-
The American Journal of Emergency... Oct 2023Metformin toxicity is a rare but serious condition that carries with it a high rate of morbidity and mortality. (Review)
Review
INTRODUCTION
Metformin toxicity is a rare but serious condition that carries with it a high rate of morbidity and mortality.
OBJECTIVE
This review highlights the pearls and pitfalls of metformin toxicity, including diagnosis, initial resuscitation, and management in the emergency department (ED) based on current evidence.
DISCUSSION
Metformin is a common medication used for treatment of diabetes mellitus. Metformin toxicity is a spectrum of conditions that may be differentiated into three subgroups: metformin-associated lactic acidosis (MALA), metformin-induced lactic acidosis (MILA), and metformin-unrelated lactic acidosis (MULA). MILA is a condition found predominantly in patients chronically taking metformin or those with large acute overdoses. Conversely, MULA occurs in patients on metformin but with a critical illness stemming from a separate cause. MALA is rare but the most severe form, with mortality rates that reach 50%. Differentiating these entities is difficult in the ED setting without obtaining metformin levels. Patients with metformin toxicity present with nonspecific gastrointestinal symptoms and vital sign abnormalities. Laboratory analysis will reveal a high lactate with anion gap metabolic acidosis. Patients presenting with elevated lactate levels in the setting of metformin use should be considered at risk for the most severe form, MALA. Patients with MALA require aggressive treatment with intravenous fluids, treatment of any concomitant condition, and early consideration of hemodialysis, along with specialist consultation such as nephrology and toxicology.
CONCLUSIONS
An understanding of metformin toxicity can assist emergency clinicians in diagnosing and managing this potentially deadly disease.
Topics: Humans; Metformin; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Acidosis, Lactic; Prevalence; Lactic Acid
PubMed: 37517113
DOI: 10.1016/j.ajem.2023.07.020 -
Nephrology, Dialysis, Transplantation :... Dec 2021Metabolic acidosis, defined as a plasma or serum bicarbonate concentration <22 mmol/L, is a frequent consequence of chronic kidney disease (CKD) and occurs in ~10-30% of... (Review)
Review
Metabolic acidosis, defined as a plasma or serum bicarbonate concentration <22 mmol/L, is a frequent consequence of chronic kidney disease (CKD) and occurs in ~10-30% of patients with advanced stages of CKD. Likewise, in patients with a kidney transplant, prevalence rates of metabolic acidosis range from 20% to 50%. CKD has recently been associated with cognitive dysfunction, including mild cognitive impairment with memory and attention deficits, reduced executive functions and morphological damage detectable with imaging. Also, impaired motor functions and loss of muscle strength are often found in patients with advanced CKD, which in part may be attributed to altered central nervous system (CNS) functions. While the exact mechanisms of how CKD may cause cognitive dysfunction and reduced motor functions are still debated, recent data point towards the possibility that acidosis is one modifiable contributor to cognitive dysfunction. This review summarizes recent evidence for an association between acidosis and cognitive dysfunction in patients with CKD and discusses potential mechanisms by which acidosis may impact CNS functions. The review also identifies important open questions to be answered to improve prevention and therapy of cognitive dysfunction in the setting of metabolic acidosis in patients with CKD.
Topics: Acidosis; Bicarbonates; Cognitive Dysfunction; Humans; Motor Disorders; Renal Insufficiency, Chronic
PubMed: 34718761
DOI: 10.1093/ndt/gfab216 -
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 -
Pediatric Nephrology (Berlin, Germany) Dec 2023Metabolic acidosis is a risk factor for faster kidney function decline in chronic kidney disease (CKD) and in adult kidney transplant recipients (KTRs). We hypothesized...
BACKGROUND
Metabolic acidosis is a risk factor for faster kidney function decline in chronic kidney disease (CKD) and in adult kidney transplant recipients (KTRs). We hypothesized that metabolic acidosis would be highly prevalent and associated with worse allograft function in pediatric KTRs.
METHODS
Pediatric KTRs at Montefiore Medical Center from 2010 to 2018 were included. Metabolic acidosis was defined as serum bicarbonate < 22 mEq/L or receiving alkali therapy. Regression models were adjusted for demographic factors and donor/recipient characteristics.
RESULTS
Sixty-three patients were identified with a median age at transplant of 10.5 (interquartile range (IQR) 4.4-15.2) years and post-transplant follow-up of 3 (IQR 1-5) years. Baseline serum bicarbonate was 21.7 ± 2.4 mEq/L, serum bicarbonate < 22 mEq/L was present in 28 (44%), and 44% of all patients were receiving alkali therapy. The prevalence of acidosis ranged from 58 to 70% during the first year of follow-up. At baseline, each 1-year higher age at transplant and every 10 ml/min/1.73 m higher eGFR were associated with 0.16 mEq/L (95% CI: 0.03-0.3) and 0.24 mEq/L (95% CI: 0.01-0.5) higher serum bicarbonate, respectively. Older age at transplant was associated with lower odds of acidosis (OR: 0.84; 95% CI: 0.72-0.97). During follow-up, metabolic acidosis was independently associated with 8.2 ml/min/1.73 m (95% CI 4.4-12) lower eGFR compared to not having acidosis; furthermore, eGFR was significantly lower among KTRs with unresolved acidosis compared with resolved acidosis.
CONCLUSIONS
Among pediatric KTRs, metabolic acidosis was highly prevalent in the first year post-transplantation and was associated with lower eGFR during follow-up. A higher resolution version of the Graphical abstract is available as Supplementary information.
Topics: Adult; Humans; Child; Child, Preschool; Adolescent; Kidney Transplantation; Bicarbonates; Acidosis; Renal Insufficiency, Chronic; Transplant Recipients; Alkalies
PubMed: 37422606
DOI: 10.1007/s00467-023-06072-z -
Nature Materials Oct 2021Therapeutic outcomes in oncology may be aided by precision diagnostics that offer early detection, localization and the opportunity to monitor response to therapy. Here,...
Therapeutic outcomes in oncology may be aided by precision diagnostics that offer early detection, localization and the opportunity to monitor response to therapy. Here, we report a multimodal nanosensor engineered to target tumours through acidosis, respond to proteases in the microenvironment to release urinary reporters and (optionally) carry positron emission tomography probes to enable localization of primary and metastatic cancers in mouse models of colorectal cancer. We present a paradigm wherein this multimodal sensor can be employed longitudinally to assess burden of disease non-invasively, including tumour progression and response to chemotherapy. Specifically, we showed that acidosis-mediated tumour insertion enhanced on-target release of matrix metalloproteinase-responsive reporters in urine. Subsequent on-demand loading of the radiotracer Cu allowed pH-dependent tumour visualization, enabling enriched microenvironmental characterization when compared with the conventional metabolic tracer F-fluorodeoxyglucose. Through tailored target specificities, this modular platform has the capacity to be engineered as a pan-cancer test that may guide treatment decisions for numerous tumour types.
Topics: Acidosis; Animals; Colorectal Neoplasms; Disease Progression; Female; Fluorodeoxyglucose F18; Mice; Mice, Inbred BALB C; Multimodal Imaging; Positron-Emission Tomography; Precision Medicine; Tumor Microenvironment
PubMed: 34267368
DOI: 10.1038/s41563-021-01042-y -
Advances in Chronic Kidney Disease Jul 2022
Topics: Acidosis; Humans
PubMed: 36175069
DOI: 10.1053/j.ackd.2022.07.008 -
The American Journal of Emergency... Nov 2023Acidosis has been reported to cause ST-segment elevation. We presented a woman with a history of rectal adenocarcinoma experienced cardiac arrest during the...
Acidosis has been reported to cause ST-segment elevation. We presented a woman with a history of rectal adenocarcinoma experienced cardiac arrest during the contrast-enhanced computed tomography examination. When spontaneous circulation returned, arterial blood gas revealed she had severe respiratory acidosis, and bedside electrocardiogram showed ST-segment elevation in anterior precordial leads. Emergent coronary angiography was normal. Echocardiography revealed no abnormality of cardiac cavity size, segmental wall motion, or pericardial echo. Carcinoma metastasis in the peritoneal cavity and lungs was detected on the contrast-enhanced computed tomography scan while the heart was not involved. The ST-segment regressed and the respiratory acidosis was corrected after she received mechanical ventilation which strongly suggested the association between acidosis and the electrocardiogram changes.
Topics: Female; Humans; Acidosis, Respiratory; Electrocardiography; Arrhythmias, Cardiac; Coronary Angiography; Acidosis; Pericardium
PubMed: 37230846
DOI: 10.1016/j.ajem.2023.05.013 -
Clinical Nephrology Jan 2021Malignancy-induced lactic acidosis (MILA), a rare paraneoplastic phenomenon, is mostly described with hematologic malignancies (lymphomas and leukemias) but has also... (Review)
Review
Malignancy-induced lactic acidosis (MILA), a rare paraneoplastic phenomenon, is mostly described with hematologic malignancies (lymphomas and leukemias) but has also been reported with solid tumors. It is a subset of type B lactic acidosis being mediated without evidence of tissue hypoperfusion. Lymphoma-induced lactic acidosis is often considered an oncologic emergency and is associated with an increased risk of mortality and poor prognosis. It has a complex pathophysiology centered in the "Warburg effect," i.e., the programming of cancer cells to depend on aerobic glycolysis for promotion of their proliferation and anabolic growth. The treatment of lymphoma-induced lactic acidosis is focused on prompt administration of chemotherapy. The role of alkali therapy in this setting is controversial and has limited proven benefit with a potential for worsening the lactic acidosis. If alkali therapy is used in the presence of severe acidemia to optimize cardiovascular status, it should be administered judiciously.
Topics: Acidosis, Lactic; Aged; Alkalies; Humans; Lymphoma; Male; Middle Aged
PubMed: 32589134
DOI: 10.5414/CN110116 -
European Journal of Medical Research May 2024The base excess value (BE, mmol/L), not standard base excess (SBE), correctly calculated including pH, pCO (mmHg), sO (%) and cHb (g/dl) is a diagnostic tool for several... (Review)
Review
The base excess value (BE, mmol/L), not standard base excess (SBE), correctly calculated including pH, pCO (mmHg), sO (%) and cHb (g/dl) is a diagnostic tool for several in vivo events, e.g., mortality after multiple trauma or shock, acidosis, bleeding, clotting, artificial ventilation. In everyday clinical practice a few microlitres of blood (arterial, mixed venous or venous) are sufficient for optimal diagnostics of any metabolic acidosis or alkalosis.The same applies to a therapeutic tool-then referred to as potential base excess (BEpot)-for several in vitro assessments, e.g., solutions for infusion, sodium bicarbonate, blood products, packed red blood cells, plasma. Thus, BE or BEpot has been a parameter with exceptional clinical significance since 2007.
Topics: Humans; Acidosis; Acid-Base Imbalance; Acid-Base Equilibrium; Alkalosis
PubMed: 38735983
DOI: 10.1186/s40001-024-01796-6 -
Praxis Sep 2020Lactic Acidosis and Other Misunderstandings Lactic acidosis is a frequently encountered clinical problem in intensive care medicine. Nevertheless, many of the...
Lactic Acidosis and Other Misunderstandings Lactic acidosis is a frequently encountered clinical problem in intensive care medicine. Nevertheless, many of the underlying biochemical processes are insufficiently understood, which leads to various misconceptions. Physiologically, lactate is an important, continuously produced carrier of energy and by no means a metabolic 'waste product'. Lactate is the corresponding base to lactic acid and is produced directly from pyruvate. In this reaction H is consumed and therefore lactate production itself cannot be directly responsible for the simultaneously arising acidosis. An elevated lactate level allows no conclusions about the underlying pathophysiological process, and, more importantly, it is not an appropriate marker for tissue oxygenation.
Topics: Acidosis; Acidosis, Lactic; Biomarkers; Critical Care; Humans; Lactic Acid
PubMed: 32933388
DOI: 10.1024/1661-8157/a003508