Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena di Milano, Università degli Studi di Milano, Via F, Sforza 35, 20122 Milan, Italy.
Crit Care. 2010;14(1):R22. doi: 10.1186/cc8885. Epub 2010 Feb 19.
Lactic acidosis can develop during biguanide (metformin and phenformin) intoxication, possibly as a consequence of mitochondrial dysfunction. To verify this hypothesis, we investigated whether body oxygen consumption (VO2), that primarily depends on mitochondrial respiration, is depressed in patients with biguanide intoxication.
Multicentre retrospective analysis of data collected from 24 patients with lactic acidosis (pH 6.93 +/- 0.20; lactate 18 +/- 6 mM at hospital admission) due to metformin (n = 23) or phenformin (n = 1) intoxication. In 11 patients, VO2 was computed as the product of simultaneously recorded arterio-venous difference in O2 content [C(a-v)O2] and cardiac index (CI). In 13 additional cases, C(a-v)O2, but not CI, was available.
On day 1, VO2 was markedly depressed (67 +/- 28 ml/min/m2) despite a normal CI (3.4 +/- 1.2 L/min/m2). C(a-v)O2 was abnormally low in both patients either with (2.0 +/- 1.0 ml O2/100 ml) or without (2.5 +/- 1.1 ml O2/100 ml) CI (and VO2) monitoring. Clearance of the accumulated drug was associated with the resolution of lactic acidosis and a parallel increase in VO2 (P < 0.001) and C(a-v)O2 (P < 0.05). Plasma lactate and VO2 were inversely correlated (R2 0.43; P < 0.001, n = 32).
VO2 is abnormally low in patients with lactic acidosis due to biguanide intoxication. This finding is in line with the hypothesis of inhibited mitochondrial respiration and consequent hyperlactatemia.
二甲双胍（二甲双胍和苯乙双胍）中毒时可能会发生乳酸酸中毒，可能是由于线粒体功能障碍所致。为了验证这一假说，我们研究了二甲双胍中毒患者的体氧消耗（VO2）是否降低，VO2 主要依赖于线粒体呼吸。
对 24 例因二甲双胍（n = 23）或苯乙双胍（n = 1）中毒导致乳酸酸中毒（入院时 pH 6.93 +/- 0.20；乳酸 18 +/- 6 mM）的患者的数据进行了多中心回顾性分析。在 11 例患者中，VO2 通过同时记录动静脉氧含量差[C(a-v)O2]和心指数（CI）来计算。在另外 13 例病例中，仅获得 C(a-v)O2，但未获得 CI。
第 1 天，尽管 CI 正常（3.4 +/- 1.2 L/min/m2），但 VO2 明显降低（67 +/- 28 ml/min/m2）。在 C(a-v)O2 监测或不监测（CI 和 VO2）的患者中，C(a-v)O2 均异常低（分别为 2.0 +/- 1.0 和 2.5 +/- 1.1 ml O2/100 ml）。蓄积药物的清除与乳酸酸中毒的缓解以及 VO2（P < 0.001）和 C(a-v)O2（P < 0.05）的平行增加相关。血浆乳酸和 VO2 呈负相关（R2 0.43；P < 0.001，n = 32）。
二甲双胍中毒导致乳酸酸中毒患者的 VO2 异常降低。这一发现与抑制线粒体呼吸和随后的高乳酸血症假说一致。
