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Lactic Acidosis Metformin Signs And Symptoms

Lactic Acidosis

Lactic Acidosis

The buildup of lactic acid in the bloodstream. This medical emergency most commonly results from oxygen deprivation in the body’s tissues, impaired liver function, respiratory failure, or cardiovascular disease. It can also be caused by a class of oral diabetes drugs called biguanides, which includes metformin (brand name Glucophage). Another biguanide called phenformin was pulled from the market in the United States in 1977 because of an unacceptably high rate of lactic acidosis associated with its use. Concerns about lactic acidosis also delayed the introduction of metformin to the U.S. market until 1995, despite the fact that it had been widely used for years in other countries. There have been reports of lactic acidosis occurring in people taking metformin, and the U.S. Food and Drug Administration estimates that lactic acidosis occurs in 5 out of every 100,000 people who use metformin for any length of time. However, this risk is much lower than it was in people taking phenformin, and it is not clear whether the episodes of lactic acidosis associated with metformin have actually been due to metformin use. In fact, the lactic acidosis could have been explained by the person’s diabetes and related medical conditions. Nonetheless, diabetes experts recommend that metformin not be used in people with congestive heart failure, kidney disease, or liver disease. They also recommend that it be discontinued (at least temporarily) in people undergoing certain medical imaging tests called contrast studies. Symptoms of lactic acidosis include feeling very weak or tired or having unusual muscle pain or unusual stomach discomfort. Continue reading >>

Metformin Associated Lactic Acidosis

Metformin Associated Lactic Acidosis

Emma Fitzgerald, specialist trainee year 2 in anaesthetics 1 , Stephen Mathieu, specialist registrar in anaesthetics and intensive care medicine 1 , Andrew Ball, consultant in anaesthesia and intensive care medicine 1 1Dorset County Hospital, Dorchester, Dorset DT1 2JY Correspondence to: E Fitzgerald zcharm6{at}hotmail.com Dehydration in patients taking metformin can lead to metformin associated lactic acidosis, a potentially fatal condition Metformin, a dimethylbiguanide, is a widely used oral antihyperglycaemic drug used in the long term treatment of type 2 diabetes mellitus. More recently it has also been used to improve fertility and weight reduction in patients with polycystic ovary syndrome. Many large studies have shown that intensive glucose control with metformin in overweight patients with type 2 diabetes is associated with risk reductions of 32% (P=0.002) for any diabetes related end point, 42% (P=0.017) for diabetes related death, and 36% (P=0.011) for all cause mortality compared with diet alone. 1 Furthermore, metformin reduces microvascular end points, and its degree of glycaemic control is similar to that sulphonylureas and insulin. Metformin is considered to be first line treatment in overweight patients with type 2 diabetes whose blood glucose is inadequately controlled by lifestyle interventions alone and should be considered as a first line glucose lowering treatment in non-overweight patients with type 2 diabetes because of its other beneficial effects. 2 It may also be useful in overweight patients with type 1 diabetes. A potential complication of metformin is the development of type B (non-hypoxic) lactic acidosis. Although metformin associated lactic acidosis is a rare condition, with an estimated prevalence of one to five cases per 100 000 popu Continue reading >>

6 Pearls About Metformin And Lactic Acidosis

6 Pearls About Metformin And Lactic Acidosis

Metformin accumulation: Lactic acidosis and high plasmatic metformin levels in a retrospective case series of 66 patients on chronic therapy. Vecchio S et al. Clin Toxicol 2014 Feb;52:129-135. Metformin is frequently used alone or in combination to treat type 2 diabetes. It lowers blood glucose by decreasing hepatic gluconeogenesis, predominantly by inhibiting mitochondrial respiratory chain complex I. The drug is eliminated mainly by the kidneys, and acute or chronic renal insufficiency may allow accumulation of the drug with increasing levels. A small percentage of patients on metformin develop severe lactic acidosis. There has been an ongoing controversy as whether this acidosis is metformin-associated or metformin-induced. This paper, from the Pavia Poison Control Centre in Northern Italy, helps shed light on this question. The authors retrospectively reviewed patients admitted to their toxicology unit over a 5-year period. Eligible patients were on chronic metformin therapy at the time of admission, had lactic acidosis (pH < 7.35, arterial lactate > 5 mmol/L), and elevated metformin levels (plasma metformin > 4 mcg/ml). Cases of acute overdose were excluded. The study objective was to correlate the metformin levels with measured pH, lactate levels, renal function, and mortality rate. Sixty-six eligible patients were identified. All patients presented with acute renal failure and severe lactic acidosis (mean pH 6.91, mean lactate 14.36 mmol/L). About half the patients had a pre-existing contraindication to metformin therapy, predominantly renal failure and/or heart disease. Approximately 75% presented after several days of a mild gastrointestinal prodrome with nausea, vomiting, and diarrhea; this may either have represented the initial manifestations of metformin po Continue reading >>

Lactic Acidosis

Lactic Acidosis

Lactic acidosis is a medical condition characterized by the buildup of lactate (especially L-lactate) in the body, which results in an excessively low pH in the bloodstream. It is a form of metabolic acidosis, in which excessive acid accumulates due to a problem with the body's metabolism of lactic acid. Lactic acidosis is typically the result of an underlying acute or chronic medical condition, medication, or poisoning. The symptoms are generally attributable to these underlying causes, but may include nausea, vomiting, rapid deep breathing, and generalised weakness. The diagnosis is made on biochemical analysis of blood (often initially on arterial blood gas samples), and once confirmed, generally prompts an investigation to establish the underlying cause to treat the acidosis. In some situations, hemofiltration (purification of the blood) is temporarily required. In rare chronic forms of lactic acidosis caused by mitochondrial disease, a specific diet or dichloroacetate may be used. The prognosis of lactic acidosis depends largely on the underlying cause; in some situations (such as severe infections), it indicates an increased risk of death. Classification[edit] The Cohen-Woods classification categorizes causes of lactic acidosis as:[1] Type A: Decreased tissue oxygenation (e.g., from decreased blood flow) Type B B1: Underlying diseases (sometimes causing type A) B2: Medication or intoxication B3: Inborn error of metabolism Signs and symptoms[edit] Lactic acidosis is commonly found in people who are unwell, such as those with severe heart and/or lung disease, a severe infection with sepsis, the systemic inflammatory response syndrome due to another cause, severe physical trauma, or severe depletion of body fluids.[2] Symptoms in humans include all those of typical m Continue reading >>

Lactic Acidosis Clinical Presentation

Lactic Acidosis Clinical Presentation

History The onset of acidosis may be rapid (ie, within minutes to hours) or progressive (ie, over a period of several days). Lactic acidosis frequently occurs during strenuous exercise in healthy people, bearing no consequence. However, development of lactic acidosis in disease states is ominous, often indicating a critical illness of recent onset. Therefore, a careful history should be obtained to evaluate the underlying pathophysiologic cause of shock that contributed to lactic acidosis. Furthermore, a detailed history of ingestion of various prescription drugs or toxins from the patient or a collateral history from the patient's family should be obtained. The clinical signs and symptoms associated with lactic acidosis are highly dependent on the underlying etiology. No distinctive features are specific for hyperlactatemia. Lactate acidosis is present in patients who are critically ill from hypovolemic, septic, or cardiogenic shock. Lactate acidosis always should be suspected in the presence of elevated anion gap metabolic acidosis. Lactic acidosis is a serious complication of antiretroviral therapy. A history of antiretroviral treatment should be obtained. Children who have a relatively mild form of congenital lactic acidosis may develop firmament metabolic acidosis during an acute illness such as respiratory infection. These patients have a deficiency in the activity of pyruvate dehydrogenase, and the stress-induced increases in the glycolytic rate may result in severe metabolic acidosis. D-lactic acidosis, a unique form of lactic acidosis, can occur in patients with jejunoileal bypass or small bowel resection causing short bowel syndrome. In these settings, the glucose and carbohydrates are metabolized in the colon into D-lactic acid, which is absorbed into systemi Continue reading >>

A Side Effect You Should Know About

A Side Effect You Should Know About

The glucose-lowering medication metformin (Glucophage) could cause lactic acidosis if your kidneys and liver are not working efficiently. Lactic acidosis is when high levels build up in the blood of a substance called lactic acid — a chemical that is normally produced by your body in small amounts and removed by your liver and kidneys. The risk of lactic acidosis goes up if you: have heart failure or a lung ailment have kidney or liver problems drink alcohol heavily In these cases, you might not be able to take metformin. If you don't have one of these problems, you are at a very low risk for developing lactic acidosis from metformin. You should, however, contact your doctor immediately if you suddenly develop any of these symptoms of lactic acidosis: diarrhea fast and shallow breathing muscle pain or cramping weakness tiredness or unusual sleepiness You should also let your doctor know if you get the flu or any illness that results in severe vomiting, diarrhea, and/or fever, or if your intake of fluids becomes significantly reduced. Severe dehydration can affect your kidney or liver function and increase your risk of lactic acidosis from metformin. Continue reading >>

Lactic Acidosis: Symptoms, Causes, And Treatment

Lactic Acidosis: Symptoms, Causes, And Treatment

Lactic acidosis occurs when the body produces too much lactic acid and cannot metabolize it quickly enough. The condition can be a medical emergency. The onset of lactic acidosis might be rapid and occur within minutes or hours, or gradual, happening over a period of days. The best way to treat lactic acidosis is to find out what has caused it. Untreated lactic acidosis can result in severe and life-threatening complications. In some instances, these can escalate rapidly. It is not necessarily a medical emergency when caused by over-exercising. The prognosis for lactic acidosis will depend on its underlying cause. A blood test is used to diagnose the condition. Lactic acidosis symptoms that may indicate a medical emergency include a rapid heart rate and disorientaiton. Typically, symptoms of lactic acidosis do not stand out as distinct on their own but can be indicative of a variety of health issues. However, some symptoms known to occur in lactic acidosis indicate a medical emergency. Lactic acidosis can occur in people whose kidneys are unable to get rid of excess acid. Even when not related to just a kidney condition, some people's bodies make too much lactic acid and are unable to balance it out. Diabetes increases the risk of developing lactic acidosis. Lactic acidosis may develop in people with type 1 and 2 diabetes mellitus , especially if their diabetes is not well controlled. There have been reports of lactic acidosis in people who take metformin, which is a standard non-insulin medication for treating type 2 diabetes mellitus. However, the incidence is low, with equal to or less than 10 cases per 100,000 patient-years of using the drug, according to a 2014 report in the journal Metabolism. The incidence of lactic acidosis is higher in people with diabetes who Continue reading >>

Metformin-induced Lactic Acidosis: No One Left Behind

Metformin-induced Lactic Acidosis: No One Left Behind

Metformin-induced lactic acidosis: no one left behind 1Centro Nazionale di Informazione Tossicologica - Centro Antiveleni, IRCCS Fondazione Salvatore Maugeri, Via S. Maugeri 10, 27100 Pavia, Italy 2Dipartimento di Anestesiologia, Terapia Intensiva e Scienze Dermatologiche, Universit degli Studi di Milano, Via F.sco Sforza 35, 20122 Milano, Italy This article has been cited by other articles in PMC. Metformin is a safe drug when correctly used in properly selected patients. In real life, however, associated lactic acidosis has been repeatedly, although rarely, reported. The term metformin-induced lactic acidosis refers to cases that cannot be explained by any major risk factor other than drug accumulation, usually due to renal failure. Treatment consists of vital function support and drug removal, mainly achieved by renal replacement therapy. Despite dramatic clinical presentation, the prognosis of metformin-induced lactic acidosis is usually surprisingly good. In the previous issue of Critical Care, Friesecke and colleagues demonstrate that the survival rate of patients with severe lactic acidosis due to metformin accumulation can be strikingly higher than expected based on the initial clinical evaluation [ 1 ]. Metformin is nowadays the first-line drug of choice for the treatment of adults with type 2 diabetes [ 2 ]. This drug is the sixth most frequently prescribed in the USA (> 50 million prescriptions in 2009) and is taken by almost 1.5% of the Italian population [ 3 , 4 ]. Metformin is a safe drug when correctly used in properly selected patients. In particular, no cases of lactic acidosis (a relatively common side effect of other biguanide compounds) were reported in 347 trials with 70,490 patient-years of metformin use [ 5 ]. Real life can differ from research s 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 >>

Side Effects Of Metformin: What You Should Know

Side Effects Of Metformin: What You Should Know

Metformin is a prescription drug used to treat type 2 diabetes. It belongs to a class of medications called biguanides. People with type 2 diabetes have blood sugar (glucose) levels that rise higher than normal. Metformin doesn’t cure diabetes. Instead, it helps lower your blood sugar levels to a safe range. Metformin needs to be taken long-term. This may make you wonder what side effects it can cause. Metformin can cause mild and serious side effects, which are the same in men and women. Here’s what you need to know about these side effects and when you should call your doctor. Find out: Can metformin be used to treat type 1 diabetes? » Metformin causes some common side effects. These can occur when you first start taking metformin, but usually go away over time. Tell your doctor if any of these symptoms are severe or cause a problem for you. The more common side effects of metformin include: heartburn stomach pain nausea or vomiting bloating gas diarrhea constipation weight loss headache unpleasant metallic taste in mouth Lactic acidosis The most serious side effect metformin can cause is lactic acidosis. In fact, metformin has a boxed warning about this risk. A boxed warning is the most severe warning from the Food and Drug Administration (FDA). Lactic acidosis is a rare but serious problem that can occur due to a buildup of metformin in your body. It’s a medical emergency that must be treated right away in the hospital. See Precautions for factors that raise your risk of lactic acidosis. Call your doctor right away if you have any of the following symptoms of lactic acidosis. If you have trouble breathing, call 911 right away or go to the nearest emergency room. extreme tiredness weakness decreased appetite nausea vomiting trouble breathing dizziness lighthea Continue reading >>

Metformin And Fatal Lactic Acidosis

Metformin And Fatal Lactic Acidosis

Publications Published: July 1998 Information on this subject has been updated. Read the most recent information. Dr P Pillans,former Medical Assessor, Centre for Adverse Reactions Monitoring (CARM), Dunedin Metformin is a useful anti-hyperglycaemic agent but significant mortality is associated with drug-induced lactic acidosis. Significant renal and hepatic disease, alcoholism and conditions associated with hypoxia (eg. cardiac and pulmonary disease, surgery) are contraindications to the use of metformin. Other risk factors for metformin-induced lactic acidosis are sepsis, dehydration, high dosages and increasing age. Metformin remains a major reported cause of drug-associated mortality in New Zealand. Of the 12 cases of lactic acidosis associated with metformin reported to CARM since 1977, 2 occurred in the last year and 8 cases had a fatal outcome. Metformin useful but small risk of potentially fatal lactic acidosis Metformin is a useful therapeutic agent for obese non-insulin dependent diabetics and those whose glycaemia cannot be controlled by sulphonylurea monotherapy. Lactic acidosis is an uncommon but potentially fatal adverse effect. The reported frequency of lactic acidosis is 0.06 per 1000 patient-years, mostly in patients with predisposing factors.1 Examples of metformin-induced lactic acidosis cases reported to CARM include: A 69-year-old man, with renal and cardiac disease, was prescribed metformin due to failing glycaemic control on glibenclamide monotherapy. He was well for six weeks, then developed lactic acidosis and died within 3 days. Post-surgical lactic acidosis caused the death of a 70-year-old man whose metformin was not withdrawn at the time of surgery. A 56-year-old woman, with no predisposing disease, died from lactic acidosis following major Continue reading >>

Lactic Acidosis: What You Need To Know

Lactic Acidosis: What You Need To Know

Lactic acidosis is a form of metabolic acidosis that begins in the kidneys. People with lactic acidosis have kidneys that are unable to remove excess acid from their body. If lactic acid builds up in the body more quickly than it can be removed, acidity levels in bodily fluids — such as blood — spike. This buildup of acid causes an imbalance in the body’s pH level, which should always be slightly alkaline instead of acidic. There are a few different types of acidosis. Lactic acid buildup occurs when there’s not enough oxygen in the muscles to break down glucose and glycogen. This is called anaerobic metabolism. There are two types of lactic acid: L-lactate and D-lactate. Most forms of lactic acidosis are caused by too much L-lactate. Lactic acidosis has many causes and can often be treated. But if left untreated, it may be life-threatening. The symptoms of lactic acidosis are typical of many health issues. If you experience any of these symptoms, you should contact your doctor immediately. Your doctor can help determine the root cause. Several symptoms of lactic acidosis represent a medical emergency: fruity-smelling breath (a possible indication of a serious complication of diabetes, called ketoacidosis) confusion jaundice (yellowing of the skin or the whites of the eyes) trouble breathing or shallow, rapid breathing If you know or suspect that you have lactic acidosis and have any of these symptoms, call 911 or go to an emergency room right away. Other lactic acidosis symptoms include: exhaustion or extreme fatigue muscle cramps or pain body weakness overall feelings of physical discomfort abdominal pain or discomfort diarrhea decrease in appetite headache rapid heart rate Lactic acidosis has a wide range of underlying causes, including carbon monoxide poisoni Continue reading >>

Diabetes And Metformin Faqs

Diabetes And Metformin Faqs

Tweet Although one of the most common drugs for type 2 diabetics, Metformin can still confuse diabetic patients. This set of FAQs are intended for information purposes, and should not replace or supersede the advice of a doctor or qualified medical professional. If you have a question about diabetes and Metformin that is not covered here, please ask the community in the Diabetes forum. Should all type 2 diabetics take Meformin? One side effect of taking Metformin is lactic acidosis, and for this reason some diabetics should not take Metformin unless specifically advised to do so by their GP or diabetes healthcare team. For this reason, diabetics with kidney problems, liver problems, and heart problems are often advised to avoid Metformin. Similarly, diabetics that are dehydrated, drink alcohol a lot, or are going to have an x-ray or surgery. For some pregnant diabetics, Metformin may not be the best choice, but in all instances this should be discussed with your doctor. Can young diabetics take Metformin? Metformin has been proven in clinical trials to lower glucose levels amongst children between 10-16 years of age suffering from type 2 diabetes. Research is less conclusive about children under 10 and children taking Metformin alongside other treatments, but your diabetes health care team should be able to elaborate on this. How much Metformin should I take? This will depend entirely on your condition, and your doctor will be able to tell you how much Metformin to take, when you should take it, and how you should take it. Usually, diabetics start out on a low dose of Metformin, and this is slowly increased until blood sugar responds. Doctors often put diabetics on combination courses with other medication, including insulin. If I take Metformin, can I stop my diet and Continue reading >>

Metformin-associated Lactic Acidosis: Predisposing Factors And Outcome

Metformin-associated Lactic Acidosis: Predisposing Factors And Outcome

Go to: Abstract Metformin is considered the first choice oral treatment for type 2 diabetes patients in the absence of contraindications. Rarely, life-threatening complications associated with metformin treatment are seen in some patients with underlying diseases. The aim of this study was to further investigate the clinical profiles and risk factors for metformin-associated lactic acidosis (MALA) and the treatment modalities according to survival. To identify MALA, we performed a retrospective study in seven diabetic patients who were taking metformin and had been diagnosed with lactic acidosis at Inha University Hospital between 1995 and 2012. For each patient, we recorded the age, sex, daily metformin dosage, laboratory test results, admission diagnosis, and risk factors. Also, concurrent conditions, treatment modalities, and outcomes were evaluated. Six patients had risk factors for lactic acidosis before admission. All patients had renal impairment on admission as a precipitating risk factor. Five patients survived and two patients died despite early renal replacement therapy. Older patients tended to have a poorer prognosis. Renal function must be monitored in elderly type 2 diabetes mellitus patients with underlying diseases and conditions causing renal impairment who begin metformin treatment. Accurate recognition of MALA and initiation of renal replacement are essential for treatment. Keywords: Metformin, Acidosis, lactic, Diabetes mellitus, type 2 Go to: INTRODUCTION Metformin is an oral antidiabetic drug in the biguanide class that is widely used, alone or in combination with a sulfonylurea or other drugs, in patients with type 2 diabetes. The drug's glucose-lowering effect results mainly from decreased hepatic glucose output with increased glucose utilizatio Continue reading >>

Glyburide And Metformin (oral Route)

Glyburide And Metformin (oral Route)

Precautions Drug information provided by: Micromedex It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly. Blood tests may be needed to check for unwanted effects. Under certain conditions, too much metformin can cause lactic acidosis. The symptoms of lactic acidosis are severe and quick to appear. They usually occur when other health problems not related to the medicine are present and very severe, such as a heart attack or kidney failure. The symptoms of lactic acidosis include abdominal or stomach discomfort; decreased appetite; diarrhea; fast, shallow breathing; a general feeling of discomfort; muscle pain or cramping; and unusual sleepiness, tiredness, or weakness. If you have any symptoms of lactic acidosis, get emergency medical help right away. It is very important to carefully follow any instructions from your health care team about: Alcohol—Drinking alcohol may cause severe low blood sugar. Discuss this with your health care team. Other medicines—Do not take other medicines unless they have been discussed with your doctor. This especially includes nonprescription medicines such as aspirin, and medicines for appetite control, asthma, colds, cough, hay fever, or sinus problems. Counseling—Other family members need to learn how to prevent side effects or help with side effects if they occur. Also, patients with diabetes may need special counseling about diabetes medicine dosing changes that might occur because of lifestyle changes, such as changes in exercise and diet. Furthermore, counseling on contraception and pregnancy may be needed because of the problems that can occur in patients with diabetes during pregnancy. Travel—Keep your recent prescription and your medical history with yo Continue reading >>

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