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BMJ Case Reports Jul 2021A 58-year-old female with known type 2 diabetes mellitus continued to take her usual medications, including metformin, an ACE inhibitor and a non-steroidal...
A 58-year-old female with known type 2 diabetes mellitus continued to take her usual medications, including metformin, an ACE inhibitor and a non-steroidal anti-inflammatory drug, while suffering from diarrhoea and vomiting. On presentation to the emergency department, she was found to have a profound lactic acidosis, cardiovascular instability and acute kidney injury. Despite a pH of 6.6, lactate of 14 mmol/L and a brief asystolic cardiac arrest, supportive treatment and the use of renal replacement therapy resulted in rapid improvement in her acid-base abnormalities and haemodynamic parameters. Metformin-associated lactic acidosis is a rare but life-threatening complication of diabetes management. Patient education and awareness amongst clinicians are paramount in the prevention and treatment of this condition.
Topics: Acidosis, Lactic; Acute Kidney Injury; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Metformin; Middle Aged
PubMed: 34244196
DOI: 10.1136/bcr-2020-239154 -
International Journal of Molecular... Jul 2022Metformin, a molecule belonging to the biguanide family, represents one of the most commonly prescribed medications for the treatment of diabetes mellitus in the world.... (Review)
Review
Metformin, a molecule belonging to the biguanide family, represents one of the most commonly prescribed medications for the treatment of diabetes mellitus in the world. Over the sixty years during which it has been used, many benefits have been described, which are not limited to the treatment of diabetes mellitus. However, since metformin is similar to other members of the same drug family, there is still much concern regarding the risk of lactic acidosis. This article aims to highlight the correlation between the use of metformin and the onset of renal damage or lactic acidosis. Metformin-associated lactic acidosis exists; however, it is rare. The appropriate use of the drug, under safe conditions, induces benefits without risks.
Topics: Acidosis, Lactic; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fear; Humans; Hypoglycemic Agents; Metformin
PubMed: 35955455
DOI: 10.3390/ijms23158320 -
Kidney International Jan 2020L-lactic acidosis (L-LA) is the most common cause of metabolic acidosis in the critical care setting, which has been associated with a large increase in mortality. The... (Review)
Review
L-lactic acidosis (L-LA) is the most common cause of metabolic acidosis in the critical care setting, which has been associated with a large increase in mortality. The purpose of this article is to provide clinicians with an overview of the biochemical and metabolic background required to understand the different pathophysiological mechanisms that may lead to the development of L-LA. We propose a classification based on whether the pathophysiology of L-LA is due predominantly to increased production or decreased removal of L-lactic acid. In this article, we provide an overview of the biochemical and metabolic aspects of glucose oxidation, the production and removal of L-lactic acid, and a discussion of the pathophysiology of the various causes of L-LA.
Topics: Acidosis, Lactic; Anions; Bicarbonates; Citric Acid Cycle; Critical Illness; Electron Transport Chain Complex Proteins; Gluconeogenesis; Glucose; Glycolysis; Hospital Mortality; Humans; Hydrogen-Ion Concentration; Hypoxia; Intensive Care Units; Kidney; Lactic Acid; Liver; Muscle, Skeletal; Oxidation-Reduction; Oxidative Phosphorylation; Oxygen
PubMed: 31784049
DOI: 10.1016/j.kint.2019.08.023 -
Kidney & Blood Pressure Research 2020The etiology of acute metabolic acidosis (aMA) is heterogeneous, and the consequences are potentially life-threatening. The aim of this article was to summarize the...
BACKGROUND
The etiology of acute metabolic acidosis (aMA) is heterogeneous, and the consequences are potentially life-threatening. The aim of this article was to summarize the causes and management of aMA from a clinician's perspective.
SUMMARY
We performed a systematic search on PubMed, applying the following search terms: "acute metabolic acidosis," "lactic acidosis," "metformin" AND "acidosis," "unbalanced solutions" AND "acidosis," "bicarbonate" AND "acidosis" AND "outcome," "acute metabolic acidosis" AND "management," and "acute metabolic acidosis" AND "renal replacement therapy (RRT)/dialysis." The literature search did not consider diabetic ketoacidosis at all. Lactic acidosis evolves from various conditions, either with or without systemic hypoxia. The incidence of metformin-associated aMA is actually quite low. Unbalanced electrolyte preparations can induce hyperchloremic aMA. The latter potentially worsens kidney-related outcome parameters. Nevertheless, prospective and controlled data are missing at the moment. Recently, bicarbonate has been shown to improve clinically relevant endpoints in the critically ill, even if higher pH values (>7.3) are targeted. New therapeutics for aMA control are under development, since bicarbonate treatment can induce serious side effects. Key Messages: aMA is a frequent and potentially life-threatening complication of various conditions. Lactic acidosis might occur even in the absence of systemic hypoxia. The incidence of metformin-associated aMA is comparably low. Unbalanced electrolyte solutions induce hyperchloremic aMA, which most likely worsens the renal prognosis of critically ill patients. Bicarbonate, although potentially deleterious due to increased carbon dioxide production with subsequent intracellular acidosis, improves kidney-related endpoints in the critically ill.
Topics: Acidosis; Acidosis, Lactic; Acute Disease; Animals; Bicarbonates; Disease Management; Electrolytes; Humans; Hypoglycemic Agents; Metformin
PubMed: 32663831
DOI: 10.1159/000507813 -
Journal of Clinical and Experimental... 2022The management of diabetes in cirrhosis and liver transplantation can be challenging. There is difficulty in diagnosis and monitoring of diabetes as fasting blood sugar... (Review)
Review
The management of diabetes in cirrhosis and liver transplantation can be challenging. There is difficulty in diagnosis and monitoring of diabetes as fasting blood sugar values are low and glycosylated hemoglobin may not be a reliable marker. The challenges in the management of diabetes in cirrhosis include the likelihood of cognitive impairment, risk of hypoglycemia, altered drug metabolism, frequent renal dysfunction, risk of lactic acidosis, and associated malnutrition and sarcopenia. Moreover, calorie restriction and an attempt to lose weight in obese diabetics may be associated with a worsening of sarcopenia. Many commonly used antidiabetic drugs may be unsafe or be associated with a high risk of hypoglycemia in cirrhotics. Post-transplant diabetes is common and may be contributed by immunosuppressive medication. There is inadequate clinical data on the use of antidiabetic drugs in cirrhosis, and the management of diabetes in cirrhosis is hampered by the lack of guidelines focusing on this issue. The current review aims at addressing the practical management of diabetes by a hepatologist.
PubMed: 35535116
DOI: 10.1016/j.jceh.2021.09.010 -
The Journal of Emergency Medicine Aug 2023The use of sodium bicarbonate to treat metabolic acidosis is intuitive, yet data suggest that not all patients benefit from this therapy. (Review)
Review
BACKGROUND
The use of sodium bicarbonate to treat metabolic acidosis is intuitive, yet data suggest that not all patients benefit from this therapy.
OBJECTIVE
In this narrative review, we describe the physiology behind commonly encountered nontoxicologic causes of metabolic acidosis, highlight potential harm from the indiscriminate administration of sodium bicarbonate in certain scenarios, and provide evidence-based recommendations to assist emergency physicians in the rational use of sodium bicarbonate.
DISCUSSION
Sodium bicarbonate can be administered as a hypertonic push, as a resuscitation fluid, or as an infusion. Lactic acidosis and cardiac arrest are two common scenarios where there is limited benefit to routine use of sodium bicarbonate, although certain circumstances, such as patients with concomitant acute kidney injury and lactic acidosis may benefit from sodium bicarbonate. Patients with cardiac arrest secondary to sodium channel blockade or hyperkalemia also benefit from sodium bicarbonate therapy. Recent data suggest that the use of sodium bicarbonate in diabetic ketoacidosis does not confer improved patient outcomes and may cause harm in pediatric patients. Available evidence suggests that alkalinization of urine in rhabdomyolysis does not improve patient-centered outcomes. Finally, patients with a nongap acidosis benefit from sodium bicarbonate supplementation.
CONCLUSIONS
Empiric use of sodium bicarbonate in patients with nontoxicologic causes of metabolic acidosis is not warranted and likely does not improve patient-centered outcomes, except in select scenarios. Emergency physicians should reserve use of this medication to conditions with clear benefit to patients.
Topics: Humans; Child; Bicarbonates; Sodium Bicarbonate; Acidosis, Lactic; Acidosis; Heart Arrest
PubMed: 37442665
DOI: 10.1016/j.jemermed.2023.04.012 -
Biomedicine & Pharmacotherapy =... Jun 2021Metformin is an oral antihyperglycemic drug widely used to treat type 2 diabetes mellitus (T2DM), acting via indirect activation of 5' Adenosine monophosphate-activated... (Review)
Review
Metformin is an oral antihyperglycemic drug widely used to treat type 2 diabetes mellitus (T2DM), acting via indirect activation of 5' Adenosine monophosphate-activated Protein Kinase (AMPK). Beyond the anti-diabetic effect, accumulative pieces of evidence have revealed that metformin also everts a beneficial effect in diverse kidney diseases. In various acute kidney diseases (AKI) animal models, metformin protects renal tubular cells from inflammation, apoptosis, reactive oxygen stress (ROS), endoplasmic reticulum (ER) stress, epithelial-mesenchymal transition (EMT) via AMPK activation. In diabetic kidney disease (DKD), metformin also alleviates podocyte loss, mesangial cells apoptosis, and tubular cells senescence through AMPK-mediated signaling pathways. Besides, metformin inhibits cystic fibrosis transmembrane conductance regulator (CFTR)-mediated fluids secretion and the mammalian target of rapamycin (mTOR)-involved cyst formation negatively regulated by AMPK in autosomal dominant polycystic kidney disease (APDKD). Furthermore, metformin also contributes to the alleviation of urolithiasis and renal cell carcinoma (RCC). As the common pathway for chronic kidney disease (CKD) progressing towards end-stage renal disease (ESRD), renal fibrosis is ameliorated by metformin, to a great extent dependent on AMPK activation. However, clinical data are not always consistent with preclinical data, some clinical investigations showed the unmeaningful even detrimental effect of metformin on T2DM patients with kidney diseases. Most importantly, metformin-associated lactic acidosis (MALA) is a vital issue restricting the application of metformin. Thus, we conclude the application of metformin in kidney diseases and uncover the underlying molecular mechanisms in this review.
Topics: AMP-Activated Protein Kinases; Acidosis, Lactic; Animals; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Endoplasmic Reticulum Stress; Humans; Hypoglycemic Agents; Kidney Diseases; Metformin; Observational Studies as Topic; Retrospective Studies; TOR Serine-Threonine Kinases
PubMed: 33714781
DOI: 10.1016/j.biopha.2021.111454 -
AJNR. American Journal of Neuroradiology May 2023An increased number of pathogenic variants have been described in mitochondrial encephalomyopathy lactic acidosis and strokelike episodes (MELAS). Different imaging... (Review)
Review
BACKGROUND AND PURPOSE
An increased number of pathogenic variants have been described in mitochondrial encephalomyopathy lactic acidosis and strokelike episodes (MELAS). Different imaging presentations have emerged in parallel with a growing recognition of clinical and outcome variability, which pose a diagnostic challenge to neurologists and radiologists and may impact an individual patient's response to therapeutic interventions. By evaluating clinical, neuroimaging, laboratory, and genetic findings, we sought to improve our understanding of the sources of potential phenotype variability in patients with MELAS.
MATERIALS AND METHODS
This retrospective single-center study included individuals who had confirmed mitochondrial DNA pathogenic variants and a diagnosis of MELAS and whose data were reviewed from January 2000 through November 2021. The approach included a review of clinical, neuroimaging, laboratory, and genetic data, followed by an unsupervised hierarchical cluster analysis looking for sources of phenotype variability in MELAS. Subsequently, experts identified "victory-variables" that best differentiated MELAS cohort clusters.
RESULTS
Thirty-five patients with a diagnosis of mitochondrial DNA-based MELAS (median age, 12 years; interquartile range, 7-24 years; 24 female) were eligible for this study. Fifty-three discrete variables were evaluated by an unsupervised cluster analysis, which revealed that two distinct phenotypes exist among patients with MELAS. After experts reviewed the variables, they selected 8 victory-variables with the greatest impact in determining the MELAS subgroups: developmental delay, sensorineural hearing loss, vision loss in the first strokelike episode, Leigh syndrome overlap, age at the first strokelike episode, cortical lesion size, regional brain distribution of lesions, and genetic groups. Ultimately, 2-step differentiating criteria were defined to classify atypical MELAS.
CONCLUSIONS
We identified 2 distinct patterns of MELAS: classic MELAS and atypical MELAS. Recognizing different patterns in MELAS presentations will enable clinical and research care teams to better understand the natural history and prognosis of MELAS and identify the best candidates for specific therapeutic interventions.
Topics: Female; Humans; Acidosis, Lactic; MELAS Syndrome; Retrospective Studies; Stroke; DNA, Mitochondrial; Phenotype
PubMed: 37024306
DOI: 10.3174/ajnr.A7837