Case of the Month #2

Kyle Gibson

A 40 year old male was found unresponsive in the garden. Initial GCS was 9 (E3V2M4) which deteriorated to 7 (E2V2M3) on arrival to the emergency department. ECG and CT brain were both normal. An ABG demonstrated a high anion gap metabolic acidosis (pH 7.0) with an increased osmolal gap (>10mOsm/kg). In view of unexplained decreased level of consciousness along with high anion gap acidosis and high osmolal gap, ethylene glycol toxicity was considered to be the most likely diagnosis.

Q1 – How does ethylene glycol ingestion present?

There are different clinical signs depending on the quantity and timing of ingestion. This can be categorised into three separate phases (according to TOXBASE):

Phase 1 (30 minutes-12 hours since ingestion):

  • Similar to being intoxicated with ethanol 
  • Nausea, vomiting, haematemesis 
  • Decreased consciousness 
  • Nystgmus, ataxia, ophthalmoplegia 
  • Papilloedema 
  • Seizures 
  • Metabolic acidosis 

Phase 2 (12-24 hours since ingestion):

  • Tachypnoea 
  • Sinus tachycardia 
  • Hypertension 
  • Congestive cardiac failure with pulmonary oedema 

Phase 3 (24-72 hours since ingestion):

  • Flank pain/renal angle tenderness 
  • Renal failure 
  • Hypocalcaemia (because calcium binds with oxalate to form crystals) 
  • Hyperkalaemia 
  • Hypomagnesaemia 

Investigation findings

  • Ethylene glycol level (difficult to obtain due to delays in sending to reference lab) 
  • High anion gap metabolic acidosis due to glycolic acid accumulation 
  • High osmolal gap 
  • The blood gas may be normal very early in the presentation. Blood lactate may be elevated because of multi-organ dysfunction, but it may also be reported as falsely high because of cross-reactivity between lactate and ethylene glycol metabolites in the blood gas analyser. 
  • Oxalate crystals in urine 

Q2 – What is osmolal gap and what causes increased osmolal gap?

Osmolal gap = measured serum osmolality – calculated osmolality

Calculated osmolality = (2 x [Na]) + [Glucose] + [Urea] (all in mmol/L)

A normal osmolal gap is < 10mOsm/kg

When the osmolal gap is increased (>10 mOsm/kg), causes to consider include:

  • Alcohols e.g. ethanol, methanol, ethylene glycol 
  • Sugars e.g. mannitol 
  • Lipids e.g. hypertriglyceridaemia 
  • Proteins e.g. Waldenstrom macroglobulinaemia 

Q3 -What is the management of ethylene glycol ingestion?

  • Consult TOXBASE for detailed management 
  • ABCDE assessment 
  • Consider gastric aspiration/lavage if within 1 hour of life-threatening dose and the airway is protected 
  • Antidotes: fomepizole or ethanol if there is a delay in sourcing fomepizole (these minimise further metabolism of ethylene glycol): TOXBASE recommends administration if suspected >10g ingestion within the last 12 hours or if osmolal gap >10mOsm/kg or high anion gap metabolic acidosis with no other likely cause; continue the antidotes until plasma ethylene glycol concentration <50 mg/L (<0.8 mmol/L) 
  • Metabolic acidosis: consider sodium bicarbonate if persisting acidosis despite correction of any hypoxia and optimal fluid balance 
  • Renal replacement therapy should be considered if there is severe metabolic acidosis, renal failure, worsening clinical picture despite optimal supportive management or severe electrolyte disturbance; haemodialysis is much more effective than haemofiltration for the clearance of ethylene glycol and its metabolites 
  • Other supportive management including magnesium replacement if low, however not replacing calcium if hypocalcaemia unless QT interval > 500ms or there are persistent convulsions (because of the risk of worsening calcium oxalate crystal formation when calcium is administered) 

Key take home messages from the case

  • Ethylene glycol ingestion can present with (and lead to) multi-organ dysfunction 
  • The anion gap and osmolal gap should both be assessed because they change over time; checking one in isolation may provide false clinical reassurance 
  • Fomepizole is the preferred antidote to minimise metabolism (and therefore toxicity) and haemodialysis may be required to facilitate clearance (of ethylene glycol and its metabolites) from the body 
  • Residual renal failure secondary to nephropathy (oxalate crystals) is common