Toxic Alcohol Ingestion

Review of: Patil N, Becker MWL, Ganetsky M (2010). Toxic Alcohols: Not Always A Clear-Cut Diagnosis. Emergency Medicine Practice, 2010;12 (11).

What’s covered in the review?

The article begins with a clinical scenario and then moves rapidly into an in-depth discussion of the relevant aetiology, pathophysiology and clinical features of toxic alcohol poisoning, focusing on the three most common toxic alcohol ingestions: methanol, ethylene glycol and isopropanol. This is followed by detailed sections on diagnosis, treatment and disposition including evidence-based treatment algorithms for toxic alcohol ingestion (these are gold!) and a step-by-step approach to calculating the osmolar gap, anion gap and estimating toxic alcohol concentrations. The review concludes with a discussion of toxic alcohol poisoning in special circumstances (paediatric patients and pregnancy), recent controversies/new developments, some common pitfalls in risk management and finally a CME quiz to assess your learning.

It is a huge review, so I have chosen to focus on the following topics:

  • Aetiology, pathophysiology and clinical features
  • Diagnosis and investigations
  • Treatment
  • Disposition

Here are some of the highlights…

Aetiology, Pathophysiology and Clinical Features

Methanol

  • Methanol is commonly found in windshield-wiper fluid and de-icing products, and may also be found in gas-line antifreeze, paint removers, shoe dyes and embalming fluid.
  • Methanol is metabolised by alcohol dehydrogenase (ADH) to formaldehyde, which is further metabolised by aldehyde dehydrogenase (ALDH) to formic acid.
  • Formic acid is the main toxic metabolite responsible for the retinal, ophthalmic and neural toxicity seen with methanol ingestion.
  • Ocular effects include blurry vision, reduced visual acuity, photophobia and the classic “snowstorm” vision. Permanent blindness may occur due to optic nerve atrophy.
  • Reported neurological effects include Parkinsonism, transverse myelitis and basal ganglia haemorrhages, as well as inebriation from the parent compound.
  • High anion gap metabolic acidosis (HAGMA) is produced due to generation of formic acid and increased production of lactic acid.

Ethylene Glycol

  • Ethylene glycol is typically found in radiator antifreeze, as well as degreasing agents, foam stabilizers and metal cleaners.
  • Ethylene glycol is metabolised by ADH to glycoaldehyde, then by ALDH to glycolic acid, which is further metabolised to glycoxylic acid and finally oxalic acid.
  • The metabolites of ethylene glycol are responsible for the toxic effects, which include neurological, cardiopulmonary and renal toxicity.
  • Neurological effects include coma, seizures, meningism, muscle spasms, external ocular paralysis and delayed onset (5-20 days) of cranial nerve deficits.
  • Cardiopulmonary effects include tachycardia and hyperventilation (due to acidosis), ARDS and heart failure.
  • Oxalic acid combines with serum calcium to form calcium oxalate, which leads to hypocalcaemia and QTc prolongation, with risk of ventricular arrhythmias.
  • Renal toxicity is produced when calcium oxalate crystals precipitate in the renal tubules, causing flank pain, oliguria and acute renal failure.
  • HAGMA is produced due to generation of glycolic, glycoxylic and oxalic acids and increased production of lactic acid.

Isopropanol (Isopropyl Alcohol)

  • Isopropanol is the most common toxic alcohol exposure in the United States; it is found in rubbing alcohol, hand sanitizer gels and other antiseptic preparations.
  • It is metabolised by ADH to acetone, without production of an anion gap acidosis.
  • Toxicity is mainly limited to gastrointestinal effects (haemorrhagic gastritis) and neurological effects (profound intoxication, cerebellar signs, coma).
  • Isopropanol is the only toxic alcohol that causes ketosis without acidosis.

Diagnosis and investigations

Making the diagnosis

  • Serum toxic alcohol concentrations, while ultimately necessary to confirm the diagnosis and guide ongoing management, are unlikely to be available within the first few hours of a suspected toxic alcohol ingestion, therefore diagnosis is based on the history, clinical features and surrogate biochemical markers such as blood gases, osmolar gap and anion gap.
  • Recommended baseline investigations include:
    • Urea, electrolytes and creatinine
    • Serum osmolarity
    • Ethanol level
    • Arterial or venous blood gases
  • The osmolar gap and the anion gap are useful in diagnosing toxic alcohol ingestion.
    • An osmolar gap of > 10-25 mOsm in the setting of high anion gap metabolic acidosis (anion gap > 12) is suggestive of toxic alcohol ingestion
  • The osmolar gap and anion gap change over time:
    • Initially there is a raised osmolar gap due to the presence of the parent compound (the toxic alcohol itself)
    • Later on, the osmolar gap decreases and the anion gap increases as the toxic alcohol is metabolised to form ketones/aldehydes and organic acids.

Other investigations

  • A spuriously elevated lactate may occur with ethylene glycol toxicity due to the structural similarity between glycolic acid and lactate.
  • Falsely elevated creatinine can be seen in isopropanol ingestion, as acetone interferes with colorimetric creatinine assays (urea remains unchanged).
  • Urine tests: The use of Wood’s lamp fluorescence to detect sodium fluoroscein (found in antifreeze) or microscopy of the urine to demonstrate urinary calcium oxalate crystals is an unreliable way to diagnose ethylene glycol poisoning.
  • Brain imaging (CT/MRI) in methanol intoxication may demonstrate bilateral putamen necrosis, basal ganglia haemorrhages and necrosis of the caudate nucleus with atrophy of the optic chiasma and lesions in the occipital cortex and subcortical white matter.

Treatment

GI decontamination

  • Gastrointestinal decontamination is not routinely recommended.

Antidotal Therapy

  • Antidotal therapy with fomepizole or ethanol will inhibit ADH and prevent the formation of toxic metabolites in methanol and ethylene glycol poisoning.
  • Fomepizole (15mg/kg loading dose then 10mg/kg Q12H) is preferred over ethanol due to its easier dosing regime and better side-effect profile (sadly not currently available in Australia).
  • Dosing regimes for fomepizole and ethanol are discussed in the article.

The indications to commence antidotal therapy are:

  • Serum concentration of methanol / ethylene glycol > 20 mg/dL
  • Confirmed or suspected methanol / ethylene glycol ingestion and two of the following:
  • Osmolar gap > 10 mOsm
  • Arterial pH < 7.3
  • Bicarbonate < 20 mmol/L
  • Presence of urinary oxalate crystals

Sodium Bicarbonate

  • Metabolic acidosis with an arterial pH < 7.3 should be treated with a sodium bicarbonate infusion to keep the pH between 7.35 and 7.45.

Haemodialysis

The indications for haemodialysis in methanol / ethylene glycol poisoning are:

  • Metabolic acidosis (pH < 7.25-7.30)
  • Visual abnormalities
  • Renal failure
  • Electrolyte abnormalities not responsive to conventional treatment
  • Haemodynamic instability refractory to ICU treatment
  • Serum concentration > 50mg/dL
  • Haemodialysis may not be needed if fomepizole is started early in ethylene glycol poisoning and there is no evidence of acidaemia or renal dysfunction.
  • Methanol is eliminated too slowly for antidotal treatment alone to be effective.

Cofactors

Administration of cofactors will promote the conversion of intermediate metabolites into non-toxic metabolites:

  • In ethylene glycol toxicity, pyridoxine (100mg IV Q6H) and thiamine (100mg IV Q6H) increase the metabolism of glycolic and glycoxlic acid to the less toxic metabolites glycine and alpha-hydroxy-beta-ketoadipate.
  • In methanol toxicity, folic acid (50mg IV Q4-6H) or folinic acid (1-2mg/kg IV Q4-6H) increases the breakdown of formic acid to carbon dioxide and water.

Isopropanol poisoning

  • In comparison to other toxic alcohols, isopropanol intoxication is usually managed supportively.
  • The main adverse effects are CNS depression (which may be profound) and gastrointestinal upset.
  • Proton pump inhibitors may be useful for haemorrhagic gastritis.
  • Intubation may be required.
  • Haemodialysis may increase the rate of elimination of both isopropanol and acetone, and should be considered for patients with deteriorating GCS or haemodynamic instability.

Disposition

  • Patients can be toxicologically cleared if they have a methanol or ethylene glycol concentration < 20mg/dL with no evidence of end-organ dysfunction or haemodynamic instability.
  • Patients with acidaemia or signs of end-organ dysfunction (renal failure, visual loss) require admission to ICU.
  • Where toxic alcohol concentrations are not readily available, patients may be cleared if they have:
    • low suspicion of ethylene glycol or methanol ingestion
    • normal anion and osmolar gaps
    • normal blood pH (7.35-7.45)
    • an improvement in their clinical picture after several hours observation
  • Transfer to a tertiary care centre is required if haemodialysis and fomepizole is not readily available.

References and Links

LITFL


CCC 700 6

Critical Care

Compendium

Emergency Physician in Prehospital and Retrieval Medicine in Sydney, Australia. He has a passion for ECG interpretation and medical education | ECG Library |

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