Department of Emergency Medicine, Kings County Hospital, Brooklyn, NY, USA.
Department of Emergency Medicine, State University of New York, Downstate Medical Center, Brooklyn, NY, USA.
J Med Toxicol. 2020 Apr;16(2):222-229. doi: 10.1007/s13181-019-00755-6. Epub 2020 Jan 6.
Metformin-associated lactic acidosis (MALA) may occur after acute metformin overdose, or from therapeutic use in patients with renal compromise. The mortality is high, historically 50% and more recently 25%. In many disease states, lactate concentration is strongly associated with mortality. The aim of this systematic review and meta-analysis is to investigate the utility of pH and lactate concentration in predicting mortality in patients with MALA.
We searched PubMed, EMBASE, and Web of Science from their inception to April 2019 for case reports, case series, prospective, and retrospective studies investigating mortality in patients with MALA. Cases and studies were reviewed by all authors and included if they reported data on pH, lactate, and outcome. Where necessary, authors of studies were contacted for patient-level data. Receiver operating characteristic (ROC) curves were generated for pH and lactate for predicting mortality in patients with MALA.
Forty-four studies were included encompassing 170 cases of MALA with median age of 68.5 years old. Median pH and lactate were 7.02 mmol/L and 14.45 mmol/L, respectively. Overall mortality was 36.2% (95% CI 29.6-43.94). Neither lactate nor pH was a good predictor of mortality among patients with MALA. The area under the ROC curve for lactate and pH were 0.59 (0.51-0.68) and 0.43 (0.34-0.52), respectively.
Our review found higher mortality from MALA than seen in recent studies. This may be due to variation in standard medical practice both geographically and across the study interval, sample size, misidentification of MALA for another disease process and vice versa, confounding by selection and reporting biases, and treatment intensity (e.g., hemodialysis) influenced by degree of pH and lactate derangement. The ROC curves showed poor predictive power of either lactate or pH for mortality in MALA. With the exception of patients with acute metformin overdose, patients with MALA usually have coexisting precipitating illnesses such as sepsis or renal failure, though lactate from MALA is generally higher than would be considered survivable for those disease states on their own. It is possible that mortality is more related to that coexisting illness than MALA itself, and many patients die with MALA rather than from MALA. Additional work looking solely at MALA in healthy patients with acute metformin overdose may show a closer relationship between lactate, pH, and mortality.
二甲双胍相关乳酸性酸中毒（MALA）可能发生在急性二甲双胍过量后，也可能发生在肾功能受损的患者的治疗中。死亡率很高，历史上为 50%，最近为 25%。在许多疾病状态下，乳酸浓度与死亡率密切相关。本系统评价和荟萃分析的目的是研究 pH 值和乳酸浓度在预测 MALA 患者死亡率中的作用。
我们从成立到 2019 年 4 月在 PubMed、EMBASE 和 Web of Science 上搜索了关于 MALA 患者死亡率的病例报告、病例系列、前瞻性和回顾性研究。所有作者都对病例和研究进行了审查，如果他们报告了 pH 值、乳酸和结果的数据，则将其纳入研究。必要时，我们联系了研究作者以获取患者水平的数据。为预测 MALA 患者的死亡率生成了 pH 值和乳酸的受试者工作特征（ROC）曲线。
共纳入 44 项研究，包括 170 例 MALA 患者，中位年龄为 68.5 岁。中位 pH 值和乳酸值分别为 7.02mmol/L 和 14.45mmol/L，总死亡率为 36.2%（95%CI 29.6-43.94）。乳酸和 pH 值均不能很好地预测 MALA 患者的死亡率。乳酸和 pH 值的 ROC 曲线下面积分别为 0.59（0.51-0.68）和 0.43（0.34-0.52）。
我们的综述发现 MALA 的死亡率高于最近的研究。这可能是由于地理位置和研究时间间隔、样本量、对 MALA 的误诊为另一种疾病过程或反之、选择和报告偏倚的混杂以及治疗强度（例如血液透析）的变化导致的，这些因素受 pH 值和乳酸紊乱程度的影响。ROC 曲线显示乳酸或 pH 值对 MALA 死亡率的预测能力较差。除了急性二甲双胍过量的患者外，MALA 患者通常还患有合并症，如败血症或肾衰竭，尽管 MALA 引起的乳酸通常高于这些疾病单独存在时的可存活水平。死亡率可能与合并症有关，而不是 MALA 本身，许多患者死于 MALA 而不是死于 MALA。仅在急性二甲双胍过量的健康患者中观察 MALA 的进一步研究可能会显示乳酸、pH 值和死亡率之间更密切的关系。
