Toxic Alcohols
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Introduction
Toxic alcohols are those other than ethanol. The most commonly encountered are methanol, ethelene glycol, and isopropanol.
Methanol is commonly seen in winshield washing fluid, gas line antifreeze, model airplane fuel, solid cooking fuel, photocopying fluid, perfumes, bingo markers, and moonshine. Over 50% of exposures involve winshield washer fluid.
Ethylene glycol is primarily used in engine coolant antifreeze.
Isopropanol is primarily available as rubbing alcohol, and can be found in many homes. It is cheap and accessible, making it the most common toxic alcohol ingestion reported in the US.
Structure and Metabolism
Alcohols are rapidly absorbed and distributed to total body water. They are eliminated primarily through the action of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), each involving the reduction of NAD+ to NADH.
Methanol is metabolized to formaldehyde, then formic acid, while ethylene glycol form glycoaldehyde, glycolic acid, and finally oxalic acid. This rate is approximately 10mg/dL/h.
Signs, Symptoms, and Diagnosis of Alcohol Toxicity
All alcohols cause inebriation in a dose-dependent manner, although these effects can be blunted in chronic alcoholics. Toxic alcohols may work in the same way as ethanol, stimulating GABA receptors and inhibiting NMDA glutamate receptors.
Metabolic acidosis follows toxic alcohol poisoning and the production of acid metabolites, which cannot be eliminated. Isopropanol is the exception, being broken down into acetone and causing ketosis rather than acidosis.
End-organ damage depends on specific alcohol.
- methanol
- ethylene glycol
- lab testing
Methanol
Formic acid is a mitochondrial toxin, working in a similar way as cyanide to obstruct oxidative phosphorylation. Ocular toxicity is prominent, causes visual effects including blurry vision, loss of colour vision, 'snowfield' vision, or total blindness. Both pancreatitis and renal failure have also been reported.
Ethylene Glycol
Ethylene glycol's effects are most important in the kidney. Oxalic acid precipitates out in combination with calcium in the tubules, leading to acute renal failure. Acute tubular necrosis can also result from direct toxicity.
- 0-12h: inebriation, n/v, coma, seizures
- 12-24h: tachycardia, pulmonary edema, hypocalcemia of ionized calcium (Ca2+ binding by oxalate)
- >24h: acute tubular necrosis, renal failure
Lab Testing
Alcohol concentrations are measured by gas chromatography, a technique not every hospital can perform. Samples should be kept airtight due to alcohol's volatility. Methanol vapours can be tested in the breath, but this test is not yet medically available. Metabolite concentrations become more important following ingestion, and rely on enzymatic assays. However, alcohol level interpretation is controversial.
Because of problems with testing and interpretation, surrogate markers are often used. Anion gap and osmolar gap have an inverse relationship.
Anion gap acidosis follows metabolite accumulation. Lactic acidosis and ketoacidosis should be excluded unless the history strongly suggests ingestion. Acidosis can take up to 24 hours to develop, especially in the presence of ethanol.
Osmolar gap is an early marker of toxic alcohols. It is not a specific test, but a gap >50 is strongly suggestive of toxic alcohols.
Ethanol levels are important to calculate osmolarity.
Lactate can be elevated following methanol and ethylene glycol ingestion. Formate's inhibition of oxidative phosphorylation can lead to anearobic metabolism, while ethylene glycol can cause a false-positive reading.
Urine oxalate crystals can be seen by microscopy, but this test is neither sensitive nor specific.
Treatments
Management of the ABCs is always the priority, and alcohols' capacity to cause respiratory depression and coma often necessitaties intubation. Hypotension and vomiting, together with alcohol-induced vasodilation, can require fluid recusitation.
Treatment endpoints include a resolution of symptoms normal osmolarity and pH. Levels suggesting treatment are:
- EG: >3 mmol/L antidote; 8 mmol/L may need dialysis
- MeOH: >6mmol/L antidote; >15 mmol/L may need dialysis
If ingestion is likely, initiate antidote immediately; do not wait for labs!
The most important treatment is blockade of ADH and prevention of toxic metabolite production. This can be done to allow preparation for further testing and treatment, or as definitive treatment.
Ethanol outcompetes toxic alcohols for ADH, and a 10% solution can be given as an IV drip to maintain a serum concentration of 100 mg/dL. Complications can include inebriation and, more rarely, hypotension, respiratory depression, hypoglycemia, flushing, hyponatremia, pancreatitis, and gastritis, necessitating ICU admission. PO ethenaol can also be given on a general ward.
It can also be difficult to dose and maintain levels.
Fomepizole is a newer option for ADH blockade. Being much stronger, it can be dosed every 12 hours. It also has fewer adverse effects and does not require ICU admission. However, it is much more expensive, although nursing and lab savings likely balance out.
Hemodialysis is the definitive treatment, clearing alcohol and their metabolites while correcting acid-base status. ADH blockage reduces the need for HD, though end-organ toxicity,severe acidosis, or renal failure are strong inducations for this invasive procedure.
Detoxification by diverting the metabolic pathway also appears useful, using folate for methanol and thiamine, B6 for ethylene glycol.
Rapid absorption and lack of binding make activated charcoal of limited value.
Resources and References
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