Antifreeze ingestions require rapid and accurate differential diagnosis to prevent fatal outcomes. An increase in the osmolal gap is evident in the presence of all of the alcohols. [16], Ethylene glycol involved in aircraft de-icing and anti-icing operations is released onto land and eventually to waterways. Ethylene glycol poisoning is poisoning caused by drinking ethylene glycol. The bittering agent is thought to stop ingestion as part of the human defense against ingestion of harmful substances is rejection of bitter tasting substances. [39][40] Despite the cost, fomepizole is gradually replacing ethanol as the antidote of choice in ethylene glycol poisoning. [1][4] The diagnosis may be suspected when calcium oxalate crystals are seen in the urine or when acidosis or an increased osmol gap is present in the blood. [17] People who develop severe central nervous system manifestations or stroke who survive may have long term neurologic dysfunction; in some cases they may recover, although convalescence may be prolonged. LA The Catachem assay is based on a bacterial enzyme, glycerol dehydrogenase.5–7 This enzyme oxidizes ethylene glycol in the presence of NAD (nicotinamide adenine dinucleotide), generating NADH (the reduced form of NAD), resulting in an increase in absorbance at 340 nm, which is detected spectrophotometrically by automated chemistry analyzers. [9] Small amounts of ethylene glycol may be contained in holiday ornaments such as snow globes. et al. "[12] Since 1994, federal airports must comply with the Glycol Guidelines of the Canadian Environmental Protection Act, monitoring and reporting on concentrations of glycols in surface water. [14][41] Hemodialysis also has the added benefit of correcting other metabolic derangements or supporting deteriorating kidney function. Antifreeze Poisoning (Ethylene Glycol Poisoning) Drugs Scan (Comprehensive Drugs Scan ) Cyanide Poisoning Detection; We are ready to serve you NOW! In addition, methanol, ethanol, and ethylene glycol also result in an increase in metabolic acidosis with an increased anion gap, separating them from isopropanol. et al. Traditionally, gastric lavage or nasogastric aspiration of gastric contents are the most common methods employed in ethylene glycol poisoning. The antidotes for ethylene glycol poisoning are ethanol and fomepizole. The formation of acid metabolites also causes inhibition of other metabolic pathways, such as oxidative phosphorylation. Antifreeze (Ethylene Glycol) Detection Steps. It does not have color or odor. The detection of glycolic acid is only of use in the setting of a delayed presentation where the entire parent ethylene glycol has been metabolized. [23], As many of the clinical signs and symptoms of ethylene glycol poisoning are nonspecific and occur in many poisonings the diagnosis is often difficult. [7][8], The most common source of ethylene glycol is automotive antifreeze or radiator coolant, where concentrations are high. Pharmaceutical grade ethanol is usually given intravenously as a 5 or 10% solution in 5% dextrose, but it is also sometimes given orally in the form of a strong spirit such as whisky, vodka, or gin. Hewlett Initially it is metabolized by alcohol dehydrogenase to glycolaldehyde, which is then oxidized to glycolic acid by aldehyde dehydrogenase. However, the measurement of the other 3 alcohols is more challenging.1,2 Some relevant laboratory tests that assist in the differential diagnosis are listed in Table 1. [18][19][20] In the EU classification of dangerous substances it is 'harmful' (Xn) while more toxic substances are classified as 'toxic' (T) or 'very toxic' (T+). [7] In this situation a helpful test to diagnose poisoning is the measurement of the osmolal gap. Online Course: Ethylene Glycol and Propylene Glycol Toxicity; Emergency Response Card: Information for First Responders Agent-specific identification, medical symptoms, prevention & personal protective equipment, fire fighting, sampling & analytical methods, decontamination, spillage disposal, packaging & labeling information. Costing US$1,000 per gram, an average course used in an adult poisoning would cost approximately $3,500 to $4,000. [12] In 2006, approximately 1540 kilotonnes of ethylene glycol were manufactured in Canada by three companies in Alberta, with most of the production destined for export. [73] Another study found the toxicity to aquatic and other organisms was relatively low, but the oxygen-depletion effect of biodegradation was more serious (p. The disadvantage of fomepizole is that it is expensive. [7] The usefulness of gastric lavage has, however, been questioned, and it is now no longer used routinely in poisoning situations. This damage can be identified in a serum biochemistry profile by increases in the metabolites creatinine and BUN (blood urea nitrogen) that are normally removed from the blood by the kidneys. In an effort to prevent poisoning, often a bittering agent called denatonium benzoate, known by the trade name Bitrex, is added to ethylene glycol preparations as an adversant to prevent accidental or intentional ingestion. Juenke Antifreeze's main component is usually ethylene glycol, and this can be detected in the blood. [37][38], Adjunct agents including thiamine and pyridoxine are often given, because they may help prevent the formation of oxalic acid. [10][24] Often both antidotal treatment and hemodialysis are used together in the treatment of poisoning. In cats, this stage occurs 12–24 hours after consuming antifreeze; in dogs, at 36–72 hours after consuming antifreeze. It has been shown to be highly effective in the removal of ethylene glycol and its metabolites from the blood. However, you'd have to think of antifreeze poisoning in the first place to think to do the test. [12], In the U.S., airports are required to obtain stormwater discharge permits and ensure that wastes from deicing operations are properly collected and treated. A test to determine the blood levels can be done at some veterinary diagnostic laboratories or human hospitals. [5] Antifreeze products sometimes have a substance to make it bitter added to discourage drinking by children and other animals but this has not been found to be effective. GA [24][36][37] Fomepizole has been shown to be highly effective as an antidote for ethylene glycol poisoning. [14] Accumulation of glycolic acid in the body is mainly responsible for toxicity. [32][unreliable source?]. Oxalate binds calcium, leading to calcium oxalate crystals, which are deposited in many tissues but are most readily detected in the urine. [64][66][67] Three follow up studies targeting limited populations or suicidal persons to assess the efficacy of bittering agents in preventing toxicity or death have, however, shown limited benefit of bittering ethylene glycol preparations in these two populations. You can hear all about cats and dogs taste buds and what they taste compared to you, in the first segment, “How Good are Pet’s Taste Buds” in the Raising Your Paws podcast episode you’ll find below. [26][27], The increased osmolal gap is caused by the ethylene glycol itself. CNS depression begins soon after exposure, lasting for up to 12 hours after ingestion. However, this is rarely immediately available, as almost all hospitals send this test to a reference lab, often to an out-of-state laboratory. [7] The rate-limiting step in this cascade is the conversion of glycolic to glyoxylic acid. Inhalation effects of ethylene glycol with an average concentration in the air up to 140-200 mg / cc. Differential Diagnosis of Alcohol Poisoning. Blackwell [75] Detailed mitigation plans include storage and handling issues (p. 27), spill response procedures, and measures taken to reduce volumes of fluid (p. Thus, for methanol and isopropanol, gas chromatography (GC) is the confirmatory assay. In this situation stabilization of the person including airway management with intubation should be performed in preference to gastrointestinal decontamination. [21] There may be a slight risk of poisoning where mists or fogs are generated, although this rarely leads to poisoning as ethylene glycol causes irritation and coughing when breathed in, alerting victims to its presence. Thus, this assay is clearly advantageous to an emergency department physician dealing with this serious disorder. ethylene glycol, but propylene glycol products are becoming more common. If antifreeze is placed in toilets, ensuring the lid is down and the door closed. [4] Deaths from ethylene glycol have been reported as early as 1930. [1], Ethylene glycol is a colorless, odorless, sweet liquid, commonly found in antifreeze. [26] People with significant poisoning often present in a critical condition. of 50% ethylene glycol for an 80 kg adult and 56 mL (2 oz.) [1] It may be drunk accidentally or intentionally in a suicide attempt. [1] Later symptoms may include a decreased level of consciousness, headache, and seizures. Ethanol is readily available in most hospitals, is inexpensive, and can be administered orally as well as intravenously. The gap is caused by the presence of osmotically active particles (eg, ethylene glycol) in the serum that are not factored into the above equation. [9], The most significant source of ethylene glycol is from aircraft de-icing and anti-icing operations, where it is released onto land and eventually to waterways near airports experiencing cold winter climates. Within 30 minutes of ingestion, they may resemble a person who has had too much to alcohol drink. Wezorek C, Hodgman M, Dean B, Krenzelok E. Inadvertent ethylene glycol inhalation resulting in a toxic level. Furthermore, there seemed to be no interference with glycerol under the defined assay conditions. [76] Considering factors such as the "seasonal nature of releases, ambient temperatures, metabolic rates and duration of exposure", Environment Canada stated in 2014 that "it is proposed that ethylene glycol is not entering the environment in a quantity or concentration or under conditions that have or may have an immediate or long-term harmful effect on the environment or its biological diversity". [2] When broken down by the body it results in glycolic acid and oxalic acid which cause most of the toxicity. S They both have a high boiling point, low vapour pressure, excellent heat transfer abilities and the ability to depress the freezing point of water, but ethylene glycol is a slightly more effective freezing point depressant. Additionally, as a side effect of the first two steps of metabolism, an increase in the blood concentration of lactic acid occurs contributing to lactic acidosis. Its adverse effects include intoxication, hypoglycemia in children, and possible liver toxicity. [55][56][57] Many cases of poisoning are the result of using ethylene glycol as a cheap substitute for alcohol or intentional ingestions in suicide attempts. As activated charcoal does not adsorb glycols, it is not recommended as it will not be effective at preventing absorption. The preferred assays are summarized in Table 1. Keeping pets and small children away from the area when draining the car radiator. Standefer Signs of ethylene glycol poisoning depend upon the time after ingestion. This test measures the level of ethylene glycol in the blood. Incoordination, excessive urination, excessive thirst, vomiting, and lethargy are amongst the first signs to appear. [22] Ethylene glycol is not well absorbed through skin meaning poisoning following dermal exposure is also uncommon. However, acidosis has a large number of differential diagnosis, including poisoning from methanol, salicylates, iron, isoniazid, paracetamol, theophylline, or from conditions such as uremia or diabetic and alcoholic ketoacidosis. [42], Treatment for antifreeze poisoning needs to be started as soon after ingestion as possible to be effective; the earlier treatment is started, the greater the chance of survival. Thus, for methanol and isopropanol, gas chromatography (GC) is the confirmatory assay. Search for other works by this author on: National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: recommendations for the use of laboratory tests to support poisoned patients who present to the emergency department, Toxic alcohol ingestions: clinical features, diagnosis, and management, Ethylene glycol intoxication: evaluation of kinetics and crystalluria, Rapid and specific quantification of ethylene glycol: adaptation of a commercial enzymatic assay to automated chemistry analyzers, Blood alcohol testing: comparison of the performance obtained with the different methods used in the Belgian External Quality Assessment schemes, Enzymatic method for measuring ethylene glycol with a centrifugal analyzer, A rapid screen for ethylene glycol: evaluation of the CATACHEM ethylene glycol enzymatic assay performed with the Olympus AU400e analyzer [abstract], Fomepizole for ethylene glycol and methanol poisoning, 1999 Annual Report of the American Association of Poison Control Centers Toxic Exposure Surveillance System, © American Society for Clinical Pathology, Multisite Quality Improvement Study of a Patient-Pathologist Consultation Program. Within 24 hours, some animals show apparent improvement which may prevent pet owners from realizing that their pet is in r… The best way to confirm ethylene glycol poisoning is by measuring the blood concentration of ethylene glycol. [10] The toxic mechanism of ethylene glycol poisoning is mainly due to the metabolites of ethylene glycol. Disposing of used antifreeze only by taking to a service station. They have taste buds that detect sugars just like we do. The ethylene glycol in antifreeze affects the central nervous system first. As the metabolism of ethylene glycol progresses there will be less ethylene glycol and this will decrease the blood ethylene glycol concentration and the osmolal gap making this test less useful. TL In this way, Juenke et al4 were able to demonstrate that the modified kinetic parameters applied to the Catachem reagent system accurately distinguished between propylene glycol, 3-butanediol, and ethanol from the true measurement of ethylene glycol. For ethylene glycol, the preferred method is GC–flame ionization detection (FID). [7] Sodium bicarbonate should be used cautiously as it can worsen hypocalcemia by increasing the plasma protein binding of calcium. Ethylene glycol is a type of alcohol found in automotive and household products. Dogs like sweet things. [12], The three main systems affected by ethylene glycol poisoning are the central nervous system, metabolic processes, and the kidneys. Most clinical laboratories are equipped to accurately quantitate ethanol levels, mainly by an enzymatic assay on an automated chemistry analyzer platform. Devleeschouwer I-3). [9] Once kidney failure develops, the prognosis is poor. McKay [2] Hemodialysis may also be used in those where there is organ damage or a high degree of acidosis. J [12] It is also used in manufacturing polyester products. Ethylene glycol toxicosis is a type of poisoning that occurs after ingestion of antifreeze or other fluids containing the ingredient ethylene glycol. [7] Urine microscopy can reveal needle or envelope-shaped calcium oxalate crystals in the urine which can suggest poisoning; although these crystals may not be present until the late stages of poisoning. Following ingestion of antifreeze products containing ethylene glycol and fluorescein, a Wood's lamp may reveal fluorescence of a person's mouth area, clothing, vomitus, or urine which can help to diagnose poisoning. JM [28] Additionally, the presence of other alcohols such as ethanol, isopropanol, or methanol or conditions such as alcoholic or diabetic ketoacidosis, lactic acidosis, or kidney failure may also produce an elevated osmolal gap leading to a false diagnosis. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. The goal of pharmacotherapy is to prevent the formation of these metabolites. ANTIFREEZE POISONING… VODKA AS AN ANTIDOTE? Poisoning of a raccoon was diagnosed in 2002 in Prince Edward Island, Canada. Furthermore, the documentation of calcium oxalate crystals is hampered the fact that it is only detected in around 50% of patients. Oxalic acid binds with calcium to form calcium oxalate crystals which may deposit and cause damage to many areas of the body including the brain, heart, kidneys, and lungs. [64][68][69] Specifically, Mullins finds that bittering of antifreeze does not reduce reported cases of poisoning of preschoolers in the US state of Oregon. TP [35] Ipecac-induced vomiting is not recommended. [9], Generally, if the person is treated and survives then a full recovery is expected. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. [1] Toxicity and death may occur after drinking even a small amount. Because hemodialysis will also remove the antidotes from the blood, doses of antidotes need to be increased to compensate. [2], More than 5000 cases of poisoning occur in the United States each year. [29] Finally, many commercial radiator antifreeze products have fluorescein added to enable radiator leaks to be detected using a Wood's lamp. Alternatively, the adverse side effects of fomepizole are minimal[clarification needed] and the approved dosing regimen maintains therapeutic concentrations without the need to monitor blood concentrations of the drug. . This testing method is very accurate, but not always available in the middle of the night. [74] Further, "Anaerobic biodegradation may also release relatively toxic byproducts such as acetaldehyde, ethanol, acetate, and methane (p. Although survival with medical treatment has occurred with doses much higher than this, death has occurred with 30 mL of the concentrate in an adult. D [2] The preferred antidote is fomepizole with ethanol used if this is not available. Urinary crystals result from. [15], Ethylene glycol has been shown to be toxic to humans[16] and is also toxic to domestic pets such as cats and dogs. Symptoms usually follow a three-step progression, although poisoned individuals will not always develop each stage. Ethylene glycol in biological fluids can be determined by gas chromatography. [7] It is only used in the presence of a toxic dose of another poison or drug. Ford That is roughly 16 mL of 50% ethylene glycol for an 80 kg adult and 4 mL for a 20 kg child. et al. Ishwarlal Jialal, MD, PhD, FRCPath, DABCC, Sridevi Devaraj, PhD, DABCC, Laboratory Diagnosis of Ethylene Glycol Poisoning: The Cup Is Half Full?, American Journal of Clinical Pathology, Volume 136, Issue 2, August 2011, Pages 165–166, [2], Signs of ethylene glycol poisoning depend upon the time after ingestion. Calcium oxalate crystalluria may be observed as early as 3 and 6 hr after ingestion in cats and dogs, respectively. [78], CS1 maint: DOI inactive as of December 2020 (. [9] Other sources of ethylene glycol include windshield deicing agents, brake fluid, motor oil, developing solutions for hobby photographers, wood stains, solvents, and paints. Addressing the Challenges of Eosinophilia and Mastocytosis: Reactive Eosinophil Proliferations in Tissue and the Lymphocytic Variant of Hypereosinophilic Syndrome: Myeloid/Lymphoid Neoplasms Associated With Eosinophilia and Rearrangements of.