Diagnosis Of Ethylene Glycol Poisoning Research Articles

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

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. 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. 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. 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.

Changes in ionized calcium in ethylene glycol poisoning

Ethylene glycol is a sweet-tasting toxic alcohol contained in a variety of chemical preparations. In patients poisoned with ethylene glycol, diagnosis is often based upon clinical suspicion and nonspecific tests. Hypocalcemia is often present due to calcium oxalate crystals formed by oxalic acid metabolite complexation. This retrospective study involved a review of clinical records of patients with a diagnosis of ethylene glycol poisoning. Results of blood gas samples, lactate, ionized calcium, and serum creatinine were documented and compared between various groups. The ionized calcium concentration was below the normal range in 59% of cases at the time of presentation and more commonly associated with a blood pH of <7.3 in 79% of cases. The number of patients with a low ionized calcium concentration increased over time. A low ionized calcium concentration was a common finding in cases of severe ethylene glycol poisoning and was more commonly associated with patients exhibiting metabolic acidosis or developing acute kidney injury or death. Ionized calcium concentration on presentation may be an additional marker in concert with blood pH that can be used in the risk assessment and stratification of severity and complications of ethylene glycol poisoning.

Une intoxication de diagnostic histologique

Ethylene glycol poisoning is relatively rare, with around a hundred cases reported each year in France. Its diagnosis is often challenging and delayed because of a several hours' free interval between ingestion of the toxic and the onset of the first symptoms. Ethylene glycol is a colorless and odorless liquid primarily found in automotive coolants, whose toxicity is linked to its hepatic metabolites. Histologically, ethylene glycol poisoning is characterized by abundant tissular deposits of calcium oxalate crystals. Under polarized light, these crystals appear birefringent and iridescent. Their microscopic appearance and their distribution are pathognomonic of oxalosis. Due to its frequent misleading presentation, the diagnosis of ethylene glycol poisoning is sometimes only made after an autopsy. Hereafter, we report the case of a 59-year-old man diagnosed with ethylene glycol intoxication after a post-mortem histopathological examination of organs.

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 β‐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.

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.

Ethylene glycol poisoning

Ethylene glycol poisoning

Validation of a rapid, automated method for the measurement of ethylene glycol in human plasma.

Background Ethylene glycol is a highly toxic compound found in various household products. Cases of poisoning are rare but may be fatal unless diagnosed and treated promptly. Early recognition of poisoning is critical for the management and recovery of patients. Indirect testing is not specific for the presence of ethylene glycol. Therefore, urgent and accurate measurement should be sought if ingestion is suspected in order to determine the need for treatment with an antidote. Here, we present the validation of an automated assay for measurement of ethylene glycol on an Abbott Architect using a commercially available kit (Catachem). Methods Analytical parameters of imprecision, linearity, stability and bias were determined using spiked human plasma samples processed on both the Catachem assay and on an in-house gas chromatography-mass spectrometry method. Interference was assessed using samples collected into a variety of sample collection tubes and spiked with a number of alcohols. Results Excellent agreement was observed between the two methodologies with the enzymatic assay demonstrating linearity and precision across the relevant clinical range (50-3000 mg/L). In addition, the Catachem assay displayed no interference from a number of different sample tubes and alcohols. However, propylene glycol interference was observed at concentrations associated with excessive use (>1 g/L) and 2,3-butanediol interference observed at concentrations associated with butanone ingestion. Inspection of the enzymatic reaction profile was found to differentiate between alcohols. Conclusions This automated assay is suitable for the diagnosis of ethylene glycol poisoning and is now in routine use, enabling the laboratory to provide a rapid 24 h service with support by gas chromatography-mass spectrometry as necessary.

Ethylene Glycol Poisoning; an Unusual Cause of Hyperglycemia: A Case Report

Background:Poisoning with ethylene glycol (EG) can be fatal even if appropriate treatments are delivered. EG poisoning usually causes central nervous system depression, cardiovascular dysfunction, metabolic acidosis and acute renal failure (ARF). Case Report:A 33-year-old man was referred to the emergency department with reduced consciousness and dyspnea of four-hour duration due to unknown reason. The patient had no history of diabetes, hypertension, cardiac disease or asthma. He was tachycardic, tachypneic and hypertensive. Laboratory investigations revealed hyperglycemia, high serum creatinine, hyponatremia, hyperkalemia, leukocytosis and high anion gap metabolic acidosis (HAGMA). He was initially managed as diabetic ketoacidosis (DKA). Alternative diagnoses of toxic alcohols poisoning was considered as there was no improvement. EG ingestion was confirmed when the relatives found an empty bottle of automotive brake oil, a poly glycol-based product, in the patient’s room. Although he was treated with ethanol and hemodialysis, renal failure worsened and finally he succumbed to death due to severe sepsis on the seventh day of EG ingestion. Discussion: This case illustrates the difficulties posed by high toxicity as well as unraveled and delayed diagnosis of EG poisoning. High anion gap and high osmolal gap are characteristics of EG poisoning. Transient pancreatitis caused by EG and insulin resistance due to ARF are the possible explanations for hyperglycemia secondary to EG poisoning. Conclusion:EG poisoning may manifest with hyperglycemia and HAGMA resembling DKA. It is important for the clinician to have high degree of suspicion for EG poisoning in case of HAGMA and ARF refractory to common treatments.

Challenges in the diagnosis of ethylene glycol poisoning

Ethylene glycol poisoning, while uncommon, is clinically significant due to the associated risk of severe morbidity or lethality and it continues to occur in many countries around the world. The clinical presentation of ethylene glycol toxicity, while classically described in three phases, varies widely and when combined with the range of differential diagnoses that must be considered makes diagnosis challenging. Early and accurate detection is important in these patients, however, as there is a need to start antidotal treatment early to prevent serious harm. In this article, we will review the literature and provide guidance regarding the diagnosis of ethylene glycol poisoning. While gas chromatography is the gold standard, the usefulness of this test is hampered by delays in access due to availability. Consequently, there are several surrogate markers that can give an indication of ethylene glycol exposure but these must be interpreted with caution and within the clinical context. An in-depth review of these tests, particularly the detection of a raised osmolar gap or an raised anion gap acidosis, will form the main focus of this article.

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.

Predictors of Ethylene Glycol Ingestion Cases Called into a Regional Poison Center

Poison center consultations for potential toxic alcohol poisonings are challenging because blood levels are typically not immediately available. The primary objective of this study was to determine whether readily obtainable laboratory values can be used to accurately and rapidly diagnose these poisonings. Over a 15-month period, patients with a history of toxic alcohol ingestion or a metabolic acidemia (pH ≤ 7.30 or serum bicarbonate ≤ 18 mEq/L) that prompted a poison center consultation were enrolled. A predictive logistic regression model was used to assess the combined ability of serum pH, calcium, osmolar gap, and anion gap levels to predict a final diagnosis of toxic alcohol poisoning. There were 102 subjects included in the analysis. A total of 44% (45/102) patients had a final diagnosis of ethylene glycol (EG) poisoning. Higher levels of calcium, osmolar gap, and anion gap were independently associated with statistically significant or marginally significant increases in the odds of a final diagnosis of EG poisoning. The c-index was estimated at 0.81, indicating that the model showed a reasonable ability to discriminate EG cases from others. The final model had a sensitivity and specificity of 78% and 89%, respectively, and positive and negative predictive values of 84% and 83% respectively. The combination of elevated calcium, osmolar gap, and anion gap is associated with a high likelihood of EG poisoning, but clinician gestalt is still essential for its diagnosis. Further refinement of the model is needed.

Elevated lactate in ethylene glycol poisoning: True or false?

Abstract Background There have been an increasing number of reports on false increase of lactate in ethylene glycol poisoning. We recently encountered two cases of ethylene glycol poisoning with very high blood lactate concentrations on ABL blood gas analyzers. Methods Patient plasma lactate concentrations were measured on different chemistry instruments in addition to ABL analyzer. Serum ethylene glycol and glycolic acid were also determined. Lactate values were determined from samples spiked with various amounts of glycolic acid. Results In case 1, all the chemistry instruments produced similar lactate results compared to that by ABL analyzer whereas in case 2, the lactate on the ABL was dramatically elevated compared to that from all the chemistry analyzers. There was no glycolic acid detected in case 1 but high glycolic acid was obtained in case 2. Increased concentrations of glycolic acid resulted in a significant positive interference on lactate measurements on the ABL analyzer but none on other instruments. Conclusions False increase of blood lactate by blood gas analyzers may occur but true increase of lactate can also be observed in ethylene glycol poisoning. Elevated lactate concentrations on blood gas analyzers should be confirmed by a chemistry analyzer in the differential diagnosis of ethylene glycol poisoning.

Elevated lactate in ethylene glycol poisoning: True or false?

Background There have been an increasing number of reports on false increase of lactate in ethylene glycol poisoning. We recently encountered two cases of ethylene glycol poisoning with very high blood lactate concentrations on ABL blood gas analyzers. Methods Patient plasma lactate concentrations were measured on different chemistry instruments in addition to ABL analyzer. Serum ethylene glycol and glycolic acid were also determined. Lactate values were determined from samples spiked with various amounts of glycolic acid. Results In case 1, all the chemistry instruments produced similar lactate results compared to that by ABL analyzer whereas in case 2, the lactate on the ABL was dramatically elevated compared to that from all the chemistry analyzers. There was no glycolic acid detected in case 1 but high glycolic acid was obtained in case 2. Increased concentrations of glycolic acid resulted in a significant positive interference on lactate measurements on the ABL analyzer but none on other instruments. Conclusions False increase of blood lactate by blood gas analyzers may occur but true increase of lactate can also be observed in ethylene glycol poisoning. Elevated lactate concentrations on blood gas analyzers should be confirmed by a chemistry analyzer in the differential diagnosis of ethylene glycol poisoning.

Uncoventional Views on Certain Aspects of Toxin-Induced Metabolic Acidosis

This discussion will highlight the following 9 specific points that related to metabolic acidosis caused by various toxins. The current recommendation suggests that alcohol dehydrogenase inhibitor fomepizole is preferred to ethanol in treatment of methanol and ethylene glycol poisoning, but analysis of the enzyme kinetics indicates that ethanol is a better alternative. In the presence of a modest increase in serum osmolal gap (<30 mOsm/L), the starting dose of ethanol should be far less than the usual recommended dose. One can take advantage of the high vapor pressure of methanol in the treatment of methanol poisoning when hemodialysis is not readily available. Profuse sweating with increased water ingestion can be highly effective in reducing methanol levels. Impaired production of ammonia by the proximal tubule of the kidney plays a major role in the development of metabolic acidosis in pyroglutamic acidosis. Glycine, not oxalate, is the main final end product of ethylene glycol metabolism. Metabolism of ethylene glycol to oxalate, albeit important clinically, represents less than 1% of ethylene glycol disposal. Urine osmolal gap would be useful in the diagnosis of ethylene glycol poisoning, but not in methanol poisoning. Hemodialysis is important in the treatment of methanol poisoning and ethylene glycol poisoning with renal impairment, with or without fomepizole or ethanol treatment. Severe leucocytosis is a highly sensitive indicator of ethylene glycol poisoning. Uncoupling of oxidative phosphorylation by salicylate can explain most of the manifestations of salicylate poisoning.

False elevation of blood lactate reveals ethylene glycol poisoning

Ethylene glycol poisoning is a medical emergency. Making a definitive diagnosis is challenging because few institutions have timely access to direct measurement of ethylene glycol. After ingestion, primary metabolism of ethylene glycol takes place in the liver, leading to glycolic acid and glyoxylic acid. These compounds may cross-react with L-lactate oxidase used in blood gas analyzers lactate electrodes to induce false elevation of blood lactate. We present the case of a 47-year-old male patient initially admitted to the intensive care unit for severe lactate acidosis of unknown cause (pH 6.96, lactate, 30 mmol/L). Knowledge of potent artifactual lactate results was the key to the diagnosis of ethylene glycol poisoning, and false lactate measurements were found at the central laboratory on our 3 different blood gas analyzers.

Artifactual elevation of lactate in ethylene glycol poisoning

The diagnosis of ethylene glycol poisoning is based on nonspecific clinical symptoms and signs and indirect and direct laboratory measurement. Few institutions have timely access to direct measurement of ethylene glycol. As a result, diagnosis sometimes can be delayed and therapy initiated late. We present two cases of ethylene glycol poisoning. These cases demonstrate the need to recognize the false elevation of lactate in some chemistry analyzers due to the interference of glycolic acid, a metabolite of ethylene glycol. Using the “lactate gap” in comparing the measurement of lactate with two commonly used chemical analyzers aids in differentiating ethylene glycol poisoning from lactic acidosis.

Measuring the lactate gap

Combined elevations of anion and osmolar gaps are characteristic of methanol and ethylene glycol poisonings. However, the rapid diagnosis of ethylene glycol poisoning can be a challenge. We describe how an error in laboratory measurement can be used to identify a third gap, the lactate gap, which is highly suggestive of ethylene glycol poisoning and can speed the diagnosis of this potentially lethal condition.

Delayed admission for ethylene glycol poisoning: lack of elevated serum osmol gap

In the absence of an immediately available serum ethylene glycol (EG) assay, the diagnosis of EG poisoning is usually based on anamnesis, clinical findings and presence of metabolic acidosis with elevated serum anion gap, elevated serum osmol gap, hypocalcemia and crystalluria. We report two cases of EG poisoning, both presenting without an elevated serum osmol gap and we discuss conditions which facilitate such a presentation, especially delayed hospital admission. Finally, we confirm the fact that determination of the osmol gap can fail as a screen for EG poisoning.

Ethylene glycol poisoning with a normal anion gap caused by concurrent ethanol ingestion: Importance of the osmolal gap

Ethylene glycol poisoning classically presents as a metabolic acidosis with an increased anion gap. Metabolism of ethylene glycol to organic acids, and increased production of lactate, are responsible for the increased gap. We report the case of an alcohol user who consumed ethanol and ethylene glycol concurrently, and presented without acidosis, with a normal anion gap. Several hours later, when his serum ethanol level had declined, he developed severe acidosis with an elevated anion gap. An increased osmolal gap, not accounted for by the serum ethanol level, proved to be an important clue to the diagnosis. In this patient, ingestion of ethanol inhibited the hepatic metabolism of ethylene glycol to organic acids, obscuring the diagnosis. In intoxicated alcohol users, even in the absence of metabolic acidosis, serum osmolality measurements and calculation of the osmolal gap may facilitate the rapid diagnosis of ethylene glycol poisoning.

2,3-Butanediol in plasma from an alcoholic mistakenly identified as ethylene glycol by gas-chromatographic analysis

2,3-Butanediol was mistakenly identified as ethylene glycol in plasma specimens from two alcoholic patients. The cyclic phenylboronate ester derivatives of 2,3-butanediol and ethylene glycol had the same retention time when OV-17 was used as the stationary phase for gas chromatography. This led to incorrect diagnosis of ethylene glycol poisoning and unnecessary invasive therapy. Plasma from two chronic alcoholics contained 2,3-butanediol at 3.5 and 3.4 mmol/L. The elimination half-life of 2,3-butanediol was 3.9 days when ethanol was administered during therapy for suspected ethylene glycol poisoning. Low concentrations of 2,3-butanediol might be present in blood of chronic alcoholics as a result of a novel pathway of intermediary metabolism associated with some forms of alcoholism. However, a more likely explanation for fairly high concentrations of 2,3-butanediol is enzymatic production from 2-butanone. This ketone occurs in denatured alcohol preparations often consumed by alcoholics in Sweden.