Severe Metabolic Acidosis Research Articles

Multiorgan recovery in a cadaver body using mild hypothermic ECMO treatment in a murine model

BackgroundTransplant candidates on the waiting list are increasingly challenged by the lack of organs. Most of the organs can only be kept viable within very limited timeframes (e.g., mere 4–6 h for heart and lungs exposed to refrigeration temperatures ex vivo). Donation after circulatory death (DCD) using extracorporeal membrane oxygenation (ECMO) can significantly enlarge the donor pool, organ yield per donor, and shelf life. Nevertheless, clinical attempts to recover organs for transplantation after uncontrolled DCD are extremely complex and hardly reproducible. Therefore, as a preliminary strategy to fulfill this task, experimental protocols using feasible animal models are highly warranted. The primary aim of the study was to develop a model of ECMO-based cadaver organ recovery in mice. Our model mimics uncontrolled organ donation after an “out-of-hospital” sudden unexpected death with subsequent “in-hospital” cadaver management post-mortem. The secondary aim was to assess blood gas parameters, cardiac activity as well as overall organ state. The study protocol included post-mortem heparin–streptokinase administration 10 min after confirmed death induced by cervical dislocation under full anesthesia. After cannulation, veno-arterial ECMO (V–A ECMO) was started 1 h after death and continued for 2 h under mild hypothermic conditions followed by organ harvest. Pressure- and flow-controlled oxygenated blood-based reperfusion of a cadaver body was accompanied by blood gas analysis (BGA), electrocardiography, and histological evaluation of ischemia–reperfusion injury. For the first time, we designed and implemented, a not yet reported, miniaturized murine hemodialysis circuit for the treatment of severe hyperkalemia and metabolic acidosis post-mortem.ResultsBGA parameters confirmed profound ischemia typical for cadavers and incompatible with normal physiology, including extremely low blood pH, profound negative base excess, and enormously high levels of lactate. Two hours after ECMO implantation, blood pH values of a cadaver body restored from < 6.5 to 7.3 ± 0.05, pCO2 was lowered from > 130 to 41.7 ± 10.5 mmHg, sO2, base excess, and HCO3 were all elevated from below detection thresholds to 99.5 ± 0.6%, − 4 ± 6.2 and 22.0 ± 6.0 mmol/L, respectively (Student T test, p < 0.05). A substantial decrease in hyperlactatemia (from > 20 to 10.5 ± 1.7 mmol/L) and hyperkalemia (from > 9 to 6.9 ± 1.0 mmol/L) was observed when hemodialysis was implemented. On balance, the first signs of regained heart activity appeared on average 10 min after ECMO initiation without cardioplegia or any inotropic and vasopressor support. This was followed by restoration of myocardial contractility with a heart rate of up to 200 beats per minute (bpm) as detected by an electrocardiogram (ECG). Histological examinations revealed no evidence of heart injury 3 h post-mortem, whereas shock-specific morphological changes relevant to acute death and consequent cardiac/circulatory arrest were observed in the lungs, liver, and kidney of both control and ECMO-treated cadaver mice.ConclusionsThus, our model represents a promising approach to facilitate studying perspectives of cadaveric multiorgan recovery for transplantation. Moreover, it opens new possibilities for cadaver organ treatment to extend and potentiate donation and, hence, contribute to solving the organ shortage dilemma.

Case report: Ethylene glycol intoxication presenting as a mimic of acute stroke: a report of three cases

Stroke is a major cause of death and disability presenting with acute focal neurological symptoms of vascular origin. Several other disorders may cause symptoms similar to a stroke, referred to as stroke mimics. The misdiagnosis of stroke mimics may lead to potentially harmful treatments, including thrombolysis. Intoxication is a rare, but possible, cause of stroke mimic. We present three cases of ethylene glycol poisoning presenting as an acute stroke mimic within the time window of thrombolytic therapy. Two of three patients (a 54-year-old male and a 78-year-old male) had dysarthria, nystagmus, and truncal ataxia on admission. The third patient with a history of chronic alcoholism presented after an epileptic seizure with mixed aphasia and confusion. Non-contrast cerebral computed tomography and computed tomography angiography were negative in all three cases. As stroke could not be excluded in any of the patients, thrombolysis was performed. However, after some hours, two of the three patients developed agitation, somnolence, and hyperventilation. One patient's consciousness deteriorated rapidly, and he became comatose and tetraplegic. A blood gas analysis showed acidosis in two of the three patients, and toxicological screening revealed ethylene glycol intoxication in all three cases. Due to the appropriate treatment, two of the three patients became symptom-free; however, one of the three patients died. Our cases show that ethylene glycol intoxication in its early phase may mimic acute stroke, resulting in unnecessary thrombolytic therapy. Symptoms not characteristic of a stroke, such as hyperventilation, agitation, and disturbance of consciousness, may appear later and warn of intoxication. The final diagnosis of ethylene glycol intoxication can be established by severe metabolic acidosis and toxicological screening. Close monitoring of symptoms might contribute to the early recognition of ethylene glycol intoxication and its effective treatment.

Sodium bicarbonate for the treatment of severe metabolic acidosis with moderate or severe acute kidney injury in the critically ill: protocol for a randomised clinical trial (BICARICU-2)

IntroductionWhen both severe metabolic acidemia (pH equal or less than 7.20; PaCO2 equal or less than 45 mm Hg and bicarbonate concentration equal or less than of 20 mmol/L) and...

A case of combined oxidative phosphorylation deficiency 32 caused by MRPS34 gene variation and literature review

Objective: To investigate the clinical features and genetic features of combined oxidative phosphorylation deficiency 32 (COXPD32) caused by MRPS34 gene variation. Methods: The clinical data and genetic test of a child with COXPD32 hospitalized in the Department of Neurology, Children's Hospital, Capital Institute of Pediatrics in March 2021 were extracted and analyzed. A literature search was implemented using Wanfang, China biology medicine disc, China national knowledge infrastructure, ClinVar, human gene mutation database (HGMD) and Pubmed databases with the key words "MRPS34" "MRPS34 gene" and "combined oxidative phosphorylation deficiency 32" (up to February 2023). Clinical and genetic features of COXPD32 were summarized. Results: A boy aged 1 year and 9 months was admitted due to developmental delay. He showed mental and motor retardation, and was below the 3rd percentile for height, weight, and head circumference of children of the same age and gender. He had poor eye contact, esotropia, flat nasal bridge, limbs hypotonia, holding instability and tremors. In addition, Grade Ⅲ/6 systolic murmur were heard at left sternal border. Arterial blood gases suggested that severe metabolic acidosis with lactic acidosis. Brain magnetic resonance imaging (MRI) showed multiple symmetrical abnormal signals in the bilateral thalamus, midbrain, pons and medulla oblongata. Echocardiography showed atrial septal defect. Genetic testing identified the patient as a compound heterozygous variation of MRPS34 gene, c.580C>T (p.Gln194Ter) and c.94C>T (p.Gln32Ter), with c.580C>T being the first report and a diagnosis of COXPD32. His parents carried a heterozygous variant, respectively. The child improved after treatment with energy support, acidosis correction, and "cocktail" therapy (vitaminB1, vitaminB2, vitaminB6, vitaminC and coenzyme Q10). A total of 8 cases with COXPD32 were collected through 2 English literature reviews and this study. Among the 8 patients, 7 cases had onset during infancy and 1 was unknown, all had developmental delay or regression, 7 cases had feeding difficulty or dysphagia, followed by dystonia, lactic acidosis, ocular symptoms, microcephaly, constipation and dysmorphic facies(mild coarsening of facial features, small forehead, anterior hairline extending onto forehead,high and narrow palate, thick gums, short columella, and synophrys), 2 cases died of respiratory and circulatory failure, and 6 were still alive at the time of reporting, with an age range of 2 to 34 years. Blood and (or) cerebrospinal fluid lactate were elevated in all 8 patients. MRI in 7 cases manifested symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia. Urine organic acid test were all normal but 1 patient had alanine elevation. Five patients underwent respiratory chain enzyme activity testing, and all had varying degrees of enzyme activity reduction. Six variants were identified, 6 patients were homozygous variants, with c.322-10G>A was present in 4 patients from 2 families and 2 compound heterozygous variants. Conclusions: The clinical phenotype of COXPD32 is highly heterogenous and the severity of the disease varies from development delay, feeding difficulty, dystonia, high lactic acid, ocular symptoms and reduced mitochondrial respiratory chain enzyme activity in mild cases, which may survive into adulthood, to rapid death due to respiratory and circulatory failure in severe cases. COXPD32 needs to be considered in cases of unexplained acidosis, hyperlactatemia, feeding difficulties, development delay or regression, ocular symptoms, respiratory and circulatory failure, and symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia, and genetic testing can clarify the diagnosis.

The debut and course of the neonatal form of propionic aciduria: a clinical case

Propionic aciduria (PA) is an autosomal recessive hereditary disease from the group of organic aciduria, caused by a deficiency of propionyl-CoA carboxylase, leading to impaired metabolism of methionine, threonine, valine, isoleucine, and fatty acids with an odd number of carbon atoms and cholesterol. The neonatal form of PA manifests itself during the first week of life, is characterized by an acute onset and a crisis course, which is accompanied by severe metabolic acidosis, hypoglycemia, hyperketonemia, hyperammonemia. Clinical symptoms are dominated by neurological disorders up to stupor or coma, which can lead to death. Since 2023, expanded neonatal screening has been introduced throughout the Russian Federation, which includes 36 groups of nosologies, as well as a number of hereditary metabolic diseases.&#x0D; Despite the inclusion of this pathology in expanded neonatal screening, doctors’ awareness of clinical manifestations and necessary therapy remains insufficient. Often such patients are diagnosed with, for example: hypoxic-ischemic damage to the central nervous system, acute meningoencephalitis, and others, which leads to inadequate therapy with the development of fatal neurological consequences.&#x0D; Therefore, the totality of knowledge and alertness of doctors regarding diseases from the group of hereditary metabolic diseases will help not only to suspect this pathology in a timely manner, but also to prescribe adequate therapy in time, which in the future will make it possible to prevent serious consequences and neurological disorders, as well as disability of patients.

Outcome of Methanol Toxicity Outbreak In Saudi Arabia: Case Series Study.

Introduction Methanol poisoning is an acute medical emergency. If not recognized in time and treated properly, it can lead to a considerable magnitude of morbidity as well as mortality. This article aims to report cases of methanol toxicity, focusing on clinical presentation, management, and outcomes. Method Nine ICU-admitted patients with confirmed positive serum methanol levels wereanalyzed in a case series at King Fahad General Hospital in Jeddah, Saudi Arabia, between November 2022 and January 2023. Results Among the nine patients admitted to the ICU due to methanol poisoning, the majority were middle-aged males, with two females included. Gastrointestinal symptoms were seen in two-thirds of patients, while three patients required immediate mechanical ventilation due to a low Glasgow Coma Scale. Severe metabolic acidosis was observed in most cases. All patients received sodium bicarbonate and hemodialysis, with six patients also receiving fomepizole. However, two patients in the study with low initial low Glasgow Coma Scale (GCS), severe metabolic acidosis, and diffuse brain edema, did not survive. One patient reported acute complete vision loss. Conclusion This case series highlights the importance of promptly recognizing and managing methanol toxicity in ICU settings. The clinical presentation of methanol toxicity can be challenging, and early diagnosis and treatment are crucial to prevent irreversible damage.

Case Reports Study on Methanol Poisoning in King Abdul Aziz Specialist Hospital, Taif, Saudi Arabia

Methanol poisoning is a challenging issue due to its inducing acute multiple organ failures, and especially due to a lack of preparedness, available antidotes, and management protocols. The current study presents six cases of methanol poisoning that attended the emergency department of King Abdul Aziz Specialist Hospital, Taif, Saudi Arabia, between March and November 2022. All of the patients suffered from severe metabolic acidosis and visual impairment following the ingestion of homemade alcoholic beverages and colonia. Three patients were comatose, suffered from post-cardiac pulmonary arrest, and, finally, died, while the other three were non-comatose and discharged from the ICU after improvement. Management was based on clinical symptoms and other laboratory findings due to a shortage of methanol level measurement resources. The antidote, fomepizole, was not given to all of the cases due to its deficiency, and ethanol was given only to one patient due to difficulties in administering it without monitoring its concentration. Methanol poisoning and its outbreak provide insights into the dangers of hazardous homemade alcohol and other pharmaceutical preparations that might be adulterated with methanol, particularly to the shortage of suitable diagnostic testing and antidotes in addition to poor resources for management of intoxicated patients in some regions of Saudi Arabia.

The accuracy of the Thompson score in predicting early outcome in neonates with hypoxic ischaemic encephalopathy treated with therapeutic cooling in a tertiary hospital.

Hypoxic ischaemic encephalopathy (HIE) is one of the major contributors to neonatal mortality and morbidity in developing countries. Scarcity of resources limits clinicians in optimally caring for these patients. Optimal utilisation of clinical tools such as the Thompson score (TS) can assist in improving care by classifying the severity of HIE followed by appropriate treatment. The primary objective was to study the correlation of the TS and early neonatal outcomes in infants with HIE who received therapeutic hypothermia (TH). Secondary objectives were to investigate the correlation of blood gas values with the TS, need for resuscitation with TS, target organ damage (TOD) with TS and the most common risk factors associated with HIE in Tembisa Provincial Tertiary Hospital (TPTH). This was a retrospective record review of infants admitted with HIE from January 2018 to August 2019 at the TPTH neonatal unit. Infants had to have successfully completed TH. Ninety-three infants met the inclusion criteria, with 32, 48 and 13 being classified into the mild, moderate and severe categories by TS, respectively. The median length of stay (LOS) was noted to rise with a rising TS, recorded to be 7, 8 and 9 days in the mild, moderate and severe groups, respectively. The mortality rate in the study was calculated to be 2.1%, and there was no significant difference across the groups (p=0.231). A need for antiseizure medication (ASM) on discharge was significantly associated with severe HIE (p=0.028). Hypertension was a frequent chronic illness, noted in 11.3% of the mothers. The most frequent perinatal risk factor was meconium aspiration (50.5%), followed by prolonged second stage of labour (PSSL) (17.2%). A higher TS (severe group) was associated with prolonged resuscitation for >10 minutes (p=0.001) and a need for adrenaline (p=0.008). The frequency of cardiac impairment, liver impairment and clinical seizures increased with a higher TS category (p=0.23, p=0.35 and p=0.51, respectively). On blood gas analysis, a low pH and a high base deficit were associated with severe HIE (p=0.027, p=0.061 respectively). The TS is still a useful clinical tool in the era of TH as it is able to predict some early neonatal outcomes such as LOS and a need for ASM at discharge. It is also able to demonstrate increased frequency of duration of resuscitation and a need for adrenaline in severely encephalopathic infants compared with mild. A high TS is also associated with severe metabolic acidosis and increased frequency of TOD. Maternal hypertension, meconium-stained liquor and PSSL are the common risk factors for HIE at TPTH.

The association of intraleucocytic malaria pigment and disease severity in Papua New Guinean children with severe P. falciparum malaria.

Plasmodium falciparum pigment-containing leucocytes (PCLs) are associated with adverse clinical manifestations of severe malaria in African children. However, limited data exist on the association of PCLs in settings outside of Africa. Thin films on peripheral blood slides obtained from children ages 6months-10y with severe malaria were examined for PCLs. The intraleucocytic pigment data were correlated with clinical phenotypic data such as severe anaemia, metabolic acidosis and coma to determine the association of PCLs with clinical phenotypes of severe malaria and outcome. Of the 169 children with severe P. falciparum malaria confirmed by microscopy, 76% (129/169) had PCLs. Compared with children without PCLs, the presence (adjusted odds ratio [AOR] 3.2 [95% confidence interval {CI} 1.5 to 6.9], p≤0.01) and quantity (AOR 1.0 [95% CI 1.0 to 1.1], p=0.04) of pigment-containing monocytes (PCMs) was significantly associated with severe anaemia, while the quantity of both PCMs (AOR 1.0 [95% CI 1.0 to 1.1], p≤0.01) and pigment-containing neutrophils (AOR 1.0 [95% CI 1.0 to 1.1], p=0.01) was significantly associated with metabolic acidosis. Plasma P. falciparum histidine-rich protein-2 level negatively correlated with the platelet count (r=-0.5, p≤0.01) in patients with PCLs and no PCLs. In Papua New Guinean children with severe P. falciparum malaria, the presence and quantity of PCLs are predictors of disease severity, severe anaemia and metabolic acidosis.

High-risk criteria for the physiologically difficult paediatric airway: A multicenter, observational study to generate validity evidence

BackgroundSingle-center studies have identified risk factors for peri-intubation cardiac arrest in the emergency department (ED). The study objective was to generate validity evidence from a more diverse, multicenter cohort of patients. MethodsWe completed a retrospective cohort study of 1200 paediatric patients who underwent tracheal intubation in eight academic paediatric EDs (150 per ED). The exposure variables were 6 previously studied high-risk criteria for peri-intubation arrest: (1) persistent hypoxemia despite supplemental oxygen, (2) persistent hypotension, (3) concern for cardiac dysfunction, (4) post-return of spontaneous circulation (ROSC), (5) severe metabolic acidosis (pH < 7.1), and (6) status asthmaticus. The primary outcome was peri-intubation cardiac arrest. Secondary outcomes included extracorporeal membrane oxygenation (ECMO) cannulation and in-hospital mortality. We compared all outcomes between patients that met one or more versus no high-risk criteria, using generalized linear mixed models. ResultsOf the 1,200 paediatric patients, 332 (27.7%) met at least one of 6 high-risk criteria. Of these, 29 (8.7%) suffered peri-intubation arrest compared to zero arrests in patients meeting none of the criteria. On adjusted analysis, meeting at least one high-risk criterion was associated with all 3 outcomes – peri-intubation arrest (AOR 75.7, 95% CI 9.7–592.6), ECMO (AOR 7.1, 95% CI 2.3–22.3) and mortality (AOR 3.4, 95% 1.9–6.2). Four of 6 criteria were independently associated with peri-intubation arrest: persistent hypoxemia despite supplemental oxygen, persistent hypotension, concern for cardiac dysfunction, and post-ROSC. ConclusionsIn a multicenter study, we confirmed that meeting at least one high-risk criterion was associated with paediatric peri-intubation cardiac arrest and patient mortality.

#4238 UNEXPLAINED METABOLIC ACIDOSIS - A DIAGNOSTIC DILEMMA

Abstract Background and Aims Metabolic Acidosis is a common condition for which nephrology consult is sought. Most often the etiology is quite obvious like renal failure, diabetic ketoacidosis, lactic acidosis etc. We describe a case of high anion gap metabolic acidosis, unresponsive to medical management requiring hemodialysis, where finding the etiology became a diagnostic challenge because of medical and social reasons prevailing in this eastern part of India. Method A 55 year old obese gentleman came to emergency department at 3 am with complains of restlessness, pain abdomen and chest discomfort for last 4-6 hours. On clinical examination he had tachycardia with normal blood pressure and oxygen saturation. His sensorium was normal and systemic examination did not reveal any major abnormality. A possibility of acute cardiac event was considered but his ECG showed sinus tachycardia, echocardiography did not show any wall motion abnormality and Troponin I was less than 0.01 ng/mL. His blood gases showed an uncompensated metabolic acidosis with an anion gap of 21 (pH 7.19 / pCO2 44 / HCO3 15). The laboratory parameters showed a serum creatinine of 0.9 mg/dL, random blood sugar of 130 mg/dL. Any history of poisoning or drug overdose was denied by patient's attendants. Pending further workup patient was admitted in intensive care unit and correction of metabolic acidosis was started with intravenous sodium bicarbonate. Results The metabolic acidosis initially improved with medical management but within next 6 hours patient again had severe metabolic acidosis. Meanwhile patient's sensorium worsened and he had an episode of seizure. Patient was intubated and mechanical ventilation started. Within 30 minutes patient had status epilepticus which ultimately required intravenous thiopentone. Hemodialysis was started for correction of metabolic acidosis. Patient's history was re-evaluated. On persistent questioning his attendants admitted that patient had consumed alcohol 4-5 hours before the symptoms started. It is important to mention here that consumption of alcohol is a punishable offence in Bihar which a state in eastern part of India. Despite alcohol being completely banned in this part of country illicit alcohol is smuggled and consumed by some. Illicit alcohol is prone to be adulterated and sub-standard. It was because of this fact that patient's attendants suppressed the facts. Also alcohol consumption is a valid ground for rejection of medical insurance claims because of obvious reasons. After obtaining the complete history a possibility of consumption of alcohol adulterated with methyl alcohol was very likely. Serum methyl alcohol estimation was not available at our institute and patient had already received hemodialysis hence it was not done. With patient already having seizures MRI (Magnetic Resonance Imaging) of brain was done. MRI brain revealed altered hyperintense signal with cytotoxic edema in bilateral basal ganglia predominantly putamen. Subcortical white matter in bilateral cerebral hemisphere and bilateral optic nerve head showed restriction on diffusion weighted imaging. These typical features on MRI were highly suggestive of methanol toxicity. These MRI features along with the clinical scenario and history of illicit alcohol intake helped us reach the diagnosis of methanol toxicity. Patient was managed with hemodialysis sessions to remove methanol from blood until he improved clinically. Conclusion The etiology of the high anion gap metabolic acidosis turned out to be methanol toxicity. Typical MRI brain findings helped confirm the diagnosis. Our case highlights the importance of obtaining the correct medical history and how social and medicolegal issues sometimes become a hindrance to obtaining the same.

#6212 SEVERE HYPERCHLOREMIC METABOLIC ACIDOSIS WITH SGLT-2 INHIBITORS IN PATIENTS WITH URINARY DIVERSION

Abstract Background and Aims Urinary diversion after cystectomy using autologous intestinal segments has been the gold standard treatment of benign and malignant diseases of urinary tract. The most frequent metabolic abnormalities is hyperchloremic metabolic acidosis, due to ammonium absorption alongside chloride gain and bicarbonate excretion in the bowel conduit. Sodium-glucose co-transporter-2 (SGLT2) inhibitors are a class of antihyperglycemic agents that recently revolutionized the paradigm of chronic kidney disease. It exerts its effect by preventing the reabsorption of filtered glucose from the tubular lumen, acting on the SGLT2 proteins in the renal proximal convoluted tubules, and thus promoting a greater urinary glucose excretion. The authors described 2 patients with bowel conduit and mild hyperchloremic metabolic acidosis, presented with severe metabolic acidosis short after starting SGLT2 inhibitors. Method Consultation of medical records. Results Case 1: 62-year-old male with an orthotopic neobladder since 2005, type 2 diabetes and nonspecific interstitial pneumonia. In 2018 arterial blood gas (ABG) was: pH 7.45, pO2 81, pCO2 28, HCO3- 19.3, Cl 107, AG 7.7 (normal albumin), K+ 3.25. In February 2022 he was sent to the emergency department (ER) from a Pneumology appointment, after an ABG showed an aggravated hyperchloremic metabolic acidosis: pH 7.25, pCO2 27.5, HCO3- 12, Cl 122, Na+ 143, K+ 3.74, AG 9, lactate 0.69, glucose 261, ketone bodies negative); blood workup added acute kidney injury (AKI), urea 81, creatinine 1.6. The patient medical history revealed: administration of 5 cycles of cyclophosphamide (7 months before) and the introduction of empagliflozin 10mg id, 10 months prior to this event, as an addition to Metformin 1000mg id. A progressive metabolic normalization was observed after the SGLT2 inhibitor was withdrawn and intravenous hydration. Case 2: A 63-year-old male with an ileal conduit since 2018 and type 2 diabetes. He had chronic renal disease since 2021 with serum creatinine 1.5-2. He presented with a 3-day history of lethargy and anorexia. He had started dapagliflozina 10mg id 10 months prior to this event. At admission the patient had normal vital signs, glasgow coma scale 15 and no major signs at observation. ABG showed severe hyperchloremic metabolic acidemia (pH 6.98, pCO2 20.5, pO2 124.4, HCO3- 4.7, Na 129, Cl 120, AG 4.3, K+ 3.54, glucose 200, lactate 0.5) alongside AKI, urea 209 and creatinine 2.8 and spot urine without ketone bodies. He was admitted for a short period to the intensive care unit, for intravenous sodium bicarbonate and hydration, on top of SGLT2 inhibitor suspension, with progressive clinical and metabolic resolution. Conclusion Chronic hyperchloremic metabolic acidosis is a frequent and known complication of urinary diversion, due to the reabsorption of solutes by the intestinal mucosa because of the presence of urine (ammonium and chloride absorption and bicarbonate excretion) and diarrhea and volume depletion due to reduced sodium absorption in the gout. Euglycemic Ketoacidosis is a well-known complication of SGLT2 Inhibitor therapy and was not this case as both patients had normal anion gap. Hyperchloremic acidosis as been rarely described but not so severe as we presented. Although both patients had AKI, was not severe. We hypothesize that SGLT2 inhibitors, could exacerbate the chronic hyperchloremic metabolic acidosis by increasing urinary sodium and glucose excretion, that could exacerbate volume depletion, diarrhea and hyperglycemia (and subsequent volume depletion). This are the first 2 cases reported of severe hyperchloremic metabolic acidosis in patients with orthotopic neobladder and SGLT2 inhibitors treatment. The physiopathology of this presentation needs to be studied.

#5987 EPIDEMIOLOGICAL AND CLINICAL PROFILE OF PATIENTS REQUIRING EMERGENCY HEMODIALYSIS

Abstract Background and Aims Dialysis can be either programmed or performed in an emergency context, which complicates the management of patients. Our objective was to study the indications as well as the epidemiological, clinical and biological elements of dialysis emergencies. Method This is a retrospective study conducted over a period of 5 months from March 2022 to September 2022 in the nephrology department of the Mongi Slim Hospital La Marsa including patients having had emergency hemodialysis sessions Results We collected a total of 32 cases with an average age of 65 years, ranging from 30 years to 93 years and a sex ratio at 1.06. The majority of patients were transferred from the emergency department (69%) and secondarily from the nephrology (6%) and cardiology (6%) departments. Sixty-five percent of the patients had arterial hypertension, 53% were diabetic, 37% had chronic kidney disease, 28% had cardiovascular complications, and 41% had an active infection with a biological inflammatory syndrome. Emergency hemodialysis was indicated for severe metabolic acidosis in 50% of the cases, threatening hyperkalemia in 41% of the cases, uremic syndrome in 28% of cases, anuria in 28% of cases, and acute lung edema resistant to medical treatment in 19% of cases. Indeed, 47% of the patients had a single dialysis emergency and 53% of them were dialyzed for several interrelated indications. The vascular approach was mainly femoral catheter in 84% of the cases followed by arteriovenous fistula in 13% and jugular catheter in 3%. The average session duration was 3.5 hours with good hemodynamic tolerance for the majority of patients. Five patients required a blood transfusion. Conclusion Severe metabolic acidosis and threatening hyperkalemia were the main indications for emergency hemodialysis. Unfortunately, the majority of our patients were dialyzed via a femoral catheter. It is therefore recommended to insist on the necessity of early preparation of patients for dialysis as early as stage 4 of chronic kidney disease if the patient obviously chooses hemodialysis as the preferred method of epuration.

Management of cardiac arrhythmias in paediatric patients with TANGO2-deficiency disorder

Abstract Funding Acknowledgements Type of funding sources: None. Background TANGO2-deficiency disorder (TDD) is a rare paediatric condition caused by bi-allelic mutations in the TANGO2 gene. TDD is characterised by susceptibility to metabolic crises with rhabdomyolysis, encephalopathy, lactic acidosis, hypothyroidism and difficult to manage tachyarrhythmias. Aim We describe the electrocardiographic (ECG) findings at baseline and during metabolic crises in patients with TDD. Methods Retrospective, single-centre, case series study of patients with TDD (&amp;lt;18 years), with ECG and subcutaneous Holter monitoring, both during metabolic crises and compensated phases. Results During the period 2013-2021, 12 patients with TDD were found (median age 6.8 years, IQR 2-11.5 years). In the inter-crisis period, bradyarrhythmias were evidenced: 2/12 patients presented sinus bradycardia, 2/12 pauses of 4 and 10 seconds, 1/12 Wenckebach type block; and tachyarrhythmias: 1/12 presented paroxysmal supraventricular tachycardia and 1/12 flutter. 25% had long QT during non-acute phases (median QTc max 476 ms, IQR 456ms-530ms). There were 14 hospitalisations for metabolic crises. 57.1% had QTc interval prolongation, 35.7% ventricular tachycardias (4/14 monomorphic VT, 1/14 torsade de prongs) and 1/14 Brugada type 3 pattern. Three patients died in the context of severe metabolic acidosis and multi-organ involvement (2/12 due to VT and 1/12 due to cardiogenic shock, bradycardia associated with QTc of 635ms and severe ventricular dysfunction). Conclusions In paediatric patients with TDD, the most frequent ECG abnormality was QTc interval prolongation with or without metabolic crises. There is a high risk of tachyarrhythmias, mainly VT, being the main cause of death in children with TDD. Subcutaneous Holter monitoring is recommended. During metabolic crises, there should be close ECG monitoring.

The Case Files

The Case Files

Severe euglycemic diabetic ketoacidosis secondary to sodium-glucose co-transporter 2 inhibitor: case report and literature review.

Forty-four-year-old female with T2DM had multiple visits to the emergency department with recurrent diarrhoea and vomiting. On her third visit, she presented with shortness of breath and tachypnoea, found to have severe metabolic acidosis with euglycemia. She was admitted to ICU with euDKA secondary to SGLT2i and was managed accordingly. The association between SGLT2i and euDKA in T2DM is controversial. SGLT2i leads to euDKA by stimulating lipolysis and ketogenesis in the setting of volume depletion, carbohydrate deficiency, and upregulation of counter-regulatory stress hormones. EuDKA can be life-threatening, especially if not diagnosed and managed properly. The treatment protocol is similar to hyperglycaemic diabetic ketoacidosis. Our case has been reported in line with the CARE criteria.34. SGLT2i benefits in diabetic patients outweigh the risks. Clinicians are advised to counsel diabetic patients maintained on SGLT2 and educate them regarding holding the medication in the setting of acute illness, volume depletion, decreased oral intake, and surgery. In addition, there should be a high index of suspicion for patients presenting with metabolic acidosis in the background of SGLT2i use to provide early diagnosis and management.

Neuroimaging in Acute Ethylene Glycol Toxicity (P8-4.006)

<h3>Objective:</h3> To describe unique neuroradiological features of Ethylene Glycol poisoning. <h3>Background:</h3> Ethylene Glycol (EG) is a sweet tasting, industrial compound that is ubiquitously found in various consumer products (antifreeze, paints, solvents, and cosmetics). Ingestion of EG results in toxicity with characteristic metabolic, pathological, and imaging findings. Toxicity classically presents with a severe anion gap metabolic acidosis, an osmolar gap, and multi-organ involvement. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 64-year-old man presented with acute onset nausea, recurrent vomiting, and ataxic gait. Within a few hours, he became progressively confused, lethargic, and eventually obtunded requiring intubation for airway protection. On physical examination, he was unresponsive but had preserved brainstem reflexes. Laboratory tests showed elevated high anion gap metabolic acidosis (HAGMA) with pH of 7.23, bicarbonate of 13 mmol/L, anion gap of 38 mmol/L, and lactic acid of 2.2 mmol/L. Ethanol, salicylates, acetaminophen, and ketones were undetectable. Further tests revealed methemoglobin level of 1%, increased serum osmolality 328 mOsm/kg, and osmolal gap 71 mOsm/kg. CT head was unrevealing. Due to the HAGMA with hyperosmolality suggesting a toxic alcohol ingestion, the patient was empirically treated with fomepizole 15 mg/kg. EEG showed severe diffuse cerebral dysfunction. He soon developed progressive renal failure requiring hemodialysis. MRI of the brain without contrast revealed bilateral and symmetric enlargement of the basal ganglia and thalami with T2-weighted hyperintensities, as well as T2-weighted hyperintensities involving the brainstem and scattered cortical areas. Ethylene glycol concentration from blood drawn on admission resulted at 1962 mg/dL confirming EG poisoning. <h3>Conclusions:</h3> This case highlights MRI brain findings of T2-weighted hyperintensities in deep gray matter structures in EG toxicity. Current scientific literature infrequently reports any neuroradiologic findings. Clinicians should be cognizant of these neuroradiologic features and use MRI as a supportive diagnostic tool in the proper clinical context while awaiting a definitive EG concentration. <b>Disclosure:</b> Dr. Hiana has nothing to disclose. Dr. Mulatu has nothing to disclose. Dr. Sharma has nothing to disclose. Dr. Askandaryan has nothing to disclose. Dr. Mulatu has nothing to disclose. Dr. Anziska has nothing to disclose.

Hypertonic sodium lactate infusion reduces vasopressor requirements and biomarkers of brain and cardiac injury after experimental cardiac arrest

IntroductionPrognosis after resuscitation from cardiac arrest (CA) remains poor, with high morbidity and mortality as a result of extensive cardiac and brain injury and lack of effective treatments. Hypertonic sodium lactate (HSL) may be beneficial after CA by buffering severe metabolic acidosis, increasing brain perfusion and cardiac performance, reducing cerebral swelling, and serving as an alternative energetic cellular substrate. The aim of this study was to test the effects of HSL infusion on brain and cardiac injury in an experimental model of CA.MethodsAfter a 10-min electrically induced CA followed by 5 min of cardiopulmonary resuscitation maneuvers, adult swine (n = 35) were randomly assigned to receive either balanced crystalloid (controls, n = 11) or HSL infusion started during cardiopulmonary resuscitation (CPR, Intra-arrest, n = 12) or after return of spontaneous circulation (Post-ROSC, n = 11) for the subsequent 12 h. In all animals, extensive multimodal neurological and cardiovascular monitoring was implemented. All animals were treated with targeted temperature management at 34 °C.ResultsThirty-four of the 35 (97.1%) animals achieved ROSC; one animal in the Intra-arrest group died before completing the observation period. Arterial pH, lactate and sodium concentrations, and plasma osmolarity were higher in HSL-treated animals than in controls (p < 0.001), whereas potassium concentrations were lower (p = 0.004). Intra-arrest and Post-ROSC HSL infusion improved hemodynamic status compared to controls, as shown by reduced vasopressor requirements to maintain a mean arterial pressure target > 65 mmHg (p = 0.005 for interaction; p = 0.01 for groups). Moreover, plasma troponin I and glial fibrillary acid protein (GFAP) concentrations were lower in HSL-treated groups at several time-points than in controls.ConclusionsIn this experimental CA model, HSL infusion was associated with reduced vasopressor requirements and decreased plasma concentrations of measured biomarkers of cardiac and cerebral injury.

Empagliflozin-associated postoperative mixed metabolic acidosis. Case report and review of pathogenesis

BackgroundEuglycemic diabetic ketoacidosis associated with SGLT2 inhibitors is a rare, relatively new and potentially fatal clinical entity, characterized by metabolic acidosis with normal or only moderately elevated glycemia. The mechanisms are not fully understood but involve increased ketogenesis and complex renal metabolic dysfunction, resulting in both ketoacidosis and hyperchloremic acidosis. We report a rare case of fatal empagliflozin-associated acidosis with profound hyperchloremia and review its pathogenesis.Case presentationA patient with type 2 diabetes mellitus treated with empagliflozin underwent an elective hip replacement surgery. Since day 4 after surgery, he felt generally unwell, leading to cardiac arrest on the day 5. Empagliflozin-associated euglycemic diabetic ketoacidosis with severe hyperchloremic acidosis was identified as the cause of the cardiac arrest.ConclusionsThis unique case documents the possibility of severe SGLT2 inhibitor-associated mixed metabolic acidosis with a predominant hyperchloremic component. Awareness of this possibility and a high index of suspicion are crucial for correct and early diagnosis.

Veno-venous extracorporeal membrane oxygenation support in the resuscitation from extreme metabolic acidosis (pH < 6.5) after drowning cardiac arrest: a case report

BackgroundResuscitation in drowning victim with cardiac arrest is difficult because of severe metabolic acidosis and multiple organ dysfunction. There is insufficient evidence to support that veno-venous extracorporeal membrane oxygenation (VV-ECMO) is beneficial for patient.Case presentationA 44-year-old female was trapped under river when she attempted to rescue her drowning father. Furthermore, she underwent a loss of consciousness, with extreme metabolic acidosis, hypothermia and hypotension. Hence, the VV-ECMO, continuous renal replacement therapy (CRRT) and other resuscitative infusion were required. In this case, the patient did not experience any complication or neurologic deficit and reaching a complete recovery after 21 days of hospitalization.ConclusionsOur case adds further concerns in supporting a patient with extreme metabolic acidosis (pH < 6.5) and hypothermia after severe drowning cardiac arrest, including extracorporeal life support, renal support, targeted temperature management, cerebral resuscitation, etc., due to the reversible nature of this condition.