Metabolic Acidosis Research Articles

Elevated osmol gaps in patients with alcoholic ketoacidosis.

The use of the osmol gap as a surrogate marker of toxic alcohol poisoning is common. Unfortunately, many patients with alcoholic ketoacidosis have elevated osmol gaps and are misdiagnosed with toxic alcohol poisoning. We aimed to characterize the range of osmol gaps in patients with alcoholic ketoacidosis. This was a retrospective poison center study. Data from 24 years were reviewed using the following case definition of alcoholic ketoacidosis: (1) documented alcohol use disorder; (2) presence of urine or serum ketones or an elevated blood beta-hydroxybutyrate concentration; (3) an anion gap ≥14 mmol/L. Potential cases of alcoholic ketoacidosis that failed to fulfill all three criteria were adjudicated by three toxicologists. Exclusion criteria included (1) detectable toxic alcohol concentration, (2) hemodialysis and/or multiple doses of fomepizole, (3) no osmol gap documented, (4) other diagnoses that lead to a metabolic acidosis. Demographics, pH, anion gap, lactate concentration, and osmol gap were extracted. Of 1,493 patients screened, 55 met criteria for alcoholic ketoacidosis. Sixty-four percent were male, and their median age was 52 years. The median osmol gap was 27 [IQR 18-36]. The largest anion gap was 57 mmol/L, and the lowest pH was 6.8. Forty-five (82%) of the patients with alcoholic ketoacidosis had osmol gaps >10; 38 (69%) had osmol gaps >20; 24 (44%) had osmol gaps >30; 11 (20%) had osmol gaps > 40. The large range of osmol gaps in patients with alcoholic ketoacidosis often reaches values associated with toxic alcohol poisoning. The study is limited by the potential for transcribing errors and the inability to identify the cause of the osmol gap. In this retrospective study, patients with alcoholic ketoacidosis had a median osmol gap of 27. Given that alcoholic ketoacidosis is easily and inexpensively treated, proper identification may prevent costly and invasive treatment directed at toxic alcohol poisoning.

Among Patients Meeting the KDIGO CKD Practice Point Criterion for Treatment of Metabolic Acidosis, Higher Serum Bicarbonate Concentrations Are Associated with Slower CKD Progression

Among Patients Meeting the KDIGO CKD Practice Point Criterion for Treatment of Metabolic Acidosis, Higher Serum Bicarbonate Concentrations Are Associated with Slower CKD Progression

Fluid bolus resuscitation with hypertonic saline albumin solution in critically ill children: a prospective observational pilot study

To evaluate the hemodynamic effects and the safety profile of fluid bolus resuscitation with hypertonic saline albumin (HSA) in critically ill children, we performed a prospective observational pilot study between October 2018 and May 2021 in the pediatric intensive care unit (PICU) in a tertiary hospital in Madrid, Spain. Sixty-four HSA boluses were analyzed in 23 patients. A mean volume of 5.7 ml/kg (Standard Deviation, SD 2.3 ml/kg) per bolus was infused. Acute hypotension was the main indication. 91% of the patients had a cardiac disease, 56% of them had undergone cardiac surgery in the previous 72 h, and 47.8% associated right ventricular dysfunction. A significant increase in systolic, mean, and diastolic blood pressure and a decrease in the vasoactive index was observed after the infusion of HSA. This effect lasted for twenty-four hours (p < 0.05). Moreover, the amount of fluid requirements decreased significantly in the 6 h following HSA infusion [8.7 ml/kg (SD 9.6) vs. 15.1 ml/kg (SD 13.6) in the previous 6 h (p < 0.05)]. Serum levels of sodium and chloride increased after the infusion, reaching their peak concentration after one hour (143 mEq/L (SD 3.5) and 109.7 mEq/L (SD 6) respectively). HSA-related metabolic acidosis or acute kidney injury were not observed in this study. Hypertonic saline albumin is safe and effective when infused at a dose of 5 ml/kg in critically ill children. However, further research is required to confirm our findings.

Effect of Sodium Bicarbonate Therapy on Calciprotein Particles in Patients with CKD Stages 3 and 4 and Mild Metabolic Acidosis

Effect of Sodium Bicarbonate Therapy on Calciprotein Particles in Patients with CKD Stages 3 and 4 and Mild Metabolic Acidosis

Revisiting the Urinary Anion Gap: A Sound Concept during Hyperchloremic Metabolic Acidosis

Revisiting the Urinary Anion Gap: A Sound Concept during Hyperchloremic Metabolic Acidosis

Dapagliflozin-associated euglycemic diabetic ketoacidosis in 66-year-old with type 2 Diabetes: A clinical case report

Euglycemic diabetic ketoacidosis (EDKA) is a rare but serious complication of type 2 diabetes, often associated with the use of SGLT2 inhibitors. This case report describes an episode of EDKA in a 66-year-old male with a long history of type 2 diabetes and multiple comorbidities, who developed this complication following the introduction of dapagliflozin. Although his blood glucose levels remained within normal limits, laboratory tests revealed elevated ketonemia and severe metabolic acidosis. The patient was successfully treated with intravenous hydration and insulin therapy, leading to a rapid improvement in his clinical condition. This case underscores the importance of clinical vigilance and patient education for those treated with SGLT2 inhibitors to prevent and effectively manage this potentially life-threatening complication.

Association between early metabolic acidosis and bronchopulmonary dysplasia/death in preterm infants born at less than 28 weeks’ gestation: an observational cohort study

BackgroundMetabolic acidosis occurs frequently during the first postnatal days in extremely preterm infants and is mainly attributed to renal immaturity. Recent studies suggested a link between metabolic acidosis and the development of BPD. The aim of this study was to systematically investigate the association between severe metabolic acidosis during the first two weeks of life and bronchopulmonary dysplasia (BPD) / mortality among preterm infants born before 28 weeks’ gestation.MethodsMonocentric observational cohort study including 1748 blood gas samples of 138 extremely preterm infants born 2020–2022. Metabolic acidosis was defined as pH < 7.2 with base excess (BE) < -10 mmol/L or standard bicarbonate (SBC) < 12 mmol/L. Primary outcome was BPD and/or death at 36 weeks postmenstrual age.ResultsFifty-six (40.6%) infants had BPD/death. Metabolic acidosis occurred in 50.0% of infants with BPD/death, compared to 22.0% of BPD-free survivors (p = 0.001) during the first 14 postnatal days. Minimum pH (median 7.12 vs. 7.19, p < 0.001), BE (median -10.9 vs. -9.5 mmol/L, p = 0.005), SBC (median 14.7 vs. 16.1 mmol/L, p < 0.001) were different between the two groups. After adjusting for confounders, pH (postnatal days 2–6), BE (postnatal day 3) and SBC (postnatal days 2–4) were significantly lower in infants with BPD/death. Metabolic acidosis on postnatal days 1–7 was associated with higher odds of BPD (adjusted Odds Ratio (aOR) 3.461, 95% CI 1.325–9.042) and BPD/death (aOR 3.087, 95% CI 1.225–7.778).ConclusionsMetabolic acidosis during the first week of life was associated with higher odds of BPD/death in extremely preterm infants.

A side effect that should be considered in patients using metformin: lactic acidosis

The most serious and life-threatening side effect seen in patients using metformin is metabolic acidosis. If there is a history of diabetes in patients with high anion gap metabolic acidosis who present to the emergency department, metformin use should be questioned. In our case, metformin-related lactic acidosis was detected in a 67-year-old female patient who applied to the emergency department with a complaint of palpitations. The patient's kidney function tests were within normal range and he did not describe excessive drug intake. Despite the treatments administered in the emergency room, the patient's blood gas lactate level continued to increase and his acidosis deepened. After other causes of lactic acidosis were excluded, the patient was consulted with internal medicine and transferred to the intensive care unit. With this case report, we tried to draw attention to the fact that the patient group for which metformin will be used in the treatment should be carefully selected and that lactic acidosis, which is a fatal side effect, should be considered in the differential diagnosis and treatment should be started in those using this drug.

Classic ketogenic diet-induced ketoacidosis in the treatment of pyruvate dehydrogenase deficiency: a case report and literature review

BackgroundAs a rare mitochondrial disorder, the pyruvate dehydrogenase complex (PDC) deficiency is a rare inborn disease characterized with glucose metabolism defects, which leads to neurological dysfunction, serum lactic acid buildup and a resultant trend of metabolic acidosis. Although the ketogenic diet (KD) is the first-line treatment for PDC deficiency, there is currently no widely accepted consensus on specific implementation of KD for this condition. Due to the combined effect of pre-existing hyperlactacidemia and KD-induced ketoacidosis that can further exacerbate metabolic disturbances, maintaining metabolic homeostasis should be prioritized during the implementation of KD.Case presentationHerein, the authors present a 6-year-old boy with lactic acidosis, ataxia, hypotonia and neuromotor development retardation. The KD was started after the patient was diagnosed with PDC deficiency based on genetic testing. The initiation with classic KD resulted in severe non-diabetic ketoacidosis with elevated anion gap, which was promptly alleviated by dextrose supplementation and dietary modification to a less-restrictive KD. Long-term supervision demonstrated the efficacy of a modified KD in improving both clinical course and metabolic acidosis of the patient.ConclusionsThis rare case adds to the limited evidence of KD application in PDC deficiency, and provides valuable insights into the importance of reasonably lowering the ketogenic ratio of KD at the start of treatment to reduce the risk of metabolic acidosis.

Drug-Related Pyroglutamic Acidosis: Systematic Literature Review.

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.

Exogenous ketosis attenuates acute mountain sickness and mitigates normobaric high-altitude hypoxemia.

Acute mountain sickness (AMS) represents a considerable issue for individuals sojourning to high altitudes with systemic hypoxemia known to be intimately involved in its development. Based on recent evidence that ketone ester (KE) intake attenuates hypoxemia, we investigated whether exogenous ketosis might mitigate AMS development and to identify underlying physiological mechanisms. Fourteen healthy, male participants were enrolled in two 29h protocols (simulated altitude of 4,000-4,500m) receiving either KE or a placebo (CON) at regular timepoints throughout the protocol in a randomized, crossover manner. Physiological responses were characterized after 15min and 4h in hypoxia, and the protocol was terminated prematurely upon development of severe AMS (Lake Louise Score ≥ 10). KE ingestion induced a consistent diurnal ketosis ([ßHB] of ~3 mM), whereas blood [ßHB] remained low (<0.6 mM) in CON. Each participant tolerated the protocol equally long or longer (n=6 or n=8, resp.) in KE. Protocol duration increased by 32% on average with KE, and doubled upon KE for severe AMS-developing participants (n=9). Relative to CON, KE induced a mild metabolic acidosis, hyperventilation, and relative sympathetic dominance. KE also inhibited the progressive hypoxemia that was observed between 15min and 4h in hypoxia in CON, while concomitantly increasing cerebral oxygenation and capillary pO2 within this timeframe despite a KE-induced reduction in cerebral oxygen supply. These data indicate that exogenous ketosis attenuates AMS development. The key underlying mechanisms include improved arterial and cerebral oxygenation, in combination with lowered cerebral blood flow and oxygen delivery, and increased sympathetic dominance.

Contaminated well water driving d‐lactic acidosis in child with short bowel syndrome

Abstractd‐lactic acidosis is a rare type of lactic acidosis that typically presents in patients with short bowel syndrome (SBS). Clinical features include a high anion‐gap metabolic acidosis and acute onset of neurological impairment. The underlying pathology is thought to be due to altered gut flora and carbohydrate malabsorption in patients with altered gut anatomy. The treatment centers on correcting acid–base derangements, dietary modifications to decrease carbohydrate intake and antibiotics. We present a case of recurrent d‐lactic acidosis in a patient with SBS. In this unique case, we highlight the importance of considering the home environment when developing a treatment plan.

Challenging management dogma where evidence is non-existent, weak, or outdated: part II.

Many dogmas influence daily clinical practice, and critical care medicine is no exception. We previously highlighted the weak, questionable, and often contrary evidence base underpinning four established medical managements-loop diuretics for acute heart failure, routine use of heparin thromboprophylaxis, rate of sodium correction for hyponatremia, and 'every hour counts' for treating bacterial meningitis. We now provide four further examples in this "Dogma II" piece (a week's course of antibiotics, diabetic ketoacidosis algorithms, sodium bicarbonate to improve ventricular contractility during severe metabolic acidosis, and phosphate replacement for hypophosphatemia) where routine practice warrants re-appraisal.

Sodium bicarbonate - known medication, new prospects?

Critical conditions frequently involve disturbances in blood gas analysis and electrolyte imbalances. Sodium bicarbonate has seen expanded medical use in recent years. The European Resuscitation Council (ERC) Guidelines endorse sodium bicarbonate for hyperkalemia, malignant hyperthermia, and specific drug intoxications. Its potential roles in treating intracranial hypertension and symptomatic hyponatremia are also being explored. However, its application in emergency departments (ED) remains inconsistent, particularly in profound metabolic acidosis cases. We conducted a review of sodium bicarbonate’s therapeutic uses. The evolving understanding of sodium bicarbonate's role in emergency medicine and intensive care highlights both its potential applications and associated risks. While not universally beneficial, especially in lactic acidosis, it may aid specific patient subgroups, such as those with acute kidney injury. Its use in hyperkalemia, intracranial hypertension and diabetic ketoacidosis (DKA) also presents mixed results, with potential benefits in particular contexts. Further large-scale, randomized controlled trials are needed to develop precise guidelines, ensuring its safe and effective use tailored to individual patient needs.

Understanding buffering of metabolic acidosis in critical illness.

Understanding buffering of metabolic acidosis in critical illness.

Metabolic Acidosis in a Diabetic Patient Treated by Jardiance

Patients affected by Type II Diabetes are often subjected to multi-drug therapy, thus they are at risk of developing several side effects. Metabolic acidosis is one of these. It has often been identified as a side effect during treatment with Metformin,

CLINICAL SPECTRUM OF DISEASE IN NEONATES BORN TO MOTHERS WITH COVID-19 IN A TERTIARY CARE HOSPITAL

COVID-19 infection during pregnancy presents potential risks to neonates, yet the full clinical spectrum in newborns born to COVID-19-positive mothers remains under investigation. Understanding the clinical outcomes in these neonates is essential for guiding management and care. Objective: To study the spectrum of clinical presentations in neonates born to mothers who tested positive for COVID-19. Methods: This prospective cross-sectional study was conducted at the Department of Pediatrics, Shifa International Hospital, from April 1, 2020, to April 30, 2021. All neonates born to COVID-19-positive mothers were included in the study and followed daily during their hospital stay. After obtaining parental consent, nasopharyngeal swabs were taken from the neonates for SARS-CoV-2 PCR testing at 24-48 hours of age. After discharge, follow-up calls were made between days 7-14. Data were entered into a predesigned proforma and analyzed using SPSS version 23. Results: A total of 82 neonates were enrolled. Approximately half were born at term, with a mean weight of &gt;2500 grams. Forty-five neonates (53%) underwent SARS-CoV-2 PCR testing within 48 hours of age; all were negative. Sixty-one neonates (74%) were shifted to the mother’s care, while 25% required admission to the neonatal intensive care unit (NICU). The most common reasons for NICU admission included respiratory distress (15%), prematurity (6%), and lethargy (5%). Radiological findings included ground-glass appearance in five neonates (6%) and lung consolidation or infiltrates in two (3%). Hematological and biochemical abnormalities included leukocytosis (7%), leucopenia (3.6%), anemia (1.2%), metabolic acidosis (6%), and respiratory acidosis (3.6%). Most neonates (78.6%) received routine care and were fed breast milk. Fourteen neonates (16.7%) required respiratory support, with 13% needing mechanical ventilation. Complications included pneumonia (7%) and respiratory failure (9%). NICU stay varied, with 11 neonates (13%) staying less than 48 hours and 10 (12%) requiring a more extended stay. Four neonates (5%) died due to multiorgan complications. Conclusion: The majority of neonates born to COVID-19-positive mothers remained asymptomatic. However, symptomatic neonates were at risk of serious complications, requiring close monitoring and management, particularly in those with additional risk factors.

The Role of MicroRNA in the Pathogenesis of Acute Kidney Injury.

Acute kidney injury (AKI) describes a condition associated with elevated serum creatinine levels and decreased glomerular filtration rate. AKI can develop as a result of sepsis, the nephrotoxic properties of several drugs, and ischemia/reperfusion injury. Renal damage can be associated with metabolic acidosis, fluid overload, and ionic disorders. As the molecular background of the pathogenesis of AKI is insufficiently understood, more studies are needed to identify the key signaling pathways and molecules involved in the progression of AKI. Consequently, future treatment methods may be able to restore organ function more rapidly and prevent progression to chronic kidney disease. MicroRNAs (miRNAs) are small molecules that belong to the non-coding RNA family. Recently, numerous studies have demonstrated the altered expression profile of miRNAs in various diseases, including inflammatory and neoplastic conditions. As miRNAs are major regulators of gene expression, their dysregulation is associated with impaired homeostasis and cellular behavior. The aim of this article is to discuss current evidence on the involvement of miRNAs in the pathogenesis of AKI.

Comparison between the dilution of electrolyte concentrate in milk or water for oral rehydration of diarrheal calves

The administration of oral electrolyte solution (OES) is the most used method to correct dehydration and electrolyte and acid-base imbalances in calves with diarrhea. To prepare OES, the electrolyte concentrate (EC) is diluted in water. Alternatively, it can be diluted in milk and the correction of dehydration depends on voluntary water intake. Although dilution in milk is used, its efficacy has not been fully proven. This study compared the effectiveness of two rehydration methods in correcting imbalances in diarrheal calves. Twenty-four neonatal calves with induced osmotic diarrhea were distributed into two treatment groups using a commercial EC: GM with EC diluted in the milk at meals; and GW with EC diluted in water (volumes of 5% BW, at 4 and 12 h). All were fed with milk (volumes of 4% BW, at 0, 8, and 16 h) and had free access to water. Clinical and laboratory variables were monitored over time up to 48 h. The calves presented moderate dehydration, hyponatremia, relative hyperchloremia and moderate strong ion metabolic acidosis. Both rehydration methods were effective in correcting imbalances and reestablishing plasma SID3 at the end of the day of treatment. Plasma volume expansion was faster in GW. Electrolyte-enriched milk is as efficient as OES for treating diarrheal calves.

Effects of dietary interventions for metabolic acidosis in chronic kidney disease: a systematic review and meta-analysis.

Metabolic acidosis is a common complication of kidney disease and can result in further disease progression. Alkali therapy has been used to treat metabolic acidosis for decades. However, some concerns have been raised regarding its safety and long-term tolerability. Existing data suggest that dietary interventions can be beneficial in the management of chronic kidney disease (CKD). This systematic review and meta-analysis aims to summarize findings from studies comparing dietary interventions with placebo/usual care/no treatment in the management of metabolic acidosis in outpatient adults with CKD. Medline, Embase, Cochrane Central, CINAHL, and Web of Science Core Collection were searched from inception to June 2022. Our primary outcome measure was change in serum bicarbonate. Any dietary intervention looking to manipulate dietary acid load was considered as an intervention. Data screening and extraction were performed by two independent reviewers. Random effects meta-analysis was performed to pool data. Dietary interventions resulted in clinically significant improvement in serum bicarbonate (mean difference (MD):2.98, 95% CI: [0.77, 5.19]; I2: 91%) and higher eGFR levels (MD: 3.16, 95%CI: [0.24, 6.08], I2: 67%) compared to controls. Serum potassium, albumin and body mass index remained unchanged. Dietary interventions were reported to be safe. Subgroup analyses indicated a superiority of plant-based over non-plant-based interventions in the improvement of acid-base balance and eGFR, however, these findings are from low quality and heterogenous studies. Our findings support the beneficial effects of dietary interventions aimed at reducing acid or adding base in the management of metabolic acidosis and kidney function in adults with CKD, with no adverse effects on serum potassium and nutritional status. Well-designed clinical trials looking at the treatment of metabolic acidosis with dietary interventions with a focus on adding base through fruit and vegetables are required.