Ethylene Glycol 3.Oct.2022-Expires: 7 days - Do not archive DESCRIPTION SUBSTANCE NAME Ethylene Glycol   SUBSTANCE CLASS Glycol   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 Intervention Level Child 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   Adult 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   Observation Period Observation at Home If the patient does not require medical observation they can be observed 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   Medical Observation 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   Investigations 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 ethylene glycol concentration (where available) Serum ethanol concentration (required for osmolar gap calculation) Osmolar gap (elevated in early stages of poisoning) 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 exposed 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:[1]   either   A history of recent ethylene glycol ingestion and osmolar gap > 25 mOsm/L   or   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 > 25 mOsm/L Presence of urinary oxalate crystals   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 Criteria Admission to an intensive care environment is recommended: Ethylene glycol concentration is > 62 mg/dL (10 mmol/L) Those receiving antidotal therapy Following symptoms occur Coma Seizures Kidney injury Hypotension   Ensure the receiving hospital is able to provide: The specific antidotes (Ethanol or Fomepizole) Advanced care/ICU facilities, and Hemodialysis   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.[2]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.[3][4]   Severe acidosis is ideally managed using extracorporeal techniques (e.g. hemodialysis). Intravenous sodium bicarbonate may be considered as an adjunctive treatment for severe acidosis. Hypocalcemia should only be reversed if cardiac dysrhythmia occurs (particularly QT prolongation), or seizures prove unresponsive to management. Hypoglycemia, hyperkalemia, and hypomagnesemia should be corrected. Calcium oxalate crystals may form in any organ with resultant multiorgan dysfunction/failure. The kidneys are often afflicted, resulting in acute kidney injury. There is also a risk of lung injury, and fluid balance will require careful monitoring. Stupor or coma indicates metabolic encephalopathy or cerebral edema.[5] Cranial nerve palsies may occur some 5 to 20 days following ingestion and usually spontaneously resolve over weeks to months without specific therapy.[6][7][8][9]   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 cardiorespiratory function Hypotension Seizure Hypoglycemia Emergency monitoring Decontamination Ingestion Nasogastric aspiration Eye Irrigate immediately Inhalation Fresh air, oxygen Skin Irrigate Antidote(s) Ethanol Fomepizole Pyridoxine Thiamine Enhanced Elimination Hemodialysis Urinary alkalinization Supportive Care Monitoring Metabolic Metabolic acidosis Renal Acute kidney injury Fluid and electrolytes Hypocalcemia Hypomagnesemia Hyperkalemia Neurologic CNS depression Seizure Neurotoxicity Cardiovascular Hypotension Hepatic Hepatotoxicity Respiratory Acute respiratory distress syndrome (ARDS) Pulmonary edema EMERGENCY STABILIZATION Ensure Adequate Cardiopulmonary Function Airway Ensure the airway is protected (intubation may be required), and administer oxygen. Establish secure intra-venous access.   Hypotension 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.   Seizure Administer a benzodiazepine as first-line treatment to patients with seizure activity.[10]   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.   Hypoglycemia 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.[11] However, these may also be due to cerebral ischemia.   Thiamine Must be administered to adult patients considered alcohol-dependent or malnourished.[2][12]   Thiamine dose   ADULT 100 mg IV, which may be repeated every 8 hours, if needed.   Emergency Monitoring 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 Ingestion Nasogastric Aspiration 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. Eye 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 while continuing to irrigate the eye. 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.   Inhalation Remove the patient from the exposure. If respiratory symptoms such as shortness of breath are present, administer oxygen and provide additional support if necessary.   Skin 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,[13] 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).[14]    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).[2]   Ethanol Fomepizole Pyridoxine Thiamine Ethanol Ethanol competitively inhibits alcohol dehydrogenase (ADH) therefore blocking the metabolism to toxic metabolites. Ethanol has a very high affinity for ADH in comparison to other substrates (for example, 100 times the affinity of ethylene glycol and 20 to 30 times the affinity of methanol). Indications Ethanol is indicated if:[1] - Plasma ethylene glycol concentration greater than 62 mg/dL (10 mmol/L), or - History of recent ingestion of a toxic quantity of ethylene glycol with osmolar gap > 25 mosm/kg, 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 > 25 mosm/kg Presence of urinary oxalate crystals   Calculation of the osmolar gap should factor in the serum ethanol concentration.   Dose and Administration To balance acceptable therapeutic efficacy with acceptable adverse effects from ethanol intoxication, the blood ethanol concentration should be maintained between 22 and 33 mmol/L (100 to 150 mg/dL).[2] To achieve this both a loading dose and maintenance dosing are required. Concentrated ethanol diluted for intravenous use may be infused (typically as either 5% or 10% ethanol solution), 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, to ensure therapeutic ethanol concentrations are maintained. Practical experience suggests that it can be challenging to maintain serum ethanol concentrations within the desired range, emphasizing the importance of regular monitoring and titration of maintenance doses.[15][16]   As ethanol may cause agitation or depress mental status and respiration, close monitoring of airway and breathing is also required.[17]   Ethanol Dose Oral ethanol dose   Intravenous ethanol dose   Oral Ethanol Dose   Use of a nasogastric tube can facilitate administration of oral ethanol and is recommended. Ethanol concentrations of 20% or less may increase tolerability and decrease stomach irritation (e.g. dilute more concentrated spirits with water or fruit juice).   The following table can be used as a guide for oral ethanol administration; titration of maintenance doses should be guided by regularly measuring serum ethanol concentrations.[1]   Oral 5% ethanol   10% ethanol 20% ethanol 40% ethanol Loading dose   15 mL/kg 7.5 mL/kg 4 mL/kg 2 mL/kg Maintenance dose/h (not regular drinker)   2 mL/kg/h 1 mL/kg/h 0.5 mL/kg/h 0.25 mL/kg/h Maintenance dose/h (regular drinker)   4 mL/kg/h 2 mL/kg/h 1 mL/kg/h 0.5 mL/kg/h Maintenance dose/h during HD (not regular drinker)   4 mL/kg/h 2 mL/kg/h 1 mL/kg/h 0.5 mL/kg/h Maintenance dose/h during HD (regular drinker) 8 mL/kg/h 4 mL/kg/h 2 mL/kg/h 1 mL/kg/h   It is not imperative that the concentration of spirits used exactly match those in the above table. The clinical goal is to achieve and maintain a therapeutic serum ethanol concentration above 22 mmol/L (100 mg/dL) as the desired outcome, while simultaneously avoiding excessively high serum ethanol concentrations as these will have adverse effects of increasing inebriation and can progress to stupor and coma.   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 Dose   Concentrated ethanol solutions need to be diluted with isotonic 5% glucose (dextrose) to prevent vascular damage from hyperosmolarity; administration via central line is essential for 10% ethanol solutions and recommended for 5% solutions. To convert concentrated ethanol formulations to 5 or 10% click here.   The following table can be used as a guide for intravenous ethanol administration; titration of infusion rates should be guided by regularly measuring serum ethanol concentrations.[1]   Intravenous   5% ethanol 10% ethanol Loading dose   15 mL/kg 7.5 mL/kg Infusion rate/h (not regular drinker)   2 to 4 mL/kg/h 1 to 2 mL/kg/h Infusion rate/h (regular drinker)   4 to 8 mL/kg/h 2 to 4 mL/kg/h Infusion rate/h during HD (not regular drinker)   4 to 8 mL/kg/h 2 to 4 mL/kg/h Infusion rate/h during HD (regular drinker) 6 to 10 mL/kg/h 3 to 5 mL/kg/h   Maintenance Dose The doses suggested above 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 initially until a stable concentration within the target range is reached. After this, measurements of serum ethanol can be performed every 2 to 4 hours, with repeated measurements 1 hour after any change of dosing rate. Serum glucose should also be monitored.   Antidote Endpoint Ethanol administration may be discontinued if ethylene glycol concentrations can no longer be detected or are less than 20 mg/dL (3.2 mmol/L) 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.[2]   In settings where serum ethylene glycol concentrations cannot be measured, resolution of the osmolar gap may be used as an imperfect surrogate for elimination.   Precautions Hypoglycemia may occur, especially in children.[18] 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 as ethanol may cause agitation or depress mental status and respiration; close monitoring of airway and breathing is required.[17]   Fomepizole While availability is limited by purchase price, fomepizole appears preferable to ethanol, especially in those with altered mental status, patients suffering hepatic disease, pregnant women, those critically ill but lacking confirmation of poisoning, or lack of local availability to measure repeated ethanol concentrations or a facility to monitor the patient closely such as an intensive care unit. Its administration to pediatric patients avoids the disadvantages of ethanol (e.g. inebriation, hypoglycemia).[2]   Indications Fomepizole is indicated if:[1] - Plasma ethylene glycol concentration greater than 62 mg/dL (10 mmol/L), or - History of recent ingestion of a toxic quantity of ethylene glycol with osmolar gap > 25 mosm/kg, 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 > 25 mosm/L Presence of urinary oxalate crystals   Dose and Administration Child and Adult Loading dose[3]   - 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[3]   - 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.   Antidote Endpoint Fomepizole may be discontinued when ethylene glycol plasma concentrations are either undetectable, or below 20 mg/dL (3.2 mmol/L) in patients with a normal pH and resolved signs of systemic toxicity.[3]   Adverse Effects Abdominal pain, skin rash, nausea, headache, dizziness, and drowsiness have been reported following fomepizole use.[3]   Pyridoxine (Vitamin B6) 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.[2]   Dose and Administration 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[19]   Precautions Profound peripheral neuropathy may occur after very large single doses[20] or a series of doses (for example a total of > 2 g/kg pyridoxine over a three day period).[21] The sensory (if not motor) disturbances are potentially irreversible.[22]   Thiamine 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.[2]   Dose and Administration ADULT - Administer 100 mg IV or IM thiamine every six hours - Continue for two days[19]   SIGNS AND SYMPTOMS Symptoms following ethylene glycol ingestion can be divided into three acute stages or phases.[23][24][6][25] The severity of these stages and their progression from one to the other often depends on the amount ingested and other circumstances (e.g. ethanol co-ingestion). Death can occur in any of the acute stages but most commonly the second stage.[19] Ethanol co-ingestion can delay the onset of toxic effects.[26] Low serum pH, decreased base excess, hyperkalemia at admission, seizures, and coma usually indicate a poor prognosis.[27]   Initial symptoms of ethylene glycol intoxication (0.5 to 12 hours after ingestion) are due to the direct toxicity of ethylene glycol. CNS effects predominate and include inebriation (without the alcohol odor on the breath), slurred speech, drowsiness, somnolence, hypotonia, hyporeflexia, ataxia, myoclonic jerks, and gastrointestinal upset. Mild metabolic acidosis may occur. In severe cases, seizures and coma may develop.[28][23][24][29][30][31][32][24][33]   In subsequent cardiopulmonary phases of intoxication (12 to 36 hours after ingestion), accumulation of acidic metabolites of ethylene glycol are responsible for the presenting abnormalities including high-anion gap metabolic acidosis and cardiopulmonary symptoms.[34][23][24][31] The anion and osmolar gaps are usually increased, but may be within normal parameters in some patients.[35][25][31] In significant poisonings, severe metabolic acidosis with compensatory hyperventilation or Kussmaul respirations can develop.[6][36][37] Tachycardia, mild hypertension followed by hypotension, pulmonary edema, and congestive heart failure are all believed to be due to the deposition of calcium oxalate crystals within the vascular tree, myocardium, and the lung parenchyma.[24][38][39]   The renal phase of intoxication, beginning 24 to 48 hours after ingestion, is marked by oliguria, flank pain acute tubular necrosis, renal failure, and occasionally bone marrow suppression.[32][36][28] Hematuria and proteinuria are also possible.[28][40] In severe poisonings, renal failure may appear early and progress to anuria.[32][2] Renal symptoms may last up to 45 days or more.[19] Acute renal failure may prove permanent in a minority of cases.[26] Subacute cranial nerve palsies usually occur within 5 to 20 days and may persist for weeks to months.[6][7][8][9]   Inhalation of ethylene glycol can cause upper respiratory tract irritation. Systemic effects are not expected unless it has been heated or aerosolized.[41]   Eye exposure to vapors or direct contact with the liquid may lead to eye irritation;[42] 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.[43] Skin absorption is limited, and systemic effects are unlikely to develop.[44]   Routes of Exposure Symptoms predominantly occur following ingestion of ethylene glycol. However, toxicity is also possible via intravenous and intramuscular routes.   Onset/Duration of Symptoms There are three acute stages[24][33][35] and one sequelae stage[8][45][46][47][25][6] that may occur following ethylene glycol ingestion. Most deaths are reported in stage II but can occur at any of the stages.[48] The severity of these stages and their progression from one to the other often depends on the amount ingested and other circumstances (e.g. ethanol co-ingestion).   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   Severity of Poisoning 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   CHRONIC EFFECTS General Effects Chronic exposures to ethylene glycol vapor may result in nystagmus, unconsciousness, and lymphocytosis.[49]   REFERENCES [1] McMartin K, Jacobsen D, Hovda KE. Antidotes for poisoning by alcohols that form toxic metabolites. Br J Clin Pharmacol 2016 Mar; 81 (3): 505-15. [2] Barceloux DG, Krenzelok EP, Olson K, Watson W. American Academy of Clinical Toxicology Practice Guidelines on the Treatment of Ethylene Glycol Poisoning. Ad Hoc Committee. J Toxicol Clin Toxicol 1999; 37 (5): 537-60. [3] Antizol Prescribing Information, USA: Paladin Labs (USA) Inc; May 2017; [cited 2018 January 4]. URL: http://www.paladin-labs.com/our_products/Antizol_en.pdf [4] DaRoza R, Henning RJ, Sunshine I, Sutheimer C. Acute ethylene glycol poisoning. Crit Care Med 1984 Nov; 12 (11): 1003-5. [5] Maier W. Cerebral computed tomography of ethylene glycol intoxication. Neuroradiology 1983; 24 (3): 175-7. [6] Spillane L, Roberts JR, Meyer AE. Multiple cranial nerve deficits after ethylene glycol poisoning. Ann Emerg Med 1991 Feb; 20 (2): 208-10. [7] Lewis LD, Smith BW, Mamourian AC. Delayed sequelae after acute overdoses or poisonings: cranial neuropathy related to ethylene glycol ingestion. Clin Pharmacol Ther 1997 Jun; 61 (6): 692-9. [8] Berger JR, Ayyar DR. Neurological complications of ethylene glycol intoxication. Report of a case. Arch Neurol 1981 Nov; 38 (11): 724-6. [9] Reddy NJ, Sudini M, Lewis LD. Delayed neurological sequelae from ethylene glycol, diethylene glycol and methanol poisonings. Clin Toxicol (Phila) 2010 Dec; 48 (10): 967-73. [10] Chen HY, Albertson TE, Olson KR. Treatment of drug-induced seizures. Br J Clin Pharmacol 2016 Mar; 81 (3): 412-9. [11] Wallis WE, Donaldson I, Scott RS, Wilson J. Hypoglycemia masquerading as cerebrovascular disease (hypoglycemic hemiplegia). Ann Neurol 1985 Oct; 18 (4): 510-2. [12] Latt N, Dore G. Thiamine in the treatment of Wernicke encephalopathy in patients with alcohol use disorders. Intern Med J 2014 Sep; 44 (9): 911-5. [13] Brent J, McMartin K, Phillips S, Burkhart KK, Donovan JW, Wells M, Kulig K. Fomepizole for the treatment of ethylene glycol poisoning. Methylpyrazole for Toxic Alcohols Study Group. N Engl J Med 1999 Mar 18; 340 (11): 832-8. [14] Porter WH. Ethylene glycol poisoning: quintessential clinical toxicology; analytical conundrum. Clin Chim Acta 2012 Feb 18; 413 (3-4): 365-77. [15] Wedge MK, Natarajan S, Johanson C, Patel R, Kanji S. The safety of ethanol infusions for the treatment of methanol or ethylene glycol intoxication: an observational study. CJEM 2012 Sep; 14 (5): 283-9. [16] Zakharov S, Navratil T, Salek T, Kurcova I, Pelclova D. Fluctuations in serum ethanol concentration in the treatment of acute methanol poisoning: a prospective study of 21 patients. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2015 Dec; 159 (4): 666-76. [17] Paasma R, Hovda KE, Hassanian-Moghaddam H, Brahmi N, Afshari R, Sandvik L, Jacobsen D. Risk factors related to poor outcome after methanol poisoning and the relation between outcome and antidotes--a multicenter study. Clin Toxicol (Phila) 2012 Nov; 50 (9): 823-31. [18] Leung AK. Ethyl alcohol ingestion in children. A 15-year review. Clin Pediatr (Phila) 1986 Dec; 25 (12): 617-9. [19] Davis DP, Bramwell KJ, Hamilton RS, Williams SR. Ethylene glycol poisoning: case report of a record-high level and a review. J Emerg Med 1997 Sep-Oct; 15 (5): 653-67. [20] Harati Y, Niakan E. Hydrazine toxicity, pyridoxine therapy, and peripheral neuropathy. [Letter] Ann Intern Med 1986 May; 104 (5): 728-9. [21] Albin RL, Albers JW, Greenberg HS, Townsend JB, Lynn RB, Burke JM Jr, Alessi AG. Acute sensory neuropathy-neuronopathy from pyridoxine overdose. Neurology 1987 Nov; 37 (11): 1729-32. [22] Albin RL, Albers JW. Long-term follow-up of pyridoxine-induced acute sensory neuropathy-neuronopathy. Neurology 1990 Aug; 40 (8): 1319. [23] Vale JA, Bluett NH, Widdop B. Ethylene glycol poisoning. Postgrad Med J 1976 Sep; 52 (611): 598-602. [24] BERMAN LB, SCHREINER GE, FEYS J. The nephrotoxic lesion of ethylene glycol. Ann Intern Med 1957 Mar; 46 (3): 611-9. [25] Palmer BF, Eigenbrodt EH, Henrich WL. Cranial nerve deficit: a clue to the diagnosis of ethylene glycol poisoning. Am J Med 1989 Jul; 87 (1): 91-2. [26] Karlson-Stiber C, Persson H. Ethylene glycol poisoning: experiences from an epidemic in Sweden. J Toxicol Clin Toxicol 1992; 30 (4): 565-74. [27] Hylander B, Kjellstrand CM. Prognostic factors and treatment of severe ethylene glycol intoxication. Intensive Care Med 1996 Jun; 22 (6): 546-52. [28] FRIEDMAN EA, GREENBERG JB, MERRILL JP, DAMMIN GJ. Consequences of ethylene glycol poisoning. Report of four cases and review of the literature. Am J Med 1962 Jun; 32 (): 891-902. [29] Hatchett R. A severe and fatal case of ethylene glycol poisoning. Intensive Crit Care Nurs 1993 Sep; 9 (3): 183-90. [30] Eder AF, McGrath CM, Dowdy YG, Tomaszewski JE, Rosenberg FM, Wilson RB, Wolf BA, Shaw LM. Ethylene glycol poisoning: toxicokinetic and analytical factors affecting laboratory diagnosis. Clin Chem 1998 Jan; 44 (1): 168-77. [31] Nagesh IV, Koley KC, Sen S, Mohan S, Sahu S. Ethylene glycol poisoning. Med J Armed Forces India 2015 Jul; 71 (Suppl 1): S36-8. [32] Bobbitt WH, Williams RM, Freed CR. Severe ethylene glycol intoxication with multisystem failure. West J Med 1986 Feb; 144 (2): 225-8. [33] Curtin L, Kraner J, Wine H, Savitt D, Abuelo JG. Complete recovery after massive ethylene glycol ingestion. Arch Intern Med 1992 Jun; 152 (6): 1311-3. [34] Hantson P, Hassoun A, Mahieu P. Ethylene glycol poisoning treated by intravenous 4-methylpyrazole. Intensive Care Med 1998 Jul; 24 (7): 736-9. [35] Huhn KM, Rosenberg FM. Critical clue to ethylene glycol poisoning. CMAJ 1995 Jan 15; 152 (2): 193-5. [36] Parry MF, Wallach R. Ethylene glycol poisoning. Am J Med 1974 Jul; 57 (1): 143-50. [37] Verrilli MR, Deyling CL, Pippenger CE, Van Lente F, Vidt DG, Sivak ED. Fatal ethylene glycol intoxication. Report of a case and review of the literature. Cleve Clin J Med 1987 Jul-Aug; 54 (4): 289-95. [38] Bove KE. Ethylene glycol toxicity. Am J Clin Pathol 1966 Jan; 45 (1): 46-50. [39] Clay KL, Murphy RC. On the metabolic acidosis of ethylene glycol intoxication. Toxicol Appl Pharmacol 1977 Jan; 39 (1): 39-49. [40] Rasic S, Cengic M, Golemac S, Macanovic M. Acute renal insufficiency after poisoning with ethylene glycol. [Letter] Nephron 1999 Jan; 81 (1): 119-20. [41] Wills JH, Coulston F, Harris ES, McChesney EW, Russell JC, Serrone DM. Inhalation of aerosolized ethylene glycol by man. Clin Toxicol 1974; 7 (5): 463-76. [42] McDonald TO, Roberts MD, Borgmann AR. Ocular toxicity of ethylene chlorohydrin and ethylene glycol in rabbit eyes. Toxicol Appl Pharmacol 1972 Jan; 21 (1): 143-50. [43] Dawson TA. Ethylene glycol sensitivity. Contact Dermatitis 1976 Aug; 2 (4): 233. [44] Sun JD, Frantz SW & Beskitt JL. In vitro skin penetration of ethylene glycol using excised skin from mice and humans. J Toxicol-Cut & Ocular Toxicol 1995; 14(4):273-286. [45] Delany C, Jay WM. Papilledema and abducens nerve palsy following ethylene glycol ingestion. Semin Ophthalmol 2004 Sep-Dec; 19 (3-4): 72-4. [46] Fellman DM. Facial diplegia following ethylene glycol ingestion. [Letter] Arch Neurol 1982 Nov; 39 (11): 739-40. [47] Mallya KB, Mendis T, Guberman A. Bilateral facial paralysis following ethylene glycol ingestion. Can J Neurol Sci 1986 Nov; 13 (4): 340-1. [48] Guggenheim MA, Couch JR, Weinberg W. Motor dysfunction as a permanent complication of methanol ingestion. Presentation of a case with a beneficial response to levodopa treatment. Arch Neurol 1971 Jun; 24 (6): 550-4. [49] TRIOSI FM. Chronic intoxication by ethylene glycol vapour. Br J Ind Med 1950 Apr; 7 (2): 65-9. Do Not Archive. This document is current on day of issue, NZ: 3.Oct.2022

Disclaimer

All information contained on this database is as accurate and up-to-date as our resources allow. Since the University of Otago, the New Zealand National Poisons Centre and Intergen cannot anticipate or control the conditions under which this information may be used, each user should view the information in the specific context of the intended application.

The University of Otago, the New Zealand National Poisons Centre and Intergen will not be responsible for damages of any nature resulting from use or reliance upon this information.

© National Poisons Centre, New Zealand. Portions © Intergen.

If you would like further information about TOXINZ, or wish to make comment, please contact us on +64 3 479 7248 or email us at TOXINZ@otago.ac.nz.

THIS SITE WILL NOT SUPPORT THE USE OF INTERNET EXPLORER AFTER 1 AUGUST 2022.   If you are using Internet Explorer, please consider changing to another web browser.