Metformin overdose effects
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Effects of Metformin Overdose
Introduction to Metformin Overdose
Metformin, a widely prescribed oral hypoglycemic agent for diabetes management, can lead to severe toxicity when overdosed. This article synthesizes findings from multiple case reports and studies to highlight the clinical manifestations, treatment interventions, and outcomes associated with metformin overdose.
Metabolic Acidosis and Hyperlactatemia
Severe Metabolic Acidosis
One of the most critical effects of metformin overdose is severe metabolic acidosis, often accompanied by hyperlactatemia. In a reported case, a 55-year-old woman who ingested 132 grams of extended-release metformin developed profound metabolic acidosis with a pH of 7.0 and lactate levels of 17 mmol/L, which worsened despite continuous venovenous hemofiltration (CVVHDF). Another study found that metformin-associated lactic acidosis (MALA) was present in 92.6% of patients with metformin toxicity, indicating its prevalence and severity.
Hyperlactatemia
Hyperlactatemia is a common finding in metformin overdose cases. In the same case of the 55-year-old woman, lactate levels peaked at 30 mmol/L, highlighting the severity of lactic acidosis. A systematic review also noted that patients with peak serum lactate levels greater than 25 mmol/L had an 83% mortality rate, underscoring the critical nature of hyperlactatemia in these cases.
Multi-Organ Failure and Complications
Distributive Shock and Organ Failure
Metformin overdose can lead to distributive shock and multi-organ failure. A 28-year-old woman who intentionally overdosed on metformin developed distributive shock, metabolic acidosis, acute respiratory distress syndrome (ARDS), kidney failure, and rhabdomyolysis. These complications necessitated the use of continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO) to stabilize her condition.
Hypoglycemia and Asphyxial Syndrome
Hypoglycemia and asphyxial syndrome are also reported in metformin overdose cases. In one instance, a 35-year-old woman developed hypoglycemia, cyanosis of the extremities, and multi-visceral congestion, leading to her death. Another case involved a 57-year-old man who experienced similar symptoms, including nail cyanosis and asphyxiation, resulting in fatality.
Treatment Interventions
Renal Replacement Therapy (RRT)
Renal replacement therapy is a critical intervention for managing metformin toxicity. In a meta-summary of case reports, 68.6% of patients received RRT for toxin removal and correction of MALA, with favorable outcomes observed in those with severe acidosis and high lactate levels. Intermittent hemodialysis (IHD) has been shown to improve metabolic acidosis more effectively than CVVHDF in some cases.
Extracorporeal Membrane Oxygenation (ECMO)
ECMO has been used in severe cases to manage respiratory failure and hemodynamic instability. The 28-year-old woman mentioned earlier was treated with venoarterial ECMO for nine days, which helped resolve her persistent acidosis and stabilize her condition.
Prognostic Indicators
Serum pH, Lactate, and Metformin Levels
The severity of metformin overdose can be gauged by serum pH, lactate, and metformin concentrations. A systematic review found that patients with a nadir serum pH greater than 6.9, peak lactate levels less than 25 mmol/L, and peak metformin concentrations less than 50 µg/mL had better survival rates. These parameters can help predict outcomes and guide treatment strategies.
Conclusion
Metformin overdose can lead to severe metabolic acidosis, hyperlactatemia, and multi-organ failure, necessitating aggressive treatment interventions such as RRT and ECMO. Prognostic indicators like serum pH, lactate, and metformin levels are crucial for assessing the severity and guiding treatment. Despite the potential for severe complications, timely and appropriate interventions can result in favorable outcomes for patients.
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