Lactic acidosis metformin

In patients taking metformin, lactic acidosis is rare (3 per 100 000 patient-years) and is most often seen when contraindications to metformin (impaired kidney or liver function, alcoholism, circulatory problems, old age) are neglected or not detected (64). Although the relative risk of lactic acidosis with metformin is significantly lower than with phenformin or buformin (65), it has been repeatedly reported (SEDA-6, 371) (66), even in the absence of known contraindications (67). 

Price G. Metformin lactic acidosis, acute renal failure and rofecoxib. Br J Anaesth 2003 91 909-10. 

C. Metformin. Lactic acidosis occurred 9 hours after ingestion of 25 g of metformin by an 83-year-old patient, and fatal lactic acidosis and cardiovascular collapse occurred 4 hours after ingestion of 35 g in a 33-year-old patient. Pediatric ingestions up to 1700 mg have been well tolerated. 

Metformin Renal or liver disease any predisposition to hypoxia Gastro intestinal upsets risk of lactic acidosis if wrongly prescribed Creatinine, Hb or Vit B12b... 

A class of drug derived from guanidine, including metformin and phenformin. Metformin is currently widely used in humans for the treatment of type 2 diabetes. Phenformin was formerly also widely used but was withdrawn because of problems with lactic acidosis. 

Under certain circumstances, and very rarely, the inhibition of gluconeogenesis by metformin may suppress lactic acid metabolism and precipitate a potentially fatal lactic acidosis. Impairment of renal function, liver disease, alcoholism, conditions that give rise to increased lactate production (e.g. congestive heart failure, infections) are therefore contraindications for the application of metformin. 

Lactic acidosis (buildup of lactic acid in the blood) may also occur with die administration of metformin. Although lactic acidosis is a rare adverse reaction, its occurrence is serious and can be fatal. Lactic acidosis occurs mainly in patients with kidney dysfunction. Symptoms of lactic acidosis include malaise (vague feeling of bodily discomfort), abdominal pain, rapid respirations, shortness of breath, and muscular pain. In some patients vitamin B12 levels are decreased. This can be reversed with vitamin B12 supplements or with discontinuation of the drug therapy. Because... 

There is a risk of acute renal failure when iodi-nated contrast material that is used for radiological studies is administered with metformin. Metformin therapy is stopped for 48 hours before and after radiological studies using iodinated material. Alcohol, amiloride, digoxin, morphine, procainamide, quini-dine, quinine ranitidine, triamterene, trimethoprim, vancomycin, cimetidine, and furosemide all increase the risk of hypoglycemia. There is an increased risk of lactic acidosis when metformin is administered with the glucocorticoids. 

MANAGING LACTIC ACIDOSIS. When taking metformin, the patient is at risk for lactic acidosis. The nurse monitors die patient for symptoms of lactic acidosis, which include unexplained hyperventilation, myalgia, malaise, gastrointestinal symptoms, or unusual somnolence If the patient experiences these symptoms, the nurse should contact the primary care provider at once. Elevated blood lactate levels of greater than 5 mmol/L are associated with lactic acidosis and should be reported immediately. Once a patient s diabetes is stabilized on metformin therapy, the adverse GI reactions that often occur at the beginning of such therapy are unlikely to be related to the drug therapy. A later occurrence of GI symptoms is more likely to be related to lactic acidosis or other serious disease. 

Metformin—there is a risk of lactic acidosis when using this drug. Discontinue die drug therapy and notify the health care provider immediately if any of the following should occur respiratory distress, muscular aches, unusual somnolence, unexplained malaise, or nonspecific abdominal distress. 

Biguanides such as metformin are thought to inhibit mitochondrial oxidation of lactic acid, thereby increasing the chance of lactic acidosis occurring. Fortunately, the incidence of lactic acidosis in clinical practice is rare. Patients at greatest risk for developing lactic acidosis include those with liver disease or heavy alcohol use, severe infection, heart failure, and shock. Thus, it is common practice to evaluate liver function prior to initiation of metformin. 

Metformin 1500-2000 mg by mouth daily in 2-3 divided doses15 Anorexia, nausea, vomiting, diarrhea, flatulence, lactic acidosis... 

Metformin is a biguanide used to treat diabetes mellitus. It is contraindicated in patients undergoing general anaesthesia since anaesthesia can interfere with renal function. The risk of lactic acidosis associated with metformin increases in patients with renal impairment. Metformin should be stopped before and during surgery where anaesthesia is indicated. Metformin should only be restarted after the renal function has returned to normal. 

Lactic acidosis Lactic acidosis is a rare, but serious, metabolic complication that can occur because of metformin accumulation during treatment when it occurs, it is fatal in approximately 50% of cases. Lactic acidosis also may occur in association with a number of pathophysiologic conditions, including diabetes mellitus, and whenever... 

The onset of lactic acidosis often is subtle and accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress. There may be associated hypothermia, hypotension, and resistant bradyarrhythmias with more marked acidosis. The patient and the patient s physician must be aware of the possible importance of such symptoms. Instruct the patient to notify the physician immediately if these symptoms occur. Withdraw metformin until the situation is clarified. Serum electrolytes, ketones, blood glucose, and, if indicated, blood pH, lactate levels, and blood... 

Levels of fasting venous plasma lactate above the upper limit of normal but less than 5 mmol/L in patients taking metformin do not necessarily indicate impending lactic acidosis and may be explained by other mechanisms, such as poorly controlled diabetes or obesity, vigorous physical activity, or technical problems in sample handling. 

Lactic acidosis is a medical emergency that must be treated in a hospital setting. In a patient with lactic acidosis who is taking metformin, immediately discontinue the drug and promptly institute general supportive measures. Because metformin is dialyzable (with a clearance of up to 170 mL/min under good hemodynamic conditions), prompt hemodialysis is recommended to correct the acidosis and remove the accumulated metformin. Such management often results in prompt reversal of symptoms and recovery. 

Renal function impairment Metformin is known to be excreted by the kidney, and the risk of metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Do not give metformin to patients with serum creatinine levels above the upper limit of normal for their age. 

Hepatic function impairment Because impaired hepatic function has been associated with cases of lactic acidosis, avoid metformin in patients with clinical or laboratory evidence of hepatic disease. 

Promptly evaluate patients previously well controlled on metformin who develop laboratory abnormalities or clinical illness for evidence of ketoacidosis or lactic acidosis. Evaluation should include serum electrolytes and ketones, blood glucose, and, if indicated, blood pH, lactate, pyruvate, and metformin levels. If acidosis of either form occurs, stop metformin immediately and initiate other appropriate corrective measures. 

Hypoxic states Cardiovascular collapse (shock), acute CHF, acute Ml, and other conditions characterized by hypoxemia have been associated with lactic acidosis and may cause prerenal azotemia. If such events occur, discontinue metformin. Surgicai procedures Temporarily suspend metformin for surgical procedures (unless minor and not associated with restricted intake of food and fluids). Do not restart until the patient s oral intake has resumed and renal function is normal. 

Elderly The initial and maintenance dosing of pioglitazone/metformin should be conservative in patients with advanced age, due to the potential for decreased renal function in this population. Any dosage adjustment should be based on a careful assessment of renal function. Generally, elderly, debilitated, and malnourished patients should not be titrated to the maximum dose of pioglitazone/metformin. Monitoring of renal function is necessary to aid in prevention of metformin-associated lactic acidosis, particularly in the elderly. 

T Pancreatic insulin release Metformin Peripheral insulin sensitivity hepatic glucose output/production i intestinal glucose absorption Dose Ist-line (naive pts), 1.25/250 mg PO daily-bid 2nd-line, 2.5/500 mg or 5/500 mg bid (max 20/2000 mg) take w/ meals, slowly T dose hold before 48 h after ionic contrast media Caution [C, -] Contra SCr >1.4 mg/dL in females or >1.5 mg/dL in males hypoxemic conditions (sepsis, recent MI) alcoholism metabolic acidosis liver Dz Disp Tabs SE HA, hypoglycemia, lactic acidosis, anorexia, N/V, rash Additional Interactions T Effects W/ amiloride, ciprofloxacin cimetidine, digoxin, miconazole, morphine, nifedipine, procainamide, quinidine, quinine, ranitidine, triamterene,... 

The drug metformin is useful in the treatment of patients with type 2 diabetes mellitus who are obese and whose hyperglycemia cannot be controlled by other agents. There are reports that some patients are predisposed to the toxic side effects of this drug, which include potentially fatal lactic acidosis. 

II.f.2.3. Biguanides. The two important drugs of this class are metformin and phenformin. Phen-formin is now rarely used due to its high risk of lactic acidosis and in many countries it is even taken... 

Adverse gastrointestinal symptoms (nausea, vomiting, anorexia, metallic taste, abdominal discomfort, and diarrhea) occur in up to 20% of individuals taking metformin this can be minimized by starting at a low dose and slowly titrating the dose upward with food. Like phenformin, metformin can cause lactic acidosis, but its occurrence is rare except when renal failure, hypoxemia, or severe congestive heart failure is present or when coadministered with alcohol. Metformin is also contraindicated in persons with hepatic dysfunction, but it appears to be safe for use in the hepatic steatosis that often occurs with fatty infiltration of the liver in poorly controlled type II diabetics. 

L A. Metformin causes lactic acidosis in patients with renal failure and severe congestive heart failure. It does not increase the risk of ketoacidosis and showed a reduction in cardiovascular comorbidities in a large study. It is contraindicated in patients with severe liver disease but does not cause hepatic necrosis. When used as monotherapy, metformin rarely causes hypoglycemia. 

Accumulation of metformin can occur in patients with renal insufficiency, and interference with pyruvate metabolism can lead to severe lactic acidosis. Lactic acidosis is more likely in situations associated with anaerobic metabolism, and metformin should not be given to patients with renal disease, liver disease, or severe pulmonary or cardiac disease predisposing to hypoxia. It is recommended to switch patients taking metformin to another oral hypoglycaemic prior to cardiac or other major surgery. 

The structure of metformin is shown below. Phenformin (an older biguanide) was discontinued in the USA because of its association with lactic acidosis and because there was no documentation of any long-term benefit from its use. 

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