Ethylene glycol poisoning

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How the diagnosis is reached

Two gaps opening at once is the finding that matters. A high anion gap acidosis alone has a long differential and a raised osmolar gap alone means little, but together they say a toxic alcohol was swallowed and is partway through being metabolised: the parent alcohol is osmotically active and widens the osmolar gap early, while its acid metabolites widen the anion gap as metabolism proceeds. Appearing drunk with no smell of alcohol fits, and the empty container beside him supplies the rest. Negative ketones, a normal glucose, undetectable ethanol and salicylate, and only a modest lactate close off the other common causes of an acidosis this severe. What distinguishes ethylene glycol from methanol at the bedside is the target organ: methanol is metabolised to formic acid, which injures the optic nerve and produces the characteristic 'snowstorm' visual blurring, whereas this patient has entirely normal vision. Ethylene glycol is instead metabolised through glycolic acid to oxalic acid, which chelates calcium: producing the hypocalcemia, the prolonged QT interval, and calcium oxalate crystals that precipitate in the renal tubules and cause the acute kidney injury seen here. Treatment is directed at blocking metabolism rather than removing the parent compound: fomepizole inhibits alcohol dehydrogenase with far greater affinity than ethanol and without the sedation of an ethanol infusion, preventing formation of the toxic metabolites. Hemodialysis is added when there is severe acidosis, renal failure, or a high measured level, since it clears both the parent alcohol and the acid metabolites. Bicarbonate only buys time and does nothing about ongoing metabolite production, while thiamine and pyridoxine are given as cofactors to shunt what is already circulating away from oxalate.

Key clinical clues

• Apparent intoxication with ataxia and nystagmus but no smell of alcohol
• Severe high anion gap metabolic acidosis with a simultaneously raised osmolar gap
• Negative ketones, undetectable ethanol and salicylate, only mildly raised lactate
• Normal vision throughout, argues against methanol and its optic nerve injury
• Hypocalcemia, prolonged QT and birefringent calcium oxalate crystals with acute kidney injury

The case in full

1

Presenting complaint

Patient history

A 51-year-old man is found on his garage floor, confused and unsteady, last seen well eight hours earlier. He seems intoxicated (slurred speech, ataxia, nystagmus) but there is no smell of alcohol. An empty container lies beside him.

2

Observations and examination

Vital signs

He is breathing deeply and rapidly with a regular, laboured pattern. Pupils are equal and reactive, and he reports no visual disturbance when asked; he says he can see the clock on the wall clearly. There are no focal neurological deficits and no signs of head injury.

Measurements

Parameter	Value	Reference
Glasgow Coma Scale	12Ref 15	15
Respiratory rate	34, deep /minRef 12–20	12–20
Heart rate	112 bpmRef 60–100	60–100
Blood pressure	106/64 mmHg	–
Temperature	36.2 °CRef 36.1–37.5	36.1–37.5
Capillary glucose	104 mg/dLRef 70–110	70–110

3

Arterial blood gas

Laboratory results

An arterial sample is taken immediately given his respiratory pattern.

Measurements

Parameter	Value	Reference
pH	7.09Ref 7.35–7.45	7.35–7.45
Bicarbonate	6 mmol/LRef 22–28	22–28
pCO₂	18 mmHgRef 35–45	35–45
pO₂	108 mmHgRef 80–100	80–100
Base excess	−22 mmol/LRef −2 to +2	−2 to +2

4

Chemistry, gaps and toxicology screen

Laboratory results

Electrolytes are sent alongside a measured serum osmolality and a broad toxicology screen.

Measurements

Parameter	Value	Reference
Sodium	140 mmol/LRef 135–145	135–145
Chloride	102 mmol/LRef 98–107	98–107
Anion gap	32 mmol/LRef 8–12	8–12
Measured osmolality	342 mOsm/kgRef 275–295	275–295
Osmolar gap	44 mOsm/kgRef <10	<10
Lactate	2.8 mmol/LRef 0.5–2.2	0.5–2.2
Serum ketones	NegativeRef Negative	Negative
Ethanol / salicylate	UndetectableRef Undetectable	Undetectable

5

Renal function and urinalysis

Laboratory results

Renal function is checked and a fresh urine sample is examined under the microscope.

Measurements

Parameter	Value	Reference
Creatinine	2.1 mg/dLRef 0.7–1.3	0.7–1.3
Corrected calcium	7.4 mg/dLRef 8.5–10.2	8.5–10.2
Urine crystals	Present, see imageRef None	None
Urine blood	1+Ref Negative	Negative
Urine output (2 h)	40 mLRef >100	>100

6

Clinical course

Clinical course

An ECG shows a prolonged QTc of 496 ms. Two ampoules of intravenous sodium bicarbonate are given and the arterial gas is repeated hourly. He continues to deny any visual symptoms, and formal bedside acuity testing is normal in both eyes.