Great CPC: Metformin toxicity

July 26, 2013, 4:19 pm


Case 23-2013: a 54-Year-old Woman with Abdominal Pain, Vomiting, and Confusion. Kalantar-Zadeh K et al. N Engl J Med 2013 Jul 25;369:374-382.

Full Text

This is a very instructive case discussion from the Massachusetts General Hospital. A plane was diverted to Boston because one passenger, a 54-year-old woman, developed increasing abdominal pain and vomiting, along with decreasing mental status. After the plane landed, EMS found that here vital signs were fairly unremarkable (HR = 52 bpm). She was not hypoglycemic.

Her medical history included type-2 diabetes, hypertension, and chronic renal disease. Medications included enalapril, metformin, glimepiride, nimesulide, imipramine, aspirin, and ibuprofen.

Hospital work-up revealed severe anion-gap metabolic acidosis (venous pH = 6.62, serum bicarbonate < 2.0 mmol/L, anion gap 61). Amylase and lipase were elevated. Lactate was 20.3 mmol/L. Admission creatinine was 7.88 mg/dL. CT scan of the abdomen showed evidence of acute pancreatitis.

Not surprisingly, the patient’s metformin level as significantly elevated (23 μg/ml, reference range 1 – 2). She improved after several days of supportive care and continuous venovenous hemofiltration.

In an excellent discussion of this case, Dr. Kamyar Kalantar-Zadeh from UC-Irvine makes the following points:

  • The history of chronic kidney disease made this patient a poor candidate for treatment with metformin, which is eliminated unchanged by the kidneys.
  • The combination of enalapril, ibuprofen, and aspirin increased the risk of worsening renal failure.
  • Although it is possible that acute pancreatitis was the primary process here, metformin accumulation itself can cause pancreatitis.

Dr. Kalanr-Zadeh mentions that in his experience, metformin toxicity as the cause of lactic acidosis is likely in patients who have all or most of the “following five criteria”:

  1. history of taking metformin
  2. lactate > 15 mmol/L
  3. anion gap > 20 mmol/L
  4. severe acidemia (pH < 7.10)
  5. serum bicarbonate level < 10 mmil/L
  6. renal insufficiency (serum creatinine > 2.0 mg/dL)

Make that six criteria. Which of course brings to mind a certain Monty Python sketch:

In any case, this CPC is well worth reading, especially since the full text is available free on line.

Related posts:

Metformin overdose and hypoglycemia

Surprise quiz: metformin overdose

Metformin and lactic acidosis

Drug-Induced Metabolic Acidosis


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