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 (VO(2)), 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, VO(2 )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, VO(2 )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 VO(2)) monitoring. Clearance of the accumulated drug was associated with the resolution of lactic acidosis and a parallel increase in VO(2 )(P < 0.001) and C(a-v)O(2 )(P < 0.05). Plasma lactate and VO(2 )were inversely correlated (R(2 )0.43; P < 0.001, n = 32). CONCLUSIONS: VO(2 )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.