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 O₂ content [C(a-v)O₂] and cardiac index (CI). In 13 additional cases, C(a-v)O₂, but not CI, was available.Results: 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).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.