Anion Gap Research Articles

12564 A Rare Case Of Pembrolizumab Induced Secondary Adrenal Insufficiency

Abstract Disclosure: L. Escano Volquez: None. P. Desai: None. Pembrolizumab is an immune check-point inhibitor that blocks the PD1 receptor and is currently used in the treatment of a vast variety of malignancies. Despite adrenal insufficiency (AI) already being documented as a rare but potential side effect, its diagnosis is usually delayed due to vague presentation, increasing the risk of deleterious outcomes. We present a case of secondary AI while on pembrolizumab in which diagnosis was delayed due to unspecific clinical picture.This is a 66-year-old male who presented to the hospital with decreased appetite, nausea and generalized weakness. Patient was seen a month prior with similar symptoms which were thought to be secondary to poor oral intake in the setting of underlying malignancy. Medical history remarkable for squamous cell carcinoma of the skin with recent lung metastasis for which he was started on pembrolizumab a year ago. On arrival to the emergency department, patient was hypertensive with BP 144/68 mmHg, HR 88, and RR 15. Orthostatic vitals were positive. Physical examination otherwise unremarkable. Laboratory tests revealed mild hypernatremia of 147, potassium of 4.7, chloride 108, HCO3 18, anion gap 21, BUN 33, elevated creatinine 1.62 and elevated beta-hydroxybutyrate 5.4. EKG revealed sinus rhythm. Patient was admitted for further evaluation of orthostasis and starvation ketosis. Initial management included IV fluids and Midodrine. However, patient continued to have episodes of orthostatic hypotension. Lack of improvement of symptoms led to further workup which revealed low AM cortisol of 1.0 and a low ACTH level <3.0 pg/ml, concerning for secondary adrenal insufficiency. Patient was administered Solu-Medrol 40 mg IV before being transitioned to a daily hydrocortisone regimen with subsequent improvement of symptoms. Pembrolizumab induced AI is a very rare event. It is estimated that the incidence approaches 1% and symptoms can develop at any time throughout treatment. Despite its low incidence, it can be life-threatening if not diagnosed and treated promptly. However, given its very heterogeneous and vague clinical presentation, a prompt diagnosis can be difficult. The clinical course of our patient and subsequent resolution of symptoms after appropriate treatment was started, supports the diagnosis of pembrolizumab induced adrenal insufficiency after a year of initiating treatment. This patient had prior hospitalizations and office visits with symptoms that are usually already present in individuals with underlying malignancy, which resulted in underestimation of his symptoms. This case highlights the importance of always considering AI as a potential adverse effect of immune check-point inhibitors. This will ensure a prompt diagnosis and treatment of an endocrine disorder that could otherwise lead to deleterious outcomes if left untreated. Presentation: 6/1/2024

9185 Pembrolizumab-Induced New-Onset Type 1 Diabetes Mellitus: A Case Report

Abstract Disclosure: D. Teng: None. T.L. Connelly: None. M. Ahmad: None. R. Saeed: None. Introduction: Immune checkpoint inhibitors are becoming essential in the treatment of various cancers. Pembrolizumab is a monoclonal antibody that binds PD-1 receptors, thereby enabling an anti-tumor response by preventing T-cell suppression. Common side effects associated with pembrolizumab include thyroid disorders, hepatitis, pneumonitis, and acute kidney injury, among others. We describe an interesting case of a woman presenting with diabetic ketoacidosis (DKA) in the setting of pembrolizumab-associated new-onset type 1 diabetes mellitus, which was reported at 0.1% during initial clinical trials but is now being increasingly recognized as a complication of immune checkpoint therapy. Case Description: The patient is a 70-year-old female with past medical history notable for stage IIIA vulvar squamous cell carcinoma initially diagnosed and treated in 2017, with recurrence in 2022 and in 2023, at which point pembrolizumab therapy was initiated. Approximately one month after her first dose, the patient presented to the emergency department with palpitations, nausea, non-bloody vomiting, polydipsia, and non-bloody diarrhea. On arrival, the patient’s vital signs were as follows: 97.2 °F, BP 128/74 mmHg, heart rate 80 bpm, respiratory rate 18 per minute, and SpO2 100% on room air. No acute findings were noted on physical exam. Initial blood work was notable for: pH 7.146, lactate 2.4 mmol/L, bicarbonate 8 mmol/L, anion gap 37 mmol/L, creatinine 1.59 mg/dL, glucose 563 mg/dL, C-peptide 0.16 ng/mL, HbA1c 6.9%, and WBC 18.8 B/L with neutrophilic predominance. Urinalysis was notable for 4+ glucose and 4+ ketones. The patient was admitted to the progressive care unit and DKA protocol was initiated including the administration of IV fluids, insulin infusion, and electrolyte replacement. Additional blood work was unrevealing, including insulin autoantibodies <0.4 U/mL, negative islet cell IgG cytoplasmic autoantibodies, and negative anti-GAD65 antibodies. The patient was eventually discharged with outpatient Endocrinology follow-up. Discussion: Immunotherapy is quickly redefining the standard of care in the treatment of several types of malignancies through the leveraging of the body’s immune defense apparatus. Pembrolizumab prevents the deactivation of T-cells via the PD-1/PD-L1 pathway. Unfortunately, this also predisposes non-cancerous cells to autoimmune destruction by these T-cells. It is proposed that such is the mechanism by which pancreatic beta islet cells are destroyed in the setting of pembrolizumab use, thereby resulting in a rapid reduction in insulin production capability. New-onset type 1 diabetes complicated by DKA is potentially life-threatening, and so we believe this case highlights the need for both pre-treatment counseling as well as follow-up screening following initiation of pembrolizumab therapy. Presentation: 6/2/2024

7137 The Sugar Saga: A Profound Case Of Diabetic Ketoacidosis Due To Enfortumab Vedotin

Abstract Disclosure: P. Aron: None. B. Connell: None. R. Longo: None. J. Upadhyay: None. This is a case of severe hyperglycemia with the use of Enfortumab Vedotin (EV) in the setting of advanced urothelial cancer. EV is a nectin-4-directed antibody-drug conjugate with a microtubule inhibitor approved for treating advanced/recurrent disease. It is the first of its class that is an antibody-drug conjugate (ADC), targeting nectin, but not the first ADC to cause hyperglycemia. Here we present a case of severe insulin resistance requiring insulin infusion at 50 units/hour in addition to subcutaneous insulin all in the setting of EV use.74 year old male with BMI of 28 and HbA1c of 7.5%, managed only with diet was started on EV for metastatic urothelial cancer. Patient received one cycle (3 doses) of EV (on days 1, 8, 15) and thereafter noticed worsening of hyperglycemia with blood glucose of 533 mg/dL, requiring subcutaneous insulin. Patient’s blood glucose readings remained elevated and he was admitted to the hospital as he was found to be in DKA with a pH of 7.2, bicarbonate 14 mmol/L, anion gap of 16 mmol/L and a glucose of 558 mg/dL. The patient was started on intravenous insulin (IV) infusion using insulin infusion protocol titrated up to 14 units an hour with an additional 30 units of glargine. Patients’ clinical condition continued to worsen and he was in septic shock with pressors and on insulin infusion exceeding 55 units/hour, NPH at 50 units, and regular insulin 30 units with glucose persistently above 400 mg/dL. Patient was started on hydrocortisone 50mg every 6h and his blood glucose readings eventually normalized over a span of 1 week. Patient eventually was able to be discharged to rehabilitation with just a correctional humalog insulin. Our case demonstrates DKA as a consequence of severe insulin resistance seen as a side effect of EV. Hyperglycemia is seen in 8% of patients using this medication, but severe cases are mostly seen with high BMI and uncontrolled diabetes. This case illustrates the fact that one needs to be cautious in ALL patients with diabetes when using this drug and warrants screening for DKA/severe insulin resistance if blood glucose is running >250mg/dL. The exact mechanism for hyperglycemia is unknown but it is likely immunomodulatory and therefore treatment with pulse dose steroids may help with overcoming insulin resistance in this setting like in our patient. More research needs to be done to understand mechanisms and establish treatment guidelines for severe insulin resistance and hyperglycemia caused by this medication. Presentation: 6/1/2024

8494 A Case of Diabetic Ketoacidosis in Setting of COVID-19 Infection and SGLT-2 Inhibitor Use

Abstract Disclosure: N. Abrahimi: None. S. Bajpay: None. A. Abrahimi: None. Background: COVID-19 infection can cause endocrine system disruptions leading to the development of diabetic ketoacidosis (DKA) in patients with type 1, 2 or new onset diabetes mellitus. (1) DKA is a side effect of SGLT-2 inhibitor use and its development on the medication can lead to discontinuation of SGLT-2 inhibitor. (2) SGLT-2 inhibitors are part of guideline directed medical therapy for management of heart failure with reduced ejection fraction (HFrEF). (3) Case: 67-year-old female history of non-insulin dependent diabetes mellitus type 2 on Empagliflozin presented with shortness of breath and hypoxia. Initial BMP: Glucose 141 mg/dL, bicarb 24 mmol/L, anion gap of 10 mmol/L. Patient test positive for COVID-19 and was admitted for acute hypoxic respiratory failure in setting of COVID-19 infection. Six hours after patient received first dose of dexamethasone, labs showed BMP: Glucose 582 mg/dL, bicarb 14 mmol/L, anion gap of 20 mmol/L. ABG: pH 7.09, bicarb 13.2 mmol/L, glucose 509 mg/dL, lactate 9.6, beta-hydroxybutyrate 1.15 mmol/L. Patient was diagnosed and treated for DKA. Patient had an echocardiogram which showed new HFrEF. There was initial hesitation to restart patient on home Empagliflozin due to recent development of DKA. Literature review showed cases of DKA associated with COVID-19 infection. Etiology of DKA remained unclear. Ultimately, it was decided to restart patient on home Empagliflozin for management of diabetes and HFrEF. Conclusion: An abundance of evidence support the benefits of SGLT-2 inhibitors for patients with and without type 2 diabetes mellitus. (4) It is important to consider other causes of DKA for patients who develop DKA on SGLT-2 Inhibitors. Furthermore, additional research into endocrinopathies related to COVID-19 infections should be considered.

7491 Post operative Euglycemic Diabetic Ketoacidosis in Type 2 Diabetic patient - A diagnostic challenge

Abstract Disclosure: S. Azmat: None. O. Lodhi: None. H. Ashok: None. M.F. Siddiqui: None. Euglycemic Diabetic Ketoacidosis (EDKA) is a rare but potentially fatal condition that is often difficult to diagnose as underlying ketoacidosis is masked by euglycemia. The diagnosis and management of this condition requires a swift and comprehensive approach to avoid delay. We report a case of 66-year-old female with Insulin-dependent Type 2 DM who developed postoperative euglycemic diabetic ketoacidosis, highlighting the significance of maintaining a high degree of suspicion for EDKA in postoperative patients, whose surgical course may obscure the underlying diabetic ketoacidosis symptoms. Clinical Case: A 66-year-old female with past medical history of Insulin dependent Type 2 DM presented to the emergency department with severe epigastric pain. CT Abdomen revealed perforated gastric ulcer with pneumoperitoneum requiring urgent laparoscopic graham patch repair. Patient’s outpatient medications include Lantus and metformin. She had mild hyperglycemia on admission with blood glucose of 176 mg/dL (140-160mg/dL) without metabolic abnormality. Insulin administration was omitted due to pre and post operative normoglycemia. The patient was NPO followed by initiation of nasogastric tube feeds. Postoperative course was complicated by hypotension, generalized abdominal discomfort and anion gap metabolic acidosis. Graham patch failure, abdominal infection, and post-surgical complications were systematically ruled out. Patient continued to decline with worsening anion gap metabolic acidosis; pH of 7.18 (7.35-7.45), HCO3 < 10 mEq/L (21 mEq/L - 31 mEq/L), anion gap15 mmol/L (8 to 12 mmol/L), blood sugar (147-208 mg/dl). There was no lactic acidosis or renal impairment. Beta hydroxybutyrate levels were elevated at > 4.5 mmol/L. Thus diagnosis of euglycemic DKA was established and treated with insulin drip per DKA protocol and dextrose fluids. EDKA resolved within five days with clinical improvement. She was transitioned to subcutaneous basal bolus insulin. She remained euglycemic and and had good surgical outcomes.Discussion: Euglycemic DKA is rare with only 2.6% to 3.2% of DKA, presenting as euglycemic. It presents as unique diagnostic challenge due to atypical DKA presentation with blood glucose less than 250 mg/dL. The primary driver for EDKA is either a reduction in hepatic glucose production at times of fasting or the overabundance of counter-regulatory hormones resulting in excess glucosuria. Literature has reported the effects short-term fasting on developing EDKA and starvation induced ketosis secondary to extreme ketogenic diets or bariatric surgery primarily among Type 1 diabetics. Clinically patients may exhibit symptoms similar to classic DKA, however, this classic picture may be confounded in a critically ill post-surgical patient, thus delaying recognition. This emphasizes the importance of including EDKA in differentials while evaluating such patients. Presentation: 6/1/2024

Suggested guide to using lactate gap as a surrogate marker in the diagnosis of ethylene glycol overdose.

Ethylene glycol (EG) poisoning, if not diagnosed rapidly, can lead to poor patient outcomes. Gas Chromatography (GC) is primarily used for EG quantitation which is rarely available, and the turn-around time may be prolonged. Most lactate results from point-of care (POCT) methods are falsely elevated in EG poisoning compared with automated chemistry analyser results. In combination the lactate gap (POCT-Automated chemistry) can be used as surrogate marker in just about all laboratories to indicate likely EG toxicity and guide treatment. A male presented by ambulance to hospital with severe agitation requiring mechanical ventilation to facilitate ongoing management. Venous blood gas analysis confirmed a high anion gap metabolic acidosis (HAGMA) with an elevated lactate. The lactate and osmolarity measured in the laboratory showed a normal lactate and high osmolarity, giving a large osmolar gap. The patient was immediately commenced on renal replacement therapy for presumed EG poisoning to minimize kidney injury, and the treatment continued for 19 hours. A very high EG concentration was confirmed by GC the next day. An elevated lactate gap along with a HAGMA and osmolar gap can provide rapid surrogate laboratory data indicating EG poisoning enabling timely treatment and better patient outcomes.

Characteristics and Treatment Outcome of Pediatric Diabetic Ketoacidosis in Mekong Delta, Vietnam: A 5-Year Retrospective Study

Background Diabetic ketoacidosis (DKA), a critical and potentially fatal complication resulting from a lack of insulin, presents with elevated blood sugar, acid-base imbalance, and increased ketone bodies. Objectives Our research was designed to assess the clinical manifestations, laboratory findings, and outcomes of treatment in children diagnosed with DKA over a span of five years in the Mekong Delta region of Vietnam. Methods This study retrospectively analyzed pediatric cases of diabetic ketoacidosis treated at a major pediatric center in the Mekong Delta between 2017 and 2021. Results Diabetic ketoacidosis was more common in older children aged 11 – 16 years (66.7%), and females (70%). The majority of cases had not been diagnosed with previous diabetes (60%) and no history of diabetic ketoacidosis (90%). In univariate analysis, female gender (OR, 13.0; 95% CI, 1.4 – 124.3; p=0.026), previous diabetes diagnosis (OR, 7.8; 95% CI, 1.5 – 41.2; p=0.016), precipitating factors (OR, 10.1; 95% CI, 1.1 – 97.0; p=0.045), tachypnea (OR, 5.5; 95% CI, 1.1 – 26.4; p=0.033), Kussmaul breathing (OR, 5.4; 95% CI, 1.1 – 26.0; p=0.036), serum potassium level (OR, 3.5; 95% CI, 1.2 – 10.4; p=0.027), and anion gap (OR, 1.6; 95% CI, 1.8 – 2.3; p=0.003) were associated factors with severe DKA. All cases in our study had a 100% survival rate. Anion gap was an independent factor associated with severe diabetic ketoacidosis after adjustment multivariate analysis. Conclusion: Female, younger age, precipitating factors, tachypnea, Kussmaul’s breathing, and relevant laboratory findings, including increased anion gap, should be considered to ensure successful management in pediatric diabetic ketoacidosis. Bangladesh Journal of Medical Science Vol. 23 No. 04 October’24 Page : 1112-1119

A-092 Siemens Healthineers Commitment to Quality - A Focus on Continuous Improvement and Customer Experience

Abstract Background It is necessary that each step of in vitro diagnostic assay development and manufacturing processes be documented and executed in alignment with established quality management systems. Here, we describe how Siemens Healthineers (SHS) maintains assay traceability and focus on continuous improvement using the Atellica® CH A-LYTE® Integrated Multisensor Technology (IMT) assays measuring electrolytes sodium (Na), potassium (K), and chloride (Cl) as a prime example. Methods Establishing an unbroken chain of comparison from the National Institute of Standards and Technology (NIST) higher standard references to the product calibrators ensures accurate value assignment within stated measurement uncertainties. Traceability and standardization are achieved by creating a panel of 10 serum anchor pools spanning the analytical measuring interval for each electrolyte: Na, K, and Cl. The concentrations of the anchor pools are determined at a reference laboratory using methods calibrated with standard solutions derived from NIST reference material. These serum anchor pools are used by SHS, assigning values to product calibrator material which maintains the chain of traceability to the primary reference methods. In addition to traceability, onboard stability for the A-LYTE® IMT multisensor is continuously monitored and evaluated against allowable drift limits for each electrolyte. Although observed drift was within allowable limits, a design change was implemented to improve recovery drift over the use life of the sensor. Results To ensure consistent, robust, and accurate performance of the A-LYTE IMT, a strict set of testing procedures are used to verify the accuracy of value assignments for each manufactured lot of master standards. The recovery of the NIST standard reference material must fall within manufacturer established acceptable bias limits. Consistency over nine master lots is shown with bias ranging from -0.9% to +1.9%, -2.4% to +1.8% and -1.8 to +0.5%, for Na, K and Cl, respectively. By further optimizing the amount of Na ionophore and the polymer matrix of the Na sensor, drift over the use life was minimized and onboard stability improved. Prior to making the sensor change, customer Na QC data at 116 mmol/L showed an SD of 1.1 mmol/L (n=585), whereas the precision improved to an SD of 0.6 mmol/L (n=470) post-optimization. As Manufacturers optimize assay performance, it may become necessary for laboratories to re-evaluate reference intervals for their patient populations. For example, one large integrated delivery network established a new reference interval for patient anion gap (AG). A re-evaluation of the historical AG reference interval which was 5-15 mmol/L identified the need for an update. AG values were calculated from 16,948 healthy patients and used to establish a new reference interval of 2-10 mmol/L. Conclusions Accurate clinical laboratory measurements are critical for diagnosing, monitoring, and treating diseases. A-LYTE assays have an unbroken chain of traceability to NIST reference material and minimal drift over the life of the multisensor. Continuous monitoring to identify improvement projects and rigorous control systems ensure sensor performance over time. This provides confidence that the patient results produced by the laboratory are accurate and consistent over time and across different laboratory locations.

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.

Hyperchloremic metabolic acidosis potentially benefiting sodium bicarbonate therapy: A multi-center cohort study

BackgroundThe use of sodium bicarbonate for metabolic acidosis has been a topic of debate, primarily due to the lack of clinical efficacy evidence. This study aims to identify which types of patients with various acid-base balance parameters can benefit from sodium bicarbonate therapy. MethodsPatients diagnosed with metabolic acidosis were screened from a large multi-center critical care database to form a retrospective cohort. Mortality curves, logistic regression analysis, simulation methods, and propensity scores were used to compare data between sodium bicarbonate (SOB group) and non-treated (Non-SOB group) patients. ResultsThere was an interaction between baseline chloride, anion gap levels and sodium bicarbonate therapy on patients' in-hospital death. As chloride levels increased, the in-hospital mortality curves of the SOB group and Non-SOB group gradually converged, with the difference narrowing from approximately 20 % to 10 %, and then gradually widened with the increase of the anion gap. Furthermore, when patients had high chloride levels (≥112 mmol/L), those in the SOB group exhibited a higher incidence of hypernatremia, hypokalemia, and hypocalcemia at 24 h, and a lower incidence of hyperchloremia. Patients in SOB group also had a lower simulated mortality. Among patients treated with sodium bicarbonate, those with low chloride had more difficulty in normalizing pH compared to those with high chloride. ConclusionsThis study identified an interaction between baseline chloride and sodium bicarbonate therapy on patient survival. Hyperchloremic metabolic acidosis may potentially benefit from sodium bicarbonate therapy. Further prospective randomized controlled studies are warranted.

Treatment of 5-oxyproline Anion Gap Acidosis with N-acetylcysteine

Treatment of 5-oxyproline Anion Gap Acidosis with N-acetylcysteine

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

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

Relationship between the albumin-corrected anion gap and short-term prognosis among patients with cardiogenic shock: a retrospective analysis of the MIMIC-IV and eICU databases

ObjectivesWe aimed to investigate the association between the albumin-corrected anion gap (ACAG) and the prognosis of cardiogenic shock (CS).DesignA multicentre retrospective cohort study.SettingData were collected from the Medical Information Mart...

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.

Increased serum albumin corrected anion gap levels are associated with poor prognosis in septic patients with liver cirrhosis

The prognosis of septic patients with cirrhosis is worse compared to septic patients without cirrhosis. Early and accurate prognosis determination in patients with cirrhosis and sepsis is pivotal for guiding treatment decisions. The aim of this study was to investigate the association between albumin-corrected anion gap (ACAG) and clinical prognosis of patients with sepsis and cirrhosis. This study extracted data of patients with sepsis and cirrhosis from the Medical Information Mart for Intensive Care (MIMIC-IV) database. A total of 1340 patients (64.6% male) were enrolled. After confounders adjusting, elevated ACAG had a significant association with 28-day mortality (HR1.604; 95% CI 1.258–2.048; P < 0.001). Restricted cubic spline revealed that a linear relationship between ACAG and 28-day mortality (P-nonlinear = 0.089, P-overall = 0.001). According to the ROC curve analysis, the ACAG demonstrated a higher area under the curve (AUC) of 0.703 compared to AG (0.675). Kaplan–Meier analysis revealed higher 28-day mortality in high ACAG group (log-rank test, χ^2 = 175.638, P < 0.001). Furthermore, subgroup analysis showed a significant interaction between ACAG and etiology of cirrhosis (P for interaction = 0.014). Therefore, ACAG could provide clinicians with valuable insights for guiding interventions in this high-risk population.

Insights into the baseline blood pH homeostasis at admission and the risk of in-hospital mortality in COVID-19 patients.

Aim: A laboratory finding in critically ill COVID-19 patients is blood academia (pH <7.35). We investigated its cause in connection with the admission baseline blood pH homeostasis.Patients & methods: We retrospectively monitored the baseline blood pH homeostasis of 1215 COVID-19 patients who were admitted with pneumonia using data-driven knowledge. Two categories of patients were identified: non-survivors (107) and survivors (1108).Results: Non-survivors showed greater levels of lactate and lower blood pH, saturation, and partial pressure of oxygen than survivors. A bivariate Spearman's correlation matrix showed that the [HCO3-]/pCO2 and pCO2 of non-survivors exhibited an unmatched connection, but not in the survivor group. When comparing non-survivors to survivors, the dendrograms derived from the bivariate comparison matrix showed differences in gasometry parameters like blood pH, [HCO3-]/pCO2 ratio, anion gap and pO2.Conclusion: The little variations in the gasometry readings between survivors and non-survivors upon admission suggested abnormal changes in the complementary renal and respiratory systems that bring blood pH back to normal. In advanced COVID-19, modest blood acid-base imbalances could become blood acidemia if these compensatory strategies were overused. Data-driven monitoring of acid-base parameters may help predict abnormal blood pH and the advancement of metabolic acidemia before it is too late.

Early Versus Late Administration of Long-Acting Insulin in Adult Diabetic Ketoacidosis.

Evidence is inconclusive if early administration of subcutaneous (SQ) long-acting insulin (LAI) in management of diabetic ketoacidosis (DKA) improves outcomes. This study compares early versus late administration of SQ LAI in time to DKA resolution. This single-center, retrospective study included patients with DKA who received ≥12 hours of continuous intravenous insulin (CIVI) with LAI overlap. Patients were compared based on LAI administration time to CIVI initiation: Early (<12 hours) versus Late (≥12 hours). The DKA resolution is defined as blood glucose < 200 mg/dL and 2 of the following: anion gap < 12 mEq/L, pH > 7.35, or serum carbon dioxide >15 mEq/L. Outcomes included time to DKA resolution, length of stay (LOS), CIVI duration, and adverse events. A total of 27 patients were included in each group. Baseline characteristics were similar between both groups. There was no difference in time to DKA resolution, Early = 17.6 (13.9-26.8) hours versus Late = 19.2 (17.1-32.1) hours, P = 0.16. The Early group had shorter CIVI duration (Early = 19.5 ± 10.3 hours vs Late = 25.6 ± 8.4 hours, P = 0.02) and received less intravenous (IV) fluids in the first 36 hours (Early = 4.04 ± 2.12 L vs Late = 5.85 ± 2.24 L, P = 0.004). No differences were identified with adverse events, including hypoglycemia, or LOS. Administration of SQ LAI < 12 hours did not decrease time to DKA resolution or LOS. Patients in the Early group had received a lower dose of LAI, shorter duration of CIVI infusion, and required less IV fluids within 36 hours of admission. This study supports the need for further research to determine the potential benefits of administering SQ insulin early in managing DKA.

Acute cyanide intoxication due to apricot seed ingestion.

Introduction: Cyanide poisoning, whether it be accidental or intentional, remains a significant danger to adults and children, especially in societies where agriculture is a primary source of income. We examined the clinical follow-up, complications, and results of cyanide poisoning cases that occurred after eating the pits and seeds of plants containing cyanide glycosides, such as apricot kernels and almonds. Methods: Between 01/01/2017 and 01/08/2022, 14 children aged 1-18 years who were followed up with a prediagnosis of cyanide poisoning in our Paediatric Intensive Care Unit (PICU) were retrospectively analysed. Results: Eight of the patients followed with a preliminary diagnosis of cyanide poisoning were female and six were male. The most common admission month was July (42.8%) coinciding with the agricultural season. The most common symptoms at presentation were weakness and fatigue (n = 7). In the PICU, 4 patients presented lip cyanosis; 3, altered level of consciousness. Vomiting, seizure, headache, dizziness and palpitatons were less frequent. Four patients were treated with hydroxocobalamin (Cyanokit®) as an antidote due to acidosis in their blood gases. All patients treated for cyanide poisoning were discharged. Conclusions: Cyanide poisoning should be considered in paediatric patients with suspicious findings, sudden loss of consciousness, increased anion gap acidosis and lactic acidosis. The history of eating the seeds of plants such as apricot and almonds should be investigated.