Lalau J D, Lacroix C, Compagnon P, de Cagny B, Rigaud J P, Bleichner G, Chauveau P, Dulbecco P, Guérin C, Haegy J M
Service d'Endocrinologie, Hôpital Universitaire, Amiens, France.
Diabetes Care. 1995 Jun;18(6):779-84. doi: 10.2337/diacare.18.6.779.
To investigate the role of metformin accumulation in the pathophysiology of metformin-associated lactic acidosis.
We used high-performance liquid chromatography to measure plasma metformin concentrations in 14 patients who experienced lactic acidosis (pH < 7.35 and lactate concentration 5 > mmol/l) while receiving chronic metformin treatment. Their treatment was generally based on alkalinization and dialysis therapy.
Clinical shock and/or evidence of tissue hypoxia was found in all patients with the exception of one who had a nonsteroidal anti-inflammatory drug-induced anuria. Ten patients had significant metformin accumulation (plasma metformin concentrations 4.1-84.9 mg/l, normal value 0.6 +/- 0.5 mg/l before drug intake), generally because of failure to withdraw metformin despite intercurrent pathological conditions affecting its renal elimination (serum creatinine concentrations ranging from 269 to 1,091 mumol/l). There was no metformin accumulation (plasma metformin 0.03-0.7 mg/l) in the four other patients, who had less severe renal failure (serum creatinine 140-349 mumol/l). The severity of the patient's general condition did not predict early hospital mortality (death before discharge from the intensive care unit) even in patients in shock. Whereas it was high in those without metformin accumulation (only 1 of 4 patients recovered), early hospital mortality was low in the 10 patients with metformin accumulation and was not related to its extent (3 patients died with end-stage hepatic failure or cardiac failure). Correlation studies showed a positive correlation between serum creatinine and plasma metformin and between plasma metformin and arterial lactate but, for the latter correlation, only in patients with metformin accumulation.
Metformin-associated lactic acidosis is not necessarily due to metformin accumulation; true type B (aerobic) lactic acidosis, i.e., without an apparent associated hypoxic factor, seems exceptional. Neither the severity of the clinical picture nor the degree of metformin accumulation predicted survival; rather, the prognosis was dependent upon the severity of the associated pathological conditions.
探讨二甲双胍蓄积在二甲双胍相关乳酸酸中毒病理生理学中的作用。
我们采用高效液相色谱法测定了14例在接受慢性二甲双胍治疗期间发生乳酸酸中毒（pH<7.35且乳酸浓度>5mmol/L）患者的血浆二甲双胍浓度。他们的治疗通常基于碱化和透析疗法。
除1例因非甾体抗炎药导致无尿的患者外，所有患者均出现临床休克和/或组织缺氧证据。10例患者有显著的二甲双胍蓄积（血浆二甲双胍浓度为4.1 - 84.9mg/L，服药前正常值为0.6±0.5mg/L），通常是由于尽管存在影响其肾脏清除的并发病理状况（血清肌酐浓度范围为269至1091μmol/L）但仍未停用二甲双胍。另外4例肾功能衰竭较轻（血清肌酐140 - 349μmol/L）的患者未出现二甲双胍蓄积（血浆二甲双胍0.03 - 0.7mg/L）。患者总体病情的严重程度并不能预测早期医院死亡率（重症监护病房出院前死亡），即使是休克患者。在无二甲双胍蓄积的患者中死亡率较高（4例患者仅1例康复），而在10例有二甲双胍蓄积的患者中早期医院死亡率较低，且与蓄积程度无关（3例患者死于终末期肝衰竭或心力衰竭）。相关性研究表明血清肌酐与血浆二甲双胍之间以及血浆二甲双胍与动脉血乳酸之间存在正相关，但对于后一种相关性，仅在有二甲双胍蓄积的患者中存在。
二甲双胍相关乳酸酸中毒不一定是由于二甲双胍蓄积所致；真正的B型（需氧型）乳酸酸中毒，即无明显相关缺氧因素的情况似乎较为罕见。临床症状的严重程度和二甲双胍蓄积程度均不能预测生存情况；相反，预后取决于相关病理状况的严重程度。
