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Severe lactic acidosis and acute renal failure following ingestion of metformin and kerosene oil: a case report.

ABSTRACT: INTRODUCTION: Kerosene is a freely accessible hydrocarbon used in Sri Lankan (and other Asian) households for cooking and for lighting lamps. Kerosene poisoning is rarely reported among adults and its toxicological effects are not well known. Metformin is a commonly used oral hypoglycemic drug and its overdose leads primarily to lactic acidosis. Combined poisoning of metformin and kerosene and their interactions have not been reported. CASE PRESENTATION: An 18-year-old, previously healthy, unmarried Sinhalese woman was referred following ingestion of 17.5 g of metformin and approximately 200 mL of kerosene oil in a suicide attempt. She had vomiting, burning epigastric pain, and a hypoglycemic seizure (capillary blood glucose of 42 mg/dL). Subsequently, she developed severe lactic acidosis followed by acute renal insufficiency, was treated with sodium bicarbonate, and underwent intermittent hemodialysis with bicarbonate. She recovered completely. CONCLUSIONS: This report proposes possible interactions that occur between metformin and kerosene that augment toxicity when the two are ingested together. It also stresses the importance of early treatment with intermittent hemodialysis in severe lactic acidosis with maintenance of blood glucose.

SUBMITTER: Rathnapala A

PROVIDER: S-EPMC3292833 | biostudies-other | 2012

REPOSITORIES: biostudies-other

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Severe lactic acidosis and acute renal failure following ingestion of metformin and kerosene oil: a case report.

Rathnapala Amila A Matthias Thushara T Jayasinghe Saroj S

Journal of medical case reports 20120117

<h4>Introduction</h4>Kerosene is a freely accessible hydrocarbon used in Sri Lankan (and other Asian) households for cooking and for lighting lamps. Kerosene poisoning is rarely reported among adults and its toxicological effects are not well known. Metformin is a commonly used oral hypoglycemic drug and its overdose leads primarily to lactic acidosis. Combined poisoning of metformin and kerosene and their interactions have not been reported.<h4>Case presentation</h4>An 18-year-old, previously h ...[more]

PMID: 22251748

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Project description:The global prevalence of type 2 diabetes (T2D) is expected to exceed 642 million people by 2040. Metformin is a widely used biguanide T2D therapy, associated with rare but serious events of lactic acidosis, in particular with predisposing conditions (e.g., renal failure or major surgery). Imeglimin, a recently approved drug, is the first in a new class (novel mode of action) of T2D medicines. Although not a biguanide, Imeglimin shares a chemical moiety with Metformin and also modulates mitochondrial complex I activity, a potential mechanism for Metformin-mediated lactate accumulation. We interrogated the potential for Imeglimin to induce lacticacidosis in relevant animal models and further assessed differences in key mechanisms known for Metformin's effects. In a dog model of major surgery, Metformin or Imeglimin (30-1000 mg/kg) was acutely administered, only Metformin-induced lactate accumulation and pH decrease leading to lactic acidosis with fatality at the highest dose. Rats with gentamycin-induced renal insufficiency received Metformin or Imeglimin (50-100 mg/kg/h), only Metformin increased lactatemia and H+ concentrations with mortality at higher doses. Plasma levels of Metformin and Imeglimin were similar in both models. Mice were chronically treated with Metformin or Imeglimin 200 mg/kg bid. Only Metformin produced hyperlactatemia after acute intraperitoneal glucose loading. Ex vivo measurements revealed higher mitochondrial complex I inhibition with Metformin versus slight effects with Imeglimin. Another mechanism implicated in Metformin's effects on lactate production was assessed: in isolated rat, liver mitochondria exposed to Imeglimin or Metformin, only Metformin (50-250 µM) inhibited the mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH). In liver samples from chronically treated mice, measured mGPDH activity was lower with Metformin versus Imeglimin. These data indicate that the risk of lactic acidosis with Imeglimin treatment may be lower than with Metformin and confirm that the underlying mechanisms of action are distinct, supporting its potential utility for patients with predisposing conditions.

Project description:BackgroundDespite strong recommendations to use metformin as first-line therapy for type 2 diabetes (T2DM), its use has been suboptimal, likely due to concerns of lactic acidosis. This study compared the association of acidosis in patients with T2DM prescribed metformin with those prescribed other antihyperglycemic medications or no medications.MethodsThis was a retrospective cohort study of patients with newly diagnosed T2DM utilizing an administrative database, which includes medical and prescription claims. Eligible patients had a diagnosis of T2DM, had continuous health plan enrollment 3 months prior to study enrollment and during the study period, and were at least 18 years of age. Mutually exclusive exposure groups were metformin only, other antihyperglycemic medications, and no medication. Acidosis cases were stratified by exposure group and risk factors for lactic acidosis (chronic obstructive pulmonary disease, hepatic dysfunction, alcohol abuse, heart failure, renal insufficiency, age of 80 years or older, and a history of acidosis). Degree of renal insufficiency was not available. Associations between exposure and acidosis were estimated, and risk factors evaluated.ResultsA total of 132,780 patients met inclusion criteria: 24,936 (20%) metformin only group, 15,059 (11%) other antihyperglycemic medication group, and 92,785 (70%) no medication group. Acidosis was observed in 1.45 per 10,000 patient months (0.78 metformin, 1.59 other antihyperglycemic medication, 1.51 no medication). The unadjusted relative risk of acidosis was 0.5 for patients prescribed metformin only compared with the other exposure groups (95% confidence interval = 0.2-1.2). There was no significant difference in risk of acidosis between exposure groups, irrespective of risk factors for lactic acidosis.ConclusionsRisk of acidosis was similar with metformin only compared with those prescribed other antihyperglycemic medications or no medication. These results support expanded use of metformin for T2DM. Additional studies are needed to understand the impact of risk factor severity on risk of lactic acidosis.

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Severe lactic acidosis and acute renal failure following ingestion of metformin and kerosene oil: a case report.

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Severe lactic acidosis and acute renal failure following ingestion of metformin and kerosene oil: a case report.

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