Real-world safety and effectiveness of intravenous fomepizole in patients with ethylene glycol and methanol poisoning in Japan: results of a 7-year post-marketing surveillance study.

BACKGROUND: Fomepizole is a competitive alcohol dehydrogenase inhibitor used for the treatment of ethylene glycol and methanol poisoning. We evaluated the safety and effectiveness of fomepizole in patients with ethylene glycol or methanol poisoning in Japan. RESEARCH DESIGN AND METHODS: This retrospective post-marketing surveillance study conducted in Japan registered patients who received fomepizole intravenous infusion per the package insert (January 2015-June 2022). Endpoints included adverse drug reactions/infections (ADRs), arterial blood pH, and treatment outcomes. RESULTS: Of 147 patients registered (91 institutions), 131 and 126 were included in the safety and effectiveness analysis set, respectively. Mean age was 43.6 years, and 66.4% were male. Mean time from poison ingestion to treatment was 15.1 hours; 66.4% received concomitant hemodialysis. No serious ADRs were reported. ADRs were reported in seven patients; the most-reported ADR was vomiting (2.3%). Seven patients died, 105 survived without sequelae, and 19 survived with sequelae. Most common sequelae were renal failure or renal dysfunction. Mean arterial blood pH increased to 7.4 by 4 hours of treatment, remaining stable for 24 hours post-treatment. CONCLUSIONS: Fomepizole is well tolerated and helps improve clinical outcomes in patients with ethylene glycol or methanol poisoning in Japan. TRIAL REGISTRATION: Japanese Pharmaceutical Information Center (JapicCTI-152817).

Beyond the Usual Suspects: Ethylene Glycol Poisoning Complicated by Rare Neurological Sequelae.

Ethylene glycol poisoning is a known clinical entity with established diagnostic and management protocols. However, instances presenting with rare neurological complications pose diagnostic challenges and necessitate prompt recognition and intervention. This report details the case of ethylene glycol poisoning in a 38-year-old male patient who initially presented with a history of brake oil consumption at his residence, followed by a delayed presentation with vomiting, abdominal pain, and reduced urine output, and subsequently developed unusual neurological sequelae, including unsteadiness, hearing difficulties, and an inability to close his eyes. Diagnostic assessment revealed cerebellar ataxia with bilateral sensory-neural hearing loss and facial nerve palsy. The patient was subsequently managed primarily for ethylene glycol poisoning, with conservative management for the neurological sequelae, and improved with no residual deficits. This case underscores the importance of promptly managing ethylene poisoning to prevent complications and sequelae as well as reduce morbidity for patients.

Ethylene Glycol Poisoning: A Case Study of a 71-Year-Old Male with a History of Alcohol Abuse and Suicide Attempts.

A 71-year-old male with a history of alcohol abuse and multiple suicide attempts was brought to the emergency department in an unconscious state. Initial assessment revealed profound obtundation and malnutrition. Laboratory findings demonstrated a significant anion gap metabolic acidosis with a high osmolar gap, suggestive of possible toxic alcohol ingestion. Despite negative serum alcohol levels, ethylene glycol poisoning was confirmed with a level of 226. Treatment included fluid resuscitation, bicarbonate therapy, and fomepizole administration. However, due to progressive multi-organ failure, continuous veno-venous hemodialysis was initiated. Despite interventions, the patient deteriorated rapidly, leading to a decision for hospice care, ultimately resulting in death. Ethylene glycol poisoning presents significant challenges in management, with potential complications including renal failure and multi-organ dysfunction. Fomepizole remains the cornerstone of treatment, but additional therapies such as ethanol administration were considered but ultimately deemed unnecessary due to associated risks. This case highlights the complexity and severity of ethylene glycol poisoning, emphasizing the need for early recognition and aggressive management strategies.

Combined Ethylene Glycol Poisoning with Methemoglobinemia Due to Antifreeze Ingestion.

BACKGROUND: Antifreeze poisoning is potentially life-threatening and often requires multiple antidotal therapies and hemodialysis. Ethylene or propylene glycol toxicity is commonly caused by antifreeze ingestion. However, ingestion of antifreeze is typically not associated with methemoglobinemia. Currently, only one other case of antifreeze ingestion causing combined ethylene glycol poisoning and methemoglobinemia has been reported. CASE REPORT: A 56-year-old man presented after a witnessed, intentional, large-volume antifreeze ingestion. Evaluation revealed dark brown blood and significantly elevated methemoglobin and ethylene glycol levels. He was successfully treated with methylene blue, fomepizole, and hemodialysis. No other potential cause for methemoglobinemia was elucidated, and further research indicated that minor components of the specific antifreeze product served as an oxidizing agent. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case highlights the impact of minor, unreported product components that may significantly contribute to clinical toxicity, as well as the need to remain vigilant when reviewing product information and potential limitations therein.

Assessing the Role of Initial Serum Calcium Concentration in Patients with Ethylene Glycol Poisoning.

INTRODUCTION: Assays for ethylene glycol (EG) with a rapid turn-around time are not routinely available. Clinicians must rely on historical features and readily available clinical tests, combined with clinical acumen, to guide the initial management of suspected EG poisoning. Hypocalcemia has been suggested as a clue supporting the diagnosis of EG poisoning in patients presenting with an unexplained high anion gap metabolic acidosis (HAGMA). A previous small study challenged this assumption. METHODS: This was a retrospective case series of one state's poison control system of confirmed EG-poisoned patients between September 2017 and April 2021. The definition of EG poisoning was based on suspected EG ingestion and a serum EG concentration > 5 mg/dL. Patients who were suspected to have EG toxicity but did not have a confirmed EG concentration or the EG concentration was less than 5 mg/dL were excluded. Routine laboratory studies were recorded for all patients. Comparisons between serum calcium on presentation to presenting blood pH, bicarbonate, anion gap, and creatinine were assessed for correlation. RESULTS: There was no correlation between the presenting calcium and either pH or creatinine. There was a weak positive correlation between the initial serum calcium and anion gap, a weak negative correlation between the initial serum calcium and bicarbonate. CONCLUSION: On hospital presentation, hypocalcemia was not associated with EG poisoning, even in patients with a HAGMA. A normal serum calcium on presentation does not exclude the diagnosis of EG poisoning.

Analysis of Fomepizole Elimination in Methanol- and Ethylene Glycol-Poisoned Patients.

INTRODUCTION: Fomepizole is an anti-metabolite therapy that is used to diminish the toxicity from methanol or ethylene glycol. Although its elimination kinetics have been well described in healthy human subjects, the elimination in poisoned patients have only been described in a few isolated cases. This study was designed to relate the elimination of fomepizole in a series of poisoned patients to that in healthy humans. METHODS: Plasma samples from 26 patients in the clinical trials of the use of fomepizole for methanol and ethylene glycol poisoning were analyzed for fomepizole concentrations. The elimination of fomepizole was assessed after individual doses, both during and without intermittent hemodialysis. RESULTS: In methanol- and ethylene glycol-poisoned patients, fomepizole had a volume of distribution of 0.66-0.68 L/kg. After repeated doses of fomepizole, the minimum trough concentration averaged 86-109 µmol/L, which is 10 times higher than the minimum therapeutic concentration. In healthy human subjects, fomepizole elimination follows Michaelis-Menten kinetics and has been calculated as zero-order elimination rates. Zero-order elimination rates averaged 13 and 17 µmol/L/h in methanol and ethylene glycol patients, respectively, compared to 6-19 µmol/L/h in healthy subjects. Elimination during intermittent hemodialysis followed first-order kinetics, with a half-life of 3 h. CONCLUSIONS: Plasma concentrations during the repeated dosing confirmed that the recommended dosing schedule, with and without intermittent hemodialysis, maintained therapeutic concentrations throughout the treatments. Fomepizole elimination in poisoned patients at therapeutic plasma concentrations appears be similar to that reported previously in healthy human subjects.

Ethylene glycol poisoning: A diagnostic challenge in a patient with persistent seizures and a severe metabolic acidosis.

INTRODUCTION: Due to the nationwide lockdown to mitigate the spread of COVID-19 and subsequent alcohol ban in South Africa, several cases of toxic alcohol ingestion presented to our emergency unit. Many of these patients admitted to making home brews of alcohol while others simply use industrial toxic alcohols. The diagnosis of these poisonings is challenging as direct assays are not available in our setting. CASE REPORT: We present a case of presumed ethylene glycol poisoning that presented with persistent seizures and a high anion gap metabolic acidosis (HAGMA). DISCUSSION: A high index of suspicion for toxic alcohol poisoning should be maintained in patients presenting with an altered mental status, seizures and a HAGMA. Indirect markers such as clinical features and laboratory results can lead to the diagnosis when direct assays are unavailable.

Calcium Oxalate Monohydrate is Associated with Endothelial Cell Toxicity But Not with Reactive Oxygen Species Accumulation.

One characteristic of ethylene glycol overdose is a cardiopulmonary syndrome including hypertension and pulmonary edema with pathology indicating damage to the endothelium of heart, lung and brain vessels. The mechanism of the cardiopulmonary toxicity is unknown, but has been linked with accumulation of the metabolite calcium oxalate monohydrate (COM) in the endothelium. These studies have evaluated the hypothesis that COM or the oxalate ion produces endothelial damage in vitro and that damage is linked with induction of reactive oxygen species (ROS). In cultured human umbilical vein endothelial cells (HUVEC), COM, but not the oxalate ion, produced cytotoxicity in a dose- and time-dependent manner. Using three ROS-sensitive dyes, HUVEC exposed to COM did not significantly increase ROS production. Additionally, co-treatment with three antioxidants that operate by different mechanisms did not reduce COM cytotoxicity. As such, an increase in ROS production does not explain cell death in endothelial cells. Aluminum citrate, uniquely among citrate compounds, significantly reduced COM cytotoxicity to endothelial cells and thus may act as an adjunct therapy for ethylene glycol poisoning to reduce endothelial damage. These results imply that accumulation of COM in endothelial cells is an important aspect of the cardiopulmonary toxicity from ethylene glycol.

Erroneously High Lactate: A Guide to Diagnosing Ethylene Glycol Poisoning.

A high lactic acid level in critically ill patients is a marker of poor prognosis. However, lactic acidosis in ethylene glycol (EG) poisoning should be interpreted cautiously as analytical interference is observed with EG metabolites.

Recurrent Ethylene Glycol Poisoning with Elevated Lactate Levels to Obtain Opioid Medications.

BACKGROUND: Malingering is when a patient feigns illness for secondary gain. While most patients with malingering manufacture or exaggerate symptoms, some patients may induce illness. Previous reports of malingering patients inducing illness include sepsis, kidney pain, migraine, and chest pain. However, acute poisoning as a manifestation of malingering appears to be rare. CASE REPORT: We describe the case of a 39-year-old man who presented to the emergency department complaining of diffuse body pain. The patient reported multiple admission at outside hospitals for "lactate" and said, "it feels like it is happening again because of how my body feels." Laboratory findings were concerning for serum lactate of >20.0 mmol/L and ethylene glycol (EG) level of 19 mg/dL. A chart review found that the man had been admitted for elevated serum lactate 8 times to area hospitals in several years, often in the setting of EG poisoning. During these episodes he required intravenous fluids and frequent intravenous pain medications. When confronted about concern regarding the recurrent fallacious lactate levels in the setting of factitious EG ingestion, the patient often became combative and left against medical advice. The primary metabolite of EG, glycolic acid, can interfere with lactate assays, causing a false elevation. Our patient apparently recognized this and took advantage of it to be admitted and receive intravenous opioids. This is the only case known to us of malingering via EG ingestion. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians should be aware that metabolites of EG may interfere with serum lactate assay. In addition, they should be aware of possible malingering-related poisoning and plausible association with requests for intravenous opioid pain medications. This represents a risk to the patient and others if undiagnosed.

Prediction and validation of the duration of hemodialysis sessions for the treatment of acute ethylene glycol poisoning.

The duration of hemodialysis (HD) sessions for the treatment of acute ethylene glycol poisoning is dependent on concentration, the operational parameters used during HD, and the presence and severity of metabolic acidosis. Ethylene glycol assays are not readily available, potentially leading to undue extension or premature termination of HD. We report a prediction model for the duration of high-efficiency HD sessions based retrospectively on a cohort study of 26 cases of acute ethylene glycol poisoning in 24 individuals treated by alcohol dehydrogenase competitive inhibitors, cofactors and HD. Two patients required HD for more than 14 days, and two died. In 19 cases, the mean ethylene glycol elimination half-life during high-efficiency HD was 165 minutes (95% confidence interval of 151-180 minutes). In a training set of 12 patients with acute ethylene glycol poisoning, using the 90th percentile half-life (195 minutes) and a target ethylene glycol concentration of 2 mmol/l (12.4 mg/dl) allowed all cases to reach a safe ethylene glycol under 3 mmol/l (18.6 mg/dl). The prediction model was then validated in a set of seven acute ethylene glycol poisonings. Thus, the HD session time in hours can be estimated using 4.7 x (Ln [the initial ethylene glycol concentration (mmol/l)/2]), provided that metabolic acidosis is corrected.

Ethylene glycol poisoning: a rare but life-threatening cause of metabolic acidosis-a single-centre experience.

BACKGROUND: Intoxication with ethylene glycol happen all around the world and without rapid recognition and early treatment, mortality from this is high. METHODS: In our study, we retrospectively analysed six cases of ethylene glycol intoxication in our department. We measured ethylene glycol or glycolate levels, lactate levels and calculated the osmolal and anion gap. RESULTS: Data from six patients admitted to the nephrology department between 1999 and 2011 with ethylene glycol poisoning are reported. All patients were men. The mean pH on admission was 7.15 ± 0.20 and the anion and osmolal gap were elevated in five of six patients. Four patients had an acute kidney injury and one patient had an acute-on-chronic kidney injury. All patients survived and after being discharged, two patients required chronic intermittent haemodialysis. Interestingly, at the time of admission, all patients had elevated lactate levels but there was no linear regression between toxic levels and lactate levels and no linear correlation was found between initial lactate levels and anion gap and osmolal gap. CONCLUSIONS: The initial diagnosis of ethylene glycol poisoning is difficult and poisoning with ethylene glycol is rare but life threatening and needs rapid recognition and early treatment. Therefore, intoxication with ethylene glycol should not be misdiagnosed as lactic acidosis in patients with metabolic acidosis and elevated lactate levels.

Intoxicación con etilenglicol. Presentación de casos y revisión de la literatura / Intoxication with ethylene glycol. Presentation of cases and review of literature

El etilénglicol es un producto utilizado en la industria química. La ingesta o aspiración de esta sustancia es una emergencia médica que se debe diagnos� ticar y tratar de inmediato. Inicialmente produce un cuadro conocido como "embriaguez sin aliento alcohólico", seguido de toxicidad cardiopulmonar y renal con grave acidosis metabólica con brecha aniónica aumentada. En la mayoría de los Centros, no es posible determinar la concentración de eti� lénglicol en sangre, por lo que el diagnóstico inicial se basa en la anamnesis y en la presencia de acidosis metabólica grave con brecha aniónica elevada. El tratamiento consiste en soporte vital, adecuada infusión de fluidos y bicar� bonato de sodio, administración de etanol o fomepizol para antagonizar la enzima alcohol deshidrogenasa y, en algunos casos, hemodiálisis.(AU)

The ethylene glycol is a product used in the chemical industry. The intake or inhalation of this substance is a medical emergency that should be diagnosed and treated early. Initially it causes a condition known as "drunkenness with� out alcoholic breath", followed by cardiopulmonary and renal dysfunctions with severe metabolic acidosis and increased anion gap. Determination of blood levels is not available in most health care centers, so initial diagnosis should be based on history and the presence of metabolic acidosis with el� evated anion gap. Treatment consists of vital support, adequate fluid and bicarbonate infusion, administration of ethanol o fomepizole to antagonize the � genase and, in some cases, hemodialysis.(AU)