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Methanol and ethylene glycol poisoning: Pharmacology, clinical manifestations, and diagnosis

Methanol and ethylene glycol poisoning: Pharmacology, clinical manifestations, and diagnosis
Author:
Marco L A Sivilotti, MD, MSc, FRCPC, FACMT, FAACT
Section Editors:
Michele M Burns, MD, MPH
Robert G Hendrickson, MD, FACMT, FAACT
Deputy Editor:
Michael Ganetsky, MD
Literature review current through: Nov 2022. | This topic last updated: Jul 09, 2022.

INTRODUCTION — Methanol and ethylene glycol poisonings cause scores of fatal intoxications annually, and even relatively small ingestions of these alcohols can produce significant toxicity. Rapid recognition and early treatment, including alcohol dehydrogenase (ADH) inhibition, are crucial. A summary table to facilitate emergency management is provided (table 1).

To provide proper management, clinicians must understand the metabolic activation of these alcohols to their toxic acid metabolites, the limitations of available laboratory tests, and the indications for treatment with antidotes, with or without hemodialysis.

The pharmacology, clinical presentation (including laboratory findings), and diagnosis of methanol and ethylene glycol intoxication are reviewed here. While there are differences between methanol and ethylene glycol poisoning, there is substantial overlap, and both the similarities and differences are described below. The management of methanol and ethylene glycol poisoning is covered separately. (See "Methanol and ethylene glycol poisoning: Management".)

Isopropyl alcohol intoxication is considerably different, and is discussed separately. (See "Isopropyl alcohol poisoning".)

The general approach to the poisoned adult or child is discussed separately. (See "General approach to drug poisoning in adults" and "Approach to the child with occult toxic exposure" and "Initial management of the critically ill adult with an unknown overdose".)

PHARMACOLOGY AND CELLULAR TOXICOLOGY — The "parent alcohols" methanol and ethylene glycol are relatively nontoxic and cause mainly central nervous system sedation. However, profound toxicity can ensue when these parent alcohols are metabolized in vivo (ie, oxidized, primarily by alcohol dehydrogenase [ADH] and aldehyde dehydrogenase) (figure 1 and figure 2).

The methanol metabolite formate and the ethylene glycol metabolites glycolate, glyoxylate, and oxalate accumulate following large ingestions. Above plasma levels of approximately 20 mg/dL (approximately 6 mmol/L of methanol or 3 mmol/L of ethylene glycol), these metabolites can cause specific end-organ damage [1-5]:

Formate causes retinal injury with optic disc hyperemia, edema, and eventually permanent blindness, as well as ischemic or hemorrhagic injury to the basal ganglia [6]. These changes are postulated to result from disruption of mitochondrial function.

Ethylene glycol metabolites target the kidney and lead to reversible oliguric or anuric acute kidney injury (acute renal failure), which in turn slows elimination of ethylene glycol [7]. The renal failure is primarily due to glycolate-induced damage to tubules, although tubule obstruction from precipitated oxalate crystals may contribute [8,9]. Hypocalcemia in ethylene glycol overdose can result from calcium oxalate formation but is uncommon [10].

With ingestions of either parent alcohol, a profound anion gap metabolic acidosis develops, which directly correlates with the accumulation of toxic acid metabolites [2,4]. Acidemia increases the ability of the toxic metabolites to penetrate cells, further depressing central nervous system function and causing a rapid downward spiral of hypoxia and acidemia [11].

KINETICS — Like other simple alcohols, methanol and ethylene glycol are rapidly and completely absorbed after oral ingestion. Peak serum alcohol concentrations are usually reached within one hour. Two-step oxidation via alcohol dehydrogenase (ADH) and aldehyde dehydrogenase leads to the production of the toxic metabolites. Methanol elimination follows zero-order kinetics in the absence of treatment and has been estimated at 8.5 mg/dL (2.7 mmol/L) per hour following overdose [12]. Ethylene glycol elimination appears to follow first-order kinetics in the absence of treatment, with an estimated serum half-life of between three and nine hours [7,11].

If hepatic oxidation is inhibited ("blocked") by an ADH antagonist such as ethanol or fomepizole, several changes occur (see "Methanol and ethylene glycol poisoning: Management", section on 'Alcohol dehydrogenase inhibition'):

For methanol, elimination shifts to the pulmonary and renal routes [13,14], becomes first order, and slows dramatically (half-life of 48 to 54 hours).

For ethylene glycol, elimination after ADH inhibition becomes almost entirely renal, with a half-life as short as 14 hours when kidney function is normal [7,15].

Elimination of formate, the toxic metabolite of methanol, is partially dependent upon tetrahydrofolate and is thought to accelerate following folic acid administration [8]. Pyridoxine and thiamine are involved in minor elimination pathways of glycolate, an ethylene glycol metabolite, but it is unclear to what extent pyridoxine and thiamine supplementation accelerates metabolism along these minor pathways [16]. (See "Methanol and ethylene glycol poisoning: Management".)

CLINICAL FEATURES OF OVERDOSE

History — The clinician should make every effort to identify the original source and nature of the exposure. This is ideally done by retrieving the original container and consulting product databases, as well as interviewing the patient, relatives, and prehospital workers. Methanol and ethylene glycol are frequently found in high concentration in automotive coolant/antifreeze and de-icing solutions, windshield wiper fluid, solvents, cleaners, fuels, and other industrial products. Most serious poisonings occur following ingestion. "Antifreeze" may also contain a different alcohol than originally suspected (eg, propylene glycol rather than ethylene glycol). Such information dramatically changes the treatment strategy, underscoring the need to obtain accurate information.

In the absence of treatment, an ingestion of approximately 1 g/kg of either methanol or ethylene glycol is potentially lethal, and serious toxicity has been reported following ingestions of as little as one teaspoon of methanol [17]. On the other hand, inhalation and dermal exposures rarely cause toxicity, even following intentional recreational inhalation of carburetor cleaner, lacquer thinner, or other products [18,19]. Product labels may provide the concentration of toxic alcohols, sometimes with misleading terms such as "wood alcohol" for methanol. As an approximate guide, a 50 percent volume/volume solution contains 0.4 g/mL of methanol or 0.6 g/mL of ethylene glycol.

It is important to clarify when the ingestion occurred and whether ethanol was also ingested. As mentioned above, ethanol competitively inhibits alcohol dehydrogenase (ADH), thereby diminishing formation of toxic metabolites of the parent compound.

The intent of the exposure (whether accidental, recreational, suicidal, or homicidal) may only become apparent with closer investigation (eg, interview of friends and family). The identification of other potential victims depends upon understanding the circumstances of the exposure (eg, occult substitution for ethanol), and active case identification is essential whenever dealing with accidental methanol ingestion [20]. (See "Methanol and ethylene glycol poisoning: Management", section on 'Adolescents' and "Methanol and ethylene glycol poisoning: Management", section on 'Multivictim outbreaks'.)

Visual complaints (eg, blurring, scotomata), which suggest methanol poisoning, or genitourinary symptoms (eg, flank pain, hematuria, and oliguria), which suggest ethylene glycol poisoning, should be elicited.

Physical examination — A brief initial screening examination, including vital signs, mental status, and pupils, should be performed to identify immediate measures required to stabilize the patient. A discussion of the fundamental evaluation of the poisoned patient is found elsewhere. (See "General approach to drug poisoning in adults" and "Approach to the child with occult toxic exposure".)

Patients with large ingestions of methanol or ethylene glycol may present with mild central nervous system effects, such as inebriation and sedation, similar to ethanol intoxication. Ethanol coingestion may exacerbate such symptoms. Coma, seizures, hyperpnea (Kussmaul-Kien respirations), and hypotension all suggest that a substantial portion of the parent alcohol has been metabolized to its toxic byproducts.

An afferent pupillary defect is an ominous sign of advanced methanol poisoning. Eye examination in methanol poisoning may also reveal mydriasis, a retinal sheen due to retinal edema, and hyperemia of the optic disk.

It is important to emphasize that the onset of methanol or ethylene glycol toxicity is delayed when ethanol is coingested. The possibility of concomitant ethanol and toxic alcohol ingestion must always be considered, particularly in alcoholics, who may ingest alcohol in any form.

Ethylene glycol metabolism can lead to cranial nerve palsies and tetany (thought to result from oxalate-induced hypocalcemia). Oliguria and hematuria may occur. Cerebral herniation and multisystem organ failure are common preterminal events in patients with profound poisoning.

Laboratory evaluation

Basic testing — Routine laboratory evaluation of any poisoned patient should include the following:

Fingerstick glucose to rule out hypoglycemia as the cause of any alteration in mental status

Acetaminophen and salicylate levels to rule out these common coingestions

Electrocardiogram (ECG) to rule out conduction system poisoning by drugs that affect the QRS or QTc interval; it is important to note that advanced ethylene glycol poisoning can affect conduction and prolong the QTc interval via its effects on serum calcium [21]

Pregnancy test in women of childbearing age

Additional tests with toxic alcohol exposure — All patients suspected of toxic alcohol exposure should undergo additional laboratory evaluation including the following:

Basic electrolytes with anion gap determination

Serum calcium

Blood urea nitrogen (BUN) and creatinine

Arterial or venous blood gas analysis

Serum ethanol concentration

Serum osmolality

Serum methanol, ethylene glycol, and isopropyl alcohol concentrations

Automotive coolant/antifreeze may also contain anticorrosive agents (eg, sodium nitrite or nitrate) that are not listed on the product label or safety data sheet. Methemoglobinemia has been reported following large intentional ingestions of such products. Thus, patients with cyanosis and findings related to tissue hypoxia (eg, tachycardia, headache, lethargy) also warrant evaluation for methemoglobinemia. (See "Methemoglobinemia", section on 'Aniline dyes and other chemicals' and "Methemoglobinemia", section on 'Evaluation and diagnosis (acquired/toxic)'.)

Pitfalls in laboratory testing

Testing for methanol and ethylene glycol — The measurement of serum methanol and ethylene glycol concentrations is usually performed by gas chromatography, but such testing is not widely available and frequently must be performed at a reference laboratory [5,22]. Such "send out" laboratory testing rarely, if ever, gives results in time to assist clinical decision-making. When specific concentrations of methanol and ethylene glycol are available, the units used (eg, mmol/L versus mg/dL) and the accompanying reference range should always be carefully examined to avoid diagnostic errors [23].

Some laboratories report a "solvent screen" that may not include ethylene glycol and may falsely reassure clinicians [24]. As with any "screen," the clinician should always clarify exactly which solvents are detected by the test.

Enzymatic methods of ethylene glycol detection are still used in many laboratories, but they can lead to false-positive results (eg, from severe acetaminophen toxicity or interference by propylene glycol, 2, 3-butanediol, or glycolate) [5,13,25]. We do not recommend relying on these tests when evaluating patients with potential ethylene glycol toxicity. Other diagnostic tests are being developed and have been studied, but none are yet generally available for rapid diagnostic confirmation [24,26].

Lactate — Patients with ethylene glycol poisoning can have elevations in their serum lactate concentration [27]. In some cases, such elevations (usually minor) can be caused by true increases in lactate. However, in other cases, the lactate concentration may be dramatically high and is likely falsely elevated due to the inability of many laboratory instruments to differentiate between lactate and either glycolate or glyoxylate, two metabolites of ethylene glycol that are structurally similar to lactate [28-33]. This falsely high lactate result is more common when using blood gas analyzers and point-of-care testing, but even some chemistry analyzers in wide use show some degree of interference [33]. Indeed, a large difference in the reported lactate concentration using two different methods may be an early, helpful sign of ethylene glycol poisoning [27,34].

A markedly elevated lactate concentration may be one of the first test results reported in a severely acidotic patient poisoned by ethylene glycol, given that lactate testing is readily available. Such a finding often suggests alternative diagnoses (eg, tissue hypoxia, metformin poisoning). However, it is important not to exclude ethylene glycol as a possible cause of acidosis merely because of a reportedly elevated lactate.

Urine testing — Examination of the urine for oxalate crystals and fluorescence is frequently performed in patients with possible ethylene glycol poisoning, but care should be taken not to overinterpret positive or negative results. The formation of oxalate crystals in the urine is a late and nonspecific finding following ethylene glycol ingestion [8,14]. Two types of calcium oxalate crystals may be seen: needle-shaped monohydrate crystals, which may be misread as hippurate crystals, and envelope-shaped dihydrate crystals (picture 1A-B) [35].

Urine fluorescence is a poor diagnostic test that uses ultraviolet light to detect the fluorescein added to most antifreeze solutions. Urine fluorescence lacks sensitivity, as not all ethylene glycol preparations contain fluorescein, and fluorescein (when present) appears only transiently in the urine following ingestion. Urine fluorescence also lacks specificity because normal urine can appear to fluoresce and other substances unrelated to ethylene glycol poisoning can cause fluorescence [16,36,37].

Plasma osmolal gap — Cryoscopic osmometry is widely used to measure plasma osmolality and to estimate the so-called osmolal gap. While the test must be interpreted cautiously, as described below, an unexplained, large osmolal gap is presumptive evidence of a recent methanol, ethylene glycol, or isopropyl alcohol exposure in the appropriate clinical setting, provided a significant ethanol ingestion has been excluded.

The osmolal gap is the difference between the measured osmolality and the calculated plasma osmolality:

Calculated Posm  =  (2  x  plasma [Na])  +  [glucose]/18  +  [BUN]/2.8

or, using standard units (mmol/L):

 Calculated Posm  =  (2  x  plasma [Na])  +  [glucose]  +  [urea]

The serum sodium is multiplied by two to account for accompanying anions (chloride and bicarbonate), and the divisors 18 and 2.8 in the first formula convert units of mg/dL into mmol/L.

Details of the plasma osmolal gap and its measurement are discussed separately, but its use in methanol and ethylene glycol intoxication will be reviewed here (see "Serum osmolal gap"). Calculators to determine the osmolal gap are provided (calculator 1 and calculator 2).

The plasma osmolal gap can provide important information in real time, costs little, and is widely available. Clinicians need to be able to interpret this test for early treatment decision-making, pending definitive poison identification by gas chromatography [14,38-41].

When interpreting the plasma osmolal gap in the setting of a toxic alcohol ingestion, clinicians should keep in mind several potential pitfalls:

The plasma osmolal gap cannot distinguish among ethanol, isopropyl alcohol, methanol, and ethylene glycol. Therefore, ethanol administration (if performed) mitigates the value of following the osmolal gap when assessing the response to treatment of toxic alcohols.

The plasma osmolal gap estimates the molar quantity of uncharged molecules and therefore increases only in the presence of the parent alcohols. The toxic acid metabolites of methanol (formate) and ethylene glycol (glycolate, glyoxylate, and oxalate) exist primarily in a dissociated (ie, charged) form at physiologic pH; since these anions must be accompanied by a cation (mostly sodium), they do not contribute to the calculated osmolal gap. As a result, the plasma osmolal gap is insensitive in late presentations, since most of the parent alcohol has already been metabolized.

The plasma osmolal gap is not sufficiently sensitive to exclude a small ingestion even shortly after ingestion. The variability of the test means that despite a substantial ingestion (eg, serum concentrations up to 50 mg/dL [8.1 mmol/L] of ethylene glycol), the plasma osmolal gap can fall within the upper limits of the normal range (generally less than 10 mOsm/L is considered normal). The plasma osmolal gap has been less than 10 in a small number of serious exposures [42-44].

Large quantities of ethanol (greater than 100 mg/dL [or 22 mmol/L]) can raise the osmolal gap more than would be expected based on its molecular weight. This occurs because serum does not behave as an ideal fluid and because mathematical approximations are used in calculating the osmolal gap. We recommend that the measured serum ethanol level be increased by 20 to 25 percent when performing plasma osmolal gap calculations to enable a more accurate interpretation [45,46].

Clinicians should also note that patients who are critically ill may have elevated plasma osmolal gaps due to so-called idiogenic osmoles. (See "Serum osmolal gap", section on 'Other'.)

In summary, the practice of categorically ruling out methanol or ethylene glycol exposure on the basis of a plasma osmolal gap less than 10 units is unjustified, as is assuming that a small elevation in the plasma osmolal gap in a patient with a low pretest probability is due to a toxic alcohol.

On the other hand, few substances cause a very high (greater than 25) plasma osmolal gap, and most severely poisoned methanol and ethylene glycol patients manifest plasma osmolal gaps of this magnitude shortly after ingestion [11]. An unexplained, large osmolal gap is presumptive evidence of a recent methanol, ethylene glycol, or isopropyl alcohol exposure in the appropriate clinical setting [14,40].

DIFFERENTIAL DIAGNOSIS — Pending definitive parent alcohol concentrations, the clinician should form a differential diagnosis based upon the available clinical information.

Few conditions other than methanol and ethylene glycol intoxication cause a profound high anion gap metabolic acidosis (serum bicarbonate less than 8 meq/L [or 8 mmol/L]), and most of these conditions present in a characteristic fashion with a high serum lactate (eg, status epilepticus, profound shock, ischemic bowel) or diabetic ketoacidosis (table 2). Although some patients with ethylene glycol poisoning present with elevated lactate levels, the rise in lactate is insufficient to account for the degree of acidosis [28]. (See "The delta anion gap/delta HCO3 ratio in patients with a high anion gap metabolic acidosis" and "Definition, classification, etiology, and pathophysiology of shock in adults".)

A lesser degree of metabolic acidosis in an alcoholic patient may also be caused by alcoholic ketoacidosis, sepsis, alcohol withdrawal seizures, diabetic ketoacidosis, or salicylate intoxication [12]. (See "Fasting ketosis and alcoholic ketoacidosis" and "Definition, classification, etiology, and pathophysiology of shock in adults" and "Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Clinical features, evaluation, and diagnosis" and "Salicylate (aspirin) poisoning in adults".)

An elevated plasma osmolal gap can be seen in patients with methanol or ethylene glycol intoxication but also in alcoholic or diabetic ketoacidosis, isopropyl alcohol ingestion, large ethanol ingestions, and other serious illnesses (eg, sepsis, ischemic bowel, shock) (table 3). (See 'Plasma osmolal gap' above and "Serum osmolal gap" and "Isopropyl alcohol poisoning".)

An elevated serum ethanol concentration, which accounts for most of the osmol gap, combined with a relatively mild degree of metabolic acidosis suggests alcoholic ketoacidosis rather than a toxic alcohol ingestion, but confirmatory testing is still recommended [47].

Traces of methanol may be detectable in alcoholic patients drinking fermented beverages such as wine [48].

DIAGNOSIS — Methanol and ethylene glycol poisoning are usually diagnosed clinically; a definitive diagnosis by gas chromatography is rarely available in time to guide management. There is, in most cases, a strong suspicion or clear history of ingestion. In addition to the dose and type of alcohol ingested, the delay to presentation and the presence of coingested ethanol determine the clinical signs and laboratory findings to be expected. Patients seen shortly after large ingestions may present with sedation or inebriation alone and have a large osmolal gap (eg, greater than 25) but minimal acidosis. If several hours have transpired in the absence of coingested ethanol, a profound metabolic acidosis with a high anion gap (eg, serum bicarbonate below 8 meq/L [or mmol/L]) will be present, often with a persistently elevated osmolal gap. In such cases, coma, Kussmaul hyperpnea, seizures, and hypotension are often present [24]. Complaints of visual blurring, central scotomata, fixed mydriasis, hyperemia of the optic disk, and blindness suggest advanced methanol poisoning; on the other hand, flank pain, hematuria, and oliguria suggest advanced ethylene glycol poisoning. Cranial nerve palsies and tetany may also occur with ethylene glycol poisoning. However, the presence of ethanol ingestion, smaller or staggered ingestions, and concomitant illness can affect the clinical progression and laboratory findings. On neuroimaging, hemorrhaging into one or both putamen or white matter necrosis of the insular subcortex suggests advanced methanol toxicity and a poor prognosis [49].

ADDITIONAL RESOURCES

Regional poison control centers — Regional poison control centers in the United States are available at all times for consultation on patients with known or suspected poisoning, and who may be critically ill, require admission, or have clinical pictures that are unclear (1-800-222-1222). In addition, some hospitals have medical toxicologists available for bedside consultation. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or overdoses. Contact information for poison centers around the world is provided separately. (See "Society guideline links: Regional poison control centers".)

Society guideline links — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: General measures for acute poisoning treatment" and "Society guideline links: Toxic alcohol poisoning" and "Society guideline links: Treatment of acute poisoning caused by specific agents other than drugs of abuse".)

SUMMARY AND RECOMMENDATIONS

Life-threatening poisoning and emergency management table – Methanol and ethylene glycol poisonings cause dozens of fatal intoxications in the United States annually. Rapid recognition and early treatment are crucial. A summary table to facilitate emergency management is provided (table 1).

Cellular toxicology and kinetics – The "parent alcohols" methanol and ethylene glycol are themselves relatively nontoxic, causing mainly central nervous system sedation. The methanol metabolite formate can cause retinal and basal ganglia injury; the ethylene glycol metabolites can cause renal failure following large ingestions. (See 'Pharmacology and cellular toxicology' above.)

Methanol and ethylene glycol are rapidly and completely absorbed after oral ingestion. Peak serum alcohol concentrations are usually reached within one hour. (See 'Kinetics' above.)

History – The clinician should make every effort to identify the source, nature, and timing of the exposure, ideally by retrieving the original container, clarifying whether ethanol was also ingested, and establishing whether the exposure was accidental, recreational, or for self-harm. (See 'History' above.)

Lethal ingestion – Ingestion of approximately 1 g/kg of either methanol or ethylene glycol is potentially lethal, and serious toxicity has been reported following ingestions of as little as 1 teaspoon of methanol.

Clinical features – Complaints of visual blurring, central scotomata, and blindness suggest methanol poisoning. Flank pain and hematuria suggest ethylene glycol poisoning. Coma, seizures, hyperpnea, and hypotension all suggest that a substantial portion of the parent alcohols has been metabolized to toxic acids. (See 'Clinical features of overdose' above.)

Differential diagnosis – Few conditions other than methanol and ethylene glycol intoxication present with a profound metabolic acidosis (serum bicarbonate less than 8 meq/L), and most of these conditions present in a characteristic fashion (eg, status epilepticus, profound shock, ischemic bowel) (table 2). (See 'Differential diagnosis' above.)

Laboratory testing – Direct testing of toxic alcohols is the preferred diagnostic test when available. If a "solvent screen" is performed, the clinician should clarify exactly which solvents are detected by the test. (See 'Laboratory evaluation' above and 'Pitfalls in laboratory testing' above.)

Osmolal gap – Few substances cause a very high (greater than 25 mOsm) osmolal gap, and most severely poisoned methanol and ethylene glycol patients manifest osmolal gaps of this magnitude shortly after ingestion. An unexplained, large osmolal gap is presumptive evidence of a recent methanol, ethylene glycol, or isopropyl alcohol exposure in the appropriate clinical setting. (See 'Plasma osmolal gap' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges James Winchester, MD, who contributed to an earlier version of this topic review.

  1. d'Alessandro A, Osterloh JD, Chuwers P, et al. Formate in serum and urine after controlled methanol exposure at the threshold limit value. Environ Health Perspect 1994; 102:178.
  2. Kerns W 2nd, Tomaszewski C, McMartin K, et al. Formate kinetics in methanol poisoning. J Toxicol Clin Toxicol 2002; 40:137.
  3. Liesivuori J, Savolainen H. Methanol and formic acid toxicity: biochemical mechanisms. Pharmacol Toxicol 1991; 69:157.
  4. Moreau CL, Kerns W 2nd, Tomaszewski CA, et al. Glycolate kinetics and hemodialysis clearance in ethylene glycol poisoning. META Study Group. J Toxicol Clin Toxicol 1998; 36:659.
  5. Fraser AD. Clinical toxicologic implications of ethylene glycol and glycolic acid poisoning. Ther Drug Monit 2002; 24:232.
  6. Sivilotti ML, Burns MJ, Aaron CK, et al. Reversal of severe methanol-induced visual impairment: no evidence of retinal toxicity due to fomepizole. J Toxicol Clin Toxicol 2001; 39:627.
  7. Sivilotti ML, Burns MJ, McMartin KE, Brent J. Toxicokinetics of ethylene glycol during fomepizole therapy: implications for management. For the Methylpyrazole for Toxic Alcohols Study Group. Ann Emerg Med 2000; 36:114.
  8. Jacobsen D, Hewlett TP, Webb R, et al. Ethylene glycol intoxication: evaluation of kinetics and crystalluria. Am J Med 1988; 84:145.
  9. Bove KE. Ethylene glycol toxicity. Am J Clin Pathol 1966; 45:46.
  10. Hodgman M, Marraffa JM, Wojcik S, Grant W. Serum Calcium Concentration in Ethylene Glycol Poisoning. J Med Toxicol 2017; 13:153.
  11. McMartin K, Jacobsen D, Hovda KE. Antidotes for poisoning by alcohols that form toxic metabolites. Br J Clin Pharmacol 2016; 81:505.
  12. Höjer J. Severe metabolic acidosis in the alcoholic: differential diagnosis and management. Hum Exp Toxicol 1996; 15:482.
  13. Malandain H, Cano Y. Interferences of glycerol, propylene glycol, and other diols in the enzymatic assay of ethylene glycol. Eur J Clin Chem Clin Biochem 1996; 34:651.
  14. Barceloux DG, Krenzelok EP, Olson K, Watson W. American Academy of Clinical Toxicology Practice Guidelines on the Treatment of Ethylene Glycol Poisoning. Ad Hoc Committee. J Toxicol Clin Toxicol 1999; 37:537.
  15. Levine M, Curry SC, Ruha AM, et al. Ethylene glycol elimination kinetics and outcomes in patients managed without hemodialysis. Ann Emerg Med 2012; 59:527.
  16. Casavant MJ, Shah MN, Battels R. Does fluorescent urine indicate antifreeze ingestion by children? Pediatrics 2001; 107:113.
  17. Roberts DM, Yates C, Megarbane B, et al. Recommendations for the role of extracorporeal treatments in the management of acute methanol poisoning: a systematic review and consensus statement. Crit Care Med 2015; 43:461.
  18. Liu YS, Lin KY, Masur J, et al. Outcomes After Recurrent Intentional Methanol Exposures Not Treated With Alcohol Dehydrogenase Inhibitors Or Hemodialysis. J Emerg Med 2020; 58:910.
  19. Bebarta VS, Heard K, Dart RC. Inhalational abuse of methanol products: elevated methanol and formate levels without vision loss. Am J Emerg Med 2006; 24:725.
  20. Hassanian-Moghaddam H, Nikfarjam A, Mirafzal A, et al. Methanol mass poisoning in Iran: role of case finding in outbreak management. J Public Health (Oxf) 2015; 37:354.
  21. Dibajnia P, Sivilotti MLA, Juurlink D, Shurrab M. ST-elevation in ethylene glycol toxicity mimicking myocardial infarction. J Electrocardiol 2020; 58:128.
  22. Church AS, Witting MD. Laboratory testing in ethanol, methanol, ethylene glycol, and isopropanol toxicities. J Emerg Med 1997; 15:687.
  23. Wu PE, Sivilotti ML. Toxic Alcohol Calculations and Misinterpretation of Laboratory Results. JAMA Intern Med 2016; 176:1227.
  24. Kraut JA, Mullins ME. Toxic Alcohols. N Engl J Med 2018; 378:270.
  25. Juenke JM, Hardy L, McMillin GA, Horowitz GL. Rapid and specific quantification of ethylene glycol levels: adaptation of a commercial enzymatic assay to automated chemistry analyzers. Am J Clin Pathol 2011; 136:318.
  26. Kraut JA. Diagnosis of toxic alcohols: limitations of present methods. Clin Toxicol (Phila) 2015; 53:589.
  27. Gabow PA, Clay K, Sullivan JB, Lepoff R. Organic acids in ethylene glycol intoxication. Ann Intern Med 1986; 105:16.
  28. Shirey T, Sivilotti M. Reaction of lactate electrodes to glycolate. Crit Care Med 1999; 27:2305.
  29. Eder AF, Dowdy YG, Gardiner JA, et al. Serum lactate and lactate dehydrogenase in high concentrations interfere in enzymatic assay of ethylene glycol. Clin Chem 1996; 42:1489.
  30. Morgan TJ, Clark C, Clague A. Artifactual elevation of measured plasma L-lactate concentration in the presence of glycolate. Crit Care Med 1999; 27:2177.
  31. Porter WH, Crellin M, Rutter PW, Oeltgen P. Interference by glycolic acid in the Beckman synchron method for lactate: a useful clue for unsuspected ethylene glycol intoxication. Clin Chem 2000; 46:874.
  32. Brindley PG, Butler MS, Cembrowski G, Brindley DN. Falsely elevated point-of-care lactate measurement after ingestion of ethylene glycol. CMAJ 2007; 176:1097.
  33. Tintu A, Rouwet E, Russcher H. Interference of ethylene glycol with (L)-lactate measurement is assay-dependent. Ann Clin Biochem 2013; 50:70.
  34. Hauvik LE, Varghese M, Nielsen EW. Lactate Gap: A Diagnostic Support in Severe Metabolic Acidosis of Unknown Origin. Case Rep Med 2018; 2018:5238240.
  35. Hanouneh M, Chen TK. Calcium Oxalate Crystals in Ethylene Glycol Toxicity. N Engl J Med 2017; 377:1467.
  36. Wallace KL, Suchard JR, Curry SC, Reagan C. Diagnostic use of physicians' detection of urine fluorescence in a simulated ingestion of sodium fluorescein-containing antifreeze. Ann Emerg Med 2001; 38:49.
  37. Sharma AN, O'Shaughnessy PM, Hoffman RS. Urine fluorescence: is it a good test for ethylene glycol ingestion? Pediatrics 2002; 109:345.
  38. Koga Y, Purssell RA, Lynd LD. The irrationality of the present use of the osmole gap: applicable physical chemistry principles and recommendations to improve the validity of current practices. Toxicol Rev 2004; 23:203.
  39. Hoffman RS, Smilkstein MJ, Howland MA, Goldfrank LR. Osmol gaps revisited: normal values and limitations. J Toxicol Clin Toxicol 1993; 31:81.
  40. Barceloux DG, Bond GR, Krenzelok EP, et al. American Academy of Clinical Toxicology practice guidelines on the treatment of methanol poisoning. J Toxicol Clin Toxicol 2002; 40:415.
  41. Lynd LD, Richardson KJ, Purssell RA, et al. An evaluation of the osmole gap as a screening test for toxic alcohol poisoning. BMC Emerg Med 2008; 8:5.
  42. Steinhart B. Case report: severe ethylene glycol intoxication with normal osmolal gap--"a chilling thought". J Emerg Med 1990; 8:583.
  43. Ammar KA, Heckerling PS. Ethylene glycol poisoning with a normal anion gap caused by concurrent ethanol ingestion: importance of the osmolal gap. Am J Kidney Dis 1996; 27:130.
  44. Purssell RA, Lynd LD, Koga Y. The use of the osmole gap as a screening test for the presence of exogenous substances. Toxicol Rev 2004; 23:189.
  45. Purssell RA, Pudek M, Brubacher J, Abu-Laban RB. Derivation and validation of a formula to calculate the contribution of ethanol to the osmolal gap. Ann Emerg Med 2001; 38:653.
  46. Silvilotti ML, Collier CP, Choi SB. Ethanol and the osmolal gap. Ann Emerg Med 2002; 40:656.
  47. Cohen ET, Su MK, Biary R, Hoffman RS. Distinguishing between toxic alcohol ingestion vs alcoholic ketoacidosis: how can we tell the difference? Clin Toxicol (Phila) 2021; 59:715.
  48. Sivilotti ML. Methanol intoxication. Ann Emerg Med 2000; 35:313.
  49. Taheri MS, Moghaddam HH, Moharamzad Y, et al. The value of brain CT findings in acute methanol toxicity. Eur J Radiol 2010; 73:211.
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