Antifreeze Poisoning

Antifreeze poisoning presents a significant challenge to medical professionals due to its potentially fatal consequences.

What is antifreeze?

Antifreeze is a liquid used in vehicle radiators to prevent freezing in cold weather. Ethylene glycol is the most common type of antifreeze. Ethylene glycol is also present in numerous solvents, polishes, paints, and car wash fluids. It can be ingested accidentally or for inebriation or attempted suicide.

Ethylene glycol itself is relatively non-toxic, and its initial central nervous system (CNS) effects resemble those of ethanol. However, the metabolism of ethylene glycol by alcohol dehydrogenase results in the formation of acid metabolites, including oxalic acid and glycolic acid. These acid metabolites are responsible for much of the toxicity of ethylene glycol. Glycolic acid is cleared by the kidney and is mainly responsible for the marked acidosis seen in severe cases.

Presentation

The clinical presentation of ethylene glycol poisoning occurs in three distinct stages:

Stage 1 (30 minutes to 12 hours after ingestion) – features include:

Patients often appear intoxicated with alcohol (but no ethanol on breath)
Nausea, vomiting, and haematemesis
Convulsions (often focal)
Ataxia
Ophthalmoplegia
Papilloedema
Hypotonia and hyporeflexia
Myoclonic jerks and tetanic contractions may occur
Coma can occur
Metabolic acidosis develops.

Stage 2 (12-24 hours after ingestion) – features include:

Increased respiratory rate
Sinus tachycardia
Hypertension
Pulmonary oedema
Congestive cardiac failure develops.

Stage 3 (24-72 hours after ingestion) – features include:

Flank pain and renal angle tenderness
Acute tubular necrosis develops
Hypocalcaemia (as a consequence of calcium complexing with oxalate), calcium oxalate monohydrate crystalluria
Hyperkalaemia and hypomagnesaemia develop.

Investigations

Helpful investigations include:

Arterial blood gas – usually shows a high anion gap metabolic acidosis, which results from the accumulation of glycolic acid.

Urea & electrolytes – monitor for hyperkalemia, hypomagnesaemia and Hypocalcaemia.

Serum osmolality – patients typically develop a high osmolar gap (>10 mOsmol/L) as they absorb the glycol over the first few hours. Subsequently, as the glycol is metabolised to acids, the osmolar gap will fall while the patient’s anion gap will climb, and acidosis will worsen. A severely poisoned patient can present early with a normal anion gap and a normal pH or hydrogen ion concentration; however, their osmolar gap will be high.

Ethylene glycol levels – detectable levels confirm exposure, but is rarely helpful during the acute presentation as the results can take a significant time to come back.

Urinalysis – to look for calcium oxalate crystals, a hallmark of ethylene glycol

Imaging studies – consider imaging studies such as a head CT scan to evaluate for cerebral oedema in patients with severe toxicity.

Management

Emergency treatment – as with all critically ill patients, use the Airway, Breathing, Circulation, Disability, Exposure (ABCDE) approach to assess and treat the patient. Contact a poison control centre or medical toxicologist for guidance on management and antidote administration.

Ethanol and fomepizole are the two main antidotes for ethylene glycol poisoning. They work by preventing the formation of the toxic metabolites of ethylene glycol.

Ethanol:

Ethanol acts by competing with ethylene glycol for alcohol dehydrogenase
Ethanol has approximately a 100-times greater affinity for alcohol dehydrogenase
Ethanol is given as a 10% solution in 5% glucose as a 40% solution
The loading dose is 7.5 mL/kg, followed by an infusion of 1-2 mL/kg/hour.

Fomepizole:

Fomepizole is a potent inhibitor of alcohol dehydrogenase
Fomepizole is preferred due to its efficacy and safety profile
The loading dose is 15 mg/kg IV diluted to a final volume of 250 mL 0.9% sodium chloride or 5% glucose over 30 minutes
This is followed by maintenance doses of 10 mg/kg IV diluted to a final volume of 250 mL in 0.9% sodium chloride or 5% glucose over 30 minutes every 12 hours (starting at 12 hours after the loading dose is given) for a maximum of 4 doses.

Severe cases require haemodialysis or haemofiltration. The indications for this are: