Metformin-associated Lactic Acidosis Research Articles

Urgent-Start Peritoneal Dialysis in Metformin-Associated Lactic Acidosis: A Critical Alternative When Immediate Hemodialysis is Unavailable.

Introduction Intermittent hemodialysis (IHD) is a preferable renal replacement therapy (RRT) option in metformin-associated lactic acidosis (MALA) due to rapid correct metabolic acidosis. However, IHD might not be started immediately. Immediate urgent-start peritoneal dialysis (iUSPD) is used as a life-saving dialysis option and then followed by IHD. The outcomes of iUSPD were compared with other extracorporeal dialysis in MALA. Methods In two tertiary hospitals in Thailand, the outcomes of patients with MALA who had received three different RRT modalities (iUSPD followed by IHD, IHD, and continuous renal replacement therapy [CRRT]) from January 2015 to December 2019 were compared. The primary outcome was 30-day mortality. The secondary outcomes were door-to-dialysis time and 90-day RRT dependence. Results 180 MALA cases that required dialysis were included (20 iUSPD, 120 IHD, and 40 CRRT). Their mean age was 64 years. Most of the patients had severe metabolic acidosis (mean pH 6.91, HCO3 6 mmol/L, and anion gap 40 mmol/L) and were critically ill. The 30-day mortality was 30% in iUSPD, 9.2% in IHD, and 32.5% in CRRT, p = 0.001). The mortality risk in the iUSPD group was not significantly different from those of the IHD and CRRT groups (adjusted HR 2.5, 95% CI 0.65-9.6 and adjusted HR 0.75, 95% CI 0.2-2.78, respectively). All dialysis modalities had comparable 90-day dialysis dependence. iUSPD exhibited the shortest door-to-dialysis time. Conclusion In MALA, iUSPD followed by IHD might be a viable RRT option to save patient lives if no other dialysis option are available.

Trends in Antidiabetic Drug Use and Safety of Metformin in Diabetic Patients with Varying Degrees of Chronic Kidney Disease from 2010 to 2021 in Korea: Retrospective Cohort Study Using the Common Data Model.

This study aimed to investigate trends in antidiabetic drug use and assess the risk of metformin-associated lactic acidosis (MALA) in patients with chronic kidney disease (CKD). A retrospective observational analysis based on the common data model was conducted using electronic medical records from 2010 to 2021. The patients included were aged ≥18, diagnosed with CKD and type 2 diabetes, and had received antidiabetic medications for ≥30 days. MALA was defined as pH ≤ 7.35 and arterial lactate ≥4 mmol/L. A total of 8318 patients were included, with 6185 in CKD stages 1-2 and 2133 in stages 3a-5. Metformin monotherapy was the most prescribed regimen, except in stage 5 CKD. As CKD progressed, metformin use significantly declined; insulin and meglitinides were most frequently prescribed in end-stage renal disease. Over the study period, the use of SGLT2 inhibitors (13.3%) and DPP-4 inhibitors (24.5%) increased significantly, while sulfonylurea use decreased (p < 0.05). Metformin use remained stable in earlier CKD stages but significantly decreased in stage 3b or worse. The incidence rate (IR) of MALA was 1.22 per 1000 patient-years, with a significantly increased IR in stage 4 or worse CKD (p < 0.001). Metformin was the most prescribed antidiabetic drug in CKD patients in Korea with a low risk of MALA. Antidiabetic drug use patterns varied across CKD stages, with a notable decline in metformin use in advanced CKD and a rise in SGLT2 inhibitor prescriptions, underscoring the need for further optimized therapy.

7643 Acute blindness due to Metformin associated lactic acidosis

Abstract Disclosure: K.N. Pereira: None. K. Desai: None. T. Khan: None. S. Yong: None. Metformin, one of the most commonly prescribed oral hypoglycemic agents, effectively lowers basal and postprandial blood glucose. However, Metformin carries a black box warning for lactic acidosis, which is more common in setting of liver and kidney dysfunction. With an incidence rate of ∼ 4.3 cases per 100,000 patient-years, Metformin associated lactic acidosis (MALA) can present with nausea, vomiting, diarrhea, encephalopathy, hypothermia, respiratory failure and hypotension. Blindness is a rarely reported outcome of MALA. We present a case of a 48 year old intellectually disabled female with a history of type 2 diabetes (on Metformin) who presented with progressive encephalopathy insetting of intractable nausea and vomiting with poor oral intake, since starting lisinopril &amp; rosuvastatin for newly diagnosed hypertension and hyperlipidemia. She was encephalopathic, hypothermic, hypotensive, tachycardic and tachypneic. Labs were notable for leukocytosis, AKI, hyperkalemia, elevated anion gap metabolic acidosis with a lactate of 13.6 and elevated lipase. She also tested positive for Influenza A. CT head showed no acute intracranial abnormality. CT chest, abdomen &amp; pelvis was concerning for aspiration, multifocal pneumonia or a combination of both as well as acute interstitial pancreatitis. She was admitted to the ICU for further management including hemodialysis. She continued to have improving but persistent lactic acidosis despite multiple dialysis sessions. On day 5 of ICU stay, with resolution of her encephalopathy, she reported new onset complete bilateral painless vision loss. General eye and neurologic exam was unrevealing except for sluggishly reactive pupils to light. MRI brain showed an new acute 2 mm lacunar infarct in the right temporal lobe. Neurology ruled out stroke as the cause for her vision loss. Emergent ophthalmology evaluation revealed no retinopathy, macular edema, acute glaucoma or thromboembolic event. The new onset vision loss was suspected to be due to MALA due to persistent metabolic disturbances. Some animal studies have shown that retinal horizontal cells are sensitive to low pH, resulting in interruption of signal transmission to the visual neurons and consequent blindness. The presence of factors like metformin metabolites may contribute to impaired function of retinal cells.On extensive literature review it was noted that only 5 cases of vision loss associated with MALA have been reported. However, in these cases, vision loss was transient and reversed following correction of acidosis with dialysis. Our case highlights a rare consequence of MALA, which can be irreversible and cause lifelong disability. Presentation: 6/1/2024

8158 Transient Blindness In Metformin-Associated Lactic Acidosis

Abstract Disclosure: Y. Abouelkheer: None. A. Nasir: None. M. Ibrahem: None. Transient Blindness in Metformin-associated Lactic Acidosis Background: Metformin-associated lactic acidosis (MALA) is a rare side effect of metformin use. MALA can result in acute transient blindness in patients with severe metabolic derangements. Clinical Case: A 62-year-old woman presented with severe diarrhea, poor oral intake, malaise, and vomiting on a background of metformin-treated type 2 diabetes mellitus. Laboratory investigations showed bicarbonate &amp;lt;2 mmol/L, anion gap 48 mmol/L, lactic acid 20.5 mmol/L, serum osmolality 352 mOsm/kg, negative urine toxicology screen, and positive SARS-CoV-2. In the emergency department, the patient developed sudden onset bilateral vision loss. The examination was remarkable for complete vision loss bilaterally in all fields, associated with minimally reactive pupils and spontaneous ocular movements with an otherwise unrevealing neurological examination. Computed Tomography (CT) of the brain with stroke protocol showed no evidence of acute intracranial process. CT angiogram of the brain and neck showed patent intracranial and cervical vasculature without high-grade stenosis, large vessel occlusion, or aneurysm. While receiving medical management with intravenous fluid resuscitation and sodium bicarbonate supplementation, the patient had a spontaneous return of vision with no additional neurological complications or deficits. The severe metabolic derangements were associated with distributive shock, requiring admission to the intensive care unit for urgent hemodialysis, pressor support, empiric antibiotics, and stress-dose steroids. Shortly after the patient’s only hemodialysis session, we noted the resolution of her critical metabolic disturbances, renal failure, and shock state. Laboratory investigations post-dialysis showed bicarbonate 12 mmol/L, anion gap 36 mmol/L, and lactic acid 10.5 mmol/L. Follow-up MRI showed chronic lacunar infarct of the left basal ganglia, and she was discharged home six days later. Conclusion: Transient blindness in MALA can mimic acute neurovascular events. Prompt correction of metabolic derangements can aid in reversing systemic symptoms and blindness. Reference: DeFronzo R, Fleming GA, Chen K, Bicsak TA. Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism. 2016;65(2):20-29. doi:10.1016/j.metabol.2015.10.014 Presentation: 6/2/2024

Effective Extracorporeal Treatment of Metformin-Associated Lactic Acidosis using Continuous Venovenous Hemodiafiltration.

The prevalence of type 2 diabetes mellitus has surged globally. Metformin is recommended as the first-line oral treatment. However, metformin-associated lactic acidosis (MALA) is recognized as a rare but potentially dangerous complication. The pathogenesis of MALA is multifactorial, primarily resulting from the interference of metformin with mitochondrial function and hepatic gluconeogenesis, leading to lactate accumulation. Risk of MALA escalates with impaired kidney function, poorly controlled diabetes, fasting, and liver dysfunction. A 57-year-old woman with diabetes and hypertension presented with prolonged gastrointestinal symptoms. During this episode she continued using metformin. She had severe metabolic acidosis and acute kidney injury. Continuous venovenous hemodiafiltration was initiated, resulting in significant clinical improvement and normalized arterial blood gas parameters within 16 hours. The pharmacokinetic properties of metformin facilitate efficient elimination via hemodialysis and/or hemofiltration. Continuous venovenous hemodiafiltration emerges as effective for MALA treatment. In the case described the calculated metformin clearance during continuous venovenous hemodiafiltration was notably higher than reported values, possibly due to residual renal clearance. Clinical improvement occurred despite elevated metformin levels, suggesting a lack of correlation between metformin levels and patient outcomes. Comorbidities rather than metformin levels guide treatment decisions in MALA. This case underscores the efficacy of continuous venovenous hemodiafiltration in the treatment of MALA, suggesting its potential as a standard therapeutic approach. However, further research is needed to elucidate the complex interplay between metformin levels, clinical presentation, (extracorporeal) treatment modalities and outcome in MALA. Continuous venovenous hemodiafiltration seems to be an efficient and effective treatment to eliminate metformin in patients with metformin-associated lactic acidosis.The metformin level does not seem to correlate with the clinical condition of the patient.For a comparison between the effectiveness of different renal replacement therapies in metformin-associated lactic acidosis, more research is needed.

Determination of metformin from micro-liter plasma and blood glucose test strip using eco-friendly micro-extraction procedures for point-of-care diagnostics

Metformin is commonly used in the treatment of type 2 diabetes and polycystic ovary syndrome. Beyond these common applications, it also holds promise in treating chronic pain, and as an antiaging and anticancer agent. In addition, it has cardiovascular protective and neuroprotective effects. However, elevated concentrations of metformin in the plasma, such as in patients with renal impairment or with conditions that can disrupt lactate clearance, could cause metformin-associated lactic acidosis. Moreover, metformin can cause a deficiency of vitamin-B12 and folic acid and impact one-carbon metabolism negatively. This study employs micro-extraction procedures to extract metformin from the human plasma and blood glucose test strips followed by detection using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Under the optimized micro-extraction procedures and by using an eco-friendly base and solvent, the proposed method required only 10 µL of the human plasma and a small piece of the blood glucose test strip for metformin analysis. The method exhibits a linear range of 0.05–5 μg mL−1 with a coefficient of determination (r2) of 0.999 and a limit of detection of 0.01 μg mL−1. The relative standard deviation (RSD) and relative error (RE) were both below 6.7 %. The test strip is a disposable product; its reuse before disposal could increase its additional applicability. Furthermore, major blood proteins and their modifications could be identified using this tiny volume of blood by mass spectrometry after protein digestion. The proposed technique could be invaluable in point-of-care diagnostics, enabling rapid monitoring of metformin plasma concentration and major plasma proteins to help patients mitigate the risk of metformin-associated lactic acidosis. To reduce organic waste in clinical applications, micro-extraction is a simple and efficient protocol for sample preparation using minute volumes of blood samples.

Metformin-associated lactic acidosis may be treatable with thiamine

Metformin is a biguanide antidiabetic and a first-line therapy for type-2 diabetes mellitus. It is highly effective, cheap, and easily available since taken in tablet form. Metformin-associated lactic acidosis (MALA) is a serious adverse event with high mortality. It is currently treated with bicarbonate and haemodialysis. The mechanism by which metformin can precipitate lactic acidosis remains subject to debate. Lactic acidosis has also been reported in thiamine (vitamin B1) deficiency. Thiamine deficiency results in a switch from aerobic to anaerobic metabolism with accumulation of lactate. MALA and thiamine-associated lactic acidosis are usually considered separate entities. Both, thiamine and metformin are competitive substrates of the organ cation and thiamine transporters. This way, metformin could cause thiamine deficiency in liver cells. We hypothesize that MALA may be treatable with thiamine. High-dose intravenous thiamine treatment is used routinely for the treatment of Wernicke’s encephalopathy and is regarded as safe. Thiamine has been reported to have improved MALA in four cases, who had been refractory to haemodialysis. Thiamine is widely available, easy to administer, and cheap. Thiamine could already be given while waiting for dialysis. Above all, thiamine could prove life-saving in the treatment of MALA in clinical settings in which dialysis is not available.

Metformin-associated lactic acidosis: A mini review of pathophysiology, diagnosis and management in critically ill patients

Metformin is a common diabetes drug that may reduce lactate clearance by inhibiting mitochondrial oxidative phosphorylation, leading to metformin-associated lactic acidosis (MALA). As diabetes mellitus is a common chronic metabolic condition found in critically ill patients, pre-existing metformin use can often be found in critically ill patients admitted to the intensive care unit or the high dependency unit. The aim of this narrative mini review is therefore to update clinicians about MALA, and to provide a practical approach to its diagnosis and treatment. MALA in critically ill patients may be suspected in a patient who has received metformin and who has a high anion gap metabolic acidosis, and confirmed when lactate exceeds 5 mmol/L. Risk factors include those that reduce renal elimination of metformin (renal impairment from any cause, histamine-2 receptor antagonists, ribociclib) and excessive alcohol consumption (as ethanol oxidation consumes nicotinamide adenine dinucleotides that are also required for lactate metabolism). Treatment of MALA involves immediate cessation of metformin, supportive management, treating other concurrent causes of lactic acidosis like sepsis, and treating any coexisting diabetic ketoacidosis. Severe MALA requires extracorporeal removal of metformin with either intermittent hemodialysis or continuous kidney replacement therapy. The optimal time to restart metformin has not been well-studied. It is nonetheless reasonable to first ensure that lactic acidosis has resolved, and then recheck the kidney function post-recovery from critical illness, ensuring that the estimated glomerular filtration rate is 30 mL/min/1.73 m2 or better before restarting metformin.

#2589 Predictive value of serum lactate in ICU dialysis-dependent AKI patients

Abstract Background and Aims Hyperlactatemia is frequently observed in critically ill patients. It is often associated with unfavorable outcomes and serves as a strong predictor of mortality. Renal replacement therapy aims to mitigate lactate accumulation in this particular subgroup of patients, but the effectiveness of this therapy in reducing morbidity and mortality in acute kidney injury (AKI) associated lactic acidosis remains inconclusive. The aim of this retrospective study was to evaluate the predictive role of serum lactate in dialysis-dependent AKI patients stratified on three different underlying etiologies (septic shock, concomitant liver failure and metformin-associated lactic acidosis). Method A retrospective, single-center cohort analysis was conducted to examine patients with AKI who underwent hemodialysis in our ICU between 2022 and 2023 and had a serum lactate &amp;gt; 4 mmol/L. Patients were stratified according to underlying etiology: isolated septic shock with AKI, shock with concomitant AKI and fulminant liver failure (serum ammonia &amp;gt; 100 µmol/L), and AKI with metformin-associated lactic acidosis (MALA). We compared patients according to age and 3-day, 30-day, and 90-day mortality. Finally, we performed receiver-operating-curve (ROC) analysis to potential predictive power of serum lactate for 30-day mortality. Results The median age of our cohort of 63 patients was 67 (range 52 - 74) years, with a median lactate level of 12.9 (7.6 – 18.0) mmol/L. The 3-day, 30-day and 90-day mortality rate was 57%, 78%, and 83%, respectively. We observed that patients with concomitant liver failure were significantly younger (p = 0.004). Interestingly, while all groups have comparable 90-day mortality, patients with septic shock exhibit extremely high 3-day mortality (74%), compared to 35% and 25% for acute liver failure and metformin-associated shock. ROC curve analysis showed that serum lactate was highly predictive of 30-day mortality in group of AKI with concomitant fulminant liver dysfunction. On the contrary, in metformin-associated hyperlactatemia the level of serum lactate showed no such prediction. Conclusion Our retrospective analysis underscores the crucial importance of differentiating between various groups of patients (septic shock, concomitant liver failure and metformin-associated lactic acidosis) in patients with hyperlactatemia. In metformin-induced kidney failure, the level of lactate does not predict mortality, while in the cases of AKI with concurrent acute liver dysfunction our results are highly suggestive that dialysis may not be effective for severe lactacidosis. The findings contribute valuable insights for designing future prospective studies in this complex patient population.

Metformin-Associated Lactic Acidosis: Which Elimination Therapy to Use in Case of Haemodynamic Instability? A Retrospective Cohort Study

Introduction: Metformin, a commonly used oral antihyperglycemic drug, poses a rare risk related to the development of metformin-associated lactic acidosis (MALA). The Extracorporeal Treatments in Poisoning (EXTRIP) group recommended intermittent haemodialysis (IHD) as a primary elimination therapy in case of severe metformin poisoning. However, in haemodynamically unstable patients, our previous observations suggested that continuous venovenous haemofiltration (CVVH) might be more effective. This retrospective cohort study aimed to contribute evidence on the use of IHD and CVVH in patients with severe MALA, particularly in haemodynamically unstable patients. Methods: Data from January 2015 to December 2020 were collected from the Leuven University Hospital. Two separate search methods, based on hospital activity records and laboratory criteria, were used to identify patients with MALA. Patients diagnosed with MALA, receiving extracorporeal treatment within 24 h of admission, were included. Patients were categorized into the IHD and CVVH groups. Patient characteristics, treatment details, and outcomes were analysed. Results: Among 358,148 patient records, 35 MALA cases were identified. IHD was chosen as the initial elimination technique in 13 cases, whereas 22 patients were first commenced on CVVH. Patients treated with CVVH were sicker, had more comorbidities and had higher ventilation and vasopressor requirements. CVVH group had longer vasopressor use, longer ICU stays, and higher in-hospital mortality. Discussion: CVVH rather than IHD seems to be the preferred elimination technique in the more critically ill patients with MALA. Due to its retrospective design, this study failed to identify the superior elimination technique in terms of efficacy. Poorer outcomes in the CVVH group are likely attributed to the severity of illness rather than the inferiority of the elimination therapy. We acknowledge the diagnostic challenges regarding MALA. Using metformin assays could be beneficial in managing these patients. Conclusions: This study suggests clinicians’ preference for CVVH in severe cases of MALA with haemodynamic instability.

Methylene Blue in Metformin Intoxication: Not Just Rescue But Also Initial Treatment.

Metformin (MTF) is a widely used oral antidiabetic medication. Regardless the reason, high doses of MTF cause lactic acidosis as a result of its effects on mitochondrial ATP production and no-mediated vascular smooth muscle relaxation. Metformin-associated lactic acidosis can be life-threatening despite all treatments. Methylene blue (MB) has the potential to reverse the toxic effects of MTF through its effects on both the mitochondrial respiratory chain and nitric oxide production. The use of MB in MTF intoxication has only been reported in a limited number of cases. Herein, we present a 16-year-old female patient who attempted suicide by ingesting high doses of MTF. Supportive treatments, such as vasopressor, inotropic treatments, and sodium bicarbonate, were started in the patient who developed fluid-resistant hypotension after pediatric intensive care unit admission. Because of rising lactate levels, Continuous renal replacement therapy (CRRT) was started immediately. Despite all treatments, hypotension and hyperlactatemia persisted; MB was given as a rescue therapy. Noticeable hemodynamic improvement was observed within 30 minutes of initiating MB infusion, allowing a gradual decrease in the doses of inotropic infusions within the first hour of therapy. Patient's cardiovascular support was discontinued on the second day, and she was discharged on the fifth day. We speculate that, considering the mechanisms of MTF toxicity and the mechanisms of action of MB, it is suggested that early administration of MB, not only as a rescue treatment but as the initial approach to MTF poisoning in combination with other treatments, may result in improved outcomes.

GC–MS analysis of 4-hydroxyproline: elevated proline hydroxylation in metformin-associated lactic acidosis and metformin-treated Becker muscular dystrophy patients

Metformin (N,N-dimethylbiguanide), an inhibitor of gluconeogenesis and insulin sensitizer, is widely used for the treatment of type 2 diabetes. In some patients with renal insufficiency, metformin can accumulate and cause lactic acidosis, known as metformin-associated lactic acidosis (MALA, defined as lactate ≥ 5 mM, pH < 7.35, and metformin concentration > 38.7 µM). Here, we report on the post-translational modification (PTM) of proline (Pro) to 4-hydroxyproline (OH-Pro) in metformin-associated lactic acidosis and in metformin-treated patients with Becker muscular dystrophy (BMD). Pro and OH-Pro were measured simultaneously by gas chromatography–mass spectrometry before, during, and after renal replacement therapy in a patient admitted to the intensive care unit (ICU) because of MALA. At admission to the ICU, plasma metformin concentration was 175 µM, with a corresponding lactate concentration of 20 mM and a blood pH of 7.1. Throughout ICU admission, the Pro concentration was lower compared to healthy controls. Renal excretion of OH-Pro was initially high and decreased over time. Moreover, during the first 12 h of ICU admission, OH-Pro seems to be renally secreted while thereafter, it was reabsorbed. Our results suggest that MALA is associated with hyper-hydroxyprolinuria due to elevated PTM of Pro to OH-Pro by prolyl-hydroxylase and/or inhibition of OH-Pro metabolism in the kidneys. In BMD patients, metformin, at the therapeutic dose of 3 × 500 mg per day for 6 weeks, increased the urinary excretion of OH-Pro suggesting elevation of Pro hydroxylation to OH-Pro. Our study suggests that metformin induces specifically the expression/activity of prolyl-hydroxylase in metformin intoxication and BMD.

Metformin-dolutegravir interaction leads to metformin-associated lactic acidosis: A case report

Metformin, a biguanide, is considered the standard first-line drug for managing type 2 diabetes mellitus (T2DM) patients owing to its safety profile. Despite having a highly safe profile, it is capable of causing serious adverse effects. Biguanides decrease gluconeogenesis from alanine, pyruvate, and lactate, which may result in lactic acidosis. The risk is high in patients with polypharmacy or comorbidities. This is a case of a 48-year-old Indian female with a known case of human immunodeficiency virus (HIV), T2DM, hypothyroidism, and hypertension who presented to the hospital with progressive right-sided weakness for the past 10 days along with transit loss of vision. The patient was diagnosed with multiple central nervous system tuberculomas, for which antitubercular treatment and dexamethasone were started. The patient was on a tenofovir, lamivudine, and dolutegravir regimen for HIV. The patient was started on metformin for sugar control, which led to metformin-associated lactic acidosis. A drug interaction between dolutegravir and metformin was attributed to this. The patient improved after metformin was replaced with glipizide, and lactate levels returned to normal. Lactic acidosis is a rare side effect of metformin. However, the risk of lactic acidosis is high when another drug interferes with metformin pharmacokinetics. Proper assessment and evaluation of potential drug–drug interactions is crucial to assure safe and effective therapy.

Renal manifestations of metformin-associated lactic acidosis; new findings

Renal manifestations of metformin-associated lactic acidosis; new findings

P-29 Metformin poisoning without lactic acidosis: Case report

Abstract Introduction Metformin is the most widely used oral antidiabetic, which belongs to the biguanide pharmacological group. Metformin-associated lactic acidosis (MALA) is a rare event with an incidence of approximately 19 cases per 100,000 patient-years. The risk of developing lactic acidosis, when taking metformin is enhanced by several factors such as: age &amp;gt; 65 years; concomitant diseases that have the ability to induce hypoxemia (chronic renal failure, congestive heart failure, cardiogenic shock, severe lung disease, sepsis, advanced liver disease, history of lactic acidosis); an excessive alcohol consumption; an administration of iodinated contrast agents. Clinical Case A 46-year-old man was urgently admitted with the following symptoms: drowsiness, repeated vomiting, lethargy, dizziness. The symptoms started after he administered outpatient and at own initiative 50 tablets of metformin, each tablet contains a dose of 500 mg (total dose 25g). Concomitant pathologies: diagnosed with Type 2 Diabetes for 8 years; Toxic liver cirrhosis, compensated Child-Pugh A (recently diagnosed); hypertension; CKD G3aA2 KDIGO. The patient's condition at admission was assessed as extremely serious, Glasgow scale - 11 points, mild hypertension, tachycardia, tachypnea. The paraclinical investigations revealed the presence of metabolic acidosis, but with lactate &amp;lt;5 mmol/l; the progressive renal dysfunction with creatinine values in the first 24 hours up to 1184 µmol/l, urea – 24.5 mmol/l; a severe hypoglycemia - 1.68 mmol/l; a moderate cytolytic syndrome; a cholestatic syndrome, an inflammatory and hepatoprive syndrome; coagulation disorders; a pancreatic dysfunction. In the context of the evident increase of urea and creatinine, the decision was made to initiate the intermittent hemodialysis, a total of 14 sessions were required during hospitalization. The particularity of this case is represented by the absence of lactic acidosis, despite metformin intoxication with altered neurological status, acute renal failure, developed due to chronic kidney disease, liver cirrhosis of toxic etiology and severe hypoglycemia. Conclusion Metformin should be administered with caution in patients with multiple comorbidities. Metformin intoxication can induce lactic acidosis with an increased risk of serious, potentially fatal adverse events. It is essential to identify metformin intoxication as early as possible, with prompt initiation of renal replacement measures and dynamic monitoring of biochemical parameters.

Analysis of Metformin-Associated Lactic Acidosis using the Japanese Adverse Drug Event Report Database

Analysis of Metformin-Associated Lactic Acidosis using the Japanese Adverse Drug Event Report Database

Metformin-Associated Lactic Acidosis Precipitated by an Acute Obstructing Ureteral Stone in a Patient with a Single Functioning Kidney

A 35-year-old male with type-2 diabetes mellitus and a history of insulin and metformin (2,000 mg/day) use presented to the emergency department (ED) with generalized weakness. Abdominal computed tomography (CT) performed 3 months prior to presentation showed a severely atrophic right kidney and a few tiny stones in the left kidney, with a serum level of creatinine of 1.14 mg/dL. At the ED, the patient’s blood pressure was 153/89 mmHg. Workup revealed acute kidney injury (creatinine, 11.97 mg/dL), high-anion-gap metabolic acidosis (pH, 6.93), and a blood lactic acid level &gt; 15 mmol/L. Based on the medication history, the patient was diagnosed with metformin-associated lactic acidosis. CT showed a left distal ureteral stone, measuring 6 mm in size, which resulted in hydroureteronephrosis. The patient was initially treated with continuous renal replacement therapy. Subsequently, left percutaneous nephrostomy was performed, which led to the return of the creatinine level to baseline, with complete resolution of lactic acidosis.

Metformin-Associated Lactic Acidosis-Is This on Your Radar?

Background: Metformin is a biguanide hyperglycemic agent used to manage non–insulin-dependent diabetes mellitus. Adverse reactions include mainly mild gastrointestinal adverse effects, but severe complications, such as metformin-associated lactic acidosis (MALA) can occur. Metformin is excreted renally and, therefore, not recommended in patients with renal impairment. The reported incidence of MALA is 3 cases per 100,000 patient-years. Case ReportA 79-year-old woman with a complex medical history, including end-stage renal disease on dialysis and type 2 diabetes, presented to the emergency department (ED) for altered mental status. Prior to arrival, she was found to be hypoglycemic. Her laboratory results were significant for creatinine of 6.56 mg/dL and an anion gap of 52 mmol/L. The venous blood gas revealed a venous pH of 6.857 [reference range (7.32–7.43)], pCO2 of 15.9 mm Hg (40.6–60 mm Hg), HCO3 of 2.7 mmol/L (21–30 mmol/L), lactate of 27 mmol/L (0.5–2 mmol/L), and ammonia of 233 µmol/L. The patient was dialyzed emergently in the ED; repeat laboratory test results showed blood urea nitrogen of 10 mg/dL, creatinine of 1.65 mg/dL, carbon dioxide of 26 mmol/L, and anion gap of 13 mmol/L. The repeat ammonia was 16 µmol/L. The patient's metabolic encephalopathy resolved, and she was discharged home on hospital day 3. Why Should an Emergency Physician Be Aware of This?MALA has a high mortality rate (36%). Laboratory markers have not been found to be a reliable predictor of mortality. Sodium bicarbonate is controversial, but a pH < 7.15 indicates consideration of its use. A pH < 7.1 and a lactate level > 20 mmol/L indicate the need for emergent hemodialysis. Prompt recognition and management in the ED with early hemodialysis can result in good patient outcomes, with a return to their baseline function despite severe laboratory findings.

Reversible acute blindness in suspected metformin-associated lactic acidosis: a case report

BackgroundMetformin is commonly used for the treatment of type 2 diabetes mellitus. Its multiple advantages include low risk of hypoglycemia, weight neutrality, low cost, and cardioprotective and anti-inflammatory effects. Renal insufficiency is one of the contraindications for its use. Inadvertent prescription in patients with renal insufficiency may lead to metformin-associated lactic acidosis, which brings a high risk of mortality. The early recognition and management of metformin-associated lactic acidosis are essential.Case reportWe present the case of a 58-year-old Hui woman with a history of type 2 diabetes mellitus with nephropathy and heart disease for which she was treated with metformin, insulin, and heart medications. She developed nausea, vomiting, anion gap metabolic acidosis due to hyperlactatemia, and acute kidney injury. She was hospitalized to receive intravenous hydration and correction of metabolic acidosis after she suddenly developed blindness. The diagnostic workup ruled out central causes and her symptoms resolved briefly after continuous venovenous hemodialysis was initiated, confirming the diagnosis of metformin-associated lactic acidosis.ConclusionsMetabolic disruption can cause acute blindness. Metabolic acidosis in a patient with a history of metformin intake should suggest the possibility of metformin-associated lactic acidosis, which must be treated immediately, without waiting for the results of other examinations, especially in patients with sudden blindness. Further study of reversible blindness-associated severe metabolic acidosis is needed.

Successful Treatment of a Rare Profound Lactic Acidosis and Anuric AKI due to Metformin-Associated Lactic Acidosis

Successful Treatment of a Rare Profound Lactic Acidosis and Anuric AKI due to Metformin-Associated Lactic Acidosis