Toxic Alcohols

Toxic alcohols are relatively benign in themselves but produce highly toxic metabolites that cause neurotoxicity as well as other organ-specific toxicities. Toxic alcohols include:

Methanol
- Found in de-icers, windshield wiper fluid, antifreeze, paint strippers, embalming fluid
- Metabolised to formaldehyde and then to formic acid
  HAGMA and ocular toxicity in addition to neurotoxicity.
Ethylene glycol
- Found in antifreeze, degreasers, and metal cleaners
- Metabolised in a series of steps to oxalic acid
  HAGMA, cardiopulmonary toxicity, and nephrotoxicity in addition to neurotoxicity.
Isopropanol
- Found in rubbing alcohol, hand sanitiser, and other antiseptics
- Metabolised to acetone and so does not produce a HAGMA
  Gastrointestinal toxicity, and ketosis without acidosis in addition to neurotoxicity.

Methanol is metabolised into formic acid, ethylene glycol is metabolised into glycolic acid.

Epidemiology and Risk Factors

Pathophysiology

Aetiology

Clinical Features

Features of Toxic Alcohol Ingestion
System	Methanol	Ethylene Glycol	Isopropanol
Cardiopulmonary		↑ HR ARDS Heart failure
Neurological	Ocular: Blurry vision ↓ Acuity Photophobia “Snowstorm” vision Permanent blindness Retinal toxicity. Other: Parkinsonism Transverse myelitis Basal ganglia haemorrhages	Coma Seizures Meningism CN deficit Often delayed by 5-20 days.	Confusion → Coma Cerebellar signs
Renal	HAGMA Formic acid Lactic acid ↑ OG	↓ Calcium Chelated by oxalic acid. AKI Precipitation of calcium oxalate crystals in renal tubule. HAGMA Glycolic acid Oxalic acid Lactic acid ↑ OG	Normal OG
GIT			Haemorrhagic gastritis

Diagnostic Approach and DDx

Investigations

Bedside:

ABG
- HAGMA
- AG

Laboratory:

The osmolar gap and anion gap change over time. Initially the OG is ↑ due to the toxic alcohols, but as the alcohol is metabolised to acids the OG ↓ and the AG ↑.

Blood
- UEC
- Osmolar gap
- Serum alcohol concentrations
  Toxic levels usually only available after commencing treatment.

If you can quantitatively measure the serum alcohol, you can also determine the contribution of that alcohol to the osmolar gap. 1mmol/L of:

Ethanol is 4.6 mg/dL
Methanol is 3.2 mg/dL
Ethylene glycol is 6.2 mg/dL
Isopropanol is 6.0 mg/dL

Methanol has the lowest molecular weight and therefore greatest ↑ in OG per unit volume.

Degree of inebriation produced is proportional to molecular weight.

Imaging:

CTB
- Methanol toxicity
  - Putamen necrosis
  - Basal ganglia haemorrhages
  - Optic chiasmal atrophy
  - Caudate nuclear necrosis

Other:

Management

Treat acidosis
Early RRT
For methanol and ethylene glycol:
- Give antidote
- Give cofactors

Resuscitation:

Specific therapy:

Pharmacological
- Antidote
  Inhibit conversion to toxic acids in methanol and ethylene glycol poisoning.
  - Agents:
    - Fomepizole 15mg/kg IV load, then 10mg/kg Q12H
    - Ethanol 0.6g/kg PO, targeting a BAC of 0.1-0.15%
      - Will contribute to CNS toxicity
  - Indicated for:
    - Osmolar gap >10mOsm
    - pH <7.3
    - Urinary oxalate crystals
- Sodium bicarbonate
  - For metabolic acidosis
- Metabolic cofactors
  ↑ Clearance of toxic metabolites to non-toxic metabolites.
  - Ethylene glycol toxicity
    - Pyridoxine 100mg IV Q6H and thiamine 100mg IV Q6H
  - Methanol toxicity
    - Folic acid 50mg IV Q4-6H
    - Folinic acid 1-2mg/kg IV Q4-6H
Procedural
- RRT
  - pH <7.25
  - Visual abnormalities
  - Renal failure
  - Refractory electrolyte derangements
  - Refractory haemodynamic instability
Physical

Fomepizole is not available in Australia.

Activated charcoal has no role as absorption of alcohols is too rapid.

Supportive care:

G
- PPI
- Thiamine
  Enhances metabolism of ethylene glycol.

Disposition:

ICU if:
- Acidaemia
- End-organ dysfunction
Toxicologically cleared if:
- Toxic alcohol concentration <20mg/dL
- No organ dysfunction
- Haemodynamic stability
- Normal pH

Preventative:

Marginal and Ineffective Therapies

Activated charcoal

Anaesthetic Considerations

Complications

Prognosis

Key Studies

References

Bersten, A. D., & Handy, J. M. (2018). Oh’s Intensive Care Manual. Elsevier Gezondheidszorg.
Mahdi AS, McBride AJ. Intravenous Injection of Alcohol By Drug Injectors: Report of Three Cases. Alcohol and Alcoholism. 1999;34(6):918-919. doi:10.1093/alcalc/34.6.918