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Emergency Medicine Clinics of North... Nov 2023Metabolic acid-base disturbances are frequently encountered in the emergency department, and many of these patients are critically ill. In the evaluation of patients... (Review)
Review
Metabolic acid-base disturbances are frequently encountered in the emergency department, and many of these patients are critically ill. In the evaluation of patients with these maladies, it is important for the emergency clinician to determine the cause, which can usually be elicited from a thorough history and physical examination. There are several mnemonics that can be used to form an appropriate list of potential causes. Most of the time, the management of these patients requires no specific treatment of the acid-base status but, rather, requires treatment of the underlying disorder that is causing the acid-base disturbance.
Topics: Humans; Acid-Base Imbalance; Acidosis; Alkalosis
PubMed: 37758428
DOI: 10.1016/j.emc.2023.06.008 -
Ugeskrift For Laeger Sep 2023Diabetic ketoacidosis (DKA) in children with severe hypertriglyceridaemia (S-HTG) is infrequent. This case report presents a seven-year-old girl without a family history...
Diabetic ketoacidosis (DKA) in children with severe hypertriglyceridaemia (S-HTG) is infrequent. This case report presents a seven-year-old girl without a family history of dyslipidaemia with moderate DKA, lipaemic plasma, retinal lipaemia, and P-triglyceride 185 mmol/l. The course was uneventful on standard treatment and lipids normalized. She had abdominal pain but no biochemical or ultrasound evidence of pancreatitis. S-HTG affected laboratory analysis; CO2 could not be analyzed, and there was haemolysis and uncertain electrolyte results with P-Na+ 125 mmol/l, i.e. pseudo hyponatraemia, despite ultracentrifugation.
Topics: Female; Humans; Child; Diabetic Ketoacidosis; Hyperlipidemias; Hypertriglyceridemia; Pancreatitis; Triglycerides; Diabetes Mellitus
PubMed: 37873990
DOI: No ID Found -
British Journal of Anaesthesia Oct 2023Use of sodium-glucose transporter-2 (SGLT2) inhibitors has dramatically increased over the past decade. This medication class predisposes patients to euglycaemic...
BACKGROUND
Use of sodium-glucose transporter-2 (SGLT2) inhibitors has dramatically increased over the past decade. This medication class predisposes patients to euglycaemic diabetic ketoacidosis, particularly during times of physiologic stress, including fasting and surgery. Beyond case reports and series, a systematic description of perioperative metabolic effects of SGLT2 inhibitors is lacking.
METHODS
We examined the degree of anion gap acidosis, controlling for non-ketone anions, in patients undergoing surgery at Massachusetts General Hospital in 2016-22. We constructed a multivariable regression model incorporating known non-ketone contributors to the postoperative anion gap (albumin, lactate, estimated glomerular filtration rate, and preoperative anion gap), hold time, and interaction terms between hold time and three previously suggested risk factors for euglycaemic diabetic ketoacidosis: emergency surgery, cardiac surgery, and insulin use.
RESULTS
In 463 patients on SGLT2 inhibitors, we observed a strong association between decreased hold time and postoperative anion gap (P<0.001 in a univariable analysis; -0.43, 95% confidence interval [-0.76 to -0.11] change in anion gap per day held, P=0.01 in a multivariable analysis). A significant interaction between hold time and emergency surgery was observed, whereas there was no apparent interaction with insulin use or cardiac surgery.
CONCLUSIONS
These findings provide the first evidence that an anion gap acidosis, likely from ketoacids, develops in all patients who do not hold SGLT2 inhibitors before surgery rather than in an idiosyncratic few. If an SGLT2 inhibitor is unable to be stopped, postoperative monitoring of anion gap and serum ketones can help detect clinically significant euglycaemic diabetic ketoacidosis, particularly in those undergoing emergency surgery.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Diabetic Ketoacidosis; Acid-Base Equilibrium; Retrospective Studies; Acidosis; Insulins; Diabetes Mellitus, Type 2
PubMed: 37541949
DOI: 10.1016/j.bja.2023.06.063 -
Frontiers in Endocrinology 2023The safety of different sodium-glucose transporter 2 (SGLT-2) inhibitors remains uncertain due to the lack of head-to-head comparisons. (Comparative Study)
Comparative Study Meta-Analysis
Comparative safety of different sodium-glucose transporter 2 inhibitors in patients with type 2 diabetes: a systematic review and network meta-analysis of randomized controlled trials.
BACKGROUNDS
The safety of different sodium-glucose transporter 2 (SGLT-2) inhibitors remains uncertain due to the lack of head-to-head comparisons.
METHODS
This network meta-analysis (NMA) was performed to compare the safety of nine SGLT-2 inhibitors in patients with type 2 diabetes (T2DM). PubMed, Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched for studies published in English before August 30, 2022. Published and unpublished randomized controlled trials (RCTs) comparing the safety of individual SGLT-2 inhibitors in patients with T2DM were included. A Bayesian NMA with random effects model was applied. Subgroup and sensitivity analyses were performed. The quality of the evidence was evaluated using the Confidence in Network Meta-Analysis framework.
RESULTS
Nine SGLT-2 inhibitors were evaluated in 113 RCTs (12 registries) involving 105,293 adult patients. Reproductive tract infections (RTIs) were reported in 1,967 (4.51%) and 276 (1.01%) patients in the SGLT-2 inhibitor and placebo groups, respectively. Furthermore, pollakiuria was reported in 233 (2.66%) and 45 (0.84%) patients, respectively. Compared to placebo, a significantly higher risk of RTIs was observed with canagliflozin, ertugliflozin, empagliflozin, remogliflozin, dapagliflozin, and sotagliflozin, but not with luseogliflozin and ipragliflozin, regardless of gender. An increased risk of pollakiuria was observed with dapagliflozin [odds ratio (OR) 10.40, 95% confidence interval (CI) 1.60-157.94) and empagliflozin (OR 5.81, 95%CI 1.79-32.97). Remogliflozin (OR 6.45, 95%CI 2.18-27.79) and dapagliflozin (OR 1.33, 95%CI 1.10-1.62) were associated with an increased risk of urinary tract infections (UTIs). Instead, the included SGLT-2 inhibitors had a protective effect against acute kidney injury (AKI). No significant differences were found for hypovolemia, renal impairment or failure, fracture, diabetic ketoacidosis (DKA), amputation, and severe hypoglycemia between the SGLT-2 inhibitor and the placebo groups.
CONCLUSION
In patients with T2DM, dapagliflozin was associated with an increased risk of RTIs, pollakiuria, and UTIs. Empagliflozin increased the risk of RTIs and pollakiuria. Remogliflozin increased the risk of UTIs. None of the SGLT-2 inhibitors showed a significant difference from the placebo for hypovolemia, renal impairment or failure, fracture, DKA, amputation, and severe hypoglycemia. The findings guide the selection of SGLT-2 inhibitors for patients with T2DM based on the patient's profiles to maximize safety.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, identifier CRD42022334644.
Topics: Adult; Humans; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Fractures, Bone; Hypoglycemia; Hypovolemia; Network Meta-Analysis; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 37701900
DOI: 10.3389/fendo.2023.1238399 -
International Journal of Molecular... Feb 2024Diets can influence the body's acid-base status because specific food components yield acids, bases, or neither when metabolized. Animal-sourced foods yield acids and... (Review)
Review
Diets can influence the body's acid-base status because specific food components yield acids, bases, or neither when metabolized. Animal-sourced foods yield acids and plant-sourced food, particularly fruits and vegetables, generally yield bases when metabolized. Modern diets proportionately contain more animal-sourced than plant-sourced foods, are, thereby, generally net acid-producing, and so constitute an ongoing acid challenge. Acid accumulation severe enough to reduce serum bicarbonate concentration, i.e., manifesting as chronic metabolic acidosis, the most extreme end of the continuum of "acid stress", harms bones and muscles and appears to enhance the progression of chronic kidney disease (CKD). Progressive acid accumulation that does not achieve the threshold amount necessary to cause chronic metabolic acidosis also appears to have deleterious effects. Specifically, identifiable acid retention without reduced serum bicarbonate concentration, which, in this review, we will call "covert acidosis", appears to cause kidney injury and exacerbate CKD progression. Furthermore, the chronic engagement of mechanisms to mitigate the ongoing acid challenge of modern diets also appears to threaten health, including kidney health. This review describes the full continuum of "acid stress" to which modern diets contribute and the mechanisms by which acid stress challenges health. Ongoing research will develop clinically useful tools to identify stages of acid stress earlier than metabolic acidosis and determine if dietary acid reduction lowers or eliminates the threats to health that these diets appear to cause.
Topics: Animals; Bicarbonates; Acid-Base Equilibrium; Diet; Acidosis; Renal Insufficiency, Chronic
PubMed: 38397012
DOI: 10.3390/ijms25042336 -
MMW Fortschritte Der Medizin Jun 2024
Topics: Humans; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Hypoglycemic Agents; Ketosis; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 38806910
DOI: 10.1007/s15006-024-3985-1 -
Diabetes, Obesity & Metabolism Oct 2023Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are particularly effective in preventing adverse outcomes of heart failure and chronic kidney disease, which are... (Meta-Analysis)
Meta-Analysis
AIM
Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are particularly effective in preventing adverse outcomes of heart failure and chronic kidney disease, which are highly prevalent in the elderly. Here, we aimed to access the safety of SGLT2i in elderly patients with type 2 diabetes.
MATERIALS AND METHODS
We performed a meta-analysis of randomized controlled trials (RCTs) reporting safety outcomes of the elderly (≥65 years) patients with type 2 diabetes, randomized to an SGLT2i or placebo. We recorded the incidence of acute kidney injury, volume depletion, genital tract infections, urinary tract infections, bone fractures, amputations, diabetic ketoacidosis, hypoglycaemia and drug discontinuation, by group of treatment.
RESULTS
Of the 130 RCTs screened, only six reported data on elderly patients. In total, 19 986 patients were included. The SGLT2i discontinuation rate was approximately 20%. The risk of acute kidney injury was significantly lower among SGLT2i users compared with placebo [risk ratio (RR) 0.73; 95% CI 0.62-0.87]. SGLT2i were associated with a six-fold increased risk of genital tract infections (RR 6.55; 95% CI 2.09-20.5). The rate of amputations was increased only among canagliflozin users (RR 1.94, 95% CI 1.25-3). The risk of fractures, urinary tract infection, volume depletion, hypoglycaemia and diabetic ketoacidosis was similar between SGLT2i and placebo.
CONCLUSIONS
SGLT2is were well tolerated in the elderly. However, older patients are underrepresented in most RCTs and a call for action is need to favour clinical trials reporting safety outcomes stratified by age.
Topics: Humans; Aged; Sodium-Glucose Transporter 2 Inhibitors; Diabetic Ketoacidosis; Randomized Controlled Trials as Topic; Diabetes Mellitus, Type 2; Hypoglycemia; Acute Kidney Injury; Glucose; Sodium
PubMed: 37402697
DOI: 10.1111/dom.15193 -
Trends in Endocrinology and Metabolism:... Apr 2024Hyperlactatemia and anemia commonly coexist and their crosstalk is a longstanding mystery with elusive mechanisms involved in physical activities, infections, cancers,... (Review)
Review
Hyperlactatemia and anemia commonly coexist and their crosstalk is a longstanding mystery with elusive mechanisms involved in physical activities, infections, cancers, and genetic disorders. For instance, hyperlactatemia leads to iron restriction by upregulating hepatic hepcidin expression. Increasing evidence also points to lactate as a crucial signaling molecule rather than merely a metabolic byproduct. Here, we discuss the mutual influence between anemia and hyperlactatemia. This opinion calls for a reconsideration of the multifaceted roles of lactate and lactylation in anemia and emphasizes the need to fill knowledge gaps, including the dose dependence of lactate's effects, its sources, and its subcellular localization.
Topics: Humans; Hyperlactatemia; Acidosis, Lactic; Lactic Acid; Anemia
PubMed: 38185594
DOI: 10.1016/j.tem.2023.12.006 -
Seminars in Respiratory and Critical... Oct 2023Disorders of acid-base status are common in the critically ill and prompt recognition is central to clinical decision making. The bicarbonate/carbon dioxide buffer...
Disorders of acid-base status are common in the critically ill and prompt recognition is central to clinical decision making. The bicarbonate/carbon dioxide buffer system plays a pivotal role in maintaining acid-base homeostasis, and measurements of pH, PCO, and HCO are routinely used in the estimation of metabolic and respiratory disturbance severity. Hypoventilation and hyperventilation cause primary respiratory acidosis and primary respiratory alkalosis, respectively. Metabolic acidosis and metabolic alkalosis have numerous origins, that include alterations in acid or base intake, body fluid losses, abnormalities of intermediary metabolism, and renal, hepatic, and gastrointestinal dysfunction. The concept of the anion gap is used to categorize metabolic acidoses, and urine chloride excretion helps define metabolic alkaloses. Both the lungs and kidneys employ compensatory mechanisms to minimize changes in pH caused by various physiologic and disease disturbances. Treatment of acid-base disorders should focus primarily on correcting the underlying cause and the hemodynamic and electrolyte derangements that ensue. Specific therapies under certain conditions include renal replacement therapy, mechanical ventilation, respiratory stimulants or depressants, and inhibition of specific enzymes in intermediary metabolism disorders.
Topics: Humans; Acid-Base Imbalance; Hydrogen-Ion Concentration; Acid-Base Equilibrium; Acidosis; Alkalosis; Carbon Dioxide
PubMed: 37369215
DOI: 10.1055/s-0043-1770341 -
Physiology (Bethesda, Md.) May 2024The discovery of insulin approximately a century ago greatly improved the management of diabetes, including many of its life-threatening acute complications like... (Review)
Review
The discovery of insulin approximately a century ago greatly improved the management of diabetes, including many of its life-threatening acute complications like ketoacidosis. This breakthrough saved many lives and extended the healthy lifespan of many patients with diabetes. However, there is still a negative perception of ketone bodies stemming from ketoacidosis. Originally, ketone bodies were thought of as a vital source of energy during fasting and exercise. Furthermore, in recent years, research on calorie restriction and its potential impact on extending healthy lifespans, as well as studies on ketone bodies, have gradually led to a reevaluation of the significance of ketone bodies in promoting longevity. Thus, in this review, we discuss the emerging and hidden roles of ketone bodies in various organs, including the heart, kidneys, skeletal muscles, and brain, as well as their potential impact on malignancies and lifespan.
Topics: Humans; Ketone Bodies; Ketosis; Diabetes Mellitus; Longevity; Heart
PubMed: 38260943
DOI: 10.1152/physiol.00031.2023