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Metformin Poisoning Management

Poisoning - Hypoglycaemic Agent - Kids Health Wa (pmh Ed Guidelines)

Poisoning - Hypoglycaemic Agent - Kids Health Wa (pmh Ed Guidelines)

Oral hypoglycaemic agents are used for type II diabetes mellitus (non-insulin dependent diabetes) Sulfonylurea agents increase pancreatic insulin secretion and are the most important cause of hypoglycaemic toxicity Modified-release preparations may delay onset of symptoms for up to 8-18 hours Metformin is a biguanide agent that acts by decreasing carbohydrate absorption from the gut, increasing glucose uptake in peripheral tissues in the presence of insulin, and reducing hepatic gluconeogenesis The thiazolidinedione agents act at a nuclear receptor to improve insulin sensitivity in adipose tissues, skeletal muscles and the liver. Minimal information is available regarding overdose. The sulfonylurea agents may cause prolonged and profound life-threatening hypoglycaemia after accidental paediatric ingestion or deliberate self-poisoning Large overdoses may require treatment for several days A single tablet in a toddler has the potential to cause life-threatening hypoglycaemia. The onset of hypoglycaemia may be delayed up to 18 hours after ingestion. Admission for a minimum of 12- 24 hours is indicated for blood glucose monitoring. Discharge from hospital should only occur in the daylight hours. Metformin ingestion is not associated with hypoglycaemia in normal patients, but may cause life-threatening lactic acidosis in large overdoses or in the presence of renal or cardiac failure, or when there are co-ingestants which impair renal perfusion. Haemodialysis resolves the acidosis as well as removing metformin from the blood Nausea and vomiting may occur in smaller overdoses Asymptomatic patients following accidental exposure to metformin do not require referral to hospital, decontamination or investigation Children who have taken an unintentional ingestion of up to 1700 mg Continue reading >>

Management Of Metformin-associated Lactic Acidosis By Continuous Renal Replacement Therapy

Management Of Metformin-associated Lactic Acidosis By Continuous Renal Replacement Therapy

Abstract Metformin-associated lactic acidosis (MALA) is a severe metabolic failure with high related mortality. Although its use is controversial, intermittent hemodialysis is reported to be the most frequently used treatment in conjunction with nonspecific supportive measures. Our aim was to report the evolution and outcome of cases managed by continuous renal replacement therapy (CRRT). Methodology and Principal Findings Over a 3-year period, we retrospectively identified patients admitted to the intensive care unit for severe lactic acidosis caused by metformin. We included patients in our study who were treated with CRRT because of shock. We describe their clinical and biological features at admission and during renal support, as well as their evolution. We enrolled six patients with severe lactic acidosis; the mean pH and mean lactate was 6.92±0.20 and 14.4±5.1 mmol/l, respectively. Patients had high illness severity scores, including the Simplified Acute Physiology Score II (SAPS II) (average score 63±12 points). Early CRRT comprised either venovenous hemofiltration (n = 3) or hemodiafiltration (n = 3) with a mean effluent flow rate of 34±6 ml/kg/h. Metabolic acidosis control and metformin elimination was rapid and there was no rebound. Outcome was favorable in all cases. Continue reading >>

Extracorporeal Treatment For Metformin Poisoning: Systematic Review And Recommendations From The Extracorporeal Treatments In Poisoning Workgroup

Extracorporeal Treatment For Metformin Poisoning: Systematic Review And Recommendations From The Extracorporeal Treatments In Poisoning Workgroup

Background:Metformin toxicity, a challenging clinical entity, is associated with a mortality of 30%. The role of extracorporeal treatments such as hemodialysis is poorly defined at present. Here, the Extracorporeal Treatments In Poisoning workgroup, comprising international experts representing diverse professions, presents its systematic review and clinical recommendations for extracorporeal treatment in metformin poisoning. Methods:A systematic literature search was performed, data extracted, findings summarized, and structured voting statements developed. A two-round modified Delphi method was used to achieve consensus on voting statements and RAND/UCLA Appropriateness Method to quantify disagreement. Anonymized votes and opinions were compiled and discussed. A second vote determined the final recommendations. Results:One hundred seventy-five articles were identified, including 63 deaths: one observational study, 160 case reports or series, 11 studies of descriptive cohorts, and three pharmacokinetic studies in end-stage renal disease, yielding a very low quality of evidence for all recommendations. The workgroup concluded that metformin is moderately dialyzable (level of evidence C) and made the following recommendations: extracorporeal treatment is recommended in severe metformin poisoning (1D). Indications for extracorporeal treatment include lactate concentration greater than 20 mmol/L (1D), pH less than or equal to 7.0 (1D), shock (1D), failure of standard supportive measures (1D), and decreased level of consciousness (2D). Extracorporeal treatment should be continued until the lactate concentration is less than 3 mmol/L (1D) and pH greater than 7.35 (1D), at which time close monitoring is warranted to determine the need for additional courses of extracorporeal Continue reading >>

Metformin Poisoning: A Complex Presentation

Metformin Poisoning: A Complex Presentation

Metformin poisoning: A complex presentation We are experimenting with display styles that make it easier to read articles in PMC. The ePub format uses eBook readers, which have several "ease of reading" features already built in. The ePub format is best viewed in the iBooks reader. You may notice problems with the display of certain parts of an article in other eReaders. Generating an ePub file may take a long time, please be patient. Metformin poisoning: A complex presentation Manish Jagia, Salah Taqi, and Mahmud Hanafi The objective of this case report is to highlight presentation, complications and treatment of metformin poisoning. Patient after ingestion of 45gms of metformin developed colicky abdominal pain, severe tachypnea and vomiting. He developed severe lactic acidosis, cardiac arrest, pancreatitis and hemolytic anemia which was treated with charcoal, sodium bicarbonate, early initiation of high volume continuous veno-venous hemofiltration and supportive therapy. Metformin poisoning is a rare presentation and we discuss course of events in the management of metformin poisoning and its associated complications. Keywords: Cardiac arrest, haemolytic anemia, lactic acidosis, metformin poisoning, pancreatitis Metformin is a biguanide oral hypoglycemic agent used for non-insulin dependent diabetes mellitus (NIDDM). Metformin poisoning can cause fatal complications like severe lactic acidosis, haemolytic anemia and pancreatitis. Early diagnosis can result in successful outcome. Here, we report a case having good recovery despite metformin induced complications and cardiac arrest. A 36-year-old man presented in the Emergency Department after ingestion of 45 g metformin. He presented with colicky abdominal pain, severe tachypnoea and vomiting. He had history of NIDDM Continue reading >>

Ph 6.68surviving Severe Metformin Intoxication

Ph 6.68surviving Severe Metformin Intoxication

Metformin, a widely used anti-diabetic agent of the biguanide family, although generally safe, 1 , 2 , 3 , 4 holds the risk of developing a potentially lethal acidosis. 5 , 6 The association between lactic acidosis and metformin is well-established but rarely seen in patients taking this medication. 7 Its elimination relies solely on kidneys excretion, 8 so its accumulation is feasible in just two circumstances: renal failure (RF) and acute overdosage. At normal dosage, a toxic accumulation of drug requires time after the development of RF, due to metformin high clearance. About 90% of the drug is eliminated by glomerular filtration and tubular secretion (serum half-life of 1.55 h). Moreover, RF is itself associated with acidosis as it impairs kidneys ability to excrete protons. Acute intoxication on the other hand is a viable option in those cases where renal function is normal and can correlate with a psychiatric disorder. The mechanism thought to be responsible for lactic acidosis is suppression of gluconeogenesis forming lactate, pyruvate, glycerol and amino acids leading to lactate accumulation, 9 a risk that is increased by either chronic or acute RF (ARF). Usually hyperlactatemia is the most common finding leaving lactic acidosis for the most severe intoxications. A 47-year-old, apparently previously fit, non-insulin-dependent diabetic male was brought to the Emergency Department for hypoglycemia, agitation and hyperventilation. Ambulance crew found blood glucose level at 1.33 mmol/l (24 mg/dl) and administered 20 ml of 33% glucose solution followed by other 250 ml at 5%. At the arrival in the Emergency Room, the patient was confused and agitated with no signs of respiratory distress or shock. Arterial blood gases (ABG) and laboratory tests are summarized in Tab Continue reading >>

Metformin Toxicity

Metformin Toxicity

Summarized from DellAglio D, Perino L, Kazzi Z et al. Acute metformin overdose: Examining serum pH lactate Levels and metformin concentrations in survivors versus nonsurvivors: A systematic review of the literature. Annals of Emerg Med 2009; 54: 818-23 Metformin, a blood-glucose-lowering drug widely used for treatment of type 2 diabetes, is associated with risk of potentially fatal metabolic (lactic) acidosis. This can occur not only following overdose but also at therapeutic dose in patients with pre-existing renal or liver disease. Results of arterial blood gas analysis reflect metabolic acidosis (reduced blood pH, reduced bicarbonate compensatory increase in pCO2) and increased plasma lactate. Is it possible, as might be intuitively expected, to predict survival in such cases from the severity of the acidosis and/or severity of the hyperlactatemia? That is the question addressed by a recent study. Investigators conducted a systematic review of the literature and identified 22 well-documented case histories of metformin overdose, five of which had a fatal outcome. For each of these cases, investigators abstracted lowest (nadir) pH, highest (peak) plasma lactate concentration and highest (peak) plasma metformin concentration. The median nadir pH among non-survivors was 6.71 (interquartile IQ range 6.71-6.73), this compared with median pH 7.30 (IQ range 7.22-7.36) for survivors. The median peak plasma lactate among non-survivors was 35 mmol/L (IQ range 33.3-39.0) and among survivors 10.8 mmol/L (IQ range 4.2-12.9). Results allowed the conclusion that patients who died following metformin overdose had much lower nadir blood pH and much higher peak plasma lactate concentration than those who survived. No patients with pH > 6.9 and plasma lactate < 25 mmol/L died. Intuiti Continue reading >>

Metabolic Acidosis In A Patient With Metformin Overdose

Metabolic Acidosis In A Patient With Metformin Overdose

We report a rare fatal case of acute metformin overdose in a 19-year-old woman. A 19-year-old woman presented to a district-level emergency centre (EC) 1 hour after an intentional 'unquantifiable' metformin overdose. Clinical examination at that time was unremarkable except for a respiratory rate (RR) of 28 breaths per minute (bpm). No specific toxidrome was identified. In the EC, 6 hours post metformin ingestion, she appeared restless and complained of severe abdominal pain for which ranitidine, hyoscine butylbromide and lorazepam were administered orally. The patient was observed overnight in the EC. Eighteen hours post ingestion her tachypnoea worsened to 40 bpm and she developed hypoglycaemia with a finger prick blood glucose reading of 1.8 mmol/L. Venous blood gas findings taken at room temperature at this time are shown in Table 1 . Calculation of the anion gap was not possible because lactate and chloride values were not readily available. Based on the patient history and biochemical findings, a diagnosis of metabolic acidosis secondary to acute metformin overdose was made. Infusions of 5% dextrose w/v and 0.5% sodium bicarbonate were initiated separately, and the patient was immediately transferred to a secondary level hospital. Ongoing hypoglycaemia and worsening tachypnoea, accompanied by a drop in Glascow Coma Scale (GCS) to 12/15, occurred en route and 50 ml of a 50% dextrose bolus was administered. The patient developed a prolonged QT interval which precipitated cardiac arrest, with a GCS of 4T/15 requiring full resuscitation including inotropes. Arterial blood gas findings on 30% oxygen at this time revealed a metabolic acidosis as shown in Table 2 . At that time her creatinine was 235 mmol/L and the calculated increased anion gap was 27.3. The patient wa Continue reading >>

Metformin Litfl Life In The Fast Lane Medical Blog

Metformin Litfl Life In The Fast Lane Medical Blog

Metformin rarely causes hypoglycaemia but it can cause a profound lactic acidosis in overdose and in patients with renal failure. Used therapeutically to inhibit glucogenogenesis and stimulate peripheral glucose uptake, in toxic doses it causes a profound lactaemia. All the mechanisms are unclear but it is in part due to the inhibition of gluconeogenesis (which lactate is required). Therefore in healthy individuals there is some build up of lactate, this is normally excreted in the urine but at impaired renal function or an acute overdose there is excess lactate. It is not metabolised and excretion relies solely on renal excretion A lactic acidosis in the context of therapeutic metformin has a high mortality rate and an underlying cause (sepsis) needs to be managed Metformin overdose is usually benign but doses > 10 grams are concerning Lactic acidosis will occur in these individuals who are susceptible (renal, cardiac, respiratory failure) or in patients who have ingested co-ingestants or are on medications that impair cardiac and renal function Severe lactic acidosis usually manifests with non-specific symptoms several hours later but can progress to coma, shock and death Children: Unintentional ingestion of up to 1700mg is benign. Hypoglycaemia, if present can be managed with dextrose . Severe acidosis and hyperkalaemia may require the administration of sodium bicarbonate (1 2 mmol/kg). However, it is likely the patient is already hyperventilating to compensate for the metabolic acidosis, haemodialysis is the ultimate priority. If in a patient on therapeutic metformin, stop further administration and seek the underlying cause for their deterioration (sepsis, acute kidney injury) Screening: 12 lead ECG, BSL, Paracetamol level 50 grams of charcoal to the co-operative Continue reading >>

Pharmacology And Toxicology: Treatment Of Poisons - Metformin Intoxication

Pharmacology And Toxicology: Treatment Of Poisons - Metformin Intoxication

Pharmacology and Toxicology: Treatment of Poisons - Metformin Intoxication Pharmacology and Toxicology: Treatment of Poisons - Metformin Intoxication Does this patient have metformin intoxication? Since its introduction to the US market in 1995, the biguinide, metformin has become one of the most prescribed oral hypoglycemics. It is now considered the first line agent to treat type 2 diabetes. Because of its similarity to the drug another biguinide, phenformin, there was concern that it might increase the risk of lactic acidosis as was seen in phenformin. This delayed its release in the United States and led to a number of safety studies in the 1990s. One such study compared the incidence of lactic acidosis in patients treated with metformin and found that among the 7,227 patients followed on metformin, there were no incidents of lactic acidosis reported. Following its introduction, there have been a number of comparative studies with other oral agents for diabetes showing that metformin has a superior safety profile and excellent efficacy. As per the manufacturer, metformin is contraindicated in patients with chronic kidney disease. This is defined as a creatinine 1.4 mg/dL in women and 1.5 mg/dL in men. There have been a number of studies in patients with diabetes and chronic kidney disease that show that metformin remains a very safe medication and a number of authors have argued that its use should no longer be restricted in chronic kidney disease. Other authors have argued that for consistency sake alone, metformin should be restricted by a creatinine clearance estimate as it is with most medications whose clearance depends on renal function rather than a serum creatinine. For the time being, this author recommends following the restricted use of metformin as desc Continue reading >>

Metformin Intoxication

Metformin Intoxication

Can we love Metformin? Need we to fear it? Or perhaps we must give it Machiavellis ultimate accolade, and love and fear the drug with equal weight? Why to love Metformin? It is endorsed in the US, UK and Europe as the initial drug treatment for adults with type 2 diabetes. It treats diabetes, does not cause weight gain, does not increase risk of hypoglycaemia, and might reduce heart attacks and strokes. One tablet costs about 0.20 ($0.29/0.26) and the drug has been widely used for upwards of 60 years. So, must the love be tempered by fear? Metformin inhibits the mitochondrial respiratory chain, driving anaerobic metabolism and increasing lactic acid production. The drug is excreted almost entirely unchanged in urine so reduced kidney function may lead to accumulation of both metformin and lactate and therefore, a metformin-associated lactic acidosis (MALA). Where ingestion of overdose doses of metformin is seen, acutely or intentionally, this may be termed metformin-induced lactic acidosis (MILA). Notoriously, a similar drug, Phenformin, was withdrawn in the late 1970s after catastrophic lactic acidosis occurred in patients. The fear of metformin has lingered ever since, despite the overall incidence of lactic acidosis in metformin users being somewhere between 3 and 10 cases per 100,000 patient years and generally indistinguishable from the base rate in diabetics. Admittedly, reliable data specifically in patients with CKD is hard to come by and UK and US recommendations are to review the dose and not start the drug at an eGFR <45ml/min and stop the drug at <30ml/min. If youve seen a case of MALA, it might have extinguished any love you had for metformin; mortality is 30-50%, serum lactate is often over 20mmol/l and pH can fall below 7. Those are frightening numbers. Continue reading >>

Metformin-related Lactic Acidosis: Case Report - Sciencedirect

Metformin-related Lactic Acidosis: Case Report - Sciencedirect

Open Access funded by Sociedad Colombiana de Anestesiologa y Reanimacin Lactic acidosis is defined as the presence of pH <7.35, blood lactate >2.0mmol/L and PaCO2 <42mmHg. However, the definition of severe lactic acidosis is controversial. The primary cause of severe lactic acidosis is shock. Although rare, metformin-related lactic acidosis is associated with a mortality as high as 50%. The treatment for metabolic acidosis, including lactic acidosis, may be specific or general, using sodium bicarbonate, trihydroxyaminomethane, carbicarb or continuous haemodiafiltration. The successful treatment of lactic acidosis depends on the control of the aetiological source. Intermittent or continuous renal replacement therapy is perfectly justified, shock being the argument for deciding which modality to use. We report a case of a male patient presenting with metformin poisoning as a result of attempted suicide, who developed lactic acidosis and multiple organ failure. The critical success factor was treatment with continuous haemodiafiltration. Definimos acidosis lctica en presencia de pH <7.35, lactato en sangre >2.0mmol/L y PaCO2 <42mmHg. Por otro lado, la definicin de acidosis lctica grave es controvertida. La causa principal de acidosis lctica grave es el estado de choque. La acidosis lctica por metformina es rara pero alcanza mortalidad del 50%. La acidosis metablica incluyendo a la acidosis lctica puede recibir tratamiento especfico o tratamiento general con bicarbonato de sodio, trihidroxiaminometano, carbicarb o hemodiafiltracin continua. El xito del tratamiento de la acidosis lctica yace en el control de la fuente etiolgica; la terapia de reemplazo renal intermitente o continua est perfectamente justificada, donde el argumento para decidir cul utilizar ser el estado de Continue reading >>

Metformin Overdosage

Metformin Overdosage

Metformin is a biguanide used to treat type 2 diabetes mellitus and most commonly prescribed oral hypoglycemic agent. Metformin is now also used to treat polycystic ovary syndrome and some malignancies. Despite a good safety profile in a majority of patients with diabetes, the risk of metformin-associated lactic acidosis is genuine when safety guidelines are ignored. Overdoses with metformin are rare, but may result in serious consequences. Case reports and small case series of serious toxicity from metformin overdosage can be found in the medical literature, often with the portrayal of extracorporeal methods for the management of the subsequent severe lactic acidosis. Lactic acidosis can defined as a metabolic acidosis with a blood pH less than 7.35 and a serum lactate more than 2 mmol per liter. It can occur either with therapeutic metformin dosing (which is rare) or in overdose situations. 0.03 cases of lactic acidosis per 1000 patient-years occur within therapeutic dosing, with a majority of these cases among patients that have contraindications to metformin (such as renal insufficiency). In overdose situations, lactic acidosis is seen much more habitually, even though the precise incidence is unclear. Lactic acidosis has been observed in 1.6% of metformin exposures reported to poison control centers; nevertheless, merely 10% of these exposures were due to deliberate overdoses. The incidence of metformin-associated lactic acidosis was 12.8% in a review of poison control center inquiries from Germany. The minimum reported lethal dose was found in a 42 year-old patient who had a blood metformin level of 188 µg/ml (e.g. therapeutic range level is usually between 0.5–2.5 µg/ml). Although the intake of 35 g of metformin has shown to be lethal, the maximum reported to Continue reading >>

Mala: Metformin-associated Lactic Acidosis

Mala: Metformin-associated Lactic Acidosis

By Charles W. O’Connell, MD Introduction Metformin is a first-line agent for type 2 diabetes mellitus often used as monotherapy or in combination with oral diabetic medications. It is a member of the biguanide class and its main intended effect is expressed by the inhibition of hepatic gluconeogenesis. In addition, metformin increases insulin sensitivity, enhances peripheral glucose utilization and decreases glucose uptake in the gastrointestinal tract. Phenformin, a previously used biguanide, as withdrawn from the market in the 1970’s due its association with numerous cases of lactic acidosis. Metformin is currently used extensively in the management of diabetes and is the most commonly prescribed biguanide worldwide. The therapeutic dosage of metformin ranges from 850 mg to a maximum of 3000 mg daily and is typically divided into twice daily dosing. It is primarily used in the treatment of diabetes but has been used in other conditions associated with insulin resistance such as polycystic ovarian syndrome. MALA is a rare but well reported event that occurs with both therapeutic use and overdose states. Case presentation A 22-year-old female presents to the Emergency Department after being found alongside a suicide note by her family. She was thought to have taken an unknown, but large amount of her husband’s metformin. She arrives at the ED nearly 10 hours after ingestion. She was agitated, but conversant. She reports having nausea and vague feelings of being unwell and is very distraught over the state of her critically ill husband. She has some self-inflicted superficial lacerations over her left anterior forearm. Her vital assigns upon arrival were: T 98.9 degrees Fahrenheit, HR initially 140 bpm which improved to 110 bpm soon after arrival, BP 100/50, RR 22, Continue reading >>

Metformin Overdose

Metformin Overdose

Tweet Save As with any medication, it is possible to overdose on metformin. Some of the effects of a metformin overdose may include low blood sugar or lactic acidosis. Symptoms of low blood sugar include blurred vision, shakiness, and extreme hunger. Some symptoms of lactic acidosis can include an irregular heartbeat, trouble breathing, and feeling tired. There are some treatment options for a metformin overdose, including dialysis or using a sugar solution to increase blood sugar levels. Metformin Overdose: An Overview Metformin (Glucophage®) is a prescription medication that has been licensed to treat type 2 diabetes. As with all medicines, it is possible to take too much metformin. Effects of a metformin overdose will vary depending on a number of factors, including how much metformin was taken and whether it was taken with any other medicines, alcohol, and/or drugs. If you happen to overdose on metformin, seek medical attention immediately. Symptoms of a Metformin Overdose The effects of a metformin overdose may include: Possible symptoms of low blood sugar include: Sweating Shakiness Extreme hunger Dizziness Cold sweats Blurry vision. More severe low blood sugar symptoms include: Changes in behavior, such as irritability Loss of coordination Difficulty speaking Confusion Loss of consciousness Coma Lactic acidosis symptoms include: Feeling tired or weak Muscle pain Trouble breathing Abdominal pain (or stomach pain) Feeling cold Dizziness or lightheadedness A slow or irregular heartbeat Loss of life. Tweet Our free DiscountRx savings card can help you and your family save money on your prescriptions. This card is accepted at all major chain pharmacies, nationwide. Enter your name and email address to receive your free savings card. Treatment for a Metformin Overdose Continue reading >>

Metformin

Metformin

Metformin, marketed under the trade name Glucophage among others, is the first-line medication for the treatment of type 2 diabetes,[4][5] particularly in people who are overweight.[6] It is also used in the treatment of polycystic ovary syndrome.[4] Limited evidence suggests metformin may prevent the cardiovascular disease and cancer complications of diabetes.[7][8] It is not associated with weight gain.[8] It is taken by mouth.[4] Metformin is generally well tolerated.[9] Common side effects include diarrhea, nausea and abdominal pain.[4] It has a low risk of causing low blood sugar.[4] High blood lactic acid level is a concern if the medication is prescribed inappropriately and in overly large doses.[10] It should not be used in those with significant liver disease or kidney problems.[4] While no clear harm comes from use during pregnancy, insulin is generally preferred for gestational diabetes.[4][11] Metformin is in the biguanide class.[4] It works by decreasing glucose production by the liver and increasing the insulin sensitivity of body tissues.[4] Metformin was discovered in 1922.[12] French physician Jean Sterne began study in humans in the 1950s.[12] It was introduced as a medication in France in 1957 and the United States in 1995.[4][13] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[14] Metformin is believed to be the most widely used medication for diabetes which is taken by mouth.[12] It is available as a generic medication.[4] The wholesale price in the developed world is between 0.21 and 5.55 USD per month as of 2014.[15] In the United States, it costs 5 to 25 USD per month.[4] Medical uses[edit] Metformin is primarily used for type 2 diabetes, but is increasingly be Continue reading >>

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