ISSN:
1432-0428
Keywords:
Metformin
;
lactic acidosis
;
acute renal failure
;
blood alanine
;
pyruvate
;
3-hydroxybutyrate
;
acetoacetate
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary Lactic acidosis occourred in 6 metformin-treated diabetic patients. Five of them had received 1.6 to 2.4 g metformin per day over a period of weeks or years. Acute renal failure, induced by i. v. pyelography, arteriography, or severe dehydration, preceded lactic acidosis by a few days and apparently precipitated it. The sixth patient had normal renal function prior to taking a massive overdose of metformin in an attempt at suicide. The metabolic pattern was very similar to that observed in phenformin-induced lactic acidosis: severe metabolic acidosis (pH: 7.02±0.95; HCO 3 − : 6.3±0.9 mmol/l; PaCO2: 25±4 mmHg; PaO2: 110±19 mmHg); hyperlactataemia (18.4±3.3 mmol/l) and high lactate/pyruvate ratio (51±5); high blood alanine (2.82±1.10 mmol/l); high 3-hydroxybutyrate (15.8±3.3 mmol/l) and high 3-hydroxybutyrate/ acetoacetate ratio (26±10). Hypoglycaemia (25 to 60 mg per 100 ml) was observed in 4 patients, in spite of high glucagon (760±148 pg/ml) and low insulin (13±5μU/ml) levels. A guanidine substance was characterized in the plasma at concentrations 45 to 110 μg/ml; it was similar to metformin and distinct from creatinine, according to chromatographic and other criteria; its concentration in the plasma decreased during dialysis, and the same substance appeared in the dialysis effluent. The treatment included massive alkalinization (710 ±130 mmol/l i. v. for 48 h), plasma volume expanders (5630±1000 ml/48 h), forced-diuresis and/or dialysis, insulin (30±10 U/48 h) and glucose (300 ±50 g/48 h). — It is concluded that: 1. metformin, like other biguanides, can induce lactic acidosis; 2. acute renal failure is a prominent causal factor; 3. pharmacokinetics of metformin account for this fact since metformin cannot be inactivated by the liver (as distinct from phenformin) and is normally excreted by the kidney; 4. accumulation of biguanide is suggested by guanidine assay in the plasma; 5. metformin should not be prescribed in the presence of renal failure.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01219702
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