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 Post-surgical lactic acidosis caused the death of a 70-year-old man whose metformin was not withdrawn at the time of surgery.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 In Vivo: Testing The Link Between Lactate Generation And H+ Accumulation In Ischemic Mouse Muscle
Lactic acidosis in vivo: testing the link between lactate generation and H+ accumulation in ischemic mouse muscle 3Bioengineering, University of Washington Medical Center, Seattle, Washington Address for reprint requests and other correspondence: K. E. Conley, Dept. of Radiology, Box 357115, Univ. of Washington Medical Center, Seattle, WA 98195-7115 (e-mail: [email protected] ). Received 2009 Oct 20; Accepted 2010 Jan 31. Copyright 2010 the American Physiological Society This article has been cited by other articles in PMC. The link between lactate generation and cellular acidosis has been questioned based on the possibility of H+ generation, independent of lactate production during glycolysis under physiological conditions. Here we test whether glycolytic H+ generation matches lactate production over a physiological pH and lactate range using ischemia applied to the hindlimb of a mouse. We measured the H+ generation and ATP level in vivo using 31P-magnetic resonance spectroscopy and chemically determined intracellular lactate level in the hindlimb muscles. No significant change was found in ATP content by chemical analysis (P > 0.1), in agreement with the stoichiometric decline in phosphocreatine (20.2 1.2 mM) vs. rise in Pi (18.7 2.0 mM), as measured by 31P-magnetic resonance spectroscopy. A substantial drop in pH from 7.0 to 6.7 and lactate accumulation to 25 mM were found during 25 min of ischemia. The rise in H+ generation closely agreed with the accumulation of lactate, as shown by a close correlation with a slope near identity (0.98; r2 = 0.86). This agreement between glycolytic H+ production and elevation of lactate is confirmed by an analysis of the underlying reactions involved in glycolysis in vivo and supports the concept of lactic acidosis under con Continue reading >>
Hiv & Aids Information :: Factsheet Lactic Acidosis
Please enter the email address. Separate multiple addresses with a comma. Lactic acidosis refers to a build-up of lactic acid in the blood. It is a rare but dangerous side-effect of some anti-HIV drugs most of these are no longer in regular use. Your HIV clinic will use blood tests to check your levels of lactic acid. Lacticacidosis is very rare. Nevertheless, it is an important subject to understandbecause people who develop the condition can become dangerously ill. Lacticacidosis is a serious side-effect of the nucleosidereverse transcriptaseinhibitor (NRTI)class of anti-HIV drugs. This class includes abacavir (Ziagen),didanosine (ddI, Videx), lamivudine (3TC, Epivir), stavudine (d4T,Zerit), tenofovir (Viread) andzidovudine (AZT, Retrovir). The drugsmost linked with lactic acidosis are stavudine and didanosine. However, neitherof these drugs is now used if any other treatment options are available, mainlybecause of the side-effects they can cause. Lactic acidosis is also apotential, but rare, side-effect of other drugs, including the commonlyprescribed diabetes drug, metformin. The term lactic acidosis is used to describehigh levels of a substance called lactate in the blood. Lactate is a by-productof the processing of sugar within the body. Lacticacidosis is one of several conditions which are believed to be caused by damage to mitochondria . Mitochondriaare found in all human cells and are involved in the production of energy.Other possible side-effects ofNRTIs which may also be associated withdamage to mitochondria include peripheral neuropathy (numbness or pain in the feetand hands); bone marrow suppression; pancreatitis (inflammation of thepancreas); hepatic steatosis (accumulation of fat in the liver); and myopathy(muscle damage). "Lactic acidosis may occurat a Continue reading >>
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To detect high levels of lactate in the blood, which may be an indication of lack of oxygen ( hypoxia ) or the presence of other conditions that cause excess production or insufficient clearing of lactate from the blood; this test is not meant to be used for screening for health status. When you have symptoms such as rapid breathing, nausea, and sweating that suggest a lack of oxygen or an abnormal blood pH (acid/base imbalance); when a health practitioner suspects that you may be experiencing sepsis , shock, heart attack , severe congestive heart failure , kidney failure , or inadequately treated (uncontrolled) diabetes ; when a health practitioner suspects that you have inherited a rare metabolic or mitochondrial disorder A blood sample drawn from a vein in your arm; sometimes a blood sample collected from an artery and, rarely, a sample of cerebrospinal fluid collected from the spine You may be told to rest prior to sample collection. Rarely, fasting may be required. You may be able to find your test results on your laboratory's website or patient portal. However, you are currently at Lab Tests Online. You may have been directed here by your lab's website in order to provide you with background information about the test(s) you had performed.You will need to return to your lab's website or portal, or contact your healthcare practitionerin order to obtainyour test results. Lab Tests Online is an award-winning patient education website offering information on laboratory tests. The content on the site, which has been reviewed by laboratory scientists and other medical professionals,provides general explanations of what results might mean for each test listed on the site, such as what a high or low value might suggest to your healthcare practitionerabout your health or Continue reading >>
Increased Blood Lactate Levels: A Marker Of...?
Increased blood lactate levels: a marker of...? Increased blood lactate levels: a marker of...? Since Meakins in 1927 described the relationship between increased blood lactate levels and the presence of oxygen debt (tissue hypoxia) in patients with circulatory shock , lactate levels have been used to diagnose and monitor the treatment of these patients. However, as lactate is a normal (end) product of metabolism the relationship between increased lactate levels in patients and shock could be much more complicated. In the current paper we discuss the metabolism of lactate and its clinical implications. Lactate is a normal end product of glycolysis (Fig.1). It can only be formed from pyruvate mediated by lactatedehydrogenase . Under normal conditions this reaction results in alactate-to-pyruvate ratio of 10:1. All cells are capable ofproducing lactate. Tissues with a high metabolic rate (gut, brain,skeletal muscle) contribute largely to the daily lactateproduction. Normal blood lactate levels are 1.3 mmol/L . Lactatemetabolism mainly occurs in the liver and kidney. Lactate can onlybe metabolized by the conversion to pyruvate. Therefore, bloodlactate levels depend on pyruvate metabolism. The irreversibleconversion of pyruvate to Acetyl-CoA (mediated by pyruvatedehydrogenase) that is subsequently metabolized in the Krebs cycleresults in the production of adenosine triphosphate (ATP), carbondioxide and water. ATP can be seen as a universal energy sourcethat is required in many vital cellular functions. Pyruvate canalso be used to regenerate glucose by the conversion tooxaloacetate. In this way lactate can be converted back to glucosethat can subsequently be converted to lactate (Cori cycle).Regeneration of glucose from lactate is an important mechanism inrestoring Continue reading >>
What Are The Tests That Will Detect Lactic Acidosis?
What are the tests that will detect lactic acidosis? With lactic acidosis, lactic acid builds accumulates in the blood stream faster than it can be removed. This can be caused by extended, intense exercise or other certain diseases, and is marked by nausea and weakness. Blood tests that check electrolyte levels are used to detect lactic acidosis. Lactic acidosis is a rare side effect of metformin. However, the risk of lactic acidosis increases in patients with poor kidney function. Your doctor should regularly monitor your kidney function while you are on metformin. Blood tests to measure your electrolyte levels can determine if you have lactic acidosis. Typically your doctor will evaluate your blood work 1 to 2 weeks after you begin taking metformin to make sure you electrolytes are within normal limits. You can also monitor for symptoms of lactic acidosis which include abdominal or stomach discomfort; decreased appetite; diarrhea; fast, shallow breathing; general feeling of discomfort; muscle pain or cramping; and unusual sleepiness, tiredness, or weakness. If symptoms of lactic acidosis occur, you should get immediate emergency medical help. Continue reading >>
Severe Lactic Acidosis Reversed By Thiamine Within 24 Hours
Severe lactic acidosis reversed by thiamine within 24 hours 1Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, A-8036 Graz, Austria Karin Amrein: [email protected] ; Werner Ribitsch: [email protected] ; Ronald Otto: [email protected] ; Harald C Worm: [email protected] ; Rudolf E Stauber: [email protected] This article has been cited by other articles in PMC. Thiamine is a water-soluble vitamin that plays a pivotal role in carbohydrate metabolism. In acute deficiency, pyruvate accumulates and is metabolized to lactate, and chronic deficiency may cause polyneuropathy and Wernicke encephalopathy. Classic symptoms include mental status change, ophthalmoplegia, and ataxia but are present in only a few patients [ 1 ]. Critically ill patients are prone to thiamine deficiency because of preexistent malnutrition, increased consumption in high-carbohydrate nutrition, and accelerated clearance in renal replacement. In retrospective [ 2 ] and prospective [ 3 , 4 ] studies, a substantial prevalence of thiamine deficiency has been described in both adult (10% to 20%) and pediatric (28%) patients. Thiamine deficiency may become clinically evident in any type of malnutrition that outlasts thiamine body stores (2 to 3 weeks), including alcoholism, bariatric surgery, or hyperemesis gravidarum, and results in high morbidity and mortality if untreated [ 1 ]. We report the case of a 56-year-old man with profound lactic acidosis that resolved rapidly after thiamine infusion. He was admitted because of a decreased level of consciousness (Glasgow Coma Scale score of 6). Vital signs, including blood pressure, heart rate, and oxygen saturation, were normal. Besides reporting regular alcohol consumption, relatives reported recen Continue reading >>
Lactic Level: Order A Lactate Test For Online Results | Walk-in Lab
3-4 days. May take longer based on weather, holiday or lab delays. The Lactic Acid Plasma Test, or Lactate Test, measures the amount of lactate in the blood to determine if a patient has lactic acidosis. When cellular oxygen levels are lowduring intense exercise or when certain infections or diseases are presentthe body switches from aerobic energy production to anaerobic energy production to produce ATP (adenosine triphosphate), the body's primary energy source. Lactate is a byproduct of this process. When lactate is produced faster than the liver breaks it down, the resulting accumulation can develop into hyperlactatemia, which can then progress to lactic acidosis. Symptoms of lactic acidosis include muscle weakness, rapid breathing or shortness of breath, nausea, vomiting, sweating, abdominal pain, and in some cases, coma. Conditions that cause insufficient oxygen uptake in the lungs (type A) Reduced blood flow that decreases transport of oxygen to tissues (type A) Excess oxygen demand or metabolic problems (type B) Examples of conditions that can lead to type A lactic acidosis are sepsis, shock, heart attack, congestive heart failure, severe lung disease, respiratory failure, pulmonary edema, and severe anemia. Examples of conditions leading to type B lactic acidosis include strenuous exercise, liver or kidney disease, uncontrolled diabetes, leukemia, AIDS, glycogen storage diseases, and a variety of drugs and toxins. A Lactate Test will not diagnose the cause of excess lactate levels, but it can help determine if lactic acidosis is the cause of the patients symptoms. Other tests may be necessary to diagnose an underlying condition. The test may be ordered at prescribed intervals to monitor lactate levels. The Lactate Test is also known as Lactic Acid, Plasma Lacta Continue reading >>
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 The Cohen-Woods classification categorizes causes of lactic acidosis as: 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 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. Symptoms in humans include all those of typical m Continue reading >>
What Is A Lactic Acid Blood Test?
It’s a test that measures the amount of lactic acid (also called “lactate”) in your blood. This acid is made in muscle cells and red blood cells. It forms when your body turns food into energy. Your body relies on this energy when its oxygen levels are low. Oxygen levels might drop during an intense workout or when you have an infection or disease. Once you finish your workout or recover from the illness, your lactic acid level tends to go back to normal. But sometimes, it doesn't. Higher-than-normal lactic acid levels can lead to a condition called lactic acidosis. If it’s severe enough, it can upset your body’s pH balance, which indicates the level of acid in your blood. Lactic acidosis can lead to these symptoms: It’s a simple blood test. Your doctor will draw blood from a vein or artery using a needle. In rare cases, he may take a sample of cerebrospinal fluid from your spinal column during a procedure called a spinal tap. Normally, you don’t have to adjust your routine to prepare for the test. If your lactic acid level is normal, you don’t have lactic acidosis. Your cells are making enough oxygen. It also tells your doctor that something other than lactic acidosis is causing your symptoms. He’ll likely order other tests to find out what it is. If your lactic acid level is high, it could be caused by a number of things. Most often, it’s because you have a condition that makes it hard for you to breathe in enough oxygen. Some of these conditions could include: Severe lung disease or respiratory failure Fluid build-up in your lungs Very low red blood cell count (severe anemia) A higher-than-normal lactic acid level in your blood can also be a sign of problems with your metabolism. And, your body might need more oxygen than normal because you have o Continue reading >>
Acute Lactic Acidosis
Author: Bret A Nicks, MD, MHA; Chief Editor: Romesh Khardori, MD, PhD, FACP more... Metabolic acidosis is defined as a state of decreased systemic pH resulting from either a primary increase in hydrogen ion (H+) or a reduction in bicarbonate (HCO3-) concentrations. In the acute state, respiratory compensation of acidosis occurs by hyperventilation resulting in a relative reduction in PaCO2. Chronically, renal compensation occurs by means of reabsorption of HCO3. [ 1 , 2 ] Acidosis arises from an increased production of acids, a loss of alkali, or a decreased renal excretion of acids. The underlying etiology of metabolic acidosis is classically categorized into those that cause an elevated anion gap (AG) (see the Anion Gap calculator) and those that do not. Lactic acidosis, identified by a state of acidosis and an elevated plasma lactate concentration is one type of anion gap metabolic acidosis and may result from numerous conditions. [ 2 , 3 , 4 ] It remains the most common cause of metabolic acidosis in hospitalized patients. The normal blood lactate concentration in unstressed patients is0.5-1 mmol/L. Patients with critical illness can be considered to have normal lactate concentrations of less than 2 mmol/L. Hyperlactatemia is defined as a mild to moderate persistent increase in blood lactate concentration (2-4 mmol/L) without metabolic acidosis, whereas lactic acidosis is characterized by persistently increased blood lactate levels (usually >4-5 mmol/L) in association with metabolic acidosis. [ 1 , 5 ] Elevated lactate levels, while typically thought of as a marker of inadequate tissue perfusion with concurrent shift toward increased anaerobic metabolism, can be present in patients in whom systemic hypoperfusion is not present and therefore should be considered wit Continue reading >>
Dlac - Clinical: D-lactate, Plasma
An adjunct to urine D-lactate (preferred), in the diagnosis of D-lactate acidosis DLAU / D-Lactate, Urine is the preferred specimen for D-lactate determinations. Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test D-lactate is produced by bacteria residing in the colon when carbohydrates are not completely absorbed in the small intestine. When large amounts of D-lactate are present, individuals can experience metabolic acidosis, altered mental status (from drowsiness to coma), and a variety of other neurologic symptoms, particularly dysarthria and ataxia. D-lactic acidosis is typically observed in patients with a malabsorptive disorder, such as short-bowel syndrome, or, following a jejunoileal bypass. In addition, healthy children presenting with gastroenteritis may also develop the critical presentation of D-lactic acidosis. Routine lactic acid determinations in blood will not reveal abnormalities because most lactic acid assays measure only L-lactate. Accordingly, D-lactate analysis must be specifically requested (eg, DLAC / D-Lactate, Plasma). However, as D-lactate is readily excreted in urine, DLAU / D-Lactate, Urine is the preferred specimen for D-lactate determinations. Continue reading >>
Lactic Acidosis In Vivo: Testing The Link Between Lactate Generation And H+ Accumulation In Ischemic Mouse Muscle.
J Appl Physiol (1985). 2010 Jun;108(6):1479-86. doi: 10.1152/japplphysiol.01189.2009. Epub 2010 Feb 4. Lactic acidosis in vivo: testing the link between lactate generation and H+ accumulation in ischemic mouse muscle. Department of Radiology, Box 357115, University of Washington Medical Center, Seattle, WA 98195-7115, USA. The link between lactate generation and cellular acidosis has been questioned based on the possibility of H+ generation, independent of lactate production during glycolysis under physiological conditions. Here we test whether glycolytic H+ generation matches lactate production over a physiological pH and lactate range using ischemia applied to the hindlimb of a mouse. We measured the H+ generation and ATP level in vivo using 31P-magnetic resonance spectroscopy and chemically determined intracellular lactate level in the hindlimb muscles. No significant change was found in ATP content by chemical analysis (P>0.1), in agreement with the stoichiometric decline in phosphocreatine (20.2+/-1.2 mM) vs. rise in Pi (18.7+/-2.0 mM), as measured by 31P-magnetic resonance spectroscopy. A substantial drop in pH from 7.0 to 6.7 and lactate accumulation to 25 mM were found during 25 min of ischemia. The rise in H+ generation closely agreed with the accumulation of lactate, as shown by a close correlation with a slope near identity (0.98; r2=0.86). This agreement between glycolytic H+ production and elevation of lactate is confirmed by an analysis of the underlying reactions involved in glycolysis in vivo and supports the concept of lactic acidosis under conditions that substantially elevate lactate and drop pH. However, this link is expected to fail with conditions that deplete phosphocreatine, leading to net ATP hydrolysis and nonglycolytic H+ generation. Thus bot Continue reading >>
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 >>
Lactate And Lactic Acidosis
The integrity and function of all cells depend on an adequate supply of oxygen. Severe acute illness is frequently associated with inadequate tissue perfusion and/or reduced amount of oxygen in blood (hypoxemia) leading to tissue hypoxia. If not reversed, tissue hypoxia can rapidly progress to multiorgan failure and death. For this reason a major imperative of critical care is to monitor tissue oxygenation so that timely intervention directed at restoring an adequate supply of oxygen can be implemented. Measurement of blood lactate concentration has traditionally been used to monitor tissue oxygenation, a utility based on the wisdom gleaned over 50 years ago that cells deprived of adequate oxygen produce excessive quantities of lactate. The real-time monitoring of blood lactate concentration necessary in a critical care setting was only made possible by the development of electrode-based lactate biosensors around a decade ago. These biosensors are now incorporated into modern blood gas analyzers and other point-of-care analytical instruments, allowing lactate measurement by non-laboratory staff on a drop (100 L) of blood within a minute or two. Whilst blood lactate concentration is invariably raised in those with significant tissue hypoxia, it can also be raised in a number of conditions not associated with tissue hypoxia. Very often patients with raised blood lactate concentration (hyperlactatemia) also have a reduced blood pH (acidosis). The combination of hyperlactatemia and acidosis is called lactic acidosis. This is the most common cause of metabolic acidosis. The focus of this article is the causes and clinical significance of hyperlactatemia and lactic acidosis. The article begins with a brief overview of normal lactate metabolism. Normal lactate production and Continue reading >>
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