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Lactic Acidosis Treatment

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 Post-surgical lactic acidosis caused the death of a 70-year-old man whose metformin was not withdrawn at the time of surgery.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 Treatment & Management

Lactic Acidosis Treatment & Management

Approach Considerations Treatment is directed towards correcting the underlying cause of lactic acidosis and optimizing tissue oxygen delivery. The former is addressed by various therapies, including administration of appropriate antibiotics, surgical drainage and debridement of a septic focus, chemotherapy of malignant disorders, discontinuation of causative drugs, and dietary modification in certain types of congenital lactate acidosis. Cardiovascular collapse secondary to hypovolemia or sepsis should be treated with fluid replacement. Both crystalloids and colloids can restore intravascular volume, but hydroxyethyl starch solutions should be avoided owing to increased mortality. [21] Excessive normal saline administration can cause a nongap metabolic acidosis due to hyperchloremia, which has been associated with increased acute kidney injury. [32] Balanced salt solutions such as Ringer lactate and Plasma-Lyte will not cause a nongap metabolic acidosis and may reduce the need for renal replacement therapy; however, these can cause a metabolic alkalosis. [33] No randomized, controlled trial has yet established the safest and most effective crystalloid. If a colloid is indicated, albumin should be used. Despite appropriate fluid management, vasopressors or inotropes may still be required to augment oxygen delivery. Acidemia decreases the response to catecholamines, and higher doses may be needed. Conversely, high doses may exacerbate ischemia in critical tissue beds. Careful dose titration is needed to maximize benefit and reduce harm. Lactic acidosis causes a compensatory increase in minute ventilation. Patients may be tachypneic initially, but respiratory muscle fatigue can ensue rapidly and mechanical ventilation may be necessary. Alkali therapy remains controversial 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 >>

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 >>

Review Metformin-associated Lactic Acidosis: Current Perspectives On Causes And Risk

Review Metformin-associated Lactic Acidosis: Current Perspectives On Causes And Risk

Abstract Although metformin has become a drug of choice for the treatment of type 2 diabetes mellitus, some patients may not receive it owing to the risk of lactic acidosis. Metformin, along with other drugs in the biguanide class, increases plasma lactate levels in a plasma concentration-dependent manner by inhibiting mitochondrial respiration predominantly in the liver. Elevated plasma metformin concentrations (as occur in individuals with renal impairment) and a secondary event or condition that further disrupts lactate production or clearance (e.g., cirrhosis, sepsis, or hypoperfusion), are typically necessary to cause metformin-associated lactic acidosis (MALA). As these secondary events may be unpredictable and the mortality rate for MALA approaches 50%, metformin has been contraindicated in moderate and severe renal impairment since its FDA approval in patients with normal renal function or mild renal insufficiency to minimize the potential for toxic metformin levels and MALA. However, the reported incidence of lactic acidosis in clinical practice has proved to be very low (< 10 cases per 100,000 patient-years). Several groups have suggested that current renal function cutoffs for metformin are too conservative, thus depriving a substantial number of type 2 diabetes patients from the potential benefit of metformin therapy. On the other hand, the success of metformin as the first-line diabetes therapy may be a direct consequence of conservative labeling, the absence of which could have led to excess patient risk and eventual withdrawal from the market, as happened with earlier biguanide therapies. An investigational delayed-release metformin currently under development could potentially provide a treatment option for patients with renal impairment pending the resu Continue reading >>

Treatment Of Metformin-associated Lactic Acidosis With Closed Recirculation Bicarbonate-buffered Hemodialysis

Treatment Of Metformin-associated Lactic Acidosis With Closed Recirculation Bicarbonate-buffered Hemodialysis

Treatment of Metformin-Associated Lactic Acidosis With Closed Recirculation Bicarbonate-Buffered Hemodialysis To the Editor. The use of massive amounts of intravenous (IV) sodium bicarbonate in the management of lactic acidosis seems necessary as soon as the acidosis becomes severe.1 However, some patients have an apparent resistance to this alkali therapy.2 In addition, intensive administration of sodium bicarbonate carries the combined risks of volume and sodium overload. Several authors tried hemodialysis (HD) or peritoneal dialysis (PD) but, most of the time, the precarious hemodynamic state of these patients limits the use of conventional HD.3,4 The new possibilities allowing the use of dialysate containing bicarbonate in HD have led us to try this method in the case of a metformin-treated diabetic with severe lactic acidosis.5 Report of a Case. A 64-year-old woman was admitted to the hospital in severe shock. Despite chronic renal failure (serum creatinine level of 300 moles/L, she was given 1,700 mg/day of metformin for six Continue reading >>

Targeting Oxygen-sensing Prolyl Hydroxylase For Metformin-associated Lactic Acidosis Treatment

Targeting Oxygen-sensing Prolyl Hydroxylase For Metformin-associated Lactic Acidosis Treatment

Targeting Oxygen-Sensing Prolyl Hydroxylase for Metformin-Associated Lactic Acidosis Treatment aDepartment of Biochemistry, Keio University School of Medicine, Tokyo, Japan bDepartment of Anesthesiology, Keio University School of Medicine, Tokyo, Japan cTranslational Research Center, Keio University School of Medicine, Tokyo, Japan dDepartment of Anatomy, Biochemistry and Physiology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA eRare Disease and LCM Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan fDivision of Cell Biology, Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan Metformin is one of the most widely used therapeutics for type 2 diabetes mellitus and also has anticancer and antiaging properties. However, it is known to induce metformin-associated lactic acidosis (MALA), a severe medical condition with poor prognosis, especially in individuals with renal dysfunction. Inhibition of prolyl hydroxylase (PHD) is known to activate the transcription factor hypoxia-inducible factor (HIF) that increases lactate efflux as a result of enhanced glycolysis, but it also enhances gluconeogenesis from lactate in the liver that contributes to reducing circulating lactate levels. Here, we investigated the outcome of pharmaceutical inhibition of PHD in mice with MALA induced through the administration of metformin per os and an intraperitoneal injection of lactic acid. We found that the PHD inhibitors significantly increased the expression levels of genes involved in gluconeogenesis in the liver and the kidney and significantly improved the survival of mice with MALA. Furthermore, the PHD inhibitor also improved the rate of survival of MALA induced in mice with chronic Continue reading >>

Treatment Of Lactic Acidosis.

Treatment Of Lactic Acidosis.

Severe lactic acidosis is often associated with poor prognosis. Recognition and correction of the underlying process is the major step in the treatment of this serious condition. Intravenous administration of sodium bicarbonate has been the mainstay in the treatment of lactic acidosis. Aggressive use of this therapeutic modality, however, can lead to serious complications and should therefore be considered with caution. Peritoneal dialysis and hemodialysis provide large amounts of alkali without causing the hypernatremia or hypervolemia commonly associated with bicarbonate infusion. Peritoneal dialysis with bicarbonate-based dialysate, in particular, appears to be an ideal means of delivering physiologic buffer. Administration of methylene blue was initially thought to increase lactate metabolism by altering the cellular oxidative state. Its subsequent clinical use, however, showed little efficacy. Sodium nitroprusside has been advocated for the treatment of some forms of lactic acidosis as a method of alleviating regional hypoperfusion. Insulin therapy has been found to be quite useful in the treatment of phenformin-associated lactic acidosis and is recommended in this setting. Since dichloroacetate activates pyruvate dehydrogenase and enhances lactate metabolism, it may be a useful adjunct in the treatment of lactic acidosis. Continue reading >>

Lactic Acidosis Update For Critical Care Clinicians

Lactic Acidosis Update For Critical Care Clinicians

Lactic Acidosis Update for Critical Care Clinicians Franz Volhard Clinic and Max Delbrck Center for Molecular Medicine, Medical Faculty of the Charit Humboldt University of Berlin, Berlin, Germany. Correspondence to Dr. Friedrich C. Luft, Wiltberg Strasse 50, 13125 Berlin, Germany. Phone: 49-30-9417-2202; Fax: 49-30-9417-2206; E-mail: luft/{at}fvk-berlin.de Abstract. Lactic acidosis is a broad-anion gap metabolic acidosis caused by lactic acid overproduction or underutilization. The quantitative dimensions of these two mechanisms commonly differ by 1 order of magnitude. Overproduction of lactic acid, also termed type A lactic acidosis, occurs when the body must regenerate ATP without oxygen (tissue hypoxia). Circulatory, pulmonary, or hemoglobin transfer disorders are commonly responsible. Overproduction of lactate also occurs with cyanide poisoning or certain malignancies. Underutilization involves removal of lactic acid by oxidation or conversion to glucose. Liver disease, inhibition of gluconeogenesis, pyruvate dehydrogenase (thiamine) deficiency, and uncoupling of oxidative phosphorylation are the most common causes. The kidneys also contribute to lactate removal. Concerns have been raised regarding the role of metformin in the production of lactic acidosis, on the basis of individual case reports. The risk appears to be considerably less than with phenformin and involves patients with underlying severe renal and cardiac dysfunction. Drugs used to treat lactic acidosis can aggravate the condition. NaHCO3 increases lactate production. Treatment of type A lactic acidosis is particularly unsatisfactory. NaHCO3 is of little value. Carbicarb is a mixture of Na2CO3 and NaHCO3 that buffers similarly to NaHCO3 but without net generation of CO2. The results from animal stud Continue reading >>

Lactic Acidosis

Lactic Acidosis

Patient professional reference Professional Reference articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use. You may find one of our health articles more useful. Description Lactic acidosis is a form of metabolic acidosis due to the inadequate clearance of lactic acid from the blood. Lactate is a byproduct of anaerobic respiration and is normally cleared from the blood by the liver, kidney and skeletal muscle. Lactic acidosis occurs when the body's buffering systems are overloaded and tends to cause a pH of ≤7.25 with plasma lactate ≥5 mmol/L. It is usually caused by a state of tissue hypoperfusion and/or hypoxia. This causes pyruvic acid to be preferentially converted to lactate during anaerobic respiration. Hyperlactataemia is defined as plasma lactate >2 mmol/L. Classification Cohen and Woods devised the following system in 1976 and it is still widely used:[1] Type A: lactic acidosis occurs with clinical evidence of tissue hypoperfusion or hypoxia. Type B: lactic acidosis occurs without clinical evidence of tissue hypoperfusion or hypoxia. It is further subdivided into: Type B1: due to underlying disease. Type B2: due to effects of drugs or toxins. Type B3: due to inborn or acquired errors of metabolism. Epidemiology The prevalence is very difficult to estimate, as it occurs in critically ill patients, who are not often suitable subjects for research. It is certainly a common occurrence in patients in high-dependency areas of hospitals.[2] The incidence of symptomatic hyperlactataemia appears to be rising as a consequence of the use of antiretroviral therapy to treat HIV infection. It appears to increase in those taking stavudine (d4T) regimens.[3] Causes of lactic acid Continue reading >>

Lactic Acidosis: Clinical Implications And Management Strategies

Lactic Acidosis: Clinical Implications And Management Strategies

Lactic acidosis: Clinical implications and management strategies Cleveland Clinic Journal of Medicine. 2015 September;82(9):615-624 Quality Officer, Medical Intensive Care Unit, Departments of Pulmonary Medicine and Critical Care Medicine, Respiratory Institute, Cleveland Clinic; Assistant Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH Department of Pharmacy, Cleveland Clinic; Assistant Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH Medical ICU Clinical Specialist, Department of Pharmacy, Cleveland Clinic Director, Medical Intensive Care Unit, Department of Critical Care Medicine, Respiratory Institute, Cleveland Clinic Address: Anita J. Reddy, MD, Department of Critical Care Medicine, Respiratory Institute, A90, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; e-mail: [email protected] ABSTRACTIn hospitalized patients, elevated serum lactate levels are both a marker of risk and a target of therapy. The authors describe the mechanisms underlying lactate elevations, note the risks associated with lactic acidosis, and outline a strategy for its treatment. Serum lactate levels can become elevated by a variety of underlying processes, categorized as increased production in conditions of hypoperfusion and hypoxia (type A lactic acidosis), or as increased production or decreased clearance not due to hypoperfusion and hypoxia (type B). The higher the lactate level and the slower the rate of normalization (lactate clearance), the higher the risk of death. Treatments differ depending on the underlying mechanism of the lactate elevation. Thus, identifying the reason for hyperlactatemia and differentiating between type A and B lactic acidosis are of the utmo Continue reading >>

Hiv & Aids Information :: Factsheet Lactic Acidosis

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 >>

Lactic Acidosis And Exercise: What You Need To Know

Lactic Acidosis And Exercise: What You Need To Know

Muscle ache, burning, rapid breathing, nausea, stomach pain: If you've experienced the unpleasant feeling of lactic acidosis, you likely remember it. It's temporary. It happens when too much acid builds up in your bloodstream. The most common reason it happens is intense exercise. Symptoms The symptoms may include a burning feeling in your muscles, cramps, nausea, weakness, and feeling exhausted. It's your body's way to tell you to stop what you're doing The symptoms happen in the moment. The soreness you sometimes feel in your muscles a day or two after an intense workout isn't from lactic acidosis. It's your muscles recovering from the workout you gave them. Intense Exercise. When you exercise, your body uses oxygen to break down glucose for energy. During intense exercise, there may not be enough oxygen available to complete the process, so a substance called lactate is made. Your body can convert this lactate to energy without using oxygen. But this lactate or lactic acid can build up in your bloodstream faster than you can burn it off. The point when lactic acid starts to build up is called the "lactate threshold." Some medical conditions can also bring on lactic acidosis, including: Vitamin B deficiency Shock Some drugs, including metformin, a drug used to treat diabetes, and all nucleoside reverse transcriptase inhibitor (NRTI) drugs used to treat HIV/AIDS can cause lactic acidosis. If you are on any of these medications and have any symptoms of lactic acidosis, get medical help immediately. Preventing Lactic Acidosis Begin any exercise routine gradually. Pace yourself. Don't go from being a couch potato to trying to run a marathon in a week. Start with an aerobic exercise like running or fast walking. You can build up your pace and distance slowly. Increase the 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 >>

Lactic Acidosis

Lactic Acidosis

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