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Ugeskrift For Laeger Aug 2021It is a common but flawed presumption that blood lactate reflects the lactic acid production in the body's tissues. Lactate is formed directly from pyruvate and... (Review)
Review
It is a common but flawed presumption that blood lactate reflects the lactic acid production in the body's tissues. Lactate is formed directly from pyruvate and functions to dampen reductions in intracellular pH through lactate-H+ cotransport to the extracellular space. Though this may give rise to elevated blood lactate, increased lactate production is not the cause of metabolic acidosis in such instances. "Lactic acidosis" is thus an inappropriate term as it indicates causality and in this review, we suggest that in the future, the term "hyperlactataemia-associated metabolic acidosis" should be used instead.
Topics: Acidosis; Acidosis, Lactic; Humans; Lactic Acid
PubMed: 34477100
DOI: No ID Found -
PLoS Pathogens Jan 2021Lactic acidosis and hyperlactatemia are common metabolic disturbances in patients with severe malaria. Lactic acidosis causes physiological adverse effects, which can... (Review)
Review
Lactic acidosis and hyperlactatemia are common metabolic disturbances in patients with severe malaria. Lactic acidosis causes physiological adverse effects, which can aggravate the outcome of malaria. Despite its clear association with mortality in malaria patients, the etiology of lactic acidosis is not completely understood. In this review, the possible contributors to lactic acidosis and hyperlactatemia in patients with malaria are discussed. Both increased lactate production and impaired lactate clearance may play a role in the pathogenesis of lactic acidosis. The increased lactate production is caused by several factors, including the metabolism of intraerythrocytic Plasmodium parasites, aerobic glycolysis by activated immune cells, and an increase in anaerobic glycolysis in hypoxic cells and tissues as a consequence of parasite sequestration and anemia. Impaired hepatic and renal lactate clearance, caused by underlying liver and kidney disease, might further aggravate hyperlactatemia. Multiple factors thus participate in the etiology of lactic acidosis in malaria, and further investigations are required to fully understand their relative contributions and the consequences of this major metabolic disturbance.
Topics: Acidosis, Lactic; Humans; Malaria; Plasmodium
PubMed: 33411818
DOI: 10.1371/journal.ppat.1009122 -
Acta Clinica Belgica 2011
Topics: Acidosis, Lactic; Acute Kidney Injury; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Metformin
PubMed: 22145266
DOI: 10.2143/ACB.66.5.2062583 -
The American Journal of the Medical... Mar 2015: Metformin is the most commonly prescribed oral antidiabetic agent. Despite a good safety profile in most patients with diabetes, the risk of metformin-associated... (Review)
Review
: Metformin is the most commonly prescribed oral antidiabetic agent. Despite a good safety profile in most patients with diabetes, the risk of metformin-associated lactic acidosis is real if safety guidelines are ignored. Experience with 3 cases of metformin-associated lactic acidosis is reported. Two cases were caused by inappropriate use of metformin in the presence of renal, cardiac and hepatic failure and 1 case followed an intentional overdose. The literature was reviewed on the clinical presentation, prevalence, pathogenesis, prognosis and management of metformin-associated lactic acidosis. This report highlights the importance of proper patient selection, clinical and laboratory monitoring and recommendation on when to stop the drug in ambulatory and hospitalized patients to prevent this unusual but potentially lethal complication.
Topics: Acidosis, Lactic; Aged; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged
PubMed: 24326619
DOI: 10.1097/MAJ.0b013e3182a562b7 -
Journal of Nephrology Aug 2021Metformin is currently considered a first-line therapy in type 2 diabetic patients. After issuing warnings for decades about the risks of lactic acidosis in patients... (Review)
Review
Metformin is currently considered a first-line therapy in type 2 diabetic patients. After issuing warnings for decades about the risks of lactic acidosis in patients with chronic nephropathy, metformin is now being re-evaluated. The most recent evidence from the literature has demonstrated both a low, acceptable risk of lactic acidosis and a series of favorable effects, which go beyond its hypoglycemic activity. Patients treated with metformin show a significant mortality reduction and lower progression towards end-stage renal disease in comparison with those treated with other hypoglycemic drugs. Concerning lactic acidosis, in the last few years it has been shown how lactic acidosis almost always developed when patients kept taking the drug in the face of a concomitant disease or situation such as sepsis, fever, diarrhea, vomiting, which reduced metformin renal clearance. Actually, clearance of metformin is mainly renal, both by glomerular filtration and tubular secretion (apparent clearance 933-1317 ml/min, half-life < 3 h). As regards treatment, in cases of lactic acidosis complicated by acute kidney injury, continuous renal replacement therapy (CRRT) plays a crucial role. Besides the elimination of metformin, CRRT improves survival by correcting acidosis, electrolyte alterations, and maintaining fluid balance. Lactic acidosis almost always develops because of preventable drug accumulation. Therefore, prevention is a key factor. Patients should be aware that discontinuation for a limited time does not affect their health, even when it may be inappropriate, but it may avoid a serious, potentially fatal adverse event.
Topics: Acidosis, Lactic; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Kidney Failure, Chronic; Metformin; Nephrologists
PubMed: 33373028
DOI: 10.1007/s40620-020-00941-8 -
Tidsskrift For Den Norske Laegeforening... Feb 2023Metformin accumulation is associated with lactic acidosis and haemodynamic instability.
BACKGROUND
Metformin accumulation is associated with lactic acidosis and haemodynamic instability.
CASE PRESENTATION
A woman in her seventies with diabetes, renal failure and hypertension presented unresponsive with severe acidosis, lactataemia, bradycardia and hypotension. After the initial survey, hypotension and bradycardia were noted before she went into cardiac arrest. After resuscitation and intubation, she was moved to the intensive care unit for dialysis and supportive care. After seven hours of dialysis, her hypotension persisted despite treatment with high levels of aminopressors. Methylene blue was given, and within hours the haemodynamic situation stabilised. She was successfully extubated the next day and has fully recovered.
INTERPRETATION
Methylene blue might be a valuable adjunct to dialysis in patients with metformin accumulation and lactic acidosis where other vasopressors cannot provide adequate peripheral vascular resistance.
Topics: Female; Humans; Acidosis, Lactic; Bradycardia; Hypoglycemic Agents; Hypotension; Metformin; Methylene Blue; Aged
PubMed: 36811419
DOI: 10.4045/tidsskr.22.0719 -
Minerva Anestesiologica Apr 2003The detection of tissue hypoxia and its correction is one of the aim of the hemodynamic monitoring. Classical hemodynamic variable often fail to achieve this goal.... (Review)
Review
The detection of tissue hypoxia and its correction is one of the aim of the hemodynamic monitoring. Classical hemodynamic variable often fail to achieve this goal. Lactate measurements may be a good indicator of tissue hypoxia. Selected review of the articles on lactate in critically ill patients. Tissue hypoxia is associated with an increase in blood lactate levels. However lactate can also be produced in aerobic conditions, in inflammated tissues, and lactate clearance is often decreased in critically ill patients. Whatever its origin, blood lactate levels have a strong predictive value. The interpretation of blood lactate levels is difficult. Nevertheless, monitoring blood lactate levels can be useful to detect tissue hypoxia and to monitor the effects of therapy.
Topics: Acidosis, Lactic; Aerobiosis; Anaerobiosis; Humans; Lactates; Prognosis; Sepsis
PubMed: 12766720
DOI: No ID Found -
PloS One 2022Metformin-associated lactic acidosis (MALA) is a rare event but underrecognition may lead to unfavorable outcomes in type 2 diabetes patients. While many risk factors of... (Observational Study)
Observational Study
BACKGROUND
Metformin-associated lactic acidosis (MALA) is a rare event but underrecognition may lead to unfavorable outcomes in type 2 diabetes patients. While many risk factors of MALA have been identified, how to reduce mortality from MALA is a matter of debate. This study aimed to explore the factors associated with 30-day mortality amongst MALA patients.
METHODS
An observational study enrolled patients diagnosed with MALA between January 2014 and December 2017. MALA was defined by a history of metformin administration, metabolic acidosis (arterial blood gas pH <7.35 or HCO3 <15 mmol/L), and elevated plasma lactate level (>5 mmol/L). We examined risk factors including age, sex, underlying diseases, current medications, blood tests, disease severity, and dialysis data. Mortality status was identified from medical records or report on telephone.
RESULTS
We included 105 MALA patients. Most patients (95.2%) were diagnosed acute kidney injury stage 3 according to KDIGO 2012 definition. The 30-day mortality rate was 36.2% and dialysis rate was 85.7%. The survivors had higher proportions of underlying chronic kidney disease, presence of metabolic acidosis, receiving renal replacement therapy within 6 hours, and haemodialysis, whereas the non-survivors had higher percentage of hypertension and disease severity. Lower APACHE II score (HR = 0.95; 95%CI, 0.91-0.99; p = 0.038), time to dialysis < 6 hours (0.31; 0.14-0.69; 0.004), and haemodialysis (0.20;0.06-0.67; 0.010) were associated with lower 30-day mortality, using multivariate Cox-regression analysis.
CONCLUSIONS
Mortality rate amongst patients with MALA was high. Early dialysis treatment within 6 hours after admission and haemodialysis were independently associated with lower 30-day mortality. The large scale, well-designed studies need to confirm these encouraging results.
Topics: Acidosis, Lactic; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Renal Dialysis
PubMed: 36040976
DOI: 10.1371/journal.pone.0273678 -
Clinical Medicine (London, England) Nov 2023Lactic acidosis is commonly associated with tissue hypoperfusion and gives rise to concern regarding hypoxia or underlying hypotension. In the cancer patient, especially...
Lactic acidosis is commonly associated with tissue hypoperfusion and gives rise to concern regarding hypoxia or underlying hypotension. In the cancer patient, especially one undergoing chemotherapy, there is always concern for sepsis; however, in the otherwise clincially stable patient with cancer, type B lactic acidosis can also be related to their underlying malignancy. It is considered a haematological emergency given its high mortality rate. However, despite the urgency to treat type B lactic acidosis in these circumstances, treatment options beyond treatment of the malignancy are limited, and its presence portends a poor prognosis. This case highlights our current understanding of type B lactic acidosis and an approach to lactic acidosis evaluation in the cancer patient.
Topics: Humans; Acidosis, Lactic; Neoplasms; Sepsis
PubMed: 38065594
DOI: 10.7861/clinmed.2023-0391 -
Biochimica Et Biophysica Acta. Reviews... Apr 2019While cancer is commonly described as "a disease of the genes", it is also a disease of metabolism. Indeed, carcinogenesis and malignancy are highly associated with... (Review)
Review
While cancer is commonly described as "a disease of the genes", it is also a disease of metabolism. Indeed, carcinogenesis and malignancy are highly associated with metabolic re-programming, and there is clinical evidence that interrupting a cancer's metabolic program can improve patients' outcomes. Notably, many of the metabolic adaptations observed in cancer are similar to the same perturbations observed in diabetic patients. For example, metformin is commonly used to reduce hyperglycemia in diabetic patients, and has been demonstrated to reduce cancer incidence. Treatment with PI3K inhibitors can induce hyperinsulinemia, which can blunt therapeutic efficacy if unchecked. While commonalities between metabolism in cancer and diabetes have been extensively reviewed, here we examine a less explored and emergent convergence between diabetic and cancer metabolism: the generation of lactic acid and subsequent acidification of the surrounding microenvironment. Extracellular lactic acidosis is integral in disease manifestation and is a negative prognostic in both disease states. In tumors, this results in important sequela for cancer progression including increased invasion and metastasis, as well as inhibition of immune surveillance. In diabetes, acidosis impacts the ability of insulin to bind to its receptor, leading to peripheral resistance and an exacerbation of symptoms. Thus, acidosis may be a relevant therapeutic target, and we describe three approaches for targeting: buffers, nanomedicine, and proton pump inhibitors.
Topics: Acidosis, Lactic; Animals; Buffers; Diabetes Mellitus; Humans; Nanomedicine; Neoplasms; Proton Pump Inhibitors
PubMed: 30708040
DOI: 10.1016/j.bbcan.2019.01.003