Raised Anion Gap Metabolic Acidosis Research Articles

Pyroglutamic Acidosis - An Underrecognised Entity Associated with Acetaminophen Use.

Pyroglutamic acidosis (PGA) is an underrecognized entity characterised by raised anion gap metabolic acidosis (RAGMA) and urinary hyper-excretion of pyroglutamic acid. It is frequently associated with chronic acetaminophen (APAP) ingestion. We report the case of a 73-year-old man with invasive pulmonary aspergillosis treated with voriconazole and APAP for analgesia with a cumulative dose of 160 g over 40 days. PGA was suspected as he developed severe RAGMA and common causes were excluded. Diagnosis was confirmed via urinary organic acid analysis which showed significant hyper-excretion of pyroglutamic acid. APAP was discontinued, and N-acetylcysteine (NAC) was administered. His RAGMA rapidly resolved following treatment.

Case Report: Acute isoniazid intoxication after intentional ingestion

Isoniazid is an anti-tuberculosis medication that is extensively used for treatment and prevention of tuberculosis. Acute isoniazid poisoning is characterized by a clinical triad of recurrent seizures, raised anion gap metabolic acidosis and coma. The seizures are unresponsive to standard anticonvulsant drugs, instead requiring pyridoxine administered in a dose equal to the amount of isoniazid consumed. Due to the high incidence of tuberculosis in low-income countries like Nepal, isoniazid intoxication should be considered in any patient who present with such unresponsive seizures and coma. We report a case of a 31 years old woman from Nepal, who intentionally ingested 12 grams of isoniazid and presented with generalized tonic-clonic seizures. She was successfully managed with 10 grams of pyridoxine along with other supportive management, including sodium bicarbonate for metabolic acidosis and mechanical ventilation. Doctors working in low-income countries, like Nepal, where tuberculosis is endemic, should be well acquainted with presentations and management of isoniazid intoxication.

Lesson of the month 1: A rare adverse reaction between flucloxacillin and paracetamol

Flucloxacillin, a beta-lactam antibiotic, is a commonly prescribed antibiotic for the treatment of infections caused by staphylococci and streptococci, most notably Staphylococcus aureus Paracetamol is one of the most dispensed medications by NHS England and is used for the treatment of fever and pain.1 However most doctors are unaware that concurrent use of these drugs can cause a potentially fatal drug interaction due to pyroglutamic acidosis (PGA), also known as 5-oxoprolinaemia. PGA is a rare cause of raised anion gap metabolic acidosis due to disruption of the γ-glutamyl cycle. We report the case of a patient with multiple comorbidities who developed PGA due to coadministration of paracetamol and flucloxacillin.

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Introduction: Acute esophageal necrosis (AEN), commonly referred to as "black esophagus", is a rare disease. Its endoscopic finding shows diffuse circumferential black mucosal discoloration in the distal esophagus. The etiology of AEN is multifactorial; a combination of an ischemic insult to the esophagus, impaired mucosal barrier systems, and a chemical injury from backflow of gastric secretions. We present a case of AEN, whose etiology is thought to be an ischemia due to alcoholic ketoacidosis (AKA). Case Description: A 48-year-old male, with a history of alcohol abuse, presented to the ED complaining of coffee ground emesis. He was in shock state on admission (BP 88/62 mmHg, HR 127 beats/min) with a score of 13 on the Glasgow coma scale. Arterial blood gas showed raised anion gap metabolic acidosis with elevated ketone bodies including beta-hydroxybutyrate. From these findings, we diagnosed as a case of AKA associated with dehydration. Initial endoscopic evaluation on admission revealed a black esophagus in the distal one-third, with clear-cut margin at the gastroesophageal junction. Hemodynamic state was recovered by aggressive fluid resuscitation, and severe metabolic acidemia was also improved by continuous renal replacement therapy. Lansoprazole had also been started on admission. Secondary endoscopic examination on day 10 showed a mixture of residual black areas and ulcer formation covered with thick white exudates. Third endoscopic examination on day 25 showed the regeneration of the esophagus mucosa. The patient was discharged without any complications on day 49. Discussion: AEN is a very rare condition and its estimated prevalence is 0.01%-0.28%. The mortality of AEN is reported to be up to 30%, depending on the underlying medical condition. In this case, dehydration and AKA associated with malnutrition were the main causes of the hemodynamic instability, which led the ischemia of distal esophagus. Conclusion: AEN is potentially fatal disease despite of its low prevalence. It should be considered as the differential diagnosis of upper GI bleeding.

Unwell after drinking homemade alcohol – A case of ethylene glycol poisoning

Delayed treatment of ethylene glycol poisoning can have catastrophic consequences that may result in death. Three young men presented to the Emergency Centre (EC) with a main complaint of feeling unwell after consuming “homemade alcohol”. A fourth person had died at home an hour earlier. Blood analysis revealed a raised anion gap metabolic acidosis as well as a raised osmolar gap in all three patients. The clinical presentation of ethylene glycol and methanol poisoning is non-specific and can be difficult to differentiate from ethanol intoxication. Homemade alcohol preparations are commonly adulterated with ethylene glycol and methanol to improve their taste and sting. Toxic alcohol analysis is not routinely carried out by most laboratory services in South Africa, and when carried out, results are only made available a few days later. A high index of suspicion coupled with early blood gas analysis and a need for prompt and effective treatment whilst awaiting toxicology analysis may limit the associated high morbidity and mortality. Le retard de traitement des empoisonnement à l’éthylène glycol peut avoir des conséquences catastrophiques pouvant entraîner la mort. Trois jeunes hommes se sont présentés au centre de traitement des urgences en se plaignant essentiellement de se sentir malades après avoir consommé de l’”alcool artisanal”. Une quatrième personne était morte au domicile une heure plus tôt. Les analyses de sang ont révélé une acidose métabolique à trou anionique augmenté ainsi qu’un trou osmolaire augmenté chez les trois patients. La présentation clinique de l’empoisonnement à l’éthylène glycol et au méthanol n’est pas spécifique et peut être difficile à différencier d’une intoxication à l’éthanol. Les préparations artisanales sont couramment frelatées par l’ajout d’éthylène glycol et de méthanol destiné à en améliorer le goût et le piquant. Les analyses de la toxicité de l’alcool ne sont pas régulièrement réalisées par la plupart des services de laboratoire en Afrique du Sud, et quand elles le sont, les résultats ne sont transmis que quelques jours plus tard. Un indice élevé de suspicion associé à une analyse précoce des gaz du sang et la nécessité d’un traitement rapide et efficace dans l’attente de l’analyse toxicologique pourrait limiter la forte morbidité et mortalité associées.

Euglycaemic ketoacidosis in patients with and without diabetes

AbstractKetoacidosis in individuals with diabetes is usually associated with a raised plasma glucose concentration. However, ketoacidosis in diabetes can occur with normal (≤11mmol/L) plasma glucose levels. Ketoacidosis is also seen in patients who do not have diabetes, most commonly in pregnancy or following alcoholic binges, rarely with starvation, anorexia nervosa or inborn errors of metabolism. The aim of this review is to compare the clinical features, pathophysiology and management of these conditions.Common clinical features due to a raised anion gap metabolic acidosis are seen. Reduced carbohydrate intake is a usual contributor to ketogenesis. Treatment is primarily with intravenous glucose, insulin if there is insulin deficiency and potassium as needed. The value of using bedside monitors to measure β‐hydroxybutyrate levels both for diagnosis and monitoring of response to treatment is emphasised. Early recognition of ketoacidosis and treatment with glucose rather than saline is important for optimum outcome. Copyright © 2013 John Wiley & Sons. Practical Diabetes 2013; 30(4): 167–171

Cyclic vomiting syndrome masking a fatal metabolic disease

Disorders of fatty acid oxidation are rare but can be fatal. Hypoglycaemia with acidosis is a cardinal feature. Cases may present during early childhood or can be delayed into adolescence or beyond. We present a case of multiple acyl-coenzyme A dehydrogenase deficiency (MADD), an extremely rare disorder of fatty acid oxidation. Our 20-year-old patient presented with cardiovascular collapse, raised anion gap metabolic acidosis and non-ketotic hypoglycaemia. She subsequently developed multi-organ failure and sadly died. She had a previous diagnosis of cyclic vomiting syndrome (CVS) for more than 10 years, warranting frequent hospital admissions. The association between CVS and MADD has been made before though the exact relationship is unclear. All patients with persistent severe CVS should have metabolic investigations to exclude disorders of fatty acid oxidation. In case of non-ketotic hypoglycaemia with acidosis, the patient should be urgently referred to a specialist in metabolic diseases. All practitioners should be aware of these rare disorders as a cause of unexplained acidosis.

Paracetamol use and High Anion Gap Metabolic Acidosis

Accumulation of 5-oxoproline (pyroglutamic acid) has been reported as a rare cause of high anion gap metabolic acidosis. Chronic paracetamol ingestion in a susceptible individual can lead to accumulation of 5-oxoproline and a high anion gap metabolic acidosis. The condition resolves with supportive care and discontinuation of paracetamol and, most importantly, it can be prevented. This case report aims to alert clinicians to the condition as well as provide insight into the underlying mechanisms of the disease process. We report two cases of high anion gap metabolic acidosis due to accumulation of 5-oxoproline. Both patients had a recent history of regular paracetamol use for back pain on a background of poor nutrition. Common causes of high anion gap metabolic acidosis were excluded in both patients systematically. The underlying cause was discovered on testing for urinary 5-oxoproline. Both patients improved and the acidosis resolved upon withdrawal of paracetamol and other supportive measures. The need for a high index of suspicion and a detailed patient drug history is highlighted in these case reports, as raised anion gap metabolic acidosis is a common finding in critically ill patients. When lactate and ketones are absent, 5-oxoproline levels should be tested in patients who are taking paracetamol; especially in those who are malnourished or have other predisposing factors to reduced glutathione levels. Once suspected, paracetamol should be stopped, full supportive care should be initiated and treatment with N-acetylcysteine considered.

Acute starvation in pregnancy: a cause of severe metabolic acidosis

We report a case of starvation-induced metabolic ketoacidosis in a previously healthy 29-year-old, nulliparous woman at 32 weeks of gestation. She was admitted to hospital with mild preeclampsia associated with persistent nausea and vomiting that progressed to severe preeclampsia requiring urgent control of hypertension before caesarean delivery. Prolonged and severe vomiting limited oral caloric intake and led to starvation ketoacidosis, characterised by ketonuria and a raised anion gap metabolic acidosis that required intensive care support. Despite significant metabolic derangement the patient appeared clinically well. Intravascular volume was replenished. Fluid restriction used as part of our preeclampsia treatment regimen delayed the therapeutic administration of sufficient dextrose, which rapidly corrected her metabolic derangement when commenced after delivery. Electrolyte supplementation was given to prevent re-feeding syndrome. Both mother and baby were discharged without sequelae.

An Unusual Case of Hyperglycemia, Abdominal Pain, and Increased Anion Gap Acidosis

In this case report we try to illustrate the importance of correct diagnostic reasoning and the misleading features of point-of-care testing. This case illustrates that even though hyperglycemia, ketonuria, a raised anion gap metabolic acidosis, and acute abdominal pain almost inevitably warrant a diagnosis of diabetic ketoacidosis, other possibilities still exist and need to be excluded. In that light, we emphasize the clinical and therapeutic importance of determining serum lactate and urinary ketones in the differential diagnosis of a raised anion gap metabolic acidosis.

Profound metabolic acidosis from pyroglutamic acidemia: an underappreciated cause of high anion gap metabolic acidosis

The workup of the emergency patient with a raised anion gap metabolic acidosis includes assessment of the components of “MUDPILES” (methanol; uremia; diabetic ketoacidosis; paraldehyde; isoniazid, iron or inborn errors of metabolism; lactic acid; ethylene glycol; salicylates). This approach is usually sufficient for the majority of cases in the emergency department; however, there are many other etiologies not addressed in this mnemonic. Organic acids including 5-oxoproline (pyroglutamic acid) are rare but important causes of anion gap metabolic acidosis. We present the case of a patient with profound metabolic acidosis with raised anion gap, due to pyroglutamic acid in the setting of malnutrition and chronic ingestion of acetaminophen.

Does alcoholic ketoacidosis go undetected?

AbstractObjectiveTo review the condition of alcoholic ketoacidosis.Data sourcesEnglish language literature search using Medline® for the period 1973 to 1993. A total of 34 articles, abstracts and book chapters were used.Data synthesisAlcoholic ketoacidosis has been recognised for over 50 years yet there seems to be a lack of knowledge about this condition. The patient usually abuses alcohol, and presents with nausea, vomiting and abdominal pain. Laboratory tests show an increased anion gap metabolic acidosis and electrolyte changes secondary to vomiting and dehydration. Urinalysis may be negative for ketones. The differential diagnosis is that of a raised anion gap metabolic acidosis in the setting of chronic alcohol consumption. Intravenous fluids and glucose are the mainstays of treatment.ConclusionAcutely unwell patients who abuse alcohol commonly present to the emergency department. Failure to consider alcoholic ketoacidosis may lead to inappropriate discharge.