Ethylene Glycol is lethal when >1 ml/kg is ingested therefore any deliberate ingestion need prompt intervention. Commonly found in radiator coolants, antifreeze (concentrations>20%), de-icing solutions, solvents and brake fluids. Unfortunately these products can taste sweet making them appealing to children.
The CNS effects are similar to ethanol but it is the metabolites that make this compound particularly dangerous (glycolic acid and calcium oxalate) Glycolic acid causes a severe anion gap metabolic acidosis and is nephrotoxic. Calcium oxalate deposits in tissues including the brain, muscles, myocardium and the renal tubules (acute renal failure).
- Rapid absortion
- Peak concentration at 1-2 hours
- Volume of distribution is low (0.6 L/kg) therefore dialysis is recommended in certain cases.
- Ethylene glycol is converted to glycoaldehyde by alcohol dehydrogenase, then to glycolic acid by aldehyde dehydrogenase. See Alcohol pathways. During these steps NAD is reduced to NADH which decreases the conversion of lactate to pyruvate, thus a lactic acidosis can be seen.
- Ethylene glycol has an elimination half-life of 3-9 hours but if alcohol dehydrogenase is interrupted either by fomepizole or ethanol (level 11-22 mmol/L or 50-100 mg/dL) thereby inhibiting the conversion of ethylene glycol to glycoaldehyde the elimination half life is increased to 14-17 hours (via the kidney).
- CNS depression: If there is any doubt over the patients ability to protect their own airway or you believe they are an aspiration risk they will require intubation and ventilation.
- Patients usually compensate the metabolic acidosis with a high respiratory rate. During intubation and ventilation it is paramount not to exacerbate the metabolic acidosis (risk of death) therefore pre-intubation a bolus of sodium bicarbonate 1-2 mmol/kg followed by hyperventilation and further boluses of sodium bicarbonate while awaiting haemodialysis is best practice.
- Seizures: IV benzodiazepines.
- Check the patient is not in a dysrhythmia
- Can be managed with benzodiazepines (varying doses in the textbooks, easy method is 0.1mg/kg IV for lorazepam (max 4mg) / midazolam (max 10mg) / diazepam (max 10mg). Or…
- Lorazepam 0.1mg/kg max 4mg
- Diazepam 0.15mg/kg max 10mg
- Midazolam 0.2mg/kg max 10mg
- Cardiovascular instability: 20ml/kg bolus of crystalloid, correct hyperkalaemia, hypoglycaemia, hypomagnesaemia. Only correct hypocalcaemia if there is a refractory seizure or prolonged QT.
- Any ingestion > 1ml/kg is potentially lethal
- A small taste or a lick do not require hospital evaluation unless symptoms develop.
- An unintentional ingestion of less than a mouthful is usually benign, all intention ingestions should be treated as lethal.
- Concomitant alcohol ingestion (although potentially protective) complicates the risk assessment.
- Dermal or inhalation exposure does not lead to intoxication
- Clinical features 1-2 hours:
- Similar to ethanol – euphoria, nystagmus, drowsiness, nausea and vomiting.
- Clinical features 4-12 hours:
- Dyspnoea, tachypnoea, tachycardia, hypertension, decreased conscious level, progressive shock, coma, seizures and death. Flank pain and oliguria indicate acute renal failure.
- Clinical features 5-20 days later:
- Cranial neuropathies II, V, VII, VIII, IX, X and XII)
- General supportive measures (i.e. IV fluids only if dehydrated), monitor for urinary retention.
- If intubated see FASTHUGSINBED for further supportive care.
- Electrolytes: correct hyperkalaemia, hypoglycaemia, hypomagnesaemia. Only correct hypocalcaemia if there is a refractory seizure or prolonged QT.
- Screening: 12 lead ECG, BSL, Paracetamol level
- EUC including chloride, serum lactate, serum osmolality, arterial blood gases and calcium, magnesium and phosphate levels.
- Elevate osmolar gap, anion gap and lactate are surrogate markers for intoxication. A normal osmolar gap does not exclude intoxication.
- Anion gap acidosis with elevated lactate (+/- elevated osmolar gap) associated with hypocalcaemia and rising creatinine is pathognomonic of ethylene glycol intoxication.
- A raised lactate needs to be interpreted with caution as some assays can not differentiate between lactate and glycolate.
- Venous bicarbonate can be used instead of an arterial blood gas in the asymptomatic patient.
- Breath or serum ethanol level – as part of the risk assessment, ethanol delays the clinical effects of ethylene glycol and also to calculate how much ethanol will be required as a temporary antidote.
- Serum ethylene glycol level is available (sometimes not back in a clinical useful timeframe)
- Urine microscopy: The presence of oxalate crystals in the urine is pathognomonic of ethylene glycol intoxication (absence does not exclude the diagnosis).
Activated charcoal does not bind to alcohol
- Haemodialysis is the definitive treatment for ethylene glycol reducing its half life to as much as 2.5 hours depending on flow rates.
- Lactate free dialyses with added bicarbonate may assist correction of acidaemia
- Indications for haemodialysis:
- History of a large ethylene glycol ingestion with an osmolar gap >10
- Academia with a pH <7.3
- Acute renal failure
- Ethylene glycol level > 8 mmol/L (50mg/dL)
- End points for haemodialysis:
- Correction of acidosis
- Osmolar gap <10
- Ethylene glycol level < 3.2 mmol/L (20mg/dL)
- Acid base status and electrolytes are repeated every four hours for 12 hours following cessation of haemodialysis to confirm wether further treatment is required.
- Children who remain well after an unintentional ingestion at 4 hours and who have a normal venous bicarbonate level (>20 mEq/L) maybe discharged home.
- Adults who remain well after an unintentional ingestion at 4 hours and who have a normal venous bicarbonate level (>20 mEq/L) and an undetectable ethanol level maybe discharged home.
- All symptomatic and deliberate ingestions need hospital admission for further evaluation and assessment. Preferably in a centre that can provide haemodialysis.
- If renal failure is established, dialysis maybe required for a number of weeks but renal function usually returns to normal.
- Patients with intoxication require follow-up to observe for any cranial neuropathies.
References and Additional Resources:
- Barceloux DG, Krenzelok EP, Olsen K et al. Ad Hoc Committee on the Treatment Guidelines for Ethylene Glycol Poisoning on behalf of the American Academy of Clinical Toxicology. American Academy of Clinical Toxicology. Practise guidelines on the treatment of ethylene glycol poisoning. Clinical Toxicology 1999; 37(5):537-560
- Caravati EM, Erdman AR, Christianson G et al. Ethylene glycol exposure: an evidence based consensus guideline for out-of-hospital management. Clinical Toxicology 2005; 43:327-345
- Jollier HA, Dart RC, Bogdan GM et al. Can the diagnosis of ethylene glycol (EG) toxicity be made without serum EG levels and osmolality values. Clinical Toxicology 2000; 38(5):539-540
- Murray L et al. Toxicology Handbook 3rd Edition. Elsevier Australia 2015. ISBN 9780729542241