Abstract
IntroductionLactic 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.MethodsMulticentre 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.ResultsOn 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).ConclusionsVO2 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.
Highlights
Lactic acidosis can develop during biguanide intoxication, possibly as a consequence of mitochondrial dysfunction
We identified 24 diabetic patients admitted to the intensive care (n = 22) or nephrology (n = 2) units with lactic acidosis attributed to either metformin (n = 23) or phenformin (n = 1) intoxication (Table 1)
Metformin and phenformin intoxication is characterized by severe lactic acidosis and abnormally low systemic oxygen consumption despite normal or even increased systemic oxygen delivery
Summary
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. Metformin is the first-line drug of choice for the treatment of adults with type 2 diabetes [1]. It is the 10th most frequently prescribed generic drug in the USA (>40 million prescriptions in 2008) and is currently used by almost one-third of diabetic patients in Italy [2,3]. Thirty cases of biguanide intoxication have been reported over the past two years to
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