The lactic acidosis from metformin is primarily type b. 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. Metforminassociated lactic acidosis is more likely to occur in patients who acutely develop renal impairment from dehydration, vomiting or. Lactic acidosis is a medical condition characterized by the buildup of lactate especially llactate in the body, with formation of an excessively low ph in the bloodstream. Metformin associated lactic acidosis is a rare and serious complication of biguanide treatment. Metforminassociated acute kidney injury and lactic acidosis. Department of emergency medicine, north shore university health systems, evanston, illinois. Though metforminassociated lactic acidosis mala is extremely rare most.
Metformin associated lactic acidosis is a potentially fatal yet rare diagnosis. We present a case of lactic acidosis secondary to metformin therapy with associated ketosis from vomiting. Risk of fatal and nonfatal lactic acidosis with metformin use in. In propensity scorematched cohorts within strata of egfr, metformin use was associated with similar risk of acidosis compared with use of alternative hypoglycemic medications at egfr 45 to 59 mlmin1. Lactic acidosis is rare, but serious, with a mortality up to 50% 3. Food and drug administration fda has given metformin a special warning, called a black box warning, about lactic acidosis. Using poisson statistics with 95% confidence intervals the upper limit for the true incidence of metforminassociated lactic acidosis was 8. An unusual case of metformin associated lactic acidosis v poulose, fccp department ofmedicine, changi general hospital, 2 simei street 3, singapore 529889 introduction lactic acidosis is a wellknown, but rare complication ofbiguanide therapy. Metformininduced lactic acidosis with emphasis on the.
Sep 16, 2009 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. However, as demonstrated in this case, extreme lactic acidosis may develop in patients on therapeutic doses of metformin in the setting of acute renal failure induced by a prolonged episode of dehydration. Metformin associated lactic acidosis mala in the absence of other risk factors, is extremely rare. Lactic acidosis associated with metformin in patients with. Very rarely, metformin can cause a lifethreatening side effect called lactic acidosis. The first case is a 77 year old female with a past medical history of hypertension and type 2 diabetes mellitus who had recently been prescribed metformin 3 gday, perindopril and acetylsalicylic acid. This consideration is especially important in patients with severe anion gaps associated with lactic acidosis out of proportion to the patients clinical presentation. Lactic acidosis refers to lactic acid build up in the bloodstream. Metformin mf accumulation during acute kidney injury is associated with high anion gap lactic acidosis type b mfassociated lactic acidosis, mala, a serious medical condition leading to high mortality. Ten years retrospective analysis of patients admitted in intensive care unit for metformin associated lactic acidosis.
Outcome of severe lactic acidosis associated with metformin. Here we describe a rare case of metformin associated lactic acidosis. Lactic acidosis is a serious complication of metformin therapy and is more frequent in patients with kidney failure and other intercurrent mdtformina. The relationship between metformin accumulation and lactic acidosis is complex and is affected by the presence of comorbid conditions such. Jan 22, 2016 metformin mf accumulation during acute kidney injury is associated with high anion gap lactic acidosis type b mfassociated lactic acidosis, mala, a serious medical condition leading to high mortality. The liver, kidney, heart, and skeletal muscle are the primary lactate metabolizers, while.
A high incidence of lactic acidosis was seen with phenformin therapy 4060100 000 patient. Metformin is a commonly used treatment modality in type 2 diabetes mellitus, with a well documented side effect of lactic acidosis. Intuitively, it would be supposed that the chance of surviving metformin associated lactic acidosis mala would be related to the severity of the lactate acidosis i. Although a very rare adverse effect, metformin associated lactic acidosis mala is significant because it has a high 3050 % mortality rate.
Lactic acidosis almost never occurs with metformin exposure during routine medical care. Oct 25, 2015 although metformin associated lactic acidosis is a rare condition, with an estimated prevalence of one to five cases per 100 000 population 3, it has a reported mortality of 3050% 4. A 60yearold male presented to the emergency department feeling tired and breathless for the preceeding 3 days. Lactic acidosis is a lifethreatening condition that is fatal in about 50 percent of cases and is caused by too much lactate in the blood and low blood ph. Lactic acidosis is commonly associated with acute metformin intoxication. First, this potential event still influences treatment strategies in type 2 diabetes mellitus, particularly in the many patients at risk of kidney failure, in those presenting contraindications to metformin and in the elderly. Mar 27, 2015 rarely, a serious condition called metformin associated lactic acidosis mala can occur in patients with predisposing factors such as renal insufficiency, hepatic disease, congestive heart failure, or sepsis. It is a form of metabolic acidosis, in which excessive acid accumulates due to a problem with the bodys oxidative metabolism lactic acidosis is typically the result of an underlying acute or chronic medical condition. Oct 31, 2007 the occurrence of metformin induced lactic acidosis is exceptional when the drug is used with caution. A 2010 study by salpeter et al found that the oral antihyperglycemic agent metformin, despite concerns to the contrary, is not associated with an increased risk for lactic acidosis compared with. Metformin and lactic acidosis there are some potential adverse side effects of metformin. Irrespective of its underlying etiology, lactic acidosis is a life threatening condition characterized by low blood ph 5. Laboratoryconfirmed metforminassociated lactic acidosis.
Extreme lactic acidosis type b associated with metformin. There is an ongoing debate on the pathogenesis of metformin associated lactic acidosis mala. Risk factors include renal insufficiency, higher doses of metformin, and alcoholism. A 60yearold male presented to the emergency department feeling tired and breathless for the preceeding 3.
This paper describes five patients admitted to chang gung memorial. Renda f, mura p, finco g, ferrazin f, pani l, landoni g. Lactic acidosis, a rare but lifethreatening complication related to metformin use, is a great concern of clinicians3. Acute and chronic use of metformin can lead to rare complication of metforminassociate lactic acidosis mala excreted unmetabolized in proximal tubules stimulates anaerobic glucose metabolism in splanchnic bed increased lactate production. Lactic acidosis associated with metformin treatment is a rare but important adverse event, and unravelling the problem is critical. Recurrent lactic acidosis and hypoglycemia with inadvertent. Metformin is the firstline treatment for type 2 diabetes mellitus dm2 when diet and exercise do not result in adequate glycaemia control, especially in overweight patients. It usually occurs when a precipitating disease induces an acute renal failure and an incidental. Rare cases of metforminassociated lactic acidosis caused by the accumulation of the drug in patients with renal dysfunction have been described, although a detailed time course of the resulting metabolic derangements has not been reported. Metformin associated lactic acidosis icm case summaries. It was a rare entity but you explained well in short time. More recently it has also been used to improve fertility and weight reduction in patients with polycystic ovary syndrome.
Certain diseases can also cause the condition including. Treatment consists of vital function support and drug. Lactate is produced by the gut, liver, and peripheral tissues during glycolysis and can accumulate during hypoxic conditions. It was the first antidiabetic agent that showed to reduce diabetic complications and overall mortality in overweight and obese dm2 patients. In the intensive care setting lactate and ph levels are regularly used as a useful predictor of poor prognosis. What is the role of metformin in the etiology of lactic acidosis. There were 59 cases of metformin associated lactic acidosis mortality rate of 25. Metformin associated lactic acidosis mala is a wellknown serious. Metforminassociated lactic acidosis litfl ccc acidbase.
Role of metformin accumulation in metforminassociated lactic acidosis. In this article we highlight how high lactate levels are not an accurate predictor of mortality in deliberate metformin overdose. Metaanalyses and large studies have been unable to establish an epidemiological association, probably due to its low incidence rate. Outcome of metforminassociated lactic acidosis in type 2. Metforminassociated lactic acidosis can occur acutely in an overdose but typically has a more gradual onset in patients with hepatic or renal dysfunction due to decreased excretion. If the inline pdf is not rendering correctly, you can download the pdf file here. In 1995, the oral antihyperglycemic agent, metformin, was introduced in the united states for treating diabetes mellitus. You are advised to consult the publishers version publishers pdf if you wish to cite from it. Metformin associated lactic acidosis mala may complicate metformin therapy, particularly if metformin accumulates due to renal dysfunction. Metforminassociated lactic acidosis, although very uncommon, carries a significant risk of mortality.
It is a type of high anion gap metabolic acidosis and is associated with various pathological processes. Pdf lactic acidosis is a widely recognized, though rare, side effect of metformin. Am i likely to get lactic acidosis from taking metformin. An unusual case of metformin associated lactic acidosis. Lactic acidosis a buildup of lactic acid in the body is a rare complication of taking metformin glucophage, fortamet, but you could be at an increased risk for this condition if youre dehydrated or if you drink large amounts of alcohol.
Metforminassociated lactic acidosis has not been thoroughly characterized. The most common cause of lactic acidosis is severe medical illness in which blood pressure is low and too little oxygen is reaching the bodys tissues. This study was designed to document the characteristics and prognostic factors of intentional and incidental metformin overdose and to determine the optimal duration of hd. Metformin associated lactic acidosis junki park 9611. Metformin should also not be administered to patients with acute or chronic metabolic acidosis. Metforminassociated lactic acidosis faisal hasan et al. Nov 21, 2012 lactic acidosis associated with metformin treatment is a rare but important adverse event, and unravelling the problem is critical.
We present two case reports of metformin associated lactic acidosis. Suspect mala in any patient on metformin who presents with abdominal pain, nausea and vomiting andor ams. It is a form of metabolic acidosis, in which excessive acid accumulates due to a problem with the bodys oxidative metabolism. The differential diagnosis at this point should include sepsis, diabetic ketoacidosis, alcoholic ketoacidosis, toxic alcohols, and biguanide metformin toxicity. It often presents with nausea, abdominal pain, tachycardia, hypotension, and tachypnea.
The incidence of lactic acidosis in patients on metformin therapy appears to be very low 4, 5, 6, but it can be fatal when it occurs. Prognosis seems to be unrelated to plasma metformin concentration or lactate level 5. Rarely, a serious condition called metforminassociated lactic acidosis mala can occur in patients with predisposing factors such as renal insufficiency, hepatic disease, congestive heart failure, or sepsis. In real life, however, associated lactic acidosis has been repeatedly, although rarely, reported. Metforminassociated lactic acidosis requiring hospitalization. Clinically it will be impossible to differentiate this from mala. Lactic acidosis unrelated to metformin is a relatively common occurrence among the critically ill and usually arises as a result of tissue hypoxia consequent on the inadequate perfusion associated. Its use has been related to the occurrence of lactic acidosis.
Hemodialysis in the treatment of lactic acidosis in diabetics treated by metformin. Lactic acid is produced when oxygen levels, become low in cells within the areas of the body where metabolism takes place. Association of metformin use with risk of lactic acidosis. Mortality rate in socalled metforminassociated lactic acidosis. While this particular patients presentation is likely multifactorial, she also has metformin associated lactic acidosis mala, secondary to metformin use during renal failure.
Metformin amplifies the degree of lactic acidosis, but its not the sole cause of the illness. Metformininduced lactic acidosis with emphasis on the anion gap. In patients with shortness of breath and clear lungs, consider metabolic acidosis with respiratory alkalis as a potential cause. Prompt recognition of even subtle symptoms can reduce mortality and preserve homeostasis. Metforminassociated lactic acidosis mala in the absence of other risk factors, is extremely rare. Of 100,000 people, the incidence of lactic acidosis was 5. Intense exercise or convulsions can cause temporary cause lactic acidosis. Patients with mala will have a low ph, a highanion gap metabolic acidosis and high lactate levels. 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. Patients with these conditions may be at increased risk for the development of lactic acidosis, which is a rare but serious metabolic complication associated with metformin accumulation in plasma usually at levels exceeding 5 mcgml. Metforminassociated lactic acidosis has been defined as a lactate value 5 mmoll and a bicarbonate level metformin concentrations as occur in individuals with renal impairment and a secondary event or condition that further disrupts lactate production or clearance e. Metforminassociated lactic acidosis faisal hasan et al case. Despite dose adjustment for renal failure, diabetic patients with chronic kidney disease ckd stage iiiiv are at risk for rapid decline in renal function by whatever reason, so that mf. Metformin associated lactic acidosis can occur acutely in an overdose but typically has a more gradual onset in patients with hepatic or renal dysfunction due to decreased excretion.
Metforminassociated lactic acidosis is a rare and serious complication of biguanide treatment. Rates of metforminassociated lactic acidosis is about nine per 100,000 personyears, which is similar to the background rate of lactic acidosis in the general population. Rare cases of metformin associated lactic acidosis caused by the accumulation of the drug in patients with renal dysfunction have been described, although a detailed time course of the resulting metabolic derangements has not been reported. Rates of metformin associated lactic acidosis is about nine per 100,000 personyears, which is similar to the background rate of lactic acidosis in the general population. The authors concluded that metformin is not associated with an. A 70yearold female with diabetes mellitus type ii and a oneweek old left frontal. 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. Risk of fatal and non fatal lactic acidosis with metformin use in type 2 diabetes mellitus.
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