Multicenter Case Series of Pediatric Metformin Ingestion

A report of two deaths from massive ibuprofen ingestion

“…(2) the patient's clinical deterioration continued despite an improvement in serum ammonia and institution of hemodialysis; (3) serum ibuprofen concentration was elevated confirming an ibuprofen ingestion; and (4) the patient's profound refractory acidosis, hypothermia, and renal insufficiency are consistent with ibuprofen poisoning [21][22][23][24][25].…”

Severe lactic acidosis and hypoglycemia due to acute metformin intoxication in a dog

“…Metformin induced hypoglycemia is thought to result from inhibition of gluconeogenesis and glycogenolysis in the liver. Although severe seizures may also cause hypoglycemia, it is less likely that observed hypoglycemia is solely due to seizure‐like activity since this dog had no previous history of seizures and seizures have been rarely reported as a direct complication of metformin intoxication in other species . Other factors that may cause hypoglycemia such as hepatic disease including a portosystemic shunt, endocrine diseases including hypoadrenocorticism, insulinoma, other toxins including xylitol toxicity, and sepsis were considered less likely in this dog based on history and blood work results.…”

“…Other common adverse effects reported with metformin administration or overdosing in both, human and veterinarian patients, are gastrointestinal signs . Human studies showed that gastrointestinal signs including nausea, were the most common clinical signs in human patients with both unintentional and intentional exposure to metformin . The APCC reported that vomiting, diarrhea, and lethargy were the most common clinical signs in dogs with metformin intoxication due to accidental ingestion .…”

Metabolic Acidosis and Rhabdomyolysis with Metformin Overdosage

“…High anion-gap metabolic acidosis with hyperlactatemia is a well-known but rare adverse effect of Metformin therapy; the reported incidence varies between 6-40 per 100,000 patient/ years; higher incidence reported with increasing severity of coexisting renal impairment [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] . Although not fully understood, uncoupling of oxidative phosphorylation by inhibition of Complex1 of the mitochondrial electron transport chain is postulated to be responsible for the severe metabolic acidosis seen with Metformin toxicity 1,16 .…”

“…Lactic acidosis is a well-known but relatively uncommon adverse effect of Metformin, especially in patients with coexisting renal failure [2][3][4] . There are several case reports of inadvertent or intentional Metformin overdosage resulting in severe metabolic acidosis with hyperlactatemia and often with a fatal outcome [5][6][7][8][9][10][11][12][13][14] .…”