ethylene glycol poisoning ethylene glycol poisoning ethylene glycol poisoning is poisoning caused by drinking ethylene glycol. early symptoms include intoxication, vomiting and abdominal pain. later symptoms may include a decreased level of consciousness, headache, and seizures. long term outcomes may include kidney failure and brain damage. toxicity and death may occur after drinking even in a small amount as ethylene glycol is more toxic than other diols. ethylene glycol poisoningother namesethylene glycol toxicity, ethylene glycol overdoseethylene glycolspecialtyemergency medicinesymptomsearly: intoxication, vomiting, abdominal painlater: decreased level of consciousness, headache, seizurescomplicationskidney failure, brain damagecausesdrinking ethylene glycoldiagnostic methodcalcium oxalate crystals in the urine, acidosis or increased osmol gap in the bloodtreatmentantidote, hemodialysismedicationfomepizole, ethanolfrequency> 5,000 cases per year (us) ethylene glycol is a colorless, odorless, sweet liquid, commonly found in antifreeze. it may be drunk accidentally or intentionally in a suicide attempt. when broken down by the body it results in glycolic acid and oxalic acid which cause most of the toxicity. 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. diagnosis may be confirmed by measuring ethylene glycol levels in the blood; however, many hospitals do not have the ability to perform this test. early treatment increases the chance of a good outcome. treatment consists of stabilizing the person, followed by the use of an antidote. the preferred antidote is fomepizole with ethanol used if this is not available. hemodialysis may also be used in those where there is organ damage or a high degree of acidosis. other treatments may include sodium bicarbonate, thiamine, and magnesium. more than 5,000 cases of poisoning occur in the united states each year. those affected are often adults and male. deaths from ethylene glycol have been reported as early as 1930. an outbreak of deaths in 1937 due to a medication mixed in a similar compound, diethylene glycol, resulted in the food, drug, and cosmetic act of 1938 in the united states, which mandated evidence of safety before new medications could be sold. antifreeze products sometimes have a substance to make them bitter added to discourage drinking by children or animals but this has not been found to be effective. signs and symptoms signs of ethylene glycol poisoning depend upon the time after ingestion. symptoms usually follow a three-step progression, although poisoned individuals will not always develop each stage. stage 1 (30 minutes to 12 hours) consists of neurological and gastrointestinal symptoms and looks similar to alcohol poisoning. poisoned individuals may appear to be intoxicated, dizzy, lacking coordination of muscle movements, drooling, depressed, and have slurred speech, seizures, abnormal eye movements, headaches, and confusion. irritation to the stomach may cause nausea and vomiting. also seen are excessive thirst and urination. over time, the body metabolizes ethylene glycol into other toxins. stage 2 (12 to 36 hours) where signs of "alcohol" poisoning appear to resolve, underlying severe internal damage is still occurring. an elevated heart rate, hyperventilation or increased breathing effort, and dehydration may start to develop, along with high blood pressure and metabolic acidosis. these symptoms are a result of accumulation of organic acids formed by the metabolism of ethylene glycol. additionally low calcium concentrations in the blood, overactive muscle reflexes, muscle spasms, qt interval prolongation, and congestive heart failure may occur. if untreated, death most commonly occurs during this period. stage 3 (24 to 72 hours) kidney failure is the result of ethylene glycol poisoning. in cats, this stage occurs 12–24 hours after consuming antifreeze; in dogs, at 36–72 hours after consuming antifreeze. during this stage, severe kidney failure is developing secondary to calcium oxalate crystals forming in the kidneys. severe lethargy, coma, depression, vomiting, seizures, drooling, and inappetence may be seen. other symptoms include acute tubular necrosis, red blood cells in the urine, excess proteins in the urine, lower back pain, decreased or absent production of urine, elevated blood concentration of potassium, and acute kidney failure. if kidney failure occurs it is typically reversible, although weeks or months of supportive care including hemodialysis may be required before kidney function returns. sources the most common source of ethylene glycol is automotive antifreeze or radiator coolant, where concentrations are high. other sources of ethylene glycol include windshield deicing agents, brake fluid, motor oil, developing solutions for hobby photographers, wood stains, solvents, and paints. some people put antifreeze into their cabin's toilet to prevent it from freezing during the winter, resulting in toxicities when animals drink from the toilet. small amounts of ethylene glycol may be contained in holiday ornaments such as snow globes. 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. it is also used in manufacturing polyester products. 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. pathophysiology glycolic acid is the major metabolite of ethylene glycol responsible for toxicity the three main systems affected by ethylene glycol poisoning are the central nervous system, metabolic processes, and the kidneys. the central nervous system is affected early in the course of poisoning as the result of a direct action of ethylene glycol. similar to ethanol, it causes intoxication, followed by drowsiness or coma. seizures may occur due to a direct effect. the toxic mechanism of ethylene glycol poisoning is mainly due to the metabolites of ethylene glycol. initially it is metabolized by alcohol dehydrogenase to glycolaldehyde, which is then oxidized to glycolic acid by aldehyde dehydrogenase. the increase in metabolites may cause encephalopathy or cerebral edema. the metabolic effects occur 12 to 36 hours post ingestion, causing primarily metabolic acidosis which is due mainly to accumulated glycolic acid. 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. the formation of acid metabolites also causes inhibition of other metabolic pathways, such as oxidative phosphorylation. the kidney toxicity of ethylene glycol occurs 24 to 72 hours post ingestion and is caused by a direct cytotoxic effect of glycolic acid. the glycolic acid is then metabolized to glyoxylic acid and finally to oxalic acid. 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. the most significant effect is accumulation of calcium oxalate crystals in the kidneys which causes kidney damage leading to oliguric or anuric acute kidney failure. the rate-limiting step in this cascade is the conversion of glycolic to glyoxylic acid. accumulation of glycolic acid in the body is mainly responsible for toxicity. toxicity ethylene glycol has been shown to be toxic to humans and is also toxic to domestic pets such as cats and dogs. a toxic dose requiring medical treatment varies but is considered more than 0.1 ml per kg body weight (ml/kg) of pure substance. that is roughly 16 ml of 50% ethylene glycol for an 80 kg adult and 4 ml for a 20 kg child. poison control centers often use more than a lick or taste in a child or more than a mouthful in an adult as a dose requiring hospital assessment. the orally lethal dose in humans has been reported as approximately 1.4 ml/kg of pure ethylene glycol. that is approximately 224 ml (7.6 oz.) of 50% ethylene glycol for an 80 kg adult and 56 ml (2 oz.) for a 20 kg child. 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. in the eu classification of dangerous substances it is 'harmful' (xn) while more toxic substances are classified as 'toxic' (t) or 'very toxic' (t+). the u.s. environmental protection agency generally puts substances which are lethal at more than 30 g to adults in toxicity class iii. ethylene glycol has a low vapor pressure; it does not evaporate readily at normal temperatures and therefore high concentrations in air or intoxication are unlikely to occur following inhalational exposures. 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. ethylene glycol is not well absorbed through skin meaning poisoning following dermal exposure is also uncommon. diagnosis urine microscopy showing calcium oxalate crystals in the urine as many of the clinical signs and symptoms of ethylene glycol poisoning are nonspecific and occur in many poisonings the diagnosis is often difficult. it is most reliably diagnosed by the measurement of the blood ethylene glycol concentration. ethylene glycol in biological fluids can be determined by gas chromatography. many hospital laboratories do not have the ability to perform this blood test and in the absence of this test the diagnosis must be made based on the presentation of the person. in this situation a helpful test to diagnose poisoning is the measurement of the osmolal gap. the person' serum osmolality is measured by freezing point depression and then compared with the predicted osmolality based on the person's measured sodium, glucose, blood urea nitrogen, and any ethanol that may have been ingested. the presence of a large osmolal gap supports a diagnosis of ethylene glycol poisoning. however, a normal osmolar gap does not rule out ethylene glycol exposure because of wide individual variability. the increased osmolal gap is caused by the ethylene glycol itself. 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. 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. other laboratory abnormalities may suggest poisoning, especially the presence of a metabolic acidosis, particularly if it is characterized by a large anion gap. large anion gap acidosis is usually present during the initial stage of poisoning. 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. the diagnosis of ethylene glycol poisoning should be considered in any people with a severe acidosis. 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. finally, many commercial radiator antifreeze products have fluorescein added to enable radiator leaks to be detected using a wood's lamp. 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. prevention antifreeze products for automotive use containing propylene glycol in place of ethylene glycol are available, and are generally considered safer to use, as it possesses an unpleasant taste in contrast to the perceived "sweet" taste of toxic ethylene glycol-based coolants, and produces only lactic acid in an animal's body, as their muscles do when exercised. when using antifreeze products containing ethylene glycol, recommended safety measures include: cleaning up any spill immediately and thoroughly. spills may be cleaned by sprinkling cat litter, sand or other absorbent material directly on the spill. once fully absorbed, while wearing protective gloves, the material may be scooped into a plastic bag, sealed and disposed. the spill area may be scrubbed with a stiff brush and warm, soapy water. the soapy water is not recommended to be drained in a storm drain. checking vehicles regularly for leaks. storing antifreeze in clearly marked original sealed containers, in areas that are inaccessible to pets or small children. keeping pets and small children away from the area when draining the car radiator. disposing of used antifreeze only by taking to a service station. if antifreeze is placed in toilets, ensuring the lid is down and the door closed. treatment stabilization and decontamination the most important initial treatment for ethylene glycol poisoning is stabilizing the person. as