Is it possible to overdose on metformin

She has been using levothyroxine. Her family history includes diabetes mellitus in her mother and sister and her father died due to a malignancy. The patient had no complaints other than fatigue. She was awake and conscious, cooperated and oriented. The patient was hydrated. Stomach lavage was done, activated charcoal was given after that. Then she was hospitalized to the intensive care unit for further follow-up.

At the intensive care unit her initial vitals were normal. Arterial blood gas ABG revealed pH: 7. The hemogram and biochemical values of the patient were normal. In the follow-up her creatinine level reached to 1. ABG revealed pH: 6. Because metformin does not induce insulin release by pancreatic beta-islet cells, exposures infrequently induce disorders of glucose homeostasis.

When abnormal glucose levels occur with metformin exposures, hypoglycemia is much more commonly seen than hyperglycemia; hypoglycemia is usually ascribed to concurrent anti-diabetic medications such as the sulfonylureas. We present the case of a year-old non-diabetic girl who took a large overdose of metformin in a suicide attempt.

She presented with severe lactic acidosis and a progressively increasing serum glucose level. The hyperglycemia might have been due to pancreatitis. A year-old female patient without history of any disease ingested metformin in a suicide attempt. The patient consumed metformin bottle that contained about 30 - 35 tablets of mg each 4 h ago. Vital signs on arrival to the PED were temperature of Glasgow coma scale score was 3.

The patient was hospitalized in pediatric intensive care unit PICU. The laboratory examinations are shown in Table 1. Serum toxicological analyze was negative for ethanol, tricyclic antidepressants, benzodiazepine, salicylate and paracetamol. Metformin level assessment is important in toxicity; however, this facility is not available in our hospital.

Electrocardiographic ECG monitoring demonstrated a narrow-complex sinus tachycardia. Abdomen ultrasound was normal with no sign of any intraperitoneal collection or splenomegaly. By the laboratory results and history, the patient was diagnosed with acute metformin poisoning. ABG analysis showed persistent metabolic acidosis. Insulin perfusion 0. Dopamine drip infusion was started for hypotension despite continued IV hydration with 0. Hemodialysis was performed two times.

Four hours after PICU admission, she arrested in at several times and was resuscitated. After the second hemodialysis, laboratory examinations showed pH 7. Her serum glucose, lactate and serum amylase levels did not return to normal levels during the clinical observation. The patient died due to multiple organ failure 48 h after hospitalization despite the supportive care in PICU.

Therefore, additional prolonged HD should be considered even in the state of cardiovascular collapse with vasopressor requirement. Metformin is widely used and is the most frequently prescribed oral antidiabetic drug of the biguanide family [ 1 ].

Metformin inhibits hepatic gluconeogenesis and glycogenolysis and enhances peripheral glucose utilisation in patients with non-insulin-dependent diabetes [ 2 , 3 ]. Metformin use is generally safe and well tolerated.

However, lactic acidosis is a well-known complication to metformin treatment, especially in intentional overdose or in cases of renal insufficiency. Metformin poisoning is a life-threatening condition with a very high mortality rate. However, those intentional overdose patients with severe acidosis pH less than 6. At the Emergency Department, an aspiration of the gastric content was performed followed by administration of activated charcoal.

The patient developed vomiting and diarrhoea. Arterial blood gas showed pH 7. The patient was transferred to a university hospital.

Three hours after ingestion of metformin, the metabolic acidosis had deteriorated with serum lactate 8. During HD, the patient became increasingly acidotic and circulatory unstable and was admitted to the intensive care unit ICU for circulatory support and continuous CVVH.

Because of filter clotting, CVVH stopped after one hour. The metabolic acidosis escalated further with a pH decreasing to 6. The patient was less conscious but managed to hyperventilate to a PaCO 2 of 2. He developed severe hypotension, oliguria, hypothermia with core temperature Bicarbonate 8.

CVVH was restarted after 3 hours. Progression of the acidosis occurred with a drop in pH whenever HD was paused Figure 1. On the second day in the ICU, the patient was intubated and mechanical ventilation was initiated, because of respiratory insufficiency due to increasing PaCO 2. The patient had an increase of international normalized ratio INR from 1.

At that time, the patient was still nourished via a percutaneous endoscopic gastrostomy tube due to dysphagia and used a walker due to polyneuropathy. Severe metformin poisoning often presents with a profound lactic acidosis followed by collapse of the cardiovascular system. Symptoms of metformin poisoning are diffuse with abdominal pain, nausea, vomiting, hypothermia, decreased level of consciousness, and circulatory instability leading to multiorgan failure.

The circulatory instability is due to peripheral vasoplegia as described in many case reports where low systemic vascular resistance was measured [ 6 ]. We observed a clinical picture of a hyperdynamic circulatory state where FATE revealed normal contractility of the heart together with severe systemic hypotension.

Vasoplegia and vasodilatation can explain hypothermia, which is a common symptom of metformin poisoning [ 6 ]. Treatment of metformin poisoning is symptomatic and supportive and there is no antidote available.

Typical treatment strategies consist of correcting acidosis with intravenous sodium bicarbonate and decreasing the blood levels of metformin. Further prevention of gastrointestinal absorption can be achieved with activated charcoal. In case of renal insufficiency, renal replacement therapy is the only option for metformin removal and acidosis correction. Metformin is readily dialyzable. Lalau et al. This two-compartment model suggests that a brief hemodialysis session is not sufficient in eliminating metformin due to a rebound phenomenon [ 7 ].

These pharmacokinetic properties indicate a need of prolonged dialysis for metformin elimination. Several case reports describe favourable outcome after severe metformin poisoning treated with prolonged intermittent HD.