[Current status of research on the diagnosis and treatment of acute ethylene glycol poisoning].

Acute ethylene glycol poisoning often leads to acute kidney injury, and delays in diagnosis and treatment can lead to severe multi-organ dysfunction and even death. At present, there is a lack of specific laboratory tests that can be used for rapid clinical diagnosis, and diagnosis and evaluation only rely on medical history, clinical symptoms, and non-specific laboratory test results. Key treatments include alcohol dehydrogenase inhibitors (fomcpizole or ethanol) and hemodialysis, which is not approved in China. A clear understanding of the mechanism of toxicity, pathophysiology, clinical manifestations, efficacy and limitations of laboratory tests, and treatment options after ethylene glycol poisoning can help accelerate the early diagnosis, treatment, and prognosis of patients after ethylene glycol poisoning. This article reviews this article in order to provide a reference for clinicians.

Development of a Rapid Detection Method for Ethylene Glycol and Glycolic Acid in Feline Samples: A Response to Increasing Antifreeze Poisoning Incidents in Korea.

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.

Isovaleramide attenuates ethylene glycol poisoning-induced acute kidney injury and reduces mortality by inhibiting alcohol dehydrogenase activity in rats.

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.

Rapid availability of ethylene glycol test results with enzymatic assay.

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.

Kidney outcomes after methanol and ethylene glycol poisoning: a systematic review and meta-analysis.

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.

Outcomes of death and prolonged renal insufficiency in ethylene glycol poisoned patients.

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.

The three biological gaps and hyperoxaluria in ethylene glycol poisoning: case presentation and review.

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.

Spurious point-of-care lactate elevation in ethylene glycol intoxication: rediscovering a clinical pearl.

A 76-year-old man was found unresponsive and brought to the emergency department. Initial workup showed profound lactic acidosis on a point-of-care arterial blood gas, without clinical signs of hypoperfusion. Investigations for types A and B lactic acidosis revealed no unifying diagnosis to explain both his altered mental status and profound lactic acidosis. A toxicology workup revealed an increased osmolar gap and an elevated ethylene glycol level. The lactic acidosis and his mental status completely normalised within 8 hours of renal replacement therapy initiation and fomepizole administration. Ethylene glycol metabolites have similar molecular structure with L-lactate. Some blood gas analysers are unable to differentiate them, resulting in an artefactual lactate elevation. Our case highlights the importance of recognising a falsely elevated lactate, which should raise clinical suspicion of ethylene glycol poisoning, as the treatment is time-sensitive to prevent complications and mortality.

[Simplified laboratory analysis of ethylene glycol allows improved management of poisoning cases]. / Förenklad analys av etylenglykol kan ge snabbare diagnos vid förgiftningsfall.

Toxicological analysis constitutes an important part of the acute treatment of poisonings. Timely laboratory results are essential for the patient to be diagnosed and treated appropriately, but also to exclude poisoning and avoid unnecessary overtreatment. Ingestion of ethylene glycol may cause acute kidney injury and, in severe cases, death, unless treated early with an antidote (ethanol infusion or fomepizole) to inhibit the formation of toxic metabolites. Diagnosis of poisoning is based on detection of ethylene glycol in plasma or serum, but a challenge remains that acute toxicology service is only available at major hospital laboratories using gas chromatography. A simple enzymatic method for the quantification of ethylene glycol (Catachem) was evaluated as a complement to currently used methods and demonstrated to provide fast and accurate measurement in a clinically relevant concentration range (1-80 mmol/l) with a minimal risk of analytical interference. The method is suitable for use on several automated clinical chemistry analyzers. Use of the enzymatic method can improve availability of acute toxicology service for ethylene glycol and contribute to better healthcare from both a patient and health resource perspective.

Ethylene glycol intoxication following brake fluid ingestion complicated with unilateral facial nerve palsy: a case report.

BACKGROUND: Brake oil is an automobile transmission fluid composed of a mixture of toxic alcohols such as ethylene glycols and glycol ethers. Both accidental and intentional ingestion cases have been reported and they can present with multisystem involvement. Life-threatening complications evolve from deleterious effects on cardiopulmonary and renal systems. Effects on neurological and gastrointestinal systems give rise to a multitude of complications although non-fatal in nature. The biochemical panel consists of a high concentration of ethylene glycol with severe metabolic acidosis, high anion gap, high osmolar gap, oxaluria, and hypocalcemia. The mainstay of treatment is enhanced elimination of ethylene glycol and its metabolites by hemodialysis, together with general supportive care, gastric decontamination, and vitamins such as thiamine and pyridoxine to minimize the adverse effects of intoxication. CASE PRESENTATION: A 26-year-old Sinhalese woman presented with reduced urine output, shortness of breath, reduced level of consciousness, abdominal pain, and vomiting with mild degree fever of 2 days' duration. She had bilateral lower limb edema, crepitations over bilateral lower lung fields, and right-sided lower motor type facial nerve palsy. Investigations showed severe metabolic acidosis with high anion gap and high osmolar gap. With regular hemodialysis she made a complete recovery after 3 months. CONCLUSION: Even without a clear history of poisoning, the presence of a high anion, high osmolar gap metabolic acidosis should prompt one to search for ethylene glycol ingestion. Uncommon manifestations like cranial neuropathies need to be examined and considered. Timely aggressive treatment leads to a better prognosis.

Stiripentol protects against calcium oxalate nephrolithiasis and ethylene glycol poisoning.

Increased urinary oxalate excretion (hyperoxaluria) promotes the formation of calcium oxalate crystals. Monogenic diseases due to hepatic enzymes deficiency result in chronic hyperoxaluria, promoting end-stage renal disease in children and young adults. Ethylene glycol poisoning also results in hyperoxaluria promoting acute renal failure and frequently death. Stiripentol is an antiepileptic drug used to treat children affected by Dravet syndrome, possibly by inhibiting neuronal lactate dehydrogenase 5 isoenzyme. As this isoenzyme is also the last step of hepatic oxalate production, we hypothesized that Stiripentol would potentially reduce hepatic oxalate production and urine oxalate excretion. In vitro, Stiripentol decreased in a dose-dependent manner the synthesis of oxalate by hepatocytes. In vivo, Stiripentol oral administration reduced significantly urine oxalate excretion in rats. Stiripentol protected kidneys against calcium oxalate crystal deposits in acute ethylene glycol intoxication and chronic calcium oxalate nephropathy models. In both models, Stiripentol improved significantly renal function. Patients affected by Dravet syndrome and treated with Stiripentol had a lower urine oxalate excretion than control patients. A young girl affected by severe type I hyperoxaluria received Stiripentol for several weeks: urine oxalate excretion decreased by two-thirds. Stiripentol is a promising potential therapy against genetic hyperoxaluria and ethylene glycol poisoning.

Ethylene glycol: Evidence of glucuronidation in vivo shown by analysis of clinical toxicology samples.

In the search for improved laboratory methods for the diagnosis of ethylene glycol poisoning, the in vivo formation of a glucuronide metabolite of ethylene glycol was hypothesized. Chemically pure standards of the ß-O-glucuronide of ethylene glycol (EG-GLUC) and a deuterated analog (d4 -EG-GLUC) were synthesized. A high-performance liquid chromatography and tandem mass spectrometry method for determination of EG-GLUC in serum after ultrafiltration was validated. Inter-assay precision (%RSD) was 3.9% to 15.1% and inter-assay %bias was -2.8% to 12.2%. The measuring range was 2-100 µmol/L (0.48-24 mg/L). Specificity testing showed no endogenous amounts in routine clinical samples (n = 40). The method was used to analyze authentic, clinical serum samples (n = 31) from patients intoxicated with ethylene glycol. EG-GLUC was quantified in 15 of these samples, with a mean concentration of 6.5 µmol/L (1.6 mg/L), ranging from 2.3 to 15.6 µmol/L (0.55 to 3.7 mg/L). In five samples, EG-GLUC was detected below the limit of quantification (2 µmol/L) and it was below the limit of detection in 11 samples (1 µmol/L). Compared to the millimolar concentrations of ethylene glycol present in blood after intoxications and potentially available for conjugation, the concentrations of EG-GLUC found in clinical serum samples are very low, but comparable to concentrations of ethyl glucuronide after medium dose ethanol intake. In theory, EG-GLUC has a potential value as a biomarker for ethylene glycol intake, but the pharmacokinetic properties, in vivo/vitro stability and the biosynthetic pathways of EG-GLUC must be further studied in a larger number of patients and other biological matrices.

[Antifreeze poisoning : The case of a patient with repeated ethylene glycol poisoning]. / Intoxikation nach Frostschutzmittelaufnahme : Der Fall eines Patienten nach wiederholter Ethylenglykolintoxikation.

Ethylene glycol poisoning of incidental or suicidal intention can cause life-threatening metabolic acidosis, diverse secondary damage, and even lead to death. Beside hemodialysis effective therapy consists of the administration of fomepizole and ethanol. We describe a patient after repeated ethylene glycol poisoning with high anion gap metabolic acidosis and acute renal failure. Using hemodialysis, with dialysate containing a specific amount of ethanol, and intravenous ethanol administration we were able to prevent severe secondary organ damage.

Ethylene glycol and methanol ingestion cared for by tele-emergency pharmacy and tele-emergency medicine.

We believe this is the first documented case of a critically ill patient managed by telepharmacy in a remote, rural critical access hospital. We outline the case and the benefits of telepharmacy in under-resourced, rural critical access emergency departments.

The importance of the histopathological examination in lethal acute intoxication with ethylene glycol. Case report.

Ethylene glycol is a toxic alcohol that is mainly introduced into an organism through the digestive pathway. Its priority toxic metabolites are glycolic acid and oxalic acid. We present the case of a young person, of the male persuasion, without any personal pathological history, found unconscious and presenting signs of violence. The patient is emergency hospitalized presenting coma, convulsive syndrome, severe metabolic acidosis and a positive result for alcoholism. Anamnestic data is extremely poor. The results of the clinical and paraclinical examinations suggest a possible poisoning with toxic alcohols. Despite the drug treatment and the hemodialysis, the evolution is unfavorable, resulting in death one week after admission. Through the forensic examination, the followings were found: cerebral and leptomeningeal edema, focal cerebral microhemorrhages, bronchopneumonia, septic spleen, shock kidney, hepatic fatty dystrophy, excoriated plaques in the head area. The histopathological (HP) examination confirms the macroscopic diagnosis and identifies the presence of calcium oxalate crystals in the kidney tubules. Subsequently, the toxicological examination of the biological samples taken from the corpse at the forensic examination, confirms the presence of the glycolic acid. Postmortem, the investigation conducted by the criminal investigation authorities confirms the oral ingestion of antifreeze. The absence of a positive history, along with alcohol consumption, nonspecific clinical symptomatology and the absence of calcium oxalate in urine are trap elements in the diagnosis of acute ethylene glycol poisoning. The presence of calcium oxalate in tissues, identified through the HP examination, is an extremely important factor when establishing the cause of death.

[CME: Ethylene Glycol Intoxication]. / CME: Ethylenglykol-Intoxikation.

CME: Ethylene Glycol Intoxication Abstract. Ethylene glycol is a sweet-tasting alcohol used in common antifreeze and other industrial solutions. Without appropriate therapy, intoxication with ethylene glycol can result in severe metabolic acidosis, acute renal failure, and in death. After gastrointestinal resorption, hepatic metabolism starts with oxidation by alcohol dehydrogenase and results in severe anion gap metabolic acidosis. Other metabolic products are calcium oxalate crystals, which can deposit in several tissues like the kidneys and lead to acute tubular necrosis with reversible renal failure. The crucial therapeutic step is rapid inhibition of alcohol dehydrogenase with fomepizole or ethanol to avoid the formation of toxic metabolites. Additionally, haemodialysis is the most effective way to eliminate ethylene glycol as well as its toxic metabolites. If therapy is initiated rapidly, prognosis is favorable.

Time-dependent changes in kidney histopathology in ethylene glycol poisoning.

Ethylene glycol (EG) may be acutely toxic following ingestion. In fatal cases, microscopic examination of urine and kidney specimens can establish a post-mortem diagnosis of EG poisoning. We describe the main renal histopathologic changes during different stages of EG poisoning, which might be helpful when dating the EG poisoning itself. A single-centre retrospective study conducted on all EG poisoning cases demonstrated that in an early stage of EG poisoning, fine dust-like crystals were deposited to the tubular cell basement membrane, followed by internalisation of calcium oxalate crystals into the epithelial cells. Later, the crystals formed larger aggregates within the epithelial cells. As the changes became advanced, pronounced tubular epithelial damage occurred, with detachment of epithelial cells from the basement membrane. In the final stage, coarse calcium oxalate crystals were recognised in the tubular lumen, with cellular debris from damaged epithelial cells. Our study shows that the time-dependent histological changes described follow the clinical stages of EG poisoning and may therefore provide a rough estimate of the time of EG ingestion before death.

Value of glycolic acid analysis in ethylene glycol poisoning: A clinical case report and systematic review of the literature.

OBJECTIVE: To evaluate the clinical utility of glycolic acid (GA) determination in the diagnosis and prognosis of ethylene glycol (EG) intoxications. METHOD: Systematic review of serum and/or urine GA concentrations available in the literature in cases of EG poisoning. Present a clinical case in which the determination of the GA was decisive. RESULTS: In total, 137 patients were included. Serum GA concentrations (but not EG) of patients who survive are different from those who die. The optimal cut-off of serum GA to predict mortality was 990.5mg/L (sensitivity 85.2%, specificity 54.3%) with an Odds Ratio of 6.838 (2.868-16.302). In our clinical case, serum EG was negative; however, urine GA was positive (1230.7mg/L). CONCLUSIONS: In all suspected cases of EG poisoning, it is advisable to carry out the simultaneous analysis of EG and GA.