Anion Gap Metabolic Acidosis Research Articles

A rare and underestimated cause of anion gap metabolic acidosis in a pediatric patient

Abstract Recognized causes of anion gap metabolic acidosis include methanol, uremia, diabetic ketoacidosis, propylene glycol, isoniazid, iron, lactic acidosis, ethylene glycol, and salicylates, which is taught as the mnemonic, MUDPILES. While this mnemonic can be a useful learning tool, it is important to consider other, atypical causes. Here, we present the case of a 9-year-old male patient with a complex medical history, including trisomy 21 and Lennox-Gastaut syndrome who presented to the emergency department (ED) in hypotensive shock. Upon admission, he was noted to have a distended abdomen, evidence of acute pancreatitis and possible sepsis. Of note, his initial labs revealed an anion gap of 30.1 mmol/L, a whole blood lactate of 4.4 mmol/L, a pH of 7.2, and a normal pCO2, indicting an anion gap metabolic acidosis. Importantly, methanol, ethylene glycol, ketones, and salicylates were not detected, and renal function was normal. However, he did have an extensive medication history, including several antiepileptic drugs (AEDs). Over the coming weeks, he recovered from the acute pancreatitis, but developed fluid overload, electrolyte derangements (hypernatremia and hypokalemia), a worsening metabolic acidosis with an anion gap up to 54.6 mmol/L, and hyperammonemia (plasma NH3 of 232 μmol/L). At this point, the metabolism team was contacted for concerns regarding the rising ammonia levels, which subsequently responded to a combination of lactulose and Rifaximin. An inborn error of metabolism (IEM) was considered, and plasma amino acid analysis was performed (Waters Acquity MassTrak AAA solution) but was not diagnostic. Notably, the patient developed a significantly elevated gamma glutamyl transpeptidase (GGT) up to 4088 U/L, suggesting glutathione depletion, however, transaminases and alkaline phosphatase were normal. The laboratory was contacted by the metabolism providers for other possible causes of metabolic acidosis and it was suggested that the patient undergo urine organic acid testing. Urine specimens were analyzed using gas chromatography/mass spectrometry (GC/MS) (Aligent system). The results were notable for marked excretion of pyroglutamic acid (5-oxoproline), which is typically associated with acetaminophen, however, the patient’s acetaminophen levels were less than 5 μg/mL, indicating another, atypical cause of increased pyroglutamic acid. In this case, vigabatrin, an anticonvulsant known to cause glutathione depletion and secondary pyroglutamic aciduria was suspected, and subsequently withdrawn. The patient was also started on a trial of N-acetylcysteine (NAC) to replenish glutathione, which resolved the pyroglutamic aciduria and anion gap, and corrected the metabolic acidosis. This case highlights the importance of recognizing pyroglutamic acid as a rare cause of anion gap metabolic acidosis, even in the setting of normal acetaminophen levels, and the importance of organic acid testing in the work-up of such patients. Wider use of the mnemonic GOLD MARK, where the “O” stands for oxoproline, may help in the differential diagnosis of anion gap metabolic acidosis.

Association between delta anion gap/delta bicarbonate and outcome of surgical patients admitted to intensive care unit

BackgroundPatients undergoing high-risk surgeries with acid-based disorders are associated with poor outcomes. The screening of mixed acid-based metabolic disorders by calculating delta anion gap (AG)/delta bicarbonate (Bic) has a clinically relevant role in patients with high AG metabolic acidosis (MA), however its utility in individuals facing high-risk surgical procedures remains unclear.ObjectiveCharacterize metabolic acidosis using delta-AG/delta-Bic and its associations in patients undergoing high-risk surgeries with possible outcome-related complications.DesignProspective observational multicentric study.SettingThree tertiary hospitals in Brazil.PatientsPatients undergoing high-risk surgeries, aged 18 years or older, requiring postoperative critical care.Main outcome measuresPatients undergoing high-risk surgeries monitored during the postoperative phase across three distinct intensive care units (ICUs), with assessment encompassing laboratory analyses upon admission and 24 h thereafter. Patients with MA and with elevated AG within 24 h were separated into 3 subgroups: [G1 – delta-AG/delta-Bic < 1.0] MA associated with hyperchloremia; [G2 – delta-AG/delta-Bic between 1.0 and 1.6] MA and no mixed disorders; and [G3 – delta-AG/delta-Bic > 1.6] MA associated with alkalosis. Primary endpoint was 30-day mortality. The secondary endpoints were cardiovascular, respiratory, renal, neurological, coagulation and infective complications.ResultsFrom the 621 surgical patients admitted to ICU, 421 (51.7%) had any type of acidosis. After 24 h, 140 patients remained with MA with elevated AG (G1: 101, G2: 18, and G3: 21). When compared to patients from subgroups 1 and 3, the subgroup with no mixed disorders 2 showed higher 30-day mortality (adjusted HR = 3.72; 95% CI 1.11–12.89, p = 0.001), cardiovascular complications (p = 0.001), ICU mortality (p = 0.03) and sum of all complications during the ICU period (p = 0.021).ConclusionIn the postoperative time, patients with metabolic acidosis and no mixed disorders present higher ICU-Mortality and higher cardiovascular postoperative complications when compared with patients with combined hyperchloremia or alkalosis. Delta-AG/delta-Bic can be a useful tool to evaluate major clinical outcomes in this population.

8075 Euglycemic Diabetic Ketoacidosis Associated With Cocaine Use

Abstract Disclosure: N.N. Solanki: None. A.N. Kiani: None. M. Feldman: None. Euglycemic diabetic ketoacidosis (EDKA) is characterized by increased anion gap metabolic acidosis, ketonemia or ketonuria, and normal blood glucose levels (&amp;lt;200 mg/dL). Due to the absence of hyperglycemia, it commonly presents as a diagnostic and therapeutic dilemma. EDKA is commonly associated with decreased caloric intake, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, recent use of insulin, heavy alcohol consumption, chronic liver disease, glycogen storage disorders, and drug-induced intoxication. Cocaine use is a lesser-known etiology for EDKA. We present a case of a 64-year-old female with a history of type 2 diabetes mellitus who presented with complaints of decreased oral intake for two days secondary to nausea and vomiting and productive cough for one week, along with cocaine use. Despite an extensive history of diabetes and no recent SGLT-2 inhibitor use, her labs were consistent with euglycemic DKA. Her imaging and further investigations revealed respiratory syncytial virus pneumonia. The patient was initially managed for starvation ketoacidosis with fluid resuscitation with no improvement in acidosis and later treated with DKA protocol with rapid correction of her anion gap metabolic acidosis. This case highlights the challenges associated with diagnosing and treating EDKA. Early initiation of DKA protocol should be considered in diabetic patients presenting with euglycemia with high anion gap metabolic acidosis with a clinical picture of starvation and cocaine use. Presentation: 6/3/2024

12397 Predictors Of Hospital Readmission Within Three Months Among Patients Admitted For Diabetic Ketoacidosis (dka)

Abstract Disclosure: O. Onwudiwe: None. L. Yerashevich: None. C. Onwudiwe: None. B. Baral: None. A. Acharya: None. H. Nguyen: None. Purpose: Diabetic ketoacidosis (DKA) represents a critical, life-threatening complication of diabetes, with higher rates of re-admission noted among individuals from lower socioeconomic backgrounds, those lacking insurance coverage, and those with suboptimal follow-up care. This study seeks to identify predictors of hospital readmission within three months among patients admitted for DKA in a community hospital setting. Methods: Patient data were extracted from electronic medical records from 2019 to 2021 for individuals admitted due to DKA using ICD codes. DKA diagnosis was based on the presence of hyperglycemia, high anion gap metabolic acidosis, and ketonemia. Demographic information, results of routine biochemical tests, insurance status, follow-up with primary care providers (PCP) or endocrinologists, and clinical progression were retrospectively collected from patients' records. Multivariable logistic regression analyses were conducted to identify predictors of readmission. Results: A total of 222 unique DKA admission visits were analyzed. The mean age (standard deviation) of the patients was 48 (16) years, and 58% of them were male. Among these visits, 39% had type 1 diabetes, 43% had type 2 diabetes, and 18% were newly diagnosed diabetes cases. The majority of patients were overweight, with a mean body mass index (BMI) of 27, and the mean glycated hemoglobin level was 10.8. Common triggers for DKA included insulin non-adherence (52%), infection (37.8%), and alcohol use (8.6%). Logistic regression analysis revealed that lack of follow-up significantly increased the odds of readmission within three months (B = 2.025, p = .003, Exp(B) = 7.576, 95% CI [1.952, 29.401]), as did having type 1 diabetes (B = 1.473, p = .019, Exp(B) = 4.364, 95% CI [1.272, 14.978]). However, the association between insulin adherence and readmission was not statistically significant at the conventional alpha level of 0.05 (B = 1.329, p = .112, Exp(B) = 3.777, 95% CI [0.733, 19.458]). Other demographic (age, gender, employment status, insurance status, medication compliance,) and clinical [insulin adherence, presence of infection, blood glucose level at diagnosis of DKA, and level of glycated hemoglobin (Hba1c)] variables did not significantly predict readmission within 3 months. Conclusion: DKA, being preventable with adequate insulin adherence, is also influenced by factors such as infection and lifestyle choices. The findings highlight the critical role of post-discharge follow-up care in reducing readmission rates among DKA patients. Healthcare providers should prioritize ensuring timely and comprehensive follow-up, particularly for patients with type 1 diabetes, to optimize post-hospitalization management and prevent avoidable readmissions. Presentation: 6/3/2024

6769 Rhabdomyolysis In Diabetic Emergencies Highlighting The Necessity Of Prompt Creatine Kinase Monitoring

Abstract Disclosure: A. Tiwari: None. M. Corsten: None. W. salari: None. N. Malik: None. A. Dabaja: None. C. Saad: None. Rhabdomyolysis results from skeletal muscle necrosis, causing the release of intracellular contents into the bloodstream. While its association with life-threatening diabetic emergencies is rare, it remains a significant complication. We detail the case of a 37-year-old male admitted with acute pancreatitis who subsequently developed a hyperosmolar hyperglycemic state accompanied by significant electrolyte imbalances. Upon arrival at our emergency department, he displayed severe dehydration, stupor, a blood glucose level surpassing 2,000 mg/dl, and high anion gap metabolic acidosis. His condition worsened when his creatine kinase levels surged from 210 U/L to 39,000 U/L, leading to oliguric renal failure and the need for hemodialysis. His thyroid profile was unremarkable and was not on any medication. Comprehensive treatment included crystalloids, parenteral insulin, and rigorous ICU monitoring with mechanical ventilation. Following this, the patient showed rapid improvement and was discharged without requiring further dialysis. A thorough history and observation established a rare but strong link between rhabdomyolysis and hyperosmolar hyperglycemic states. These situations can intensify nephrotoxic events, especially in patients already facing severe dehydration and prerenal factors. This case emphasizes the critical need for consistent monitoring of creatine kinase levels in diabetic emergencies. Such monitoring ensures early detection and facilitates effective management of rhabdomyolysis-induced acute kidney injury, reducing potential complications and improving patient outcomes. Presentation: 6/3/2024

6541 Recurrent Euglycemic Diabetic Ketoacidosis And Myonecrosis In A Patient Previously Thought To Have Type 2 Diabetes Mellitus

Abstract Disclosure: K. Haridas: None. M.M. McConnell : None. Introduction: Euglycemic diabetic ketoacidosis (DKA) is a well-recognized complication with the use of sodium linked cotransport of glucose-2 (SGLT2) inhibitors. Diabetic myonecrosis is a rare complication of diabetes mellitus caused by spontaneous death of muscle due to microvascular ischemia. Clinical Case: A 48-year-old male diagnosed with Type 2 Diabetes Mellitus with HbA1c 11.3%, treated with Empagliflozin and basal-bolus insulin was admitted to the hospital with left thigh pain and anorexia. Physical examination was notable for BMI of 19kg/m2 and left lateral thigh induration. Laboratory evaluation revealed venous pH 7.1, bicarbonate 10mmol/L (20-30), anion gap 32mmol/L(8-12), glucose 168mg/dl (65-99), ESR 67mm/h (&amp;lt;=12), Creatinine Kinase 31 U/L (63-473), glucosuria (4+) and ketonuria (4+). He was diagnosed with euglycemic DKA due to SGLT2 inhibitor. He was also diagnosed with Type 1 Diabetes Mellitus (T1DM) based on undetectable C-peptide and GAD antibody titer 64.3IU/ml(&amp;lt;5). MRI of the left thigh revealed an area of diabetic myonecrosis, measuring 11cm. He was treated with continuous insulin infusion. On hospital day 3, after resolution of the anion gap metabolic acidosis, transition was made to basal-bolus insulin. On hospital day 5, recurrent euglycemic DKA was diagnosed with bicarbonate 15mmol/L, anion gap 18mmol/L, beta-hydroxybutyrate 49.6mg/dl (&amp;lt;=3mg/dl), glucose 185mg/dl, glucosuria (4+) and ketonuria (4+). Continuous insulin infusion was restarted. On hospital day 8, transition was made to subcutaneous insulin. Diabetic myonecrosis was initially managed conservatively with analgesics, aspirin, and physical therapy. Due to worsening leukocytosis on hospital day 13, Ceftriaxone was started and surgical debridement was performed, revealing a loculated abscess within necrotic muscle. Empagliflozin was discontinued at discharge. Discussion: The risk of euglycemic DKA with SGLT2i use is increased in patients with T1DM and decreased oral intake, and insults like trauma or surgery as seen in this patient. Although the half-life of empagliflozin is 12 to 14 hours, there have been case reports of persistent or recurrent euglycemic DKA for 7-12 days from the time of last dose. The continued glucosuria and ketonuria in this patient with serum glucose levels below the renal threshold confirmed the recurrence. Diabetic myonecrosis usually affects the muscles of the proximal lower extremities and is seen in patients with poorly controlled diabetes with microvascular complications, between one and two decades after diagnosis, as in this patient. Conclusion: A high index of suspicion for recurrent euglycemic DKA must be maintained in patients who have new or persistent high anion gap metabolic acidosis until 2 weeks from last dose of SGLT2 inhibitor. Diabetic myonecrosis, especially if complicated by abscess formation, may require surgical intervention. Presentation: 6/1/2024

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 &amp;lt; 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 &amp;gt; 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

7643 Acute blindness due to Metformin associated lactic acidosis

Abstract Disclosure: K.N. Pereira: None. K. Desai: None. T. Khan: None. S. Yong: None. Metformin, one of the most commonly prescribed oral hypoglycemic agents, effectively lowers basal and postprandial blood glucose. However, Metformin carries a black box warning for lactic acidosis, which is more common in setting of liver and kidney dysfunction. With an incidence rate of ∼ 4.3 cases per 100,000 patient-years, Metformin associated lactic acidosis (MALA) can present with nausea, vomiting, diarrhea, encephalopathy, hypothermia, respiratory failure and hypotension. Blindness is a rarely reported outcome of MALA. We present a case of a 48 year old intellectually disabled female with a history of type 2 diabetes (on Metformin) who presented with progressive encephalopathy insetting of intractable nausea and vomiting with poor oral intake, since starting lisinopril &amp; rosuvastatin for newly diagnosed hypertension and hyperlipidemia. She was encephalopathic, hypothermic, hypotensive, tachycardic and tachypneic. Labs were notable for leukocytosis, AKI, hyperkalemia, elevated anion gap metabolic acidosis with a lactate of 13.6 and elevated lipase. She also tested positive for Influenza A. CT head showed no acute intracranial abnormality. CT chest, abdomen &amp; pelvis was concerning for aspiration, multifocal pneumonia or a combination of both as well as acute interstitial pancreatitis. She was admitted to the ICU for further management including hemodialysis. She continued to have improving but persistent lactic acidosis despite multiple dialysis sessions. On day 5 of ICU stay, with resolution of her encephalopathy, she reported new onset complete bilateral painless vision loss. General eye and neurologic exam was unrevealing except for sluggishly reactive pupils to light. MRI brain showed an new acute 2 mm lacunar infarct in the right temporal lobe. Neurology ruled out stroke as the cause for her vision loss. Emergent ophthalmology evaluation revealed no retinopathy, macular edema, acute glaucoma or thromboembolic event. The new onset vision loss was suspected to be due to MALA due to persistent metabolic disturbances. Some animal studies have shown that retinal horizontal cells are sensitive to low pH, resulting in interruption of signal transmission to the visual neurons and consequent blindness. The presence of factors like metformin metabolites may contribute to impaired function of retinal cells.On extensive literature review it was noted that only 5 cases of vision loss associated with MALA have been reported. However, in these cases, vision loss was transient and reversed following correction of acidosis with dialysis. Our case highlights a rare consequence of MALA, which can be irreversible and cause lifelong disability. Presentation: 6/1/2024

9332 Breathless Struggle: Unraveling The Interplay Between DKA And Acute Respiratory Distress Syndrome

Abstract Disclosure: S. Zahra: None. R. Subramani: None. M. Abbas: None. K.Y. Hasan: None. F. Manas: None. C. Bajracharya: None. Introduction: Diabetic Ketoacidosis (DKA) is a life threatening emergency with mortality rate of 0.15%-0.30%. Acute Respiratory Distress Syndrome (ARDS) is a rare complication of DKA which presents as a sudden onset of dyspnea and progressive hypoxia. It is an inflammatory process that damages the alveolar-capillary membrane leading to the fluid leakage into the alveolar space. The incidence of ARDS in DKA remains unknown. It is more commonly seen in adolescents and young adults. The exact pathogenesis of ARDS in DKA is currently unknown. Some proposed mechanisms are that a severe metabolic acidosis in DKA along with increased cytokines production due to long standing hyperglycemia leads to increased capillary membrane permeability allowing fluid to accumulate in the alveolar space. TNF-a and IL-6 along with other pro-inflammatory cytokines are known to cause endothelial damage and increase pulmonary permeability leading to pulmonary edema. However most DKA patients with severe metabolic acidosis do not develop ARDS. Case Presentation:Case 1: A 19 year old male with uncontrolled type I diabetes mellitus presented with altered mental status. On examination, he was tachycardic and tachypneic with dry mucous membranes. Lab workup revealed leukocytosis, severe hyperglycemia, and severe anion gap metabolic acidosis with beta hydroxybutyrate level of 14.20 mmol/L (normal: 0.02-0.27 mmol/L). He was diagnosed with DKA and started on intravenous fluids, and insulin as per institutional DKA protocol. Approximately 12 hours post-admission, the patient experienced sudden-onset dyspnea with deteriorating hypoxia, necessitating emergent intubation and mechanical ventilation. Chest radiography displayed bilateral patchy ground-glass opacifications consistent with acute respiratory distress syndrome (ARDS). Despite the administration of 8 liters of intravenous fluids, the patient exhibited a negative net fluid balance of 2.3 liters, implicating fluid shift. Further investigations, including bronchoscopy and bronchoalveolar lavage, revealed an unobstructed airway, minimal secretions, and no evidence of hemorrhage or infection. Comprehensive infectious work-ups yielded negative results as well, reinforcing the diagnosis of DKA as the underlying cause of ARDS. Conclusion: Acute Respiratory Distress Syndrome is a rare but potentially fatal complication of Diabetic Ketoacidosis. Early recognition of this serious pulmonary complication of DKA and its prompt management is essential to prevent respiratory failure and mortality. Presentation: 6/1/2024

8243 Euglycemic Diabetic Ketoacidosis Unveiled: Delayed Presentation and Complications of SGLT-2 Inhibitor Therapy in a Multimorbid Patient - A Case Report

Abstract Disclosure: T. Amin: None. A.K. Bala: None. M.A. Jones: None. M.S. Akula: None. K. Chalasani: None. M. Patel: None. J. Cheng: None. Introduction: Normal serum glucose levels (&amp;lt;200 mg/dL) in euglycemic diabetic ketoacidosis (EDKA) can complicate the typical clinical presentation of diabetic ketoacidosis (DKA), posing a diagnostic challenge. SGLT-2 inhibitors, a class of antihyperglycemic drugs, have been rarely but significantly associated with EDKA. These inhibitors enhance renal glucose clearance by preventing glucose reabsorption via sodium-glucose cotransport. The increased renal clearance may contribute to the euglycemic picture, potentially leading to an underestimation of required insulin dosage, thereby precipitating ketoacidosis in EDKA. Although the mechanisms of EDKA are not fully understood, the association with SGLT-2 inhibitors is becoming increasingly evident. Case A 53-year-old male with a medical history of type 2 Diabetes Mellitus, coronary artery disease, chronic kidney disease, hyperlipidemia, was admitted to the trauma bay after a fall. Medications included empagliflozin, metformin, aspirin, amlodipine, spironolactone, and carvedilol. Upon presentation, he had a brief loss of consciousness, complained of headache and chest pain, and was found to have an epidural hematoma with regional brain compression on the CT head. Admission labs showed a blood glucose level of 172, an unremarkable anion gap, and normal renal and liver function tests. Due to traumatic brain injury, he was admitted to the ICU for neurological monitoring. Despite remaining neurologically stable, he developed hypoxia, necessitating intubation. After successful extubation, he exhibited worsening metabolic acidosis on the fourth day, with an elevated anion gap of 22 and a blood glucose level of 174. Arterial blood gas analysis revealed a pH of 7.3 (and elevated beta-hydroxybutyrate (&amp;gt;4), while lactic acid levels remained normal. Urine analysis showed elevated blood glucose (&amp;gt;1000) and ketones (&amp;gt;40). Home medications, metformin, and empagliflozin were appropriately withheld, but euglycemic DKA attributed to empagliflozin was diagnosed. Treatment included intravenous fluid resuscitation and insulin infusion, leading to resolution of acidosis and improved mentation within 24 hours. Conclusion: EDKA is a diagnosis of exclusion often overlooked in ICU patients due to diverse causes of high-anion gap metabolic acidosis. Typical cases occur while the patient is using the drug, often associated with triggers like illness, alcohol use, surgery, or starvation. SGLT2 inhibitors, such as empagliflozin, with a half-life of 12.4 hours, are expected to clear the bloodstream in about 48 hours, yet this case suggests an association with EDKA both during use and after drug cessation. This delayed presentation highlights additional risk considerations associated with SGLT2 inhibitors, guiding future clinical diagnoses of EDKA even several days post discontinuation. Presentation: 6/3/2024

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.

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.

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.

Clinical characteristics and genetic profile of children with WDR72-associated distal renal tubular acidosis: a nationwide experience.

Limited data, primarily from small case series, exist regarding the clinical profile, genetic variants, and outcomes of WDR72-associated distal renal tubular acidosis (WDR72-dRTA). Our study enrolled children diagnosed with WDR72-dRTA below 18years of age from 9 Indian centers and analyzed their clinical characteristics, genetic profiles, and outcomes. Potential genotype-phenotype correlations were explored. We report 22 patients (59% female) with WDR72-dRTA who were diagnosed at a median age of 5.3 (3, 8) years with polyuria (n = 17; 77.3%), poor growth (16; 72.7%), and rickets (9; 40.9%). Amelogenesis imperfecta was present in 21 (95.5%) cases. At presentation, all patients had normal anion gap metabolic acidosis; hypokalemia and nephrocalcinosis were seen in 17 (77.3%) patients each. Seven (31.8%) patients had concomitant proximal tubular dysfunction. Genetic analysis identified biallelic nonsense variants in 18 (81.8%) patients, including novel variants in 6 cases. A previously reported variant, c.88C > T, and a novel variant, c.655C > T, were the most frequent variants, accounting for 10 (45.5%) cases. Over a median follow-up of 1.3 (1, 8) years, the height velocity improved by 0.74 (0.2, 1.2) standard deviation scores, while 3 children (13.6%) progressed to chronic kidney disease (CKD) stage 2, with eGFR ranging from 67 to 76mL/min/1.73 m2, respectively, after 11.3-16years of follow-up. No specific genotype-phenotype correlation could be established. WDR72-dRTA should be considered in children with typical features of amelogenesis imperfecta and dRTA. Biallelic nonsense variants are common in Asians. While most patients respond well to treatment with improved growth and preserved eGFR, on long-term follow-up, a decline in eGFR may occur.

A case report of Paracetamol related pyroglutamic acidosis: mind the gap in a malnourished patient

BackgroundPyroglutamic acidosis is a rare cause of high anion gap metabolic acidosis. Most cases of paracetamol related pyroglutamic acidosis are described in malnourished women and patients with kidney/liver failure, alcohol use or severe sepsis. In this report, we describe how pyroglutamic acidosis could be related to the use of chronic therapeutic paracetamol with only malnutrition as an associated risk factor.Case presentationWe report a case of a 67-year-old male patient developing a pyroglutamic acidosis. The patient was initially admitted to hospital for infectious osteoarthritis and developed a metabolic acidosis during his hospital stay. Analgesics included daily therapeutic doses of paracetamol. What makes our case unusual is that our malnourished male patient did not have renal or hepatic failure. The diagnosis of paracetamol related pyroglutamic acidosis was made after ruling out the main causes of metabolic acidosis. It was further confirmed by urine organic acids measurement showing a markedly elevated level of pyroglutamic aciduria. Paracetamol was discontinued allowing a prompt correction of the anion gap.ConclusionThis case is a representative of pyroglutamic acidosis related to chronic therapeutic paracetamol with only malnutrition as an associated risk factor. Physicians should be aware of such unusual cause of metabolic acidosis, which may be more common than expected in hospitalized patients. A high clinical suspicion is needed when urine organic acids analysis is not available.

Failure to Thrive, Metabolic Acidosis, and Diarrhea in a 7-Week-Old Infant.

A 7-week-old infant presented to the emergency department with fussiness, decreased oral intake, loose stool, and respiratory distress for 2 days. The patient was born full-term with an uncomplicated birth history but had a history of slow weight gain. He was alert, but toxic-appearing at presentation, hypothermic with signs of dehydration, and with respiratory failure. He was found to have severe anion gap metabolic acidosis, hypokalemia, elevated lactate, and hyperammonemia. He responded well to initial resuscitation and was admitted to the ICU for intravenous electrolyte replacement, bowel rest, and respiratory support. A workup was pursued for failure to thrive with severe malnutrition, hyperammonemia, hyperlactatemia, anemia, vitamin D deficiency, and electrolyte abnormalities. After stabilization, he was restarted on enteral feeds and had a recurrence of loose stool and severe electrolyte abnormalities, which were refractory to enteral supplementations and required readmission to the ICU. His hospital course extended several weeks, included several subspecialty consultations, and ended with a surprising diagnosis of exclusion based on his clinical response to therapy.

Lactated Ringer's versus normal saline in the management of acute diabetic ketoacidosis (RINSE-DKA).

A mainstay in the acute management of diabetic ketoacidosis (DKA) is fluid resuscitation. Normal saline is recommended by the American Diabetes Association; however, it has been associated with hyperchloremic metabolic acidosis and acute kidney injury. Limited literature is available to determine the most appropriate crystalloid fluid to treat patients with DKA. The purpose of this study was to compare lactated Ringer's (LR) to normal saline (NS) in the acute management of DKA. This was a retrospective, multicenter single health system cohort study. The primary outcome was to evaluate the time to high anion gap metabolic acidosis (HAGMA) resolution using LR compared to NS. Secondary outcomes included the incidence of nongap metabolic acidosis, hyperchloremia, acute kidney injury, and new renal replacement therapy. Other secondary outcomes included insulin infusion duration and hospital and intensive care unit length of stay. The Cox proportional hazards model was used for the primary outcome. A total of 771 patient encounters were included. Lactated Ringer's was associated with faster time to HAGMA resolution compared to NS (adjusted hazard ratio 1.325; 95% confidence interval 1.121-1.566; p < 0.001). No difference was found in complications such as incidence of nongap metabolic acidosis, hyperchloremia, acute kidney injury, and new renal replacement therapy between the LR and NS groups. Additionally, there was no difference in insulin infusion duration and hospital or intensive care unit length of stay. Treatment with LR as the primary crystalloid for acute DKA management was associated with faster HAGMA resolution compared with NS. Similar incidence in complications and length of stay was observed between the two groups. The findings of this study add to the accumulating literature suggesting that balanced crystalloids may offer an advantage over NS for the treatment of patients with DKA.

The Δ Anion Gap/Δ Bicarbonate Ratio in Lactic Acidosis: Time for a New Baseline?

The ratio of delta anion gap and delta bicarbonate (ΔAG/ΔHCO3) is used to detect co-existing acid-base disorders in patients with high anion gap metabolic acidosis. The ΔAG/ΔHCO3 ratio of 1.6-1.8:1 in lactic acidosis is derived from limited data using mean normal values for AG and serum HCO3. The objective of this study was to be the first to examine the ΔAG/ΔHCO3 using each patient's individual baseline AG and serum HCO3. This was a retrospective cohort study of adult ICU patients with sepsis. Lab data from simultaneously drawn chemistry panel, including anion gap and serum lactate on admission to the ICU was obtained. Baseline AG, HCO3 and albumin measurements were obtained 1-24 months prior to ICU admission. The ΔAG/ΔHCO3 was calculated using an albumin-corrected anion gap and each patient's individual baseline AG and serum HCO3. 344 patients were included. 128 patients had normal serum lactate levels (≤1.9 mmol/L) and 216 patients had elevated serum lactate levels (>1.9 mmol/L). ΔAG/ΔHCO3 was calculated for the 216 patients who had elevated serum lactate levels (>1.9 mmol/L). The mean ΔAG/ΔHCO3 for all patients with elevated serum lactate levels was 1.20 (SD 1.50). The mean ΔAG/ΔHCO3 calculated using an albumin-corrected anion gap and each patient's individual baseline AG and serum HCO3 was 1.20. The ΔAG/ΔHCO3 reported in prior literature which used mean normal AG and serum HCO3 was 1.6-1.8, highlighting that use of mean normal values affects the calculation of the ΔAG/ΔHCO3 and subsequent conclusions about underlying pathophysiology. The use of these mean normal values can result in misdiagnosis of complex acid-base disorders and inappropriate treatment. Our analysis indicates that the elevated ΔAG/ΔHCO3 is likely due to unmeasured anions contributing to an elevation in AG.

Acetaminopheninduced high anion gap metabolic acidosis: a potentially under-recognized consequence from a common medication.

While metabolic acidosis is one of the most common complications in patients with chronic kidney disease (CKD), there are several uncommon etiologies that are challenging to diagnose. Here, we describe a patient on peritoneal dialysis who developed high anion gap metabolic acidosis secondary to acquired 5-oxoprolinemia from acetaminophen use. While CKD is a known risk factor for developing this potentially serious complication, this case further highlights how 5-oxoproline accumulation can occur, even with therapeutic dosing of acetaminophen.

Euglycemic Ketoacidosis Induced by SGLT2 Inhibitor in Latent Autoimmune Diabetes in Adults: A Case Report

Background: Euglycemic ketoacidosis (EKA) is a medical condition characterized by the presence of ketoacidosis without significant hyperglycemia. It is particularly challenging to diagnose due to normal or near-normal blood glucose levels. SGLT2 inhibitors, used in managing type 2 diabetes mellitus, are known to cause EKA. This risk is increased in patients with latent autoimmune diabetes in adults (LADA), a type of Type 1diabetes presented in adult (Hybrid form of diabetes) Case Report: A 64-year-old male with a history of diabetes mellitus and hypothyroidism presented with shortness of breath, nausea, and dizziness. Despite taking Metformin, Glimepride, Thyroxin, and Empagliflozin, he had poor glycemic control (HbA1c 9%) Physical examination showed generalized vitiligo and tachycardia. Initial laboratory results revealed high anion gap metabolic acidosis with normal blood glucose, consistent with EKA. Extensive diagnostic workup confirmed the presence of LADA and SGLT2 inhibitor induced EKA. Result: The patient was diagnosed with type 1 diabetes mellitus (LADA) and EKA induced by SGLT2 inhibitors. Management included discontinuation of the SGLT2 inhibitor, initiation of insulin therapy, and monitoring of metabolic parameters. Conclusion: Euglycemic ketoacidosis induced by SGLT2 inhibitors in patients with LADA is a serious condition requiring prompt recognition and treatment. Clinicians should be vigilant in monitoring adult patients with diabetes and other autoimmune conditions who are on SGLT2 inhibitors for symptoms of ketoacidosis even when blood glucose levels are normal. Recommendations: Regular monitoring of blood ketone levels in patients on SGLT2 inhibitors. Consideration of alternative glucose-lowering therapies in patients with LADA. Education for patients and healthcare providers on the risks of EKA. Keywords: Euglycemic ketoacidosis, SGLT2 inhibitors, Latent autoimmune diabetes in adults, Diabetes management, Metabolic acidosis.