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.

Acute intoxication by phenformine hyperlactatemia reversible with extra-renal purification.

The authors report the observation of an acute intoxication with 25.5 g of metaformin, 2.5 g of phenobarbital and 12.5 g of belladonna extract in a 53 year-old diabetic patient having been treated with metformin for 5 years. The evolution was dominated by the association of a barbituric coma with an hyperlactatemia which reached 21 mmol/l during the 18th hour and normalized at the 36th hour thanks to an hemodialysis on polyacrilonitrile membrane, which was carried out for 24 hours. The biological evolution was determined in considering the barbitemia, lactacidemia and metforminemia rates. An hepatic biopsy made during the decrease of the hyperlactatemia enabled to consider histological lesions of steatosis and ultrastructural lesions of mitochondrial alteration, already described in the course of pathological hyperlactatemia.

The interaction between alcohol, chlorpropamide and phenformin in a severe combined poisoning: case report.

A young non-diabetic woman ingested 2.5-3.7 g of chlorpropamide and 0.6-0.9 g of phenformin together with a large dose of alcohol, nitrofurantoin and promethazine in a suicidal attempt. She developed severe metabolic acidosis, hypokalemia, polyuria and prolonged hypoglycemia in the absence of typical hypoglycemic symptoms. These unusual clinical features were in part explained on the basis of the interactions between alcohol and the other drugs.

Acute muscle necrosis after chronic overdosage of phenformin and fenfluramine.

A case of acute muscle necrosis with probable myoglobinuria is presented. The patient had been taking excessive doses of phenformin and fenfluramine, and a toxic etiology is suggested. Muscle necrosis is tentatively attributed either to the combined effect of these drugs on some underlying biochemical abnormality of muscle or to a defect of oxygen utilization secondary to myoglobin alterations.

Acute self-poisoning with phenformin.

The case is reported of a non-diabetic young woman who attempted suicide by ingesting 2,500 mg of phenformin. The most marked clinical and laboratory findings during the first 24 hrs included nausea, vomiting, anxiety, agitation, polydipsia, polyuria, increased appetite, tachycardia, tachypnea, persistent lactic acidosis, hypoglycemia and hypokalemia. Treatment at the ICU 10 hrs after ingestion of the overdose was essentially symptomatic and included measures to correct acidosis and hypoglycemia. The patient recovered completely.