Oxygen consumption is depressed in patients with lactic acidosis due to biguanide intoxication

Introduction: 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. Methods: 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 O-2 content [C(a-v) O-2] and cardiac index (CI). In 13 additional cases, C(a-v) O-2, but not CI, was available. Results: On day 1, VO2 was markedly depressed (67 +/- 28 ml/min/m(2)) despite a normal CI (3.4 +/- 1.2 L/min/m(2)). C(a-v) O-2 was abnormally low in both patients either with (2.0 +/- 1.0 ml O-2/100 ml) or without (2.5 +/- 1.1 ml O-2/100 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)O-2 (P < 0.05). Plasma lactate and VO2 were inversely correlated (R-2 0.43; P < 0.001, n = 32). Conclusions: 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.