Overdose of metformin
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Metformin Overdose: Clinical Manifestations and Management
Introduction to Metformin Overdose
Metformin, a widely used oral hypoglycemic agent, is generally well-tolerated but can cause severe toxicity in cases of overdose. This article synthesizes research findings on the clinical manifestations, prognostic factors, and management strategies for metformin overdose.
Clinical Manifestations of Metformin Overdose
Metabolic Acidosis and Hyperlactatemia
One of the most critical complications of metformin overdose is metabolic acidosis, often accompanied by hyperlactatemia. Studies have shown that patients with severe metformin toxicity frequently present with significantly elevated lactate levels and low serum pH, indicative of lactic acidosis . For instance, a case study reported a patient with a pH of 6.83 and lactate levels of 24 mmol/L, which worsened despite initial treatment.
Renal and Multi-Organ Failure
Acute renal failure is a common occurrence in metformin overdose, often exacerbating the drug's toxic effects. This renal impairment can lead to multi-organ dysfunction, including respiratory failure, cardiovascular instability, and hepatic dysfunction . In one case, a patient developed acute renal insufficiency, severe lactic acidosis, and hyperglycemia, ultimately leading to multiple cardiac arrests and death.
Neurological and Gastrointestinal Symptoms
Patients with metformin toxicity may also exhibit neurological symptoms such as altered mental status and obtunded consciousness, as well as gastrointestinal symptoms like nausea and vomiting . These symptoms are often early indicators of severe toxicity and necessitate immediate medical intervention.
Prognostic Factors in Metformin Overdose
Serum pH, Lactate, and Metformin Levels
Research indicates that serum pH, lactate levels, and metformin concentrations are critical prognostic factors in metformin overdose. Patients with a nadir serum pH greater than 6.9, peak serum lactate concentrations less than 25 mmol/L, or peak metformin concentrations less than 50 µg/mL have a higher likelihood of survival. Conversely, lower pH and higher lactate and metformin levels are associated with increased mortality .
Organ Dysfunction Scores
The severity of organ dysfunction, as measured by scores like the Logistic Organ Dysfunction System (LODS), is another significant predictor of mortality. Acute liver dysfunction, indicated by low prothrombin activity, has been identified as an independent predictive factor of death in metformin-associated lactic acidosis (MALA).
Management Strategies for Metformin Overdose
Hemodialysis and Renal Replacement Therapy
Hemodialysis (HD) is a cornerstone in the management of severe metformin overdose, particularly in cases complicated by lactic acidosis. HD effectively reduces metformin levels and corrects metabolic acidosis, often leading to rapid clinical improvement . Continuous renal replacement therapy (CRRT) is also used, although its efficacy may vary .
Supportive Care and Extracorporeal Support
Supportive care, including the use of vasopressors and mechanical ventilation, is crucial in managing the hemodynamic instability and respiratory failure associated with metformin toxicity . In extreme cases, extracorporeal membrane oxygenation (ECMO) has been employed to stabilize patients with refractory acidosis and multi-organ failure.
Conclusion
Metformin overdose is a medical emergency characterized by severe metabolic acidosis, renal failure, and multi-organ dysfunction. Prognostic factors such as serum pH, lactate, and metformin levels are critical in assessing the severity and guiding treatment. Hemodialysis remains the most effective intervention for reducing metformin toxicity, while supportive care and extracorporeal support are essential for managing complications. Early recognition and aggressive treatment are vital for improving patient outcomes in metformin overdose cases.
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