Search Results (12)

Metabolic acidosis is a common complication of chronic kidney disease (CKD). The kidneys play a crucial role in acid–base balance, maintaining pH within the normal range (isohydria) by following mechanisms: bicarbonate reabsorption, ammogenesis, and titratable acidity. The anion gap describes the amount of unmeasured anions and is classically evaluated as the difference between the major cation (sodium) and the sum of the two major anions (chloride and bicarbonate). Metabolic acidosis can be divided into two types: normal anion gap metabolic acidosis and high anion gap metabolic acidosis. A high anion gap level is considered unfavorable in terms of prognosis as it is associated with increased mortality. Treatment of metabolic acidosis in patients with chronic kidney disease, despite available therapeutic options, is a challenge. Supplementation with bicarbonates does not improve prognosis on the one hand, and on the other hand, it may be harmful. The new KDIGO guidelines for 2024 have been significantly modified compared to 2012 after negative results of studies on bicarbonate supplementation. Bicarbonate supplementation is currently recommended only when levels are less than 18 mmol/L. This review provides an overview of the current knowledge on the pathophysiology, classification, and therapeutic options, including dietary recommendations and new pharmacology agents. Full article

Background/Objectives: In diabetic ketoacidosis (DKA), absolute insulin deficiency and elevation of counter-regulatory hormones may cause osmotic diuresis and water and electrolyte loss, which may lead to dehydration and renal failure. Fluids with high Na content are preferred in the DKA fluid therapy algorithm due to the association of Na with β-Hydroxybutyrate (β-HB) and the renal excretion of Na-β-HB. However, these fluids may cause hyperchloremic metabolic acidosis due to their high chloride concentration. In the literature, base-excess chloride (BE_Cl) has been suggested as a better approach for assessing the effect of chloride on acid–base status. Our aim in this study was to investigate the effect of fluids with BE_Cl values less than zero versus those with values equal to or greater than zero on the metabolic acid–base status in the first 6 h of DKA. Methods: This retrospective study included DKA cases managed in the tertiary intensive care units of five hospitals in the last 10 years. Patients were divided into two groups according to the Na-Cl difference of the administered fluids during the first 6 h of treatment: Group I [GI, fluids with Na-Cl difference = 0, chloride-rich group] and Group II [GII, fluids with Na-Cl difference > 32 mmol, chloride non-rich group]. Demographic data, blood gas analysis results, types and amounts of administered fluids, urea–creatinine values, and urine ketone levels were recorded. Results: Thirty-five patients with DKA in the ICU were included in the study (GI; 22 patients, GII; 13 patients). There was no difference between the patients in the two groups in terms of age, gender, and LOS-ICU. According to the distribution of the administered fluids, the main fluid administered in GI was 0.9% NaCl, whereas in the GII, it was bicarbonate, Isolyte-S, and 0.9% NaCl. In GI, the chloride load administered was higher; the BE_Cl level of the fluids was lower than in GII. At the end of the first 6 h, although sodium and strong ion gap values were similar, patients in GI were more acidotic due to iatrogenic hyperchloremia and, as a result, were more hypocapnic than GII. Conclusions: In conclusion, administering chloride-rich fluids in DKA may help reduce unmeasured anion acidosis. Still, risks cause iatrogenic hyperchloremic acidosis, which can hinder the expected resolution of acidosis and increase respiratory workload. Therefore, it is suggested that DKA guidelines be revised to recommend an individualized approach that avoids chloride-rich fluids and includes monitoring of metabolic parameters like Cl and BE_Cl. Full article

Sodium bicarbonate has been used in the treatment of different pathologies, such as hyperkalemia, cardiac arrest, tricyclic antidepressant toxicity, aspirin toxicity, acute acidosis, lactic acidosis, diabetic ketoacidosis, rhabdomyolysis, and adrenergic receptors’ resistance to catecholamine in patients with shock. An ongoing debate about bicarbonate’s efficacy and potential harm has been raised for decades because of the lack of evidence supporting its potential efficacy. Despite the guidelines’ restrictions, sodium bicarbonate has been overused in clinical practice. The overuse of sodium bicarbonate could be because of the desire to correct the arterial blood gas parameters rapidly instead of achieving homeostasis by treating the cause of the metabolic acidosis. Moreover, it is believed that sodium bicarbonate may reverse acidosis-induced myocardial depression, hemodynamic instability, ventricular arrhythmias, impaired cellular energy production, resistance to catecholamines, altered metabolism, enzyme suppression, immune dysfunction, and ineffective oxygen delivery. On the other hand, it is crucial to pay attention to the potential harm that could be caused by excessive sodium bicarbonate administration. Sodium bicarbonate may cause paradoxical respiratory acidosis, intracellular acidosis, hypokalemia, hypocalcemia, alkalosis, impaired oxygen delivery, cerebrospinal fluid acidosis, and neurologic dysfunction. In this review, we discuss the pathophysiology of sodium bicarbonate-induced adverse effects and potential benefits. We also review the most recent clinical trials, observational studies, and guidelines discussing the use of sodium bicarbonate in different pathologies. Full article

Background: Inborn errors of glutathione metabolism may cause high anion gap metabolic acidosis due to pyroglutamic acid accumulation. Since 1988, cases of this acidosis have been reported in individuals without these defects. Methods: Given the poorly characterized predisposing factors, presentation, management, and prognosis of acquired pyroglutamic acidosis, we conducted a systematic review using the National Library of Medicine, Excerpta Medica, Web of Science, and Google Scholar databases. Results: A total of 131 cases were found. Most patients were females (79%), adults (92%) aged 51 years or older (66%) with pre-existing conditions (74%) such as undernutrition, alcohol-use disorder, or kidney disease, and had an ongoing infection (69%). The clinical features included diminished consciousness (60%), Kussmaul breathing (56%), and nausea or vomiting (27%). At least 92% of patients were on paracetamol therapy for >10 days at an appropriate dose, 32% on a β-lactamase-resistant penicillin, and 2.3% on vigabatrin. Besides severe anion gap acidosis, patients also presented with hypokalemia (24%) and kidney function deterioration (41%). Management involved discontinuing the offending drug (100%), bicarbonate (63%), acetylcysteine (42%), and acute kidney replacement therapy (18%). The fatality rate was 18%, which was higher without acetylcysteine (24%) compared to with it (11%). Conclusions: Acquired pyroglutamic acidosis is a rare, potentially fatal metabolic derangement, which usually occurs after paracetamol use, frequently combined with a β-lactamase-resistant penicillin or vigabatrin. This condition predominantly affects adults, especially women with factors like undernutrition, alcohol-use disorder, or kidney disease, often during infection. Increased awareness of this rare condition is necessary. Full article

A 13-year-old male undergoing maintenance chemotherapy with methotrexate and 6-mercaptopurine (6MP), for very high-risk B-cell acute lymphoblastic leukemia (ALL), presented with vomiting due to severe hypoglycemia with metabolic acidosis. While his laboratory values were concerning for a critically ill child, the patient was relatively well appearing. Hypoglycemia is a rare but serious side effect of 6MP with an unexpectedly variable presentation; therefore, a high index of suspicion is needed for its prompt detection and treatment. This patient also had severe metabolic acidosis, likely secondary to hypoglycemia, creating a serious clinical picture despite a well-appearing child. This example of incongruity between laboratory tests and clinical appearance adds nuance to the existing literature. Moreover, although 6MP-associated hypoglycemia is rare, it may be more prevalent than the literature suggests, as symptoms of hypoglycemia—nausea, vomiting, and somnolence—mirror common chemotherapy side effects. 6MP-induced hypoglycemia can be ameliorated with the addition of allopurinol to shunt metabolism in favor of the production of therapeutic metabolites over hepatotoxic metabolites. Additionally, a morning administration of 6MP and frequent snacks may also help to prevent hypoglycemia. Overall, this case adds to the literature of unusual reactions to 6MP including hypoglycemia in an older child without traditional risk factors. Full article

Background: Normal-anion-gap metabolic acidosis (AGMA) and high-anion-gap metabolic acidosis (HAGMA) are two forms of metabolic acidosis, which is a common complication in patients with chronic kidney disease (CKD). The aim of this study is to identify the prevalence of various acid–base disorders in patients with advanced CKD using point-of-care testing (POCT) and to determine the relationship between POCT parameters. Methods: In a group of 116 patients with CKD in stages G4 and G5, with a mean age of 62.5 ± 17 years, a sample of arterial blood was taken during the arteriovenous fistula procedure for POCT, which enables an assessment of the most important parameters of acid–base balance, including: pH, base excess (BE), bicarbonate (HCO₃⁻), chloride(Cl⁻), anion gap (AG), creatinine and urea concentration. Based on this test, patients were categorized according to the type of acidosis-base disorder. Results: Decompensate acidosis with a pH < 7.35 was found in 68 (59%) patients. Metabolic acidosis (MA), defined as the concentration of HCO₃⁻ ≤ 22 mmol/L, was found in 92 (79%) patients. In this group, significantly lower pH, BE, HCO₃⁻ and Cl⁻ concentrations were found. In group of MA patients, AGMA and HAGMA was observed in 48 (52%) and 44 (48%) of patients, respectively. The mean creatinine was significantly lower in the AGMA group compared to the HAGMA group (4.91 vs. 5.87 mg/dL, p < 0.05). The AG correlated positively with creatinine (r = 0.44, p < 0.01) and urea (r = 0.53, p < 0.01), but there was no correlation between HCO₃⁻ and both creatinine (r = −0.015, p > 0.05) and urea (r = −0.07, p > 0.05). The Cl⁻ concentrations correlated negatively with HCO₃⁻ (r = −0.8, p < 0.01). Conclusions: The most common type of acid–base disturbance in CKD patients in stages 4 and 5 is AGMA, which is observed in patients with better kidney function and is associated with compensatory hyperchloremia. The initiation of renal replacement therapy was significantly earlier for patients diagnosed with HAGMA compared to those diagnosed with AGMA. The more advanced the CKD, the higher the AG. Full article

In recent decades, infusion solutions such as NaCl 0.9% and lactate Ringer’s solution have been replaced in clinical practice. Since 2017, the national guidelines for perioperative infusion therapy in children recommend balanced isotonic solutions to maintain fluid balance. The composition of balanced infusion solutions varies with respect to their electrolyte content. Hyperchloremia may be mistaken for hypovolemia and may interfere with volume therapy in pediatric patients. Sterofundin ISO^® balanced solution contains 127 mmol/L chloride and may cause hyperchloremic acidosis if administered in large volumes. Objectives: The purpose of this study was to compare the effects of Sterofundin ISO^® (SF) therapy with the balanced isochloremic solution Deltajonin^® (DJ) (106 mmol/L chloride) on the acid–base status in infants undergoing craniofacial surgery. Methods: This retrospective, non-blinded study included 100 infants undergoing craniectomy due to isolated nonsyndromic sagittal craniosynostosis. The first 50 infants received Sterofundin ISO^®. Due to changes in national guidelines, the infusion was changed to the isoionic Deltajonin^® in an additional 50 infants in 2017. Pre- and postoperative values of chloride, pH, base excess, bicarbonate, and albumin and phosphate were determined, and the strong-ion difference, strong-ion gap, anion gap, and weak acids were calculated. Results: Both groups were comparable in terms of their age, sex, underlying disease, preoperative electrolytes (except K at 3.9 ± 0.3 mmol/L (SF) vs. 4.1 ± 0.3 mmol/L (DJ) and lactate 8.7 ± 2.1 (SF) vs. 9.6 ± 2.6 mmol/L (DJ)). In the Sterofundin ISO^® group, hyperchloremic metabolic acidosis was observed in 19 patients, whereas only 2 infants in the Deltajonin^® group had hyperchloremic metabolic acidosis. The postoperative chloride level was 111 ± 2.7 mmol/L (SF) vs. 108 ± 2.4 mmol/L (DJ). The difference in anion gap was 12.5 ± 3.0 mmol/L (SF) vs. 14.6 ± 2.8 mmol/L (DJ), and the difference in SIDa (apparent strong-ion difference) was 30.9 mmol/L (SF) vs. 33.8 mmol/L (DJ). Conclusions: Hyperchloremic acidosis can be induced by the volume replacement with high-chloride-concentration crystalloids such as Sterofundin ISO^®. This can be detected using the Stewart model. Full article

Metabolic acidosis (MA) is a highly prevalent disorder in a significant proportion of the population, resulting from imbalance in blood pH homeostasis. The heart, being an organ with very low regenerative capacity and high metabolic activity, is vulnerable to chronic, although low-grade, MA. To systematically characterize the effect of low-grade MA on the heart, we treated male and female mice with NH₄Cl supplementation for 2 weeks and analyzed their blood chemistry and transcriptomic signature of the heart tissue. The reduction of pH and plasma bicarbonate levels without an associated change in anion gap indicated a physiological manifestation of low-grade MA with minimal respiratory compensation. On transcriptomic analysis, we observed changes in cardiac-specific genes with significant gender-based differences due to MA. We found many genes contributing to dilated cardiomyopathy to be altered in males, more than in females, while cardiac contractility and Na/K/ATPase-Src signaling were affected in the opposite way. Our model presents a systems-level understanding of how the cardiovascular tissue is affected by MA. As low-grade MA is a common ailment with many dietary and pharmaceutical interventions, our work presents avenues to limit chronic cardiac damage and disease manifestation, as well as highlighting the sex differences in MA-induced cardiovascular damage. Full article

The variants of electron transfer flavoprotein (ETFA, ETFB) and ETF dehydrogenase (ETFDH) are the leading cause of glutaric aciduria type II (GA-II). In this study, we identified 13 patients harboring six variants of two genes associated with GA-II. Out of the six variants, four were missense, and two were frameshift mutations. A missense variant (ETFDH:p.Gln269His) was observed in a homozygous state in nine patients. Among nine patients, three had experienced metabolic crises with recurrent vomiting, abdominal pain, and nausea. In one patient with persistent metabolic acidosis, hypoglycemia, and a high anion gap, the ETFDH:p.Gly472Arg, and ETFB:p.Pro94Thrfs*8 variants were identified in a homozygous, and heterozygous state, respectively. A missense variant ETFDH:p.Ser442Leu was detected in a homozygous state in one patient with metabolic acidosis, hypoglycemia, hyperammonemia and liver dysfunction. The ETFDH:p.Arg41Leu, and ETFB:p.Ile346Phefs*19 variants were observed in a homozygous state in one patient each. Both these variants have not been reported so far. In silico approaches were used to evaluate the pathogenicity and structural changes linked with these six variants. Overall, the results indicate the importance of a newborn screening program and genetic investigations for patients with GA-II. Moreover, careful interpretation and correlation of variants of uncertain significance with clinical and biochemical findings are needed to confirm the pathogenicity of such variants. Full article

Background and Objective: Lactation ketoacidosis is a rare cause of high anion gap metabolic acidosis affecting breastfeeding mothers. We aim to review and analyze all cases of lactation ketoacidosis reported. Materials and Methods: A systematic search of PubMed/MEDLINE and Cumulative Index to Nursing and Allied Health Literature (CINAHL), identifying relevant case reports published from 1 January 1970 to 31 December 2019. We extracted the following data: the first author, country, year of publication, age of the mother, age of the child, weight/body mass index (BMI) of the mother, precipitating factors, presenting symptoms, biochemical results, treatment, breastfeeding, and time from presentation to the resolution of ketoacidosis. Results: Sixteen case reports and 1 case series reporting 18 cases of lactation ketoacidosis were found. Presenting symptoms were nausea (72%, 13/18), vomiting (67%, 12/18), malaise (56%, 10/18), abdominal pain (44%, 8/18), dyspnea (33%, 6/18), headache (22%, 4/18), and palpitation (11%, 2/18). Dieting and physical exercise to lose weight were reported in 76% (14/18). The treatments included IV dextrose, sodium bicarbonate, insulin, rehydration, monitoring and replacement of electrolytes, and resumption of a balanced diet. The prognoses were good, with no mortalities. Conclusions: lactation ketoacidosis should be suspected in unwell breastfeeding women with high anion gap metabolic acidosis, after excluding other causes. Full article

Asthma is a common illness throughout the world that affects the respiratory system function, i.e., a system whose operational adequacy determines the respiratory gases exchange. It is therefore expected that acute severe asthma will be associated with respiratory acid-base disorders. In addition, the resulting hypoxemia along with the circulatory compromise due to heart–lung interactions can reduce tissue oxygenation, with a particular impact on respiratory muscles that have increased energy needs due to the increased workload. Thus, anaerobic metabolism may ensue, leading to lactic acidosis. Additionally, chronic hypocapnia in asthma can cause a compensatory drop in plasma bicarbonate concentration, resulting in non-anion gap acidosis. Indeed, studies have shown that in acute severe asthma, metabolic acid-base disorders may occur, i.e., high anion gap or non-anion gap metabolic acidosis. This review briefly presents studies that have investigated acid-base disorders in asthma, with comments on their underlying pathophysiology. Full article

Insulin therapy is often needed to overcome insulin receptor resistance in type 2 diabetes; however, the impact of providing additional insulin to already hyperinsulinemic subjects is not clear. We infused male TALLYHO/Jng (TH) mice (insulin resistant) with insulin (50 U/kg·bw/d) or vehicle (control) by osmotic minipump for 14 days. One group of insulin-infused mice was switched to 4% NaCl diet (high-sodium diet, HSD) in the second week. Blood chemistry revealed a significantly higher anion gap and blood sodium concentrations with insulin infusion, i.e., relative metabolic acidosis. Systolic BP and heart rate were slightly (~5 mm Hg) higher in insulin-infused versus control mice. HSD resulted in a modest and transient rise in mean arterial blood pressure (BP), relative to control or insulin-infused, normal-NaCl-fed mice. In kidney, insulin infusion: (1) increased total and phosphorylated (serine-1177) endothelial nitric oxide synthase (eNOS) band densities; (2) reduced band density of the uncoupled form of eNOS; and (3) increased renal homogenate nitric oxide synthase (NOS) activity. Despite this, plasma and urine levels of nitrates plus nitrites (NOx) fell with insulin infusion, by day 14 (40–50%) suggesting worsening of resistance. Overall, insulin infusion ramps up the cellular means in kidney to increase vasodilatory and natriuretic NO, but in the long term may be associated with worsening of insulin receptor resistance. Full article