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Metformin toxicity: Rapid overview of emergency management

Metformin toxicity: Rapid overview of emergency management
To obtain emergency consultation with a medical toxicologist, in the United States, call 1-800-222-1222 for the nearest regional poison center. Contact information for poison centers around the world is available at the WHO website and in the UpToDate topic on regional poison centers (society guideline links).
Clinical presentation
Metformin is an antihyperglycemic agent whose major toxicity is metformin-associated lactic acidosis (MALA), which can occur following acute overdose (intentional ingestion or supratherapeutic dosing) or from accumulation in patients with kidney insufficiency, liver disease, or a precipitating illness causing hypoperfusion or hypoxemia (eg, infection, dehydration, decompensated heart failure, acute or progressive reduction in kidney function, bowel ischemia).
Metformin may exacerbate hypoglycemia caused by other agents; taken alone it rarely causes hypoglycemia.
Patients with toxicity (ie, MALA) may complain of nausea, vomiting, abdominal pain, or trouble breathing.
Examination findings may include tachycardia, tachypnea, hyperpnea, agitation, confusion, lethargy, coma, recalcitrant hypotension, ventricular dysrhythmias, or cardiac arrest.
Diagnostic evaluation
A fingerstick blood glucose measurement should be obtained immediately in any patient with altered mental status.
For a patient with concern for metformin poisoning/MALA: obtain serum chemistries, arterial or venous blood gas, serum lactate concentration, liver biochemical tests, coagulation studies, complete blood count, and pregnancy test in females of childbearing age.
If there is concern for intentional ingestion, we also obtain acetaminophen, salicylate, and ethanol concentrations and an electrocardiogram.
Treatment
Provide supportive care:
  • If tracheal intubation is needed in a patient with severe metabolic acidosis, approach the procedure as a "physiologically difficult airway" because administration of induction medications and neuromuscular blocking agents may make the apneic phase of rapid sequence intubation intolerable and create a risk for circulatory collapse.
  • Treat hypotension with intravenous fluids, followed by vasopressors if needed.
  • Treat hypoglycemia with intravenous dextrose 10 to 25 g (20 to 50 mL of 50% solution) in adults, 0.5 to 1 g/kg (2 to 4 mL/kg of 25% solution, maximum 25 g/dose) in children.
For acute ingestions, give single-dose activated charcoal: 1 g/kg (generally 50 g in adults; 0.5 to 1 g/kg maximum 50 g in children) orally.
For patients with profound acidosis (eg, pH <7.1 or <7.2 in patients with severe acute kidney injury), administer sodium bicarbonate (eg, give 1 to 2 mEq/kg [maximum 50 mEq] IV push; followed by a sodium bicarbonate infusion of 150 mEq [150 mL of 8.4% solution] in 1 L D5W run at 250 mL/hour in adults, or twice maintenance fluid infusion rate in children)
For patients with recalcitrant vasoplegic shock (ie, persistent hypotension despite adequate intravenous fluids and vasopressor therapy), methylene blue 1 to 2 mg/kg IV (repeated up to 6 mg/kg total) is an option.
For patients with profound acidosis (pH ≤7.1, highly elevated lactate (>15 mmol/L), failure to improve within two to four hours despite appropriate supportive care, or presence of comorbid conditions (shock, kidney impairment, liver failure, or decreased level of consciousness), obtain immediate nephrology consultation; hemodialysis will correct metformin-associated acid-base disturbance and slightly increase metformin clearance.
IV: intravenous.
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