Abstract:
Metformin is a common diabetes drug that may reduce lactate clearance by inhibiting mitochondrial oxidative phosphorylation, leading to metformin-associated lactic acidosis (MALA). As diabetes mellitus is a common chronic metabolic condition found in critically ill patients, pre-existing metformin use can often be found in critically ill patients admitted to the intensive care unit or the high dependency unit. The aim of this narrative mini review is therefore to update clinicians about MALA, and to provide a practical approach to its diagnosis and treatment. MALA in critically ill patients may be suspected in a patient who has received metformin and who has a high anion gap metabolic acidosis, and confirmed when lactate exceeds 5 mmol/L. Risk factors include those that reduce renal elimination of metformin (renal impairment from any cause, histamine-2 receptor antagonists, ribociclib) and excessive alcohol consumption (as ethanol oxidation consumes nicotinamide adenine dinucleotides that are also required for lactate metabolism). Treatment of MALA involves immediate cessation of metformin, supportive management, treating other concurrent causes of lactic acidosis like sepsis, and treating any coexisting diabetic ketoacidosis. Severe MALA requires extracorporeal removal of metformin with either intermittent hemodialysis or continuous kidney replacement therapy. The optimal time to restart metformin has not been well-studied. It is nonetheless reasonable to first ensure that lactic acidosis has resolved, and then recheck the kidney function post-recovery from critical illness, ensuring that the estimated glomerular filtration rate is 30 mL/min/1.73 m2 or better before restarting metformin.
摘要:
二甲双胍是一种常见的糖尿病药物,可能通过抑制线粒体氧化磷酸化来降低乳酸清除率,导致二甲双胍相关性乳酸性酸中毒(MALA)。由于糖尿病是危重病人常见的慢性代谢性疾病,预先存在的二甲双胍的使用通常可以在重症监护病房或高度依赖病房的重症患者中发现。因此,这个叙述性迷你审查的目的是更新临床医生关于MALA的信息,并为其诊断和治疗提供切实可行的方法。危重患者中的MALA可能在接受二甲双胍且具有高阴离子间隙代谢性酸中毒的患者中被怀疑。并确认乳酸超过5mmol/L时风险因素包括那些减少二甲双胍的肾脏消除(任何原因引起的肾脏损害,组胺-2受体拮抗剂,ribociclib)和过量饮酒(因为乙醇氧化会消耗乳酸代谢所需的烟酰胺腺嘌呤二核苷酸)。MALA的治疗包括立即停止二甲双胍,支持性管理,治疗乳酸性酸中毒的其他并发原因,如脓毒症,并治疗任何并存的糖尿病酮症酸中毒。重度MALA需要通过间歇性血液透析或连续肾脏替代疗法体外去除二甲双胍。重新启动二甲双胍的最佳时间尚未得到很好的研究。尽管如此,首先确保乳酸性酸中毒已经解决是合理的,然后从危重疾病恢复后重新检查肾功能,确保在重新启动二甲双胍之前估计的肾小球滤过率为30mL/min/1.73m2或更高。