Metformin-related Lactic Acidosis Research Articles

Metformin-related lactic acidosis with acute kidney injury: results of a French observational multicenter study

Background: Metformin-associated lactic acidosis (MALA) and metformin-induced lactic acidosis (MILA) remain controversial entities. Metformin toxic effect depends on accumulation to lead to lactic acidosis (LA), particularly during an episode of acute kidney injury (AKI). In MILA, no other condition contributing to LA is found. The aims of this study were to describe the characteristics and prognosis of AKI associated with LA in metformin users and to clarify the role of this drug in the different types of LA.Methods: We performed a French multicenter retrospective study in diabetic patients treated by metformin presenting with LA in a context of AKI in 2015. 126 nephrology units (NU) and 23 intensive care units (ICU) were contacted. We individualized MILA and MALA patients in order to illustrate the role of metformin.Results: We included 173 patients (109 MILA, 64 MALA). 103 patients presented without hemodynamic instability (82 MILA and 21 MALA) whereas 70 patients were shocked including 27 MILA. The shock was associated with death with an odds ratio (OR) of 12.92 (p < .001). Digestive disorders (DD) were strongly associated with MILA (p = .0001). MALA was significantly associated with shock (p < .0001). The mortality rate was higher in MALA (26%) when compared with MILA (7%). Dialysis performed in 133 patients was significantly associated with shock, kalemia, lactate and serum creatinine levels. In multivariate analysis, metformin level was independently associated with pH or lactate level only in MILA patients.Conclusions: MILA is associated with DD and death is due to severe refractory acidosis leading to cardiovascular collapse attributed to metformin accumulation mainly via AKI. MALA patients are more frequently shocked and death is related to their underlying condition, metformin accumulation increasing LA.

Acidosis láctica por metformina: reporte de caso

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.

Metformin-related lactic acidosis: Case report

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.

Clinical imaging contrast agents - inception through lifecycle

Event Abstract Back to Event Clinical imaging contrast agents - inception through lifecycle Benjamin Yeh1 1 University of California, San Francisco, Radiology and Biomedical Imaging, United States Introduction The introduction of injectable contrast agents transformed medical imaging such that CT and MRI became critical first line tests for broad spectrums of clinical diagnosis and treatment monitoring. Importantly, it was the interplay between medical scanner breakthroughs and contrast agent availability that was central driving up the value of diagnostic imaging in the past half century. As medical imaging scanners improved, our understanding of how contrast agents can be tailored to optimally highlight disease became amongst the most critical topics of medical research. Discussion The usage of existing clinical contrast agents is now radically different than what was initially conceived when the agents were first introduced. For example, iodinated contrast agents were initially introduced for the sole purpose of highlighting the renal excretory system at plain film imaging. Since then, iodinated agents have taken on vastly increased roles for defining vasculature at minimally invasive angiographic studies and for defining global anatomy in CT scans. Further introduction of variant iodinated benzene rings with different physicochemical properties opened new imaging applications, such as cholangiographic and safer intravenous imaging. Similarly, the introduction of new imaging technology such as helical multislice CT and dual energy imaging dramatically changed the capabilities of the entire class of iodinated agents. Similar changes occurred with gadolinium-based MRI contrast material which quickly altered the landscape of MR imaging across all organ systems. However, as usage proliferated, so did the understanding of toxicities from contrast agents. Some toxicities, such as preventative measures for contrast-induced nephropathy and metformin-related lactic acidosis, became deeply ingrained in clinical practice even though the prevalence and severity of such entities were not well studied and subsequently were found to be far lower than initially thought. Conversely, toxicities of gadolinium chelates were exposed only after decades of use and resulted in near crisis as the magnitude of the contrast-related disease was studied. Conclusion: The understanding of the intimate connection between medical scanner capabilities and inevitable evolution and biomedical contrast material physicochemical properties is critical to consider for the development of any new contrast agent. Keywords: MRI, contrast agent, biomedical application Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: New Frontier Oral Topic: Imaging with biomaterials Citation: Yeh B (2016). Clinical imaging contrast agents - inception through lifecycle. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.02933 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Benjamin Yeh Google Benjamin Yeh Google Scholar Benjamin Yeh PubMed Benjamin Yeh Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Metformin-related lactic acidosis in patients with acute kidney injury

Metformin is nowadays considered as first-line therapy in individuals with non-insulin dependent diabetes mellitus (NIDDM). Metformin-related lactic acidosis (MALA) occurs more frequently after inappropriate use especially in patients with acute kidney injury (AKI) or chronic kidney disease (CKD). Thus, its prescription in these patients is contraindicated, while the role of dialysis is under evaluation. We describe two cases of severe metformin-related lactic acidosis with underlying acute kidney injury, which were treated with dialysis. In both cases, lactic acidosis occurred on a background of acute decline in renal function, possibly due to drug accumulation. It is interesting that metformin was contraindicated in one case. Lactic acidosis is a rare but potentially fatal adverse effect of metformin, particularly in patients with AKI, which should always be considered in clinical practice. Dialysis seems to contribute significantly to the management of this life-threatening condition and the improvement in outcome.

Three cases of severe metformin-related lactic acidosis

The American Diabetes Association and the European Association for the Study of Diabetes published a consensus statement on the approach to hyperglycaemia in individuals with type 2 diabetes.1 In accordance with this statement, metformin is widely prescribed, as it is the first-line drug for type 2 diabetes treatment. Lactic acidosis incidence during metformin therapy is estimated to be two to nine cases per 100 000 patients per year, an incidence not too different from that reported in patients with type 2 diabetes who do not take metformin.2 In fact, there is some controversy concerning the association between metformin and lactic acidosis. Metformin does not seem to be the initial cause of lactic acidosis but could, possibly, precipitate the acid–base imbalance and contribute to the severity of the acidosis.3 The risk factors for metformin-related lactic acidosis include decreased renal, cardiac and hepatic functions and/or suspected tissue hypoxia. On the contrary, in recent years, several cases of severe lactic acidosis have been reported in the literature, even in the absence of these risk factors. Medical therapy for metformin-associated lactic acidosis includes management of concurrent diseases; mechanical ventilation to prevent muscle fatigue, to help to maintain respiratory compensation for metabolic acidosis and to optimize oxygenation; bicarbonate haemodialysis or continuous veno-venous haemofiltration (CVVH) to decrease the metformin level and correct acidosis; and intensive vasoactive support with norepinephrine or epinephrine. The use of bicarbonate is known to worsen intracellular acidosis and hyperlactacidaemia and remains controversial. In the last 14 months, three patients undergoing chronic metformin therapy have been admitted to our critical care unit for severe lactic acidosis (Table 1).Table 1: Patient characteristicsAll patients we saw were hypothermic with a high Simplified Acute Physiology Score II (SAPS II) score at admission. Two patients required high doses of epinephrine due to hypotension refractory to norepinephrine–dobutamine association. Liver function was never affected. Patient 1 and patient 2 had risk factors for lactic acidosis, as they had mild and moderate previous elevation of creatinine level, respectively; in these cases, metformin should be withdrawn. Patient 3 had no contraindication to metformin use.4 Two out of three had a mild infection before admission (patients 1 and 3). Diabetic nephropathy often develops insidiously. Moreover, infection or dehydration can rapidly lead to renal function impairment. Cohen and Woods divided lactic acidosis into two categories. Type A is lactic acidosis occurring in association with clinical evidence of poor tissue perfusion or oxygenation, whereas type B occurs when no clinical evidence of poor tissue perfusion or oxygenation exists. All three patients had developed acute renal failure, a known cause of type B lactic acidosis. Two patients had infections, which may also have contributed to tissue hypoxia and type A lactic acidosis. Regardless of the type of lactic acidosis in our patients, the incidence of metformin toxicity can be reduced with close monitoring of renal function. Serum creatinine should be checked at least annually, and probably more often in patients with exposure to risk factors for renal impairment.5 These cases suggest a high index of suspicion for metformin-associated lactic acidosis in older patients, a prompt metformin withdrawal during periods of suspected tissue hypoxia or impaired renal function and the importance of giving patients full information about this side-effect. We have outlined the importance of taking into account risk factors for lactic acidosis and contraindications in prescribing metformin. We also would like to emphasize that, despite the severity of clinical presentation, two patients had an excellent recovery.

Metformin-related lactic acidosis: A case series

Metformin-related lactic acidosis: A case series

Drug administration in patients with diabetes mellitus. Safety considerations.

Diabetes mellitus is associated with alterations in a number of key metabolic pathways. Despite theoretical concerns, clinically significant alterations in the pharmacokinetic properties of commonly prescribed drugs are relatively uncommon. Indeed, dose adjustment is rarely required in the setting of well controlled diabetes mellitus. However, significant alterations in drug handling may occur in the context of poor metabolic control or in the presence of complications such as nephropathy. Metformin use may be complicated by lactic acidosis. Fortunately, this is a rare occurrence providing that the agent is not used in circumstances in which it is contraindicated. Indeed, the risk of death from metformin-related lactic acidosis is similar in magnitude to the risk of death related to hypoglycaemia in sulphonylurea-treated patients. The novel hypoglycaemic agent troglitazone may be associated with abnormalities in liver function in approximately 2% of patients. Discontinuation of treatment is followed by normalisation of liver enzyme levels. Current prescribing information recommends frequent monitoring of liver function tests and immediate cessation of therapy if abnormalities develop. In addition to disturbances in intermediary metabolism, diabetes mellitus may also lead to chronic microvascular and marcovascular complications. Thus, in addition to the use of drugs for the control of blood glucose, patients with diabetes mellitus are likely to be prescribed medication for associated conditions such as cardiovascular disease. Such medication includes the ACE inhibitors which are contraindicated in patients with bilateral renal artery stenosis. This complication may be theoretically more common in patients with diabetes mellitus because of accelerated atherosclerosis. However, in clinical practice this is an uncommon occurrence in the absence of clinical features that should alert the treating clinician that an individual patient might be at high risk. Although caution should also be used with beta-blocker therapy in patients with diabetes mellitus, current evidence suggests that, like ACE inhibitors, these drugs may be particularly useful in this patient group.