DESCRIPTION
USES
Ethylene glycol is predominantly used as a deicer or antifreeze in cooling systems. It is also used in hydraulic brake fluids, as a solvent, a chemical intermediate, and as an industrial humectant. It may also be used as a glycerin substitute in commercial products including paints, detergents, and cosmetics. |
INTERVENTION CRITERIA
Medical assessment and observation in an emergency department is recommended for: - Ingestions greater than a witnessed lick or exploratory taste of ethylene glycol - Symptomatic ingestions - Symptomatic eye exposures (other than mild resolving symptoms following flushing) - Significantly symptomatic patients (more than mild irritation) following skin or inhalation exposure |
Medical assessment and observation in an emergency department is recommended for: - Ingestions greater than 10 mL of ethylene glycol - Symptomatic ingestions - Symptomatic eye exposures (other than mild resolving symptoms following flushing) - Significantly symptomatic patients (more than mild irritation) following skin or inhalation exposure - Exposures with intent to self-harm |
If the patient does not require medical observation they can be monitored at home for 8 hours in the care of a reliable observer. |
The patient should be medically assessed if any symptoms develop, including: Nausea Vomiting Drowsiness Slurred speech Stumbling or difficulty in moving Confusion Decreased urine output |
If medical observation is required, patients with an undetectable serum ethanol should be monitored until 8 hours post-exposure for the onset of symptoms or biochemical evidence of evolving toxicity. Patients co-ingesting ethanol should be monitored until 12 hours post-exposure. If the patient is asymptomatic at the end of the observation period, with normal serum pH, bicarbonate, and creatinine concentrations and their serum (or breath) ethanol concentration is undetectable they may be: Discharged into the care of a reliable observer, or Referred for psychological assessment if the overdose or exposure was with intent to self-harm |
Patients, particularly children, presenting within an hour of suspected ethylene glycol ingestion or those who have concurrently co-ingested ethanol may not have any abnormal surrogate markers of poisoning. In these instances, close observation and serial monitoring of acid-base profile and renal function status should be performed. Any development of early metabolic acidosis would be highly suggestive of recent ethylene glycol exposure. Serum ethanol concentration (required for osmolar gap calculation) Serum electrolytes including: Sodium (required for anion gap calculation) Chloride (required for anion gap calculation) Bicarbonate (required for anion gap calculation) Calcium Potassium Anion gap (elevated in later stages of poisoning) Blood gas analysis including: Serum pH Creatinine and BUN Urine output Urinalysis including: Proteinuria Hematuria Examination under UV light (Wood’s lamp) for fluorescence (present in many antifreeze solutions and with urinary elimination the urine will fluoresce when expose to UV light). A negative result does not completely rule out ethylene glycol exposure. Microscopic examination for crystalluria (calcium oxalate crystals) If a serum ethylene glycol concentration measurement is not available a presumptive diagnosis of poisoning may be based on: either A history or suspicion of ethylene glycol ingestion plus any 2 of the following;  Arterial pH < 7.3 Serum bicarbonate < 20 mmol/L (20 mEq/L) Osmolar gap > 10 mOsm/L Presence of urinary oxalate crystals or A history or suspicion of ethylene glycol ingestion within the last 1 hour and osmolar gap > 10 mOsm/L A serum ethylene glycol is the preferred investigation, but is often not readily available. A significant ethylene glycol ingestion may be inferred from an increased osmolar gap (in the early stages of intoxication) indicating a solute (glycol) load. However, a normal osmolar gap cannot rule out ethylene glycol exposure. Once the glycol is metabolized the osmolar gap will drop and may be replaced by an increased anion gap, indicating an increased organic acids (glycol metabolites) load, with an accompanying metabolic acidosis. Presence in the urine of either fluorescein or calcium oxalate crystals indicates ethylene glycol exposure, but their absence does not exclude this poisoning. Calcium oxalate crystals may not be present until the later stages of intoxications. Fluorescein is rapidly eliminated by the kidneys and may have already been excreted prior to presentation. Also, the ingested ethylene glycol may not contain fluorescein. Care must be exercised when checking for fluorescence as plastic containers may exhibit some degree of fluorescence under a UV light. A glass container is preferable and previous experience with visualizing fluorescein containing urine is useful. |
Admission to an intensive care environment is recommended when: Ethylene glycol concentrations are > 20 mg/dL (3.2 mmol/L) Those receiving antidotal therapy Following symptoms occur Coma Seizures Kidney injury Hypotension Ensure the receiving hospital is able to provide: Advanced care/ICU facilities, and |
TREATMENT
TREATMENT SUMMARY
Initial management includes airway protection and adequate minute ventilation, administration of IV fluids, treating seizures with benzodiazepines or barbiturates, and correcting hypoglycemia (unless rapid glucose screen indicates otherwise); concurrently administer thiamine and pyridoxine to support metabolism of ethylene glycol to less toxic products. Nasogastric aspiration may be performed within 1 hour of ingestion provided the airway is protected. Ethanol and fomepizole are effective antidotes and should be administered to patients as early as possible. Hemodialysis is effective in excreting glycols and their toxic metabolites and should be considered in acute renal failure, severe metabolic acidosis, or if other indications are present. Doses of ethanol and fomepizole need to be increased during hemodialysis. Eye exposures require a 15 minute irrigation with saline or water and if more than mild, resolving symptoms are present following irrigation, an ophthalmologic examination should be undertaken, including slit lamp examination and fluorescein staining. If there is evidence of injury an ophthalmologist should be consulted. Treatment should follow standard protocols for the management of eye irritation. |
EMERGENCY STABILIZATION
Ensure Adequate Cardiopulmonary Function |
Ensure the airway is protected (intubation may be required), and administer oxygen. Establish secure intra-venous access. |
Hypotension may be present due to gastrointestinal fluid loss and alcohol-induced vasodilation, and in such cases fluid replacement with a crystalloid should be performed, having regard to adequate urine output. |
CHILD Hypotension in children is determined by age and systolic blood pressure Age | Hypotension if Systolic Blood Pressure (mm Hg) is: | 0 to 28 days | < 60 | 1 to 12 months | < 70 | 1 to 10 years | < 70 + (age in years x 2) | > 10 years | < 90 |
Administer an isotonic crystalloid fluid 10 mL/kg IV over 5 to 10 minutes If the systolic blood pressure does not return to the normal range, give a further 10 mL/kg body weight of the isotonic crystalloid over 5 to 10 minutes. The intraosseous route can be used if IV access is difficult or delayed. ADULT Administer a bolus of isotonic crystalloid fluid if systolic blood pressure is less than 100 mmHg. Isotonic crystalloid fluid dose: 20 mL/kg IV over 5 to 10 minutes If the systolic blood pressure does not return to the normal range, give a further 10 mL/kg body weight normal saline over 5 to 10 minutes. The intraosseous route can be used if IV access is difficult or delayed. |
Administer a benzodiazepine as first-line treatment to patients with seizure activity. Blood glucose concentration should be promptly determined. If the result indicates hypoglycemia, or is unobtainable, supplemental dextrose should be administered IV. |
Check for hypoxia and electrolyte disturbances. Correct acid base and metabolic disturbances. Seizures due to ethylene glycol intoxication may prove unresponsive to standard management unless hypocalcemia is corrected. |
IV dextrose is indicated (even if blood glucose cannot be quickly measured) in patients with altered mental status, unusual behavior, coma, or seizures. Hypoglycemic patients may present with focal neurological deficits. However, these may also be due to cerebral ischemia. |
Must be administered to adult patients considered alcohol-dependent or malnourished. |
Thiamine dose ADULT 100 mg IV, which may be repeated every 8 hours, if needed. |
Blood pressure ECG Respiratory rate Oxygen saturation Serum ethylene glycol concentration (if available) Serum ethanol concentration (used in calculation of osmolar gap) Osmolar gap (elevated early in poisoning) Electrolytes including: Sodium (required for anion gap calculation) Chloride (required for anion gap calculation) Bicarbonate (required for anion gap calculation) Calcium Potassium Anion gap (elevated later in poisoning) Blood gas analysis including: Serum pH Creatinine and BUN Urine output Urinalysis including: Proteinuria Hematuria Microscopic examination for crystalluria Blood glucose Liver function |
DECONTAMINATION
Nasogastric aspiration is recommended if the quantity of liquid ingested is both systemically toxic and in sufficient volume to aspirate. As this procedure may increase the risk of vomiting and pulmonary aspiration, the airway must be protected in all patients. Accurate placement of the nasogastric tube must also be ensured in all patients. |
Nasogastric aspiration is recommended if the patient has presented early (within 1 hour) following ingestion of ethylene glycol. |
Single Dose Activated Charcoal |
Activated charcoal is not considered an effective decontaminant for this ingestion as ethylene glycol is rapidly absorbed from the gastrointestinal tract and has poor binding affinity for activated charcoal. Unless there is concern for coingestants, there is little benefit from activated charcoal administration in ethylene glycol ingestions.
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Remove contact lenses. Irrigate immediately with water or saline for at least 15 minutes. If the eye is contaminated with solid particles, the eyelid should be completely everted and any solid material removed as quickly as possible whilst continuing to irrigate. A topical anesthetic should be considered for all patients to enable the patient to open the lids sufficiently for effective irrigation. |
If, following irrigation, any of the following are apparent: Ocular pain (other than mild and resolving) Redness (other than mild and resolving) Decreased visual acuity Ocular discharge/crusting The patient should receive a full ophthalmologic examination, including slit lamp examination and fluorescein staining. If there is evidence of injury an ophthalmologist should be consulted. |
Remove the patient from the exposure. If respiratory symptoms such as shortness of breath are present, administer oxygen and provide additional support if necessary. |
Remove any contaminated clothing or jewelry. Wash the affected area thoroughly with soap and water until all of the contaminant is removed. |
ANTIDOTE(S)
Appropriate use of antidotes in glycol poisoning is essential. Ethanol has long been regarded as an effective intervention, is cheap and available but requires longer periods of monitoring due to the risk of ethanol intoxication. Fomepizole has proven efficacy, but suffers the disadvantage of expense and may not be immediately available. Both effectively act (via different mechanisms) by inhibiting the role of alcohol dehydrogenase in ethylene glycol metabolism, thus reducing the metabolic conversion of glycol to toxic metabolites (including glycolic, glyoxylic, and oxalic acid). Thiamine and pyridoxine may be indicated as therapeutic adjuncts. Theoretically, they act as cofactors in the formation of non-toxic metabolites of ethylene glycol. No data exists to support this assumption, but they may benefit those with a history of ethanol abuse or inadequate nutrition (e.g. vitamin deficient patients). |
Ethanol is indicated if: - Reliable history of ingestion of a toxic quantity of ethylene glycol; or - Plasma ethylene glycol concentration is greater than 3.2 mmol/L (20 mg/dL) or; - History or clinical suspicion of ethylene glycol poisoning and at least two of the following: Arterial pH < 7.3 Serum bicarbonate < 20 mmol/L (20 mEq/L) Osmolar gap > 10 mosm/L Presence of urinary oxalate crystals |
For acceptable efficacy, the blood ethanol concentration should be maintained between 22 and 33 mmol/L (100 to 150 mg/dL). To achieve this both a loading dose and maintenance infusion are required. Either 100% ethanol diluted for intravenous use may be infused, or liquor (e.g. vodka, gin) may be administered orally. Prior to use of ethanol therapy a blood ethanol determination should be made to identify if the patient has an existing ethanol concentration requiring a modification of the loading dose. Monitoring in an intensive care setting is required during administration. Because of the large inter-individual variability in ethanol metabolism, serum ethanol concentrations should be monitored every 1 to 2 hours if this is available. Ideally effectiveness of blocking can be monitored by analysis of metabolite concentrations, or blood gases if metabolite and ethanol analyses are not available. As ethanol may depress respiration, mechanical hyperventilation is recommended in those with reduced level of consciousness. |
Oral Ethanol Loading Dose To calculate the loading dose of oral ethanol from common concentrations in spirits use the appropriate calculation below. The dose should be administered as a 20% or less solution (e.g. diluted with water or fruit juice). Ethanol % | Dose (mL) | 37/37.5% | body weight x 2.5 | 40% | body weight x 2.3 | 42% | body weight x 2.2 | 45% | body weight x 2.04 |
If the concentration of spirits does not match those in the above table the dose can be calculated by clicking here. Note: The term "proof" describing alcohol content of beverages should be halved to obtain the proper % v/v value (e.g. 60 proof = 30% v/v ethanol). Intravenous Ethanol Loading Dose Concentrated ethanol solutions need to be diluted with isotonic 5% glucose (dextrose) to prevent vascular damage. To convert concentrated ethanol formulations to 5 or 10% click here. To reach the desired blood ethanol concentration of 22 to 33 mmol/L (100 to 150 mg/dL) administer: 5% v/v ethanol: 15 to 22 mL/kg over 30 minutes 10% v/v ethanol: 8 to 11 mL/kg over 30 minutes 10% solution are hyperosmolar and irritant and should be administered via a central venous line If you have w/v formulations please click here to convert to v/v |
The doses suggested below are only a starting point. Maintenance doses should be titrated aiming to achieve the desired blood ethanol concentration of 22 to 33 mmol/L (100 to 150 mg/dL); this is best guided by frequently repeated measurements of serum ethanol concentrations (ideally every 1 to 2 hours). |
Oral Ethanol Maintenance Dose Ethanol % | Children (mL/h) | Adults (non-alcohol dependent) (mL/h) | Adults (alcohol dependent) (mL/h) | 37% | 0.61 x body weight | 0.41 x body weight | 0.82 x body weight | 40% | 0.57 x body weight | 0.38 x body weight | 0.76 x body weight | 42% | 0.54 x body weight | 0.36 x body weight | 0.72 x body weight | 45% | 0.5 x body weight | 0.33 x body weight | 0.67 x body weight |
This should be administered as a 20% or less solution (e.g. diluted with water or fruit juice). If the concentration of spirits does not match those in the above table the dose can be calculated by clicking here. Intravenous Ethanol Maintenance Dose Concentrated ethanol solutions need to be diluted with isotonic 5% glucose (dextrose) to prevent vascular damage. To convert concentrated ethanol formulations to 5 or 10% click here. 5% v/v solution: CHILD 4.5 mL/kg/h ADULT Non-alcohol dependent: 2 to 3 mL/kg/h Alcohol dependent: 4 to 6 mL/kg/h 10 % v/v solution: CHILD 2.25 mL/kg/h ADULT Non-alcohol dependent: 1 to 1.5 mL/kg/h Alcohol dependent: 2 to 3 mL/kg/h 10% solution are hyperosmolar and irritant and should be administered via a central venous line If you have w/v formulations please click here to convert to v/v. Dosing requirements will change if hemodialysis is required. See enhanced elimination section. |
Ethanol administration may be discontinued if ethylene glycol concentrations can no longer be detected or are less than 3.2 mmol/L (20 mg/dL) with a normalized arterial pH and resolved signs of systemic toxicity - this is likely to take 2 to 3 days given ethylene glycol's typical elimination half-life of around 17 to 18 hours in the presence of ethanol, if hemodialysis is not applied. |
Hypoglycemia may occur, especially in children. Once an infusion has been commenced blood glucose concentrations must be determined on a frequent basis (every 1 to 2 hours). It may be necessary to add dextrose to intravenous solutions, or give glucose if ethanol is being administered orally. It is recommended that patients receiving ethanol therapy be monitored in an intensive care setting and any decline in respiratory drive countered with hyperventilation. |
While availability is limited by purchase price, fomepizole appears preferable to ethanol. It is more particularly indicated in those with altered mental status, patients suffering hepatic disease, pregnant women, or those critically ill but lacking confirmation of poisoning. Its administration to pediatric patients avoids the disadvantages of ethanol (e.g. inebriation, hypoglycemia). |
Fomepizole is indicated if: - Plasma ethylene glycol concentration greater than 3.2 mmol/L (20 mg/dL) or; - Recent ingestion of a toxic amount of ethylene glycol and presence of osmolar gap greater than 10 mosm/L or; - History or clinical suspicion of ethylene glycol poisoning and at least two of the following Arterial pH < 7.3 Serum bicarbonate < 20 mmol/L (20 mEq/L) Osmolar gap > 10 mosm/L Presence of urinary oxalate crystals Particular indications: - Altered mental status - Co-ingestion of other drugs that may cause CNS depression (e.g. opioids, sedatives, antidepressants, anticonvulsants, antihistamines, hypnotics, muscle relaxants) - Patients taking disulfiram or metronidazole - Hepatic disease - Critically ill patients lacking confirmation of ethylene glycol toxicity - Pregnancy - Pediatric patients (avoids the inebriation and hypoglycemia that may occur with ethanol administration) - Inability of local laboratory to measure repeated ethanol concentrations - Lack of local availability of a facility to monitor the patient closely such as an intensive care unit |
Loading dose - 15 mg/kg diluted in 100 mL of normal saline or 5% dextrose in water and administered by IV infusion over 30 minutes Maintenance doses - 10 mg/kg should be administered every 12 hours for 4 doses, then; - 15 mg/kg every 12 hours thereafter if indicated Maintenance fomepizole should be administered in the same fashion as the loading dose. Dosing requirements will change if hemodialysis is required – as outlined in the enhanced elimination section. |
Fomepizole may be discontinued when ethylene glycol plasma concentrations are either undetectable, or below 3.2 mmol/L (20 mg/dL) in patients with a normal pH and resolved signs of systemic toxicity. |
Abdominal pain, skin rash, nausea, headache, dizziness, and drowsiness have been reported following fomepizole use. |
Pyridoxine acts as a co-factor in the conversion of glyoxylic acid to the non-toxic metabolite glycine. While the clinical benefit of pyridoxine administration for the treatment of ethylene glycol poisoning has not been demonstrated in healthy individuals, it is recommended for use in malnourished or alcohol dependent patients who may have vitamin deficiencies. |
The formulation should be diluted at least 1 to 5. ADULT - 50 to 100 mg pyridoxine given as an IV infusion over 15 to 30 minutes every six hours - Continue for two days |
Profound peripheral neuropathy may occur after very large single doses or a series of doses (for example a total of > 2 g/kg pyridoxine over a three day period). The sensory (if not motor) disturbances are potentially irreversible. |
Thiamine acts as a co-factor in the conversion of glyoxylic acid to the non-toxic metabolite alpha-hydroxy-beta-ketoadipate. While the clinical benefit of thiamine administration for the treatment of ethylene glycol poisoning has not been demonstrated in healthy individuals, it is recommended for use in malnourished or alcohol dependent patients who may have vitamin deficiencies. |
ADULT - Administer 100 mg IV or IM thiamine every six hours - Continue for two days |
SIGNS AND SYMPTOMS
Inhalation of ethylene glycol can cause upper respiratory tract irritation. Systemic effects are not expected unless it has been heated or aerosolized. Eye exposure to vapors or direct contact with the liquid may lead to eye irritation; significant eye injury would not be expected. Brief or occasional skin exposure is unlikely to cause harm to the skin but prolonged or repeated exposure may lead to significant irritation and sensitivity. Skin absorption is limited, and systemic effects are unlikely to develop. |
Symptoms predominantly occur following ingestion of ethylene glycol. However, toxicity is also possible via intravenous and intramuscular routes. |
Onset/Duration of Symptoms |
Stage I: Neurological Phase 0.5 to 12 hours post-ingestion Inebriation Nausea Vomiting/hematemesis Metabolic acidosis/elevated anion gap/elevated osmolar gap CNS depression Coma Hypocalcemia Calcium oxalate crystalluria Stage II: Cardiopulmonary Phase 12 to 24 hours post-ingestion Hypertension Tachycardia Tachypnea Severe metabolic acidosis Pulmonary edema Congestive heart failure Stage III: Renal Phase 24 to 72 hours post-ingestion Proteinuria Oliguria Anuria Acute tubular necrosis Renal failure Sequelae Onset several (5 to 20) days after ingestion Cranial nerve neuropathies |
| Mild Ethylene Glycol Toxicity | Moderate Ethylene Glycol Toxicity | Severe Ethylene Glycol Toxicity | Nausea Vomiting Ataxia Slurred speech Confusion Drowsiness | Mild metabolic acidosis Tachycardia Hypertension Hypocalcemia Calcium oxalate crystalluria Oliguria Hematuria Proteinuria | Pulmonary edema Anuria Hyperventilation/Kussmaul respirations Hyperkalemia Elevated anion and osmolar gaps Severe metabolic acidosis Seizures Acute kidney injury Multiple organ failure Cranial nerve defects Coma Death |
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CHRONIC EFFECTS
Chronic exposures to ethylene glycol vapor may result in nystagmus, unconsciousness, and lymphocytosis. |
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NZ: 22.Jun.2021 |
