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

Crit Care. 2010;14(1):R22. doi: 10.1186/cc8885. Epub 2010 Feb 19.


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.

Publication types

  • Multicenter Study

MeSH terms

  • Acidosis, Lactic / chemically induced
  • Acidosis, Lactic / physiopathology*
  • Aged
  • Female
  • Humans
  • Hypoglycemic Agents / poisoning*
  • Male
  • Metformin / poisoning*
  • Middle Aged
  • Oxygen Consumption*
  • Phenformin / poisoning*
  • Retrospective Studies


  • Hypoglycemic Agents
  • Metformin
  • Phenformin