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We explored the potential value of the alcohol dehydrogenase (ADH) inhibitor isovaleramide (ISO) in the treatment of acute ethylene glycol (EG) poisoning‐induced acute kidney injury. Sprague–Dawley rats were divided into the control, EG, EG + ISO (10 mg/kg) and EG + ISO (20 mg/kg) groups. It is found that ISO intervention significantly reduced the ADH activity in liver tissue by using visible spectrophotometry, inhibited the in vivo metabolism of EG by using gas chromatography, lowered the levels of toxic metabolites glycolic acid and oxalic acid by using high‐performance liquid chromatography and decreased the expression of kidney injury markers serum creatinine (sCr), KIM‐1, neutrophil gelatinase‐associated lipocalin (NGAL) and liver fatty acid‐binding protein (L‐FABP) by ELISA. Additionally, Western blotting results showed that ISO down‐regulated the expression of apoptotic factors Bax and cleaved caspase‐3 in the kidneys and upregulated the expression of antiapoptotic factor Bcl‐2. Pizzolato staining and polarized light microscopy results revealed the reduced deposition of calcium oxalate crystals in the kidney tubules. Using haematoxylin and eosin (H&E), periodic acid‐Schiff (PAS) and Masson staining, we found attenuated kidney tissue pathological injury. Finally, ISO significantly reduced the mortality rate. In conclusion, ISO has the potential to be a valuable drug for the treatment of EG poisoning‐induced acute kidney injury. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

AbstractEthylene glycol (EG) is a toxic alcohol that causes central nervous system depression and multiple metabolic abnormalities including a high anion gap metabolic acidosis (HAGMA), elevated osmolal gap (OG), and acute kidney injury. Few case reports of EG intoxication report brain MRI findings. We describe an elderly female who was brought to the hospital because of altered mentation. We diagnosed her with EG toxicity and treated with fomepizole based on metabolic abnormalities and presence of urine calcium oxalate crystals. Our patient’s brain MRI showed T2-hyperintense signals located in the midbrain, hippocampi, basal nuclei, and thalami consistent with previous MRI reports with confirmed EG toxicity. As in this case, a clear history of poisoning is not always available. However, antidote therapy with alcohol dehydrogenase blockade should be initiated if clinical data suggests EG intoxication. Our patient’s EG concentration returned elevated two days after admission blood draw confirming the initial diagnosis. MRI of the brain may add diagnostic support to laboratory findings while awaiting a definitive EG concentration.

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. 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. 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. [ABSTRACT FROM AUTHOR]

Ethylene glycol (EG) is a toxic alcohol that causes central nervous system depression and multiple metabolic abnormalities including a high anion gap metabolic acidosis (HAGMA), elevated osmolal gap (OG), and acute kidney injury. Few case reports of EG intoxication report brain MRI findings. We describe an elderly female who was brought to the hospital because of altered mentation. We diagnosed her with EG toxicity and treated with fomepizole based on metabolic abnormalities and presence of urine calcium oxalate crystals. Our patient's brain MRI showed T2-hyperintense signals located in the midbrain, hippocampi, basal nuclei, and thalami consistent with previous MRI reports with confirmed EG toxicity. As in this case, a clear history of poisoning is not always available. However, antidote therapy with alcohol dehydrogenase blockade should be initiated if clinical data suggests EG intoxication. Our patient's EG concentration returned elevated two days after admission blood draw confirming the initial diagnosis. MRI of the brain may add diagnostic support to laboratory findings while awaiting a definitive EG concentration. [ABSTRACT FROM AUTHOR]

Recently, cases of antifreeze poisoning in companion animals, particularly cats, have surged in the Republic of Korea. Ethylene glycol (EG), the toxic primary component of antifreeze, is metabolized into glycolic acid (GA), leading to severe metabolic acidosis, acute kidney injury, and death. Traditional detection methods, although effective, are often time-consuming owing to complex sample preparation. This study involved a novel analytical method utilizing GC-MS for EG and LC-MS/MS for GA detection, which streamlined the detection process by eliminating the need for derivatization. The method was validated for accuracy and reliability, enabling the rapid and precise identification of EG and GA in biological samples. This study also included the successful application of this method in a case where initial exposure to antifreeze was not apparent, which highlighted the effectiveness of this method in diagnosing poisoning even in cases where clinical history is unclear. The development of this rapid diagnostic approach addresses the urgent need for the efficient detection of antifreeze poisoning, improving animal welfare and supporting forensic investigations.

Abstract: Vape juice is a diluent for e-cigarette active ingredients, nicotine or tetrahydrocannabinol (THC). Lack of strict regulation in vape juice production is a concern as ingredients and their concentrations may vary widely from the labeling.A 43-year-old woman was transported via ambulance to the hospital after ingesting homemade vape juice, presenting unresponsive with decerebrate posturing. She reportedly made a tincture combining a vape juice purchased online (containing "ethylene glycol") and THC for "endometriosis-related pain relief." Laboratory evaluation revealed anion gap metabolic acidosis, elevated serum lactate, and high serum osmolality. Urine fluoresced under Wood's lamp, and fomepizole was administered as an ethylene glycol antidote, but she expired the following afternoon. Clinical serum toxicology results returned after death revealed 235 mg/dL of methanol, and no ethylene glycol.Autopsy findings included ischemic changes of the gastrointestinal tract and cerebral edema with herniation. Postmortem toxicology performed on hospital admission blood revealed methanol (220 mg/dL), propylene glycol (59 mg/dL), Δ-9 THC and metabolites, and medications administered during hospitalization. The medical examiner determined the cause of death to be methanol and propylene glycol toxicity.To our knowledge, this is the first report of accidental death from ingestion of vape juice contaminated with toxic alcohol., Competing Interests: The authors report no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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. [ABSTRACT FROM AUTHOR]

Background: Ethylene glycol poisoning causes metabolic acidosis, organ injury, and death. Ethylene glycol testing is unavailable in many areas. Our laboratory uses an automated glycerol dehydrogenase enzymatic assay to screen for ethylene glycol. We sought to determine how often ethylene glycol results were available within 12 h of the first dose of fomepizole., Methods: Records from a single poison center were reviewed from December 2016 to December 2019. Cases were identified by searching for cases that received fomepizole. Outcomes included whether results were available within 12 h, and the turnaround time from time of laboratory order to result., Results: Of the 125 cases of suspected toxic alcohol poisoning identified, 73 had screening for ethylene glycol by enzymatic assay. Results were available within 12 h of the initial fomepizole dose in 58 (79%) cases with a median turnaround time of 391 min., Discussion: We have demonstrated clinically acceptable turnaround times using an automated screening ethylene glycol assay. The major limitations include lack of approval for this test at this time, the use of voluntarily reported poison center data, and lack of assessment of patient outcomes., Conclusion: Enzymatic screening for ethylene glycol yielded results within 12 h in 79% of cases.

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 sets, 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).

Background: Alcohol poisoning is a significant global problem that has become an epidemic. The determination of the alcohol type is hereby essential as it may affect the course of the treatment; however, there is no routine laboratory diagnostic method for alcohol types other than for ethanol. In this study, we aimed to define a simple method for alcohol type differentiation by utilizing a combination of breathalyzer and spectrophotometrically measured serum ethanol results., Methods: A breathalyzer and spectrophotometry were used to measure four different types of alcohol: ethanol, isopropanol, methanol, and ethylene glycol. To conduct serum alcohol analysis, four serum pools were created, each containing a different type of alcohol. The pools were analyzed using the spectrophotometric method with an enzymatic ethanol test kit. An experiment was conducted to measure the different types of alcohol using impreg-nated cotton and a balloon, simulating a breathalyzer test. An algorithm was created based on the measurements., Results: Based on the results, the substance consumed could be methanol or isopropanol if the breathalyzer test indicates a positive reading and if the blood ethanol measurement is negative. If both the breathalyzer and the blood measurements are negative, the substance in question may be ethylene glycol., Conclusions: This simple method may determine methanol or isopropanol intake. This straightforward and innovative approach could assist healthcare professionals in different fields with diagnosing alcohol intoxication and, more precisely, help reducing related morbidity and mortality.

Ethylene glycol is a toxic alcohol which may induce significant toxicity when ingested accidentally or intentionally. The main clinical complications of EG poisoning include central nervous system depression, cardiorespiratory instability and renal failure, which may be lethal if improperly treated. Although the demonstration of high plasma levels of ethylene glycol confirms the intoxication, such measurements are generally not obtained in the acute setting and can be misleading due to the rapid metabolism of EG. This implies the need for alternative, indirect, diagnostic methods, which reflect the metabolic fate of EG. These include an early and transient osmolar gap, followed by an anion gap metabolic acidosis and hyperoxaluria. Another frequent finding is a lactate gap between various methods of lactate measurements. An appropriate knowledge of these laboratory findings is essential for the diagnosis of EG poisoning, and for the initiation of antidote therapy (fomepizole) and hemodialysis in selected cases. These features are illustrated by the presentation of a prototypical case of EG poisoning, in which an incomplete diagnostic workup on hospital admission resulted in an unnecessary laparotomy and a significant delay in the management of the intoxication. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.

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. [ABSTRACT FROM AUTHOR]

Introduction: Delayed treatment of ethylene glycol poisoning can have catastrophic consequences that may result in death. Case report: 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. Discussion: 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.

Introduction: Ingestions with methanol, ethylene glycol, diethylene glycol, propylene glycol, and isopropanol are rare yet exceedingly dangerous conditions that may require emergent management with kidney replacement therapy. Little is known regarding short- and long-term kidney outcomes post-ingestion., Objectives: To comprehensively synthesize existing evidence regarding short- and long-term kidney and other outcomes of adult patients following these poisonings., Methods: We developed a search strategy in MEDLINE via OVID and then translated it into other databases including EMBASE (via OVID), PubMed, CENTRAL (via OVID). The databases were searched from their dates of inception to 29 July 2021. A grey literature search was conducted in the International Traditional Medicine Clinical Trial Registry and ClinicalTrials.gov. All interventional and observational studies and case series with ≥ five participants that reported on the outcomes of toxic alcohol (methanol, ethylene glycol, diethylene glycol, propylene glycol and isopropanol) poisonings in adult patients ≥18 years old were included. Studies that reported mortality, kidney outcomes and/or complications attributed to toxic alcohol poisoning were eligible., Results: The search strategy identified 1,221 citations. Sixty-seven studies (13 retrospective observational studies, one prospective observational study, 53 case series) met inclusion criteria (total N  = 2,327 participants). No randomized controlled trials were identified per our prespecified criteria. Generally, included studies had small sample sizes (median of 27 participants) and were of low quality. Methanol and/or ethylene glycol poisoning made up 94.1% of included studies, whereas one study reported on isopropanol and none reported on propylene glycol. Results of the 13 observational studies of methanol and/or ethylene glycol poisoning were pooled for meta-analyses. The pooled in-hospital mortality estimates amongst patients with methanol and ethylene glycol poisoning were 24 and 11%, respectively. A more recent year of publication, female sex and mean age were associated with lower in-hospital mortality amongst individuals with ethylene glycol poisoning. Although hemodialysis was the most frequently employed kidney replacement therapy, the indications for initiation of this therapy were not reported in the majority of studies. At hospital discharge, kidney recovery occurred in 64.7-96.3% of patients with ethylene glycol poisoning. In studies of methanol and/or ethylene glycol poisoning, 2-3.7% of individuals required ongoing dialysis. Only one study reported post-discharge mortality. Furthermore, long-term toxic alcohol-mediated sequelae, such as visual and neurologic outcomes, were scarcely reported., Discussion: Ingestions of methanol and ethylene glycol were associated with a significant short-term risk of mortality. Although a wealth of literature in the form of case reports and case series exists, high-quality evidence regarding kidney outcomes after these poisonings is lacking. We identified a paucity of standardized reporting in clinical presentations, therapeutics and outcomes amongst adults with toxic alcohol poisoning. Amongst the included studies, there was substantial heterogeneity encompassing study type, outcomes, duration of follow-up and treatment modalities. These sources of heterogeneity restricted our ability to perform comprehensive meta-analyses of all outcomes of interest. An additional limitation is the lack of studies pertaining to propylene glycol and the paucity of data on isopropanol., Conclusions: The indications for hemodialysis, long-term kidney recovery and long-term mortality risk vary widely in these poisonings and are inconsistently reported in the literature. This highlights the need for further research with standardized reporting of baseline kidney function, indications for initiation of kidney replacement therapy and short-term and long-term kidney outcomes., Registration: This systematic review protocol is registered at PROSPERO, CRD42018101955.

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. We present a case of presumed ethylene glycol poisoning that presented with persistent seizures and a high anion gap metabolic acidosis (HAGMA). 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. [ABSTRACT FROM AUTHOR]

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Background/Aims: Renal damage from ethylene glycol and primary hyperoxaluria is linked to accumulation of calcium oxalate monohydrate (COM) crystals in the renal proximal tubule (PT). In vitro studies have shown that aluminum citrate (AC), uniquely among citrate salts, blocks COM cytotoxicity to tubular cells. These studies were designed to evaluate the interaction of COM with membrane phospholipids and the ability of AC to reduce COM toxicity by interfering with this interaction. Methods: Interaction of COM with phospholipids was assessed using differential scanning calorimetric analysis of structural changes in specific liposomes. Interaction of COM with cell membranes was studied by measuring binding of radiolabeled crystals by human PT (HPT) cells. Results: Analysis of liposomes prepared from phosphatidylserine (PS) or phosphatidylcholine (PC) showed that COM interfered with the gel-liquid transition of PS liposomes, but not that of PC liposomes. AC reversed the COM-induced changes in liposomal structure. AC inhibited the binding of [14C]-COM by HPT cells in a concentration-dependent manner. AC blocked COM binding by interacting with the crystal surface and not the cell membrane. Conclusion: These results indicate that AC blocks the binding of COM by PT cells, and consequently its cytotoxicity, by attaching to the surface of the crystal. Thus, AC, or a related compound that works by the same mechanism, could be a useful adjunct therapy to reduce the renal damage produced by severe hyperoxaluria. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Ethylene glycol poisoning is a common form of poisoning worldwide. The clinical course of ethylene glycol poisoning usually follows a three-stage progression, although these stages may overlap. A fourth stage of delayed neurological dysfunction consisting of cranial neuropathies has been suggested in several case reports. We describe a patient with unique findings of postural hypotension and gastroparesis following ethylene glycol toxicity with the additional uncommon features of albuminocytologic dissociation and increased intracranial pressure with papilledema. In addition, we provide a review of the literature on delayed neurological manifestations in ethylene glycol toxicity and further elucidate a description of a fourth stage of delayed neurological dysfunction following ethylene glycol poisoning. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]

Objective. Fomepizole is the antidote of choice in toxic alcohol poisonings. Potential side effects from frequent use of fomepizole were studied in a patient admitted 154 times with ethylene glycol (EG) poisoning. The intra-individual correlation between the serum-ethylene glycol (serum-EG) and the osmolal gap (OG) EG-kinetics, and other laboratory parameters were also studied. Methods. Combined pro- and retrospective collection of material from three different hospitals, and results from autopsy. Results. A 26-year-old female with a dissociative disorder was admitted with EG poisoning a total of 154 times. Her admission data revealed a median pH of 7.31 (range 6.87--7.49), pCO2: 4.2 kPa (1.2--6.7) (32 mmHg [9--50]), HCO--3: 15 mmol/L (4--26) (15 mEq/L [4--26]), base deficit (BD): 10 mmol/L (−− 4 to 27) (10 mEq/L [--4 to 27]), serum-creatinine 65 μμmol/L (40--133) (0.74 mg/dL [0.45--1.51]), OG 81 mOsm/kgH2O (25--132), and serum-EG 44 mmol/L (4--112) (250 mg/dL [25--700]). She was treated with fomepizole 99 times, ethanol 60 times (with a combination of both six times), and dialysis 73 times. The correlation between serum-EG and OG was good (r2 == 0.76). She was finally found dead outside hospital with an EG blood concentration of 81 mmol/L (506 mg/dL). An autopsy revealed calcium oxalate crystals in the kidneys, slight liver steatosis, and slight edema of the lungs. Discussion. The frequent use of fomepizole in this young patient was not associated with any detectable side effects; neither on clinical examination and lab screening, nor on the later autopsy. Regarding the sequelae from the repetitive EG-poisoning episodes, her kidney function seemed to normalize after each overdose. She was treated with buffer and antidote without hemodialysis 81 times without complications, supporting the safety of this approach in selected cases. [ABSTRACT FROM AUTHOR]

Abstract: Ethylene glycol exposure can lead to the development of renal failure due to the metabolic formation of calcium oxalate monohydrate (COM) crystals. The renal damage is closely linked to the degree of COM accumulation in the kidney and most likely results from a COM-induced injury to proximal tubule (PT) cells. The present studies have measured the binding and internalization of COM by primary cultures of normal PT cells from humans and from Wistar and Fischer-344 rats in order to examine the roles of these uptake processes in the resulting cytotoxicity. Internalization was determined by incubation of cells with [14C]-COM at 37°C, removal of bound COM with an EDTA incubation, followed by solubilization of cells, as well as by transmission electron microscopy of COM-exposed cells. COM crystals were internalized by PT cells in time- and concentration-dependent manners. COM crystals were bound to and internalized by rat cells about five times more than by human cells. Binding and internalization values were similar between PT cells from Wistar and Fischer-344 rats, indicating that a differential uptake of COM does not explain the known strain difference in sensitivity to ethylene glycol renal toxicity. Internalization of COM correlated highly with the degree of cell death, which is greater in rat cells than in human cells. Thus, surface binding and internalization of COM by cells play critical roles in cytotoxicity and explain why rat cells are more sensitive to COM crystals. At the same level of COM accumulation after ethylene glycol exposure or hyperoxaluria in vivo, rats would be more susceptible than humans to COM-induced damage. [Copyright &y& Elsevier]

Background. Legislation requiring bittering of antifreeze enables assessment of the impact on frequency, volume, and severity of pediatric antifreeze ingestions. Methods. US poison control data for antifreeze ingestions in children younger than 5 years were analyzed comparing 232 ingestions occurring in states after enactment of bittering requirements with 6218 cases occurring in states (or at times) where bittering was not required. Results. The frequency of pediatric antifreeze ingestions was unchanged after implementation of bittering in Oregon and California. The medical outcome distribution, median volume ingested, and observed clinical effects were no different in bittered compared with nonbittered groups. Likewise, the rates of hospital admission, critical care treatment, and use of alkalinization, hemodialysis, or intubation showed no differences with bittering. Conclusion. Despite the appealing logic of limiting the ingested volume and thereby the severity of poisonings by adding aversive agents, and despite promising results in volunteer studies, bittering agents do not decrease the frequency or severity of pediatric antifreeze poisonings. The addition of bittering agents to household products cannot be justified based on actual poisoning data. [ABSTRACT FROM AUTHOR]

Ethylene glycol (EG)-induced hyperoxaluria is the most commonly employed experimental regimen as an animal model of calcium oxalate (CaOx) stone formation. The variant sensitivity to CaOx among different rat strains has not been fully explored, although the Wistar rat is known to accumulate more CaOx in kidney tissue after low{dose EG exposure than in the Fischer 344 (F344) rats. Supersaturation of CaOx in tubular fluid contributes to the amount of CaOx crystal formation in the kidney. We hypothesized that the urinary supersaturation of CaOx in Wistar rats is higher than that of F344 rats, thereby allowing for greater CaOx crystal deposition in the Wistar rat. matched male Wistar and F344 rats were treated with 0.75% EG or drinking water for 8 wk. Twenty-four-hour urine was collected at 0, 2, 4, 6, and 8 wk for analysis of key electrolytes to calculate the CaOx supersaturation. Plasma oxalate level was also measured. Our data confirmed the different sensitivity to renal toxicity from EG between the two rat strains (Wistar > F344). After EG treatment, the plasma oxalate level and urine oxalate excretion were markedly greater n the Wistar rats than in the F344 rats, while urine calcium was slightly decreased in Wistars. Thus, the CaOx supersaturation in urine of Wistar rats was higher, which led to a greater crystal deposition in kidney in Wistar rats. These studies suggest that during EG treatment, changes in urine electrolytes and in CaOx supersaturation occur to a greater extent in the Wistar rat, in agreement with its greater sensitivity to EG toxicity. [ABSTRACT FROM AUTHOR]

Acute renal failure is a major complication in patients with increased oxalate serum concentration. To describe the metabolic mechanisms of oxalate-induced glomerular and tubular damage, we report a case of ethylene glycol intoxication as well as a case of xylitol infusion in a patient with previously unknown primary hyperoxaluria type 1. Both patients presented with acute renal failure associated with histologically proven renal oxalate accumulation. This excessive ox- abate overloading resulted from elimination and metabolization of ethylene glycol or xylitol. Thus, key enzymes in the elimination pathway of these substances represent targets for pharmacological treatment. Simultaneous hemodialysis is often necessary to reduce oxalate serum concentration. Whereas renal function of the ethylene glycol-poisoned patient recovered, the second patient who received xylitol infusion required chronic hemodialysis due to the unmasked hyperoxaluria type 1. Our cases demonstrate that patients with excessive endogenous oxalate generation are at high risk to develop acute renal failure. There fore, to prevent end-stage renal failure in these patients, important clinical factors should be considered as indicators for the underlying cause: history of alcohol abuse and severe high anion gap acidosis for ethylene glycol intoxication or history of long-lasting parenteral nutrition for xylitol-associated acute renal failure. [ABSTRACT FROM AUTHOR]

Ethylene glycol poisoning can produce acute renal failure, requiring long-term hemodialysis to restore function. The mechanism of the renal failure is unknown, but is associated with tubular cell necrosis and ethylene glycol metabolism. The end metabolite of ethylene glycol is oxalic acid, the precipitation of which as calcium oxalate monohydrate (COM) crystals in the tubular lumen has been linked with the renal toxicity. Our recent studies suggest that COM is an intracellular toxicant to normal human proximal tubule cells in culture. The present studies were designed to assess whether COM or ionic oxalate alters mitochondrial function so as to lead to renal cell death. In isolated rat kidney mitochondria, COM produced a dose-dependent decrease in State 3 respiration (40% decrease at 0.05 mM COM with either succinate or glutamate/malate as substrate), without affecting either State 4 respiration or the ADP/O ratio. COM, from 0.01–0.05 mM also dose-dependently increased mitochondrial swelling, which was completely blocked by cyclosporin A. The inhibition of State 3 respiration, however, was not reversed by cyclosporin A administration. Potassium oxalate, at concentrations up to 5 mM did not inhibit mitochondrial respiration or induce swelling. These results suggest that COM, and not the oxalate ion, damages rat kidney mitochondria and induces the mitochondrial permeability transition, which may then lead to renal cell death. Since COM is transported intracellularly by kidney cells, the renal toxicity of ethylene glycol may result from inhibition of mitochondrial respiratory function in proximal tubular cells by COM crystals. [ABSTRACT FROM PUBLISHER]

Background. Ethylene glycol, usually ingested by coincidence, causes uncommon but serious poisoning which could have fatal consequences without prompt diagnosis and treatment. Ethylene glycol itself has a low toxicity but is rapidly degraded to toxic metabolites, that are responsible for typical clinical presentation. Metabolic acidosis, increased anion and osmolal gap are typical laboratory findings. Application of antidotes ethanol and fomepizol, hemodyalisis and correction of metabolic acidosis are mainstays of therapy.Patients and methods. A case of concurrent ethanol and ethylene glycol ingestion is presented. On admission diagnosis of ethylene glycol poisoning was supported by heteroanamnestic data, typical clinical presentation and laboratory findings and latter confirmed with body fluid analysis. Despite therapy with ethanol, sodium hydrogencarbonate and parenteral hydration patient developed acute renal failure which required hemodyalisis.Conclusions. Concurrent ingestion of spirit improved prognosis of ingestion of lethal ethylene glycol dose. Due to late arrival adequate and immediate in-hospital management could not prevent acute renal failure and subsequent hemodyalisis.

Background: Despite the severity of ethylene glycol intoxication, there is a paucity of studies that analyze prognostic factors. This study aims to determine prognostic factors with impact on core outcomes like death and prolonged kidney injury (KI) in ethylene glycol poisoned patients., Methods: We retrospectively assessed prevalence, clinical and biochemical features in one large data set from two regional hospitals from the North-East region of Romania, between January 2012 and October 2017. Secondly, we compared prognostic factors of cases treated with dialysis plus antidote (N = 28 patients) with cases who received antidote only and supportive therapy (N = 28 patients)., Results: Of the 56 cases included, 16 deaths (28.57%) were recorded. The symptomatology at admission was more severe among patients requiring hemodialysis: a lower mean value for initial pH, lower initial alkaline reserve (AR) and higher mean values for initial serum creatinine (Cr1). The data analysis (survivors/deceased) showed a correlation between pH, Glasgow Coma Score (GCS), and increased mortality. In addition, we found a correlation between initial mean values for pH, AR (mmol/L), Cr1 (mg/dL), and peak Cr24 (mg/dL) with outcomes of RI or death., Conclusions: Compared with survivors, patients who died or had prolonged kidney injury were more likely to exhibit clinical signs such as coma, seizures, and acidosis. Hemodialysis and antidote should be started early and continued until acidosis is corrected., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

4-Methylpyrazole (4-MP), a potent inhibitor of alcohol dehydrogenase activity, is a candidate to replace ethanol as the antidote for methanol and ethylene glycol intoxications, because It has a longer duration of action and apparently fewer adverse effects. To study a probable mutual inhibitory effect between ethanol and 4-MP on their elimination, two studies were performed in healthy human volunteers using double-blind crossover designs. In study A, 4-MP in the presumed therapeutic dose range of 10 to 20 mg/kg caused a 40% reduction in the rate of elimination of ethanol in 12 subjects given 0.5 to 0.7 g/kg of ethanol. These data suggest that such doses of CMP inhibit alcohol dehydrogenase activity in humans in vivo and would be effective at blocking methanol or ethylene glycol metabolism. In study B, ethanol (0.6 g/kg followed by 0.2 g/kg twice) significantly decreased the rate of elimination of 4-MP (5 mg/kg, given intravenously to four subjects). These moderate doses of ethanol also inhibited the rate of urinary excretion of 4-carboxypyrazole, the primary metabolite of 4-MP in humans. Data suggest that ethanol inhibits 4-MP metabolism, thereby increasing the duration of therapeutic blood levels of CMP in the body. This mutual interaction may have clinical implications, because most self-poisoned patients have also ingested ethanol. Theoretically, methanol and ethylene glycol might also show such interactions with 4-MP. [ABSTRACT FROM AUTHOR]

Context: Anion gap metabolic acidosis (AGMA) is common in patients presenting for emergency care. While some disease processes and ingestions are easily excluded, diagnosing toxic alcohol (TA) ingestion can be challenging. This is especially true if drug concentrations are not readily available, which forces clinicians to rely on surrogate markers. Like TA ingestion, alcoholic ketoacidosis (AKA) produces an elevated osmol gap and an AGMA. The aim of this study was to identify risk factors suggestive of AKA when TA ingestion was the primary alternative differential diagnosis. We hypothesized that the odds of an AKA diagnosis would increase as ethanol concentration increased., Methods: This was a retrospective analysis of data from 2000 through 2019 from a single US Poison Control Center. Records were reviewed to identify cases coded as "methanol" or "ethylene glycol"; or coded as "alcohol" or "ethanol with acidosis." The case definition for AKA required: (1) documented alcohol use disorder; (2) urine or serum ketones or elevated blood beta-hydroxybutyrate concentration; (3) anion gap ≥ 14 mmol/L. The inclusion criterion for TAs was a detectable methanol or ethylene glycol concentration., Results: Of 699 patients screened, 86 were diagnosed with AKA and 36 were diagnosed with TA ingestion. As ethanol concentration increased, the odds of an AKA diagnosis significantly increased (OR = 1.016, 95% CI 1.002-1.031, p  = .03)., Conclusions: In this retrospective analysis, the odds of diagnosing AKA instead of TA ingestion increased as ethanol concentration increased. The limited ability of common clinical factors to differentiate these diagnoses highlights the need to obtain quantitative TA concentrations in real time. Until prospective validation, interpretation of ketone concentrations and toxic alcohol concentrations (when available) will continue to guide decision making.