Background

Lactate is a robust prognostic marker for the outcome of critically ill patients. Several small studies reported that metformin users have higher lactate levels at ICU admission without a concomitant increase in mortality. However, this has not been investigated in a larger cohort. We aimed to determine whether the association between lactate levels around ICU admission and mortality is different in metformin users compared to metformin nonusers.

Methods

This cohort study included patients admitted to ICUs in northern Denmark between January 2010 and August 2017 with any circulating lactate measured around ICU admission, which was defined as 12 h before until 6 h after admission. The association between the mean of the lactate levels measured during this period and 30-day mortality was determined for metformin users and nonusers by modelling restricted cubic splines obtained from a Cox regression model.

Results

Of 37,293 included patients, 3183 (9%) used metformin. The median (interquartile range) lactate level was 1.8 (1.2–3.2) in metformin users and 1.6 (1.0–2.7) mmol/L in metformin nonusers. Lactate levels were strongly associated with mortality for both metformin users and nonusers. However, the association of lactate with mortality was different for metformin users, with a lower mortality rate in metformin users than in nonusers when admitted with similar lactate levels. This was observed over the whole range of lactate levels, and consequently, the relation of lactate with mortality was shifted rightwards for metformin users.

Conclusion

In this large observational cohort of critically ill patients, early lactate levels were strongly associated with mortality. Irrespective of the degree of hyperlactataemia, similar lactate levels were associated with a lower mortality rate in metformin users compared with metformin nonusers. Therefore, lactate levels around ICU admission should be interpreted according to metformin use.

中文翻译：

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乳酸水平升高对危重病患者接受或不接受二甲双胍治疗的死亡率的预后影响：一项基于丹麦注册研究的队列研究

背景

乳酸是危重病人预后的有力标志。几项小型研究报告说，二甲双胍使用者在ICU入院时具有较高的乳酸水平，而死亡率并未随之增加。但是，尚未在更大的队列中对此进行研究。我们旨在确定二甲双胍使用者与非二甲双胍使用者之间在ICU入院时乳酸水平与死亡率之间的相关性是否不同。

方法

这项队列研究包括2010年1月至2017年8月在丹麦北部重症监护病房（ICU）入院的患者，其在入院前约12小时至入院后6小时内测量了任何循环乳酸。通过对从Cox回归模型获得的受限三次样条进行建模，确定了此期间测得的乳酸水平平均值与30天死亡率之间的相关性。

结果

在37293名患者中，有3183名（9％）使用了二甲双胍。二甲双胍使用者的乳酸中位数水平（四分位数范围）为1.8（1.2-3.2），非二甲双胍使用者的乳酸水平中值为1.6（1.0-2.7）mmol / L。乳酸水平与二甲双胍使用者和非使用者之间的死亡率密切相关。但是，服用二甲双胍的人中乳酸与死亡率的相关性有所不同，当服用相似的乳酸水平时，服用二甲双胍的人的死亡率低于未服用二甲双胍的人。在乳酸水平的整个范围内都可以观察到这一点，因此，二甲双胍使用者的乳酸与死亡率的关系向右移动。

结论

在这个危重病人的大型观察队列中，早期乳酸水平与死亡率密切相关。不论高乳酸血症的程度如何，与不服用二甲双胍的人相比，相似的乳酸水平与二甲双胍使用者的死亡率较低有关。因此，应根据二甲双胍的使用来解释ICU入院前后的乳酸水平。