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Ethylene Glycol Toxicity

  • Author: Daniel C Keyes, MD, MPH; Chief Editor: Asim Tarabar, MD  more...
 
Updated: Jun 24, 2016
 

Background

Several toxic alcohols are of medical and toxicological importance; the principal ones include ethanol, ethylene glycol (EG), methanol, and isopropanol. See Alcohol Toxicity. This article discusses ethylene glycol, which is extremely toxic. If untreated, ingestion of ethylene glycol can be fatal.

Ethylene glycol is the major ingredient of almost all radiator fluid products in the United States. It is used to increase the boiling point and decrease the freezing point of radiator fluid, which circulates through the automotive radiator. These changes to the boiling and freezing points result from the colligative properties of the solute (ie, they depend on the number of particles in the solution). Hence, ethylene glycol is added to prevent the radiator from overheating or freezing, depending on the season.

Fluorescein dye is often added to radiator fluid to help mechanics identify the source of a radiator leak. The fluorescein in the fluid fluoresces when viewed under ultraviolet light.

Ethylene glycol tastes sweet, which is why some animals are attracted to it. Many veterinarians are familiar with ethylene glycol toxicity because of the frequent cases that involve dogs or cats that drink radiator fluid.

Initially, patients with ethylene glycol intoxication may be asymptomatic; with time they will develop altered mental status and dyspnea. The classic laboratory profile is an early osmolar gap that later transitions to an anion gap metabolic acidosis. Initial treatment includes infusion of crystalloids to enhance renal clearance of the toxic metabolites. Ethyl alcohol has traditionally been used for antidotal treatment, but it has largely been supplanted by fomepizole.

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Pathophysiology

Like the other toxic alcohols mentioned above (see Background), ethylene glycol is a parent compound that exerts most of its toxicity by conversion to metabolites. Ethylene glycol itself may cause some alteration of mental status but it is a relatively nontoxic compound before it is metabolized. The metabolites cause the distinctive toxicity associated with this compound.

Knowing the pathway of ethanol metabolism is necessary to understand ethylene glycol toxicity properly. Ethanol is metabolized by the enzyme alcohol dehydrogenase (ADH) pathway, which is located in the liver and gastric mucosa, and by the cytochrome P-450 mixed function oxidase (MFO) system in the liver. The mixed function oxidase component is subject to greater inducibility than alcohol dehydrogenase.

As with ethyl alcohol and methanol, ethylene glycol is metabolized by the enzyme alcohol dehydrogenase. In this step it forms glycoaldehyde. Through interaction with aldehyde dehydrogenase, ethylene glycol is then metabolized to glycolic acid (GA). A profound acidosis often ensues with this intoxication which is attributable to the glycolic acid in circulation. This glycolate is then transformed into glyoxylic acid. At this point, the molecule may be transformed into the highly toxic oxalate or the safer glutamate or α-ketoadipic acid metabolites.

Calcium oxalate crystals may form and accumulate in blood and other tissues. The precipitation of calcium oxalate in the renal cortex results in decreased glomerular filtration and renal insufficiency. The formation of these crystals consumes circulating calcium, and hypocalcemia may occur.

The rate-limiting step of ethylene glycol metabolism is the alcohol dehydrogenase–catalyzed step. Common ethyl alcohol (ethanol) binds much more easily to alcohol dehydrogenase than ethylene glycol or methanol does. Because ethanol is the preferred substrate for alcohol dehydrogenase, the presence of ethanol may essentially block metabolism of ethylene glycol. In addition, this enzyme is blocked by the administration of fomepizole (4-methylpyrazole [4-MP]), which is discussed below (see Emergency Department Care). This is the basis of one therapy used in the United States.

Upon oral ingestion, serum levels of ethylene glycol peak within 1-4 hours. The elimination half-life (assuming preserved renal function) is 3 hours.

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Epidemiology

Frequency

United States

Ethylene glycol is a relatively common cause of overdose in US emergency departments. In 2009, there were 5282 single exposures to ethylene glycol reported to the American Association of Poison Control Centers (AAPCC).[1] In 20142, the number of single exposures to ethylene glycol in antifreeze and other automotive products had increased to 5552.[2]

Mortality/Morbidity

According to the AAPCC's National Poison Data System, in 2009, 773 had minor outcomes, 376 had moderate outcomes, 134 had severe outcomes, and 10 deaths were documented.[1] In 2014, 916 had minor outcomes, 411 had moderate outcomes, 141 had severe outcomes, and 16 deaths were documented.[2]

Age

The annual report of the AAAPCC's National Poison Data System in 2014 documented ethylene glycol exposure in 432 children younger than 6 years, 560 in those aged 6-19 years, and 3942 in those 20 years and older.[2]

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Contributor Information and Disclosures
Author

Daniel C Keyes, MD, MPH Associate Chair, Academic Affairs, Department of Emergency Medicine, St Joseph Mercy Hospital; Clinical Faculty, Emergency Medicine Residency, University of Michigan Medical School; Clinical Associate Professor, Department of Surgery, Division of Emergency Medicine and Toxicology, University of Texas Southwestern School of Medicine

Daniel C Keyes, MD, MPH is a member of the following medical societies: American College of Emergency Physicians, American College of Medical Toxicology, American College of Occupational and Environmental Medicine, American College of Physicians-American Society of Internal Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

John T VanDeVoort, PharmD Regional Director of Pharmacy, Sacred Heart and St Joseph's Hospitals

John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists

Disclosure: Nothing to disclose.

John G Benitez, MD, MPH Associate Professor, Department of Medicine, Medical Toxicology, Vanderbilt University Medical Center; Managing Director, Tennessee Poison Center

John G Benitez, MD, MPH is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College of Medical Toxicology, American College of Preventive Medicine, Undersea and Hyperbaric Medical Society, Wilderness Medical Society, American College of Occupational and Environmental Medicine

Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Disclosure: Nothing to disclose.

Additional Contributors

Miguel C Fernandez, MD, FAAEM, FACEP, FACMT, FACCT Associate Clinical Professor, Department of Surgery/Emergency Medicine and Toxicology, University of Texas School of Medicine at San Antonio; Medical and Managing Director, South Texas Poison Center

Miguel C Fernandez, MD, FAAEM, FACEP, FACMT, FACCT is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, Society for Academic Emergency Medicine, Texas Medical Association, American College of Occupational and Environmental Medicine

Disclosure: Nothing to disclose.

Acknowledgements

Abid A Kagalwalla, MD Resident Physician, Department of Emergency Medicine, St Joseph Mercy Hospital, University of Michigan Health System

Abid A Kagalwalla, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, Emergency Medicine Residents Association, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

References
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Oxalate crystals. Courtesy of John D Schaldenbrand, MD, Department of Pathology, St Joseph Mercy Health System, Ann Arbor, MI.
Ethylene glycol.
 
 
 
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