Oxygen consumption is depressed in patients with lactic acidosis due to biguanide intoxication.
BACKGROUND
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.
Protti
Alessandro
A
Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena di Milano, Università degli Studi di Milano, Via F, Sforza 35, 20122 Milan, Italy. alessandro.protti@policlinico.mi.it
Russo
Riccarda
R
Tagliabue
Paola
P
Vecchio
Sarah
S
Singer
Mervyn
M
Rudiger
Alain
A
Foti
Giuseppe
G
Rossi
Anna
A
Mistraletti
Giovanni
G
Gattinoni
Luciano
L
D000140:Acidosis, Lactic / Q000139:chemically induced / Q000503:physiopathology*; D000368:Aged; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000506:poisoning*; D008297:Male; D008687:Metformin / Q000506:poisoning*; D008875:Middle Aged; D010101:Oxygen Consumption; D010629:Phenformin / Q000506:poisoning*; D012189:Retrospective Studies
D007004:Hypoglycemic Agents; D008687:Metformin; D010629:Phenformin