkelens D W, Holleman F, Hoekstra J B L
Department of Internal Medicine, Diakonessenhuis, Utrecht, The Netherlands.
J Intern Med. 2004 Feb;255(2):179-87. doi: 10.1046/j.1365-2796.2003.01271.x.
Metformin has been associated with the serious side-effect lactic acidosis. However, it remains unclear whether the use of metformin was a cause or a coincidence in lactic acidosis.
A literature search of the Index Medicus (1959-66) and of the databases Embase, Medline, Medline Express (1966-99) was performed using the keywords metformin, biguanides and lactic acidosis. All articles of cases with metformin-induced lactic acidosis (MILA) were cross-referenced.
Cases were included for analysis if they met the following criteria: serum pH < or =7.35, lactate concentration > or =5 mmol L(-1).
A forum of six experts in intensive care medicine independently categorized the cases in MILA unlikely (score 0), possible MILA (score 1) or probable MILA (score 2).
Statistical analysis included the paired interobserver agreement (kappa) and multivariate regression analysis.
Of 80 reported cases, 33 were excluded because of insufficient quality. The forum scores of the remaining 47 cases were distributed normally with a mean score of 7 (range 2-10). The kappa-value was 0.041 (SD = 0.24, range -0.514, 0.427). Neither lactate concentration nor mortality correlated with serum metformin concentrations.
Given the low interobserver agreement and the lack of any relationship between metformin levels and outcome parameters, the concept that there is a simple, causal relationship between metformin use and lactic acidosis in diabetic patients has to be reconsidered.
二甲双胍与严重副作用乳酸性酸中毒有关。然而，二甲双胍的使用在乳酸性酸中毒中是病因还是巧合仍不清楚。
使用关键词二甲双胍、双胍类和乳酸性酸中毒对医学索引（1959 - 1966年）以及Embase、Medline、Medline Express数据库（1966 - 1999年）进行文献检索。对所有二甲双胍诱发乳酸性酸中毒（MILA）病例的文章进行交叉引用。
符合以下标准的病例纳入分析：血清pH≤7.35，乳酸浓度≥5 mmol/L。
一个由六位重症医学专家组成的小组独立将病例分为MILA不太可能（评分0）、可能MILA（评分1）或很可能MILA（评分2）。
统计分析包括观察者间一致性配对（kappa）和多变量回归分析。
在80例报告病例中，33例因质量不足被排除。其余47例病例的小组评分呈正态分布，平均评分为7分（范围2 - 10分）。kappa值为0.041（标准差 = 0.24，范围 - 0.514，0.427）。乳酸浓度和死亡率均与血清二甲双胍浓度无关。
鉴于观察者间一致性较低以及二甲双胍水平与结局参数之间缺乏任何关联，必须重新考虑糖尿病患者使用二甲双胍与乳酸性酸中毒之间存在简单因果关系这一概念。
