Metformin lactic acidosis, acute renal failure and rofecoxib

A patient with acute renal failure associated with lactic acidosisas a result of concurrent treatment with metformin is described.Rofecoxib may have been a precipitating factor. The risk ofrenal failure with the use of traditional NSAIDs is well known.However, what is less well appreciated is the role that theCOX 2 inhibitors may play in the development of renal failurewhich, when it occurs in a patient on metformin, can lead toa potentially disastrous outcome. Br J Anaesth 2003; 91: 909–10     

Acute renal failure with lactic acidosis

This study examined the acid base disturbances in 18 adults with acute renal failure (ARF) from one of new aspects, which is lactate metabolism and pathophysiology. 10 patients (55%) of them were accompanied by lactic acidosis and 9 patients (90%) of those with lactic acidosis also had severe hepatic failure. Mortality of patients with lactic acidosis was 80%, and much higher than that of ARF (66.7%). Lactate, pyruvate, lactate-to-pyruvate ratio (L/P) were 76.7 +/- 15.66 mg/dl, 3.30 +/- 0.74 mg/dl and 19.9 +/- 1.41, respectively. All of them significantly raised, compared to values of healthy adults, patients with liver cirrhosis, chronic renal failure and diabetes mellitus. Arterial pH and HCO3- levels were 7.20 +/- 0.04 and 10.6 +/- 1.20 mEq/l. Anion gap (AG) was 30.0 +/- 3.66 mEq/l. Significant correlations of lactate with pH, HCO3-, AG and L/P were demonstrated, while correlations of lactate with BUN, CR and prothrombin time were not significantly observed. Lactic acidosis results from two mechanisms. One is lactate overproduction (e.g tissue hypoxia) and the other is lactate underutilization (e.g severe liver and/or renal failure). Whenever lactic acidosis occurred, both mechanisms were present simultaneously and continuously. Especially, the latter mechanism had a very important role on it, and seemed to decide the prognosis of the patients with lactic acidosis. Therapy of lactic acidosis was very difficult. First of all, we tried to improve the circulatory failure and severe acidemia (pH less than 7.20) not to fall into vicious cycle. Then, CAVH, if combined with alkali infusion, seemed to be the most useful technique in managing lactic acidosis with ARF.     

Metformin-associated lactic acidosis: case reports and literature review

BACKGROUND: Lactic acidosis is a widely recognized, though rare, side effect of metformin. This paper describes five patients admitted to Chang Gung Memorial Hospital from 1 September 1998 to 31 May 2001 suffering severe lactic acidosis caused by metformin, and reviews the literature. PATIENTS: Five cases diagnosed as having meftormin-associated lactic acidosis (MALA) were discovered during the study period. Three had normal renal function before the onset of MALA and two had attempted suicide bytaking large amounts of metformin. One patient with end-stage renal disease developed MALA despite regularhemodialysis three times a week. One of the patients who had taken metformin to attempt suicide was not diabetic. RESULTS: All patients suffered severe metabolic acidosis with a high anion gap and blood lactate level. Four developed profound hypotension, and three of these also suffered acute respiratory failure. Three patients received conventional hemodialysis and two continuous renal replacement therapy. A young non-diabetic female who had taken a large dose of metformin to commit suicide died from multiple organ failure despite aggressive treatment. CONCLUSIONS: Lactic acidosis is a serious reaction to metformin, and hemodialysis (the treatment of choice) should be done urgently to prevent serious complications. MALA should be suspected in patients presenting with wide anion gap metabolic acidosis and high blood lactate, even when they are non-diabetic.     

Metformin-associated lactic acidosis remains a serious complication of metformin therapy

We report 4 cases of lactic acidosis in diabetic patients usually treated with metformin. For the first 3 patients, the clinical history was similar because lactic acidosis was precipitated by gastro-intestinal disorders whereas all of them were simultaneously treated with several nephrotoxic drugs. These 3 patients presented with acute renal failure on arrival at hospital. Their issue was fatal whereas any obvious cause of overproduction of lactate was found. The fourth case, which was due to a voluntary intoxication, was the only one presenting with a favourable evolution. The metformin plasma and red blood cell levels were performed for 2 of 4 patients and confirmed the overdose. These observations remind that metformin-associated lactic acidosis remains a serious complication, and that medical doctors must respect strictly contra-indications and guidelines for withdrawing metformin.     

Metformin-associated lactic acidosis: incidence, diagnosis, prognostic factors and treatment

We describe the case of a patient with severe lactic acidosis, as well as presenting some data on its incidence, diagnosis, prognostic factors, and the most appropriate treatment. A 76 year-old male patient with diabetes on treatment with metformin, hypertension, dyslipaemia, and with mild cognitive impairment, was admitted to the Intensive Care Unit in a state of circulatory shock, requiring aggressive treatment with vasopressors and volume. The patient had acute kidney injury with an anuria of 3 days, probably secondary to dehydration to vomiting and to NSAIDs. As a result of the acute renal damage, the patient suffered a severe metformin-associated lactic acidosis. The rest of the causes of metabolic acidosis with an increased anion gap were ruled out, as well as a possible sepsis or rhabdomyolysis. Metformin-associated lactic acidosis is an uncommon metabolic condition, but with a high mortality. To reduce the mortality of these patients, it is important to make an early diagnosis using the clinical records, physical examination, and laboratory tests, with an early resuscitation with volume, vasopressors, bicarbonate, and renal replacement therapy.     

Anuric renal failure precipitated by indomethacin and triamterene

We report a patient with compensated congestive heart failure who developed acute anuric renal failure immediately after indomethacin and triamterene had been added to the treatment regimen. Renal function failed to improve promptly with discontinuation of these medications, anuria persisting for 11 days. While it is well known that patients suffering from edematous states are prone to develop renal insufficiency when given nonsteroidal anti-inflammatory agents, it is not generally appreciated that the specific combination of prostaglandin inhibitors with triamterene may carry a particularly high risk of acute renal failure, even in euvolemic subjects.     

Acute renal failure from multiple myeloma precipitated by ACE inhibitors

Renal failure in multiple myeloma can be precipitated during hemodynamic perturbances of renal blood flow, as seen secondary to volume depletion, radiocontrast dye, and nonsteroidal anti-inflammatory agents. We report two cases of acute renal failure that developed suddenly after initiation of angiotensin-converting enzyme (ACE) inhibitor, both with biopsy-proven cast nephropathy. ACE inhibitors may contribute to the intratubular light chain cast formation and acute “myeloma kidney” in susceptible patients.     

Impact of acute kidney injury on metformin-associated lactic acidosis

Objectives  

Metformin has been shown to reduce diabetic complications in overweight patients, and is increasingly used to treat this condition. However, this agent is associated with a rare but serious risk of lactic acidosis.     

Combined renal replacement therapy for severe metformin-induced lactic acidosis.

Sir, This report is on a 68-year-old woman with a history of type2 diabetes mellitus treated with metformin 850 mg thrice daily,and mild chronic renal failure, who underwent cardiopulmonaryresuscitation for cardiovascular collapse because of severemetformin-associated lactic acidosis. Even after 12 h of continuousvenovenous