Ethylene glycol poisoning

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Ethylene glycol poisoning
Other namesEthylene glycol toxicity, ethylene glycol overdose
Calcium oxalate crystals in the urine, acidosis or increased osmol gap in the blood[1]
TreatmentAntidote, hemodialysis[2]
MedicationFomepizole, ethanol[2]
Frequency> 5,000 cases per year (US)[3]

Ethylene glycol poisoning is

brain damage.[1] Toxicity and death may occur after drinking even in a small amount[1] as ethylene glycol is more toxic than other diols
.

Ethylene glycol is a colorless, odorless, sweet liquid, commonly found in

calcium oxalate crystals are seen in the urine or when acidosis or an increased osmol gap is present in the blood.[1] Diagnosis may be confirmed by measuring ethylene glycol levels in the blood; however, many hospitals do not have the ability to perform this test.[1]

Early treatment increases the chance of a good outcome.

organ damage or a high degree of acidosis.[2] Other treatments may include sodium bicarbonate, thiamine, and magnesium[clarification needed].[2]

More than 5,000 cases of poisoning occur in the United States each year.

Food, Drug, and Cosmetic Act of 1938 in the United States, which mandated evidence of safety before new medications could be sold.[5] 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.[2]

Signs and symptoms

Signs of ethylene glycol poisoning depend upon the time after ingestion.[6] Symptoms usually follow a three-step progression, although poisoned individuals will not always develop each stage.[7][8]

Sources

The most common source of ethylene glycol is automotive

snow globes.[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.[12] It is also used in manufacturing polyester products.[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.[12]

Pathophysiology

Glycolic acid is the major metabolite of ethylene glycol responsible for toxicity

The three main systems affected by ethylene glycol poisoning are the

metabolized by alcohol dehydrogenase to glycolaldehyde, which is then oxidized to glycolic acid by aldehyde dehydrogenase.[7]

The increase in metabolites may cause encephalopathy or cerebral edema.[13] 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.[7]

The kidney toxicity of ethylene glycol occurs 24 to 72 hours post ingestion and is caused by a direct

acute kidney failure.[7] The rate-limiting step in this cascade is the conversion of glycolic to glyoxylic acid.[14] Accumulation of glycolic acid in the body is mainly responsible for toxicity.[15]

Toxicity

Ethylene glycol has been shown to be toxic to humans

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.[17]

The orally

Toxicity Class III.[citation needed
]

Ethylene glycol has a low

dermal exposure is also uncommon.[23]

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.[24] 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.[25] 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.[7]

In this situation a helpful test to diagnose poisoning is the measurement of the

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.[26][27]

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.

isopropanol, or methanol or conditions such as alcoholism or diabetic ketoacidosis, lactic acidosis, or kidney failure may also produce an elevated osmolal gap leading to a false diagnosis.[7]

Other laboratory abnormalities may suggest poisoning, especially the presence of a metabolic acidosis, particularly if it is characterized by a large

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.

vomitus, or urine which can help to diagnose poisoning.[30][31]

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.[32][unreliable source?]

When using antifreeze products containing ethylene glycol, recommended safety measures include:

  • Cleaning up any spill immediately[33] and thoroughly. Spills may be cleaned by sprinkling cat litter, sand or other absorbent material directly on the spill.[34] Once fully absorbed, while wearing protective gloves, the material may be scooped into a plastic bag, sealed and disposed.[34] The spill area may be scrubbed with a stiff brush and warm, soapy water.[34] The soapy water is not recommended to be drained in a storm drain.[34]
  • Checking vehicles regularly for leaks.[33]
  • Storing antifreeze in clearly marked original sealed containers, in areas that are inaccessible to pets[33] or small children.[34]
  • Keeping pets and small children away from the area when draining the car radiator.[33]
  • Disposing of used antifreeze only by taking to a service station.[34]
  • If antifreeze is placed in toilets, ensuring the lid is down and the door closed.[6]

Treatment

Stabilization and decontamination

The most important initial treatment for ethylene glycol poisoning is stabilizing the person. As ethylene glycol is rapidly absorbed,

vasopressors.[36]

Antidotes

Following decontamination and the institution of supportive measures, the next priority is inhibition of further ethylene glycol metabolism using

dextrose, but it is also sometimes given orally in the form of a strong spirit such as whisky, vodka, or gin.[7]

Fomepizole is a potent inhibitor of alcohol dehydrogenase; similar to ethanol, it acts to block the formation of the toxic metabolites.

U.S. Food and Drug Administration for the treatment of ethylene glycol poisoning.[7] Both antidotes have advantages and disadvantages. Ethanol is readily available in most hospitals, is inexpensive, and can be administered orally as well as intravenously. Its adverse effects include intoxication, hypoglycemia in children, and possible liver toxicity.[26] People receiving ethanol therapy also require frequent blood ethanol concentration measurements and dosage adjustments to maintain a therapeutic ethanol concentration. People therefore must be monitored in an intensive care unit. 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. The disadvantage of fomepizole is that it is expensive. Costing US$1,000 per gram, an average course used in an adult poisoning would cost approximately $3,500 to $4,000.[39][40] Despite the cost, fomepizole is gradually replacing ethanol as the antidote of choice in ethylene glycol poisoning.[37][38]

Adjunct agents including

alcoholic.[24]

Hemodialysis

In addition to antidotes, an important treatment for poisoning is the use of hemodialysis. Hemodialysis is used to enhance the removal of unmetabolized ethylene glycol, as well as its metabolites from the body. It has been shown to be highly effective in the removal of ethylene glycol and its metabolites from the blood.[14][41] Hemodialysis also has the added benefit of correcting other metabolic derangements or supporting deteriorating kidney function. Hemodialysis is usually indicated in people with severe metabolic acidosis (blood pH less than 7.3), kidney failure, severe electrolyte imbalance, or if the person's condition is deteriorating despite treatment.[10][24] Often both antidotal treatment and hemodialysis are used together in the treatment of poisoning. Because hemodialysis will also remove the antidotes from the blood, doses of antidotes need to be increased to compensate.[7] If hemodialysis is not available, then peritoneal dialysis also removes ethylene glycol, although less efficiently.[42]

Prognosis

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.[6][43] Cats must be treated within 3 hours of ingesting of antifreeze to be effective, while dogs must be treated within 8–12 hours of ingestion.[9] Once kidney failure develops, the prognosis is poor.[9]

Generally, if the person is treated and survives then a full recovery is expected.[44] People who present early to medical facilities and have prompt medical treatment typically will have a favorable outcome.[45] Alternatively, people presenting late with signs and symptoms of coma, hyperkalemia, seizures, or severe acidosis have a poor prognosis.[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.[46][47][48][49] The most significant long-term complication is related to the kidneys. Cases of permanent kidney damage, often requiring chronic dialysis or kidney transplantation, have been reported after severe poisoning.[50][51]

Epidemiology

Ethylene glycol poisoning is a relatively common occurrence worldwide.

Victorian poison center and 30 cases reported to the New South Wales poison center in 2007.[61][62] However, these numbers may underestimate actual numbers because not all cases attributable to ethylene glycol are reported to poison control centers.[63] Most deaths from ethylene glycol are intentional suicides; deaths in children due to unintentional ingestion are extremely rare.[64]

In an effort to prevent poisoning, often a

Washington) have made the addition of bittering agents to antifreeze compulsory.[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.[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.[68] Similarly, White found that adding bittering agents did not decrease the frequency or severity of antifreeze poisonings in children under the age of 5.[69] Additionally, another study by White found that suicidal persons are not deterred by the bittered taste of antifreeze in their attempts to kill themselves.[64]
These studies did not focus on poisoning of domestic pets or livestock, for example, or inadvertent exposure to bittered antifreeze among a large population (of non-preschool age children).

Poisoning of a raccoon was diagnosed in 2002 in Prince Edward Island, Canada.[70] An online veterinary manual provides information on lethal doses of ethylene glycol for chicken, cattle, as well as cats and dogs, adding that younger animals may be more susceptible.[71]

History

Ethylene glycol was once thought innocuous; in 1931 it was suggested as being suitable for use as a vehicle or solvent for injectable pharmaceutical preparations.[72] Numerous cases of poisoning have been reported since then, and it has been shown to be toxic to humans.[16]

Environmental effects

Ethylene glycol involved in aircraft de-icing and anti-icing operations is released onto land and eventually to waterways.[12] A report prepared for the World Health Organization in 2000 stated that laboratory tests exposing aquatic organisms to stream water receiving runoff from airports have shown toxic effects and death (p. 12).[73] Field studies in the vicinity of an airport have reported toxic signs consistent with ethylene glycol poisoning, fish kills, and reduced biodiversity, although those effects could not definitively be ascribed to ethylene glycol (p. 12).[73] The process of biodegrading of glycols also increases the risk to organisms, as oxygen levels become depleted in surface waters (p. 13).[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. 245).[74] Further, "Anaerobic biodegradation may also release relatively toxic byproducts such as acetaldehyde, ethanol, acetate, and methane (p. 245)."[74]

In Canada,

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".[12]

In the U.S., airports are required to obtain

deicing fluid directly to waters of the U.S. must also meet numeric discharge requirements for chemical oxygen demand.[77] A report in 2000 stated that ethylene glycol was becoming less popular for aircraft deicing in the U.S., due to its reporting requirements and adverse environmental impacts (p. 213), and noted a shift to the use of propylene glycol (p. I-3).[74]

Other animals

Once kidney failure has developed in dogs and cats, the outcome is poor.[9] The treatment is generally the same, although vodka or rectified spirits may be substituted for pharmaceutical grade ethanol in IV injections.[78]

See also

  • Methylmalonic acidemia – an autosomal recessive metabolic disorder that mimics the effects of ethylene glycol poisoning.
  • 1985 diethylene glycol wine scandal
  • Elixir sulfanilamide, a banned medicine that caused mass poisoning because it used ethylene glycol as a solvent
  • Methanol poisoning

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External links

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