Blame it on the A A A A A Alcohol

February 19, 2019

Isopropyl, methyl, and ethyl alcohol are the three main alcohols in existence, and guess what? They are all toxic!

 

Isopropyl alcohol is well known to healthcare providers as it is the main ingredient in hand sanitizers and screen cleaners.

 

Methyl alcohol is commonly used in window washer fluid, fuels, paint thinner’s and in the manufacture of explosives!

 

Ethyl is everyone’s favorite and is what you down at 0730 following a horrible shift as families look at you in utter disgust at the pancake house. Its also used as industrial solvents and even fuel and can be just as toxic as the other two if consumed faster than the liver can process it!

 

All of these alcohols are extremely common, which means, poisonings, either accidental or purposeful are also common.

 

In medicine we will most often see methanol and ethylene glycol poisonings. These alcohols are both commonly used in automotive applications as de-icing agents. Ethylene glycol is the main ingredient in anti-freeze and radiator coolants and because it is naturally sweet tasting, leads to many child and pet poisonings.

The danger in these alcohols are how they are metabolized by the body. When ingested, they will of course cause intoxication symptoms, much like alcoholic beverages, but even when this subsides the toxic effects are still at work. The liver enzyme, alcohol dehydrogenase will begin to breakdown the alcohols into formic acid and formaldehyde if methanol was ingested, or  glycolaldehyde, glyoxylic acid and finally to oxalic acid if ethylene glycol was ingested. These metabolites are extremely toxic to the body and will eventually kill days later due to multi-organ system failure.

 

So how do we treat these poisonings? Well surprisingly Ethanol is one of the most effective antidotes and is still used to treat alcohol poisonings around the world. In developed countries, a relatively new medication (1997), fomepizole is first used if available, but costs $1,000 a vial. Pharmaceutical grade ethanol is markedly cheaper and usually given intravenously as a 5 or 10% solution in 5% dextrose, but it is also sometimes given orally in the form of a strong spirit like vodka, whiskey or gin. Both ethanol and fomepizole work the same way by competitively blocking the formation of the toxic metabolites in toxic by having a higher affinity for the enzyme Alcohol Dehydrogenase. Because the toxic alcohols are not able to degrade into the more toxic metabolites, they are eventually excreted in the urine.

 

 'The goal in therapy is to maintain the poisoned patient at a serum ethanol concentration of 100-200 mg/dL. A 10% ethanol solution should be utilized for IV administration, or a 20%-40% ethanol solution (strong spirit diluted with water or juice) can be administered orally or through a nasogastric tube. Due to its erratic absorption (and consequently, difficulty to maintain goal ethanol serum concentrations), oral ethanol therapy is ONLY warranted in situations when neither fomepizole nor IV ethanol are available (1)'. If no quick access to a hospital or vet exists, it is a good idea to drink some liquor to prevent the toxic degradation cascades. 

 

Ethanol dosing is as follows:

 

Oral or Nasogastirc:

  • Loading dose = 1.8 ml/kg of ~40% ethanol, or 3 x 40ml shots of vodka in a 70 Kg adult. (No need to load if already under the influence!

  • Maintenance = 0.2 – 0.4 ml/kg/hour of  ~40% ethanol, or 40ml shot each hour.

Intravenous:

  • Loading dose = 8 ml/kg of 10% ethanol

  • Maintenance = 1-2 ml/kg/hour of 10% ethanol

  • Depending on your institution the pharmacist will have to make this up otherwise is is made by adding 100ml of 100% ethanol to 900ml of 5% dextrose.

 

 

If you are practicing medicine in North America, then most likely Fomepizole will be available and is dosed as follows:

 

Intravenous:

 

  • Loading dose = 15 mg/kg in 100ml of 0.9% saline or 5% dextrose IV over 30 minutes.

  • Maintenance dose = 10 mg/kg in 100ml of 0.9% saline or 5% dextrose IV over 30 minutes every 12 hours for 48 hours.

  • If given for >48 hours you will need to increase the dose to 15 mg/kg to compensate for induction of metabolism.

  • If the patient undergoes dialysis, fomepizole should be given every 4 hours or as a continuous infusion at 1 mg/kg/hour for the entire duration of the hemodialysis

 

 

Obviously supportive treatment, fluids and in extreme cases, dialysis is needed to reduce levels quickly and prevent severe CNS depression.

 

 

 

 

 

Sources:

  • (1)Toxicology Library Life in the FastLane | Antidotes | Ethanol as an antidote

    by Dr Mike Cadogan, Last updated November 26, 2015

  • Mingzohn Ellen Tsay, PharmD Clinical Toxicology Fellow Maryland Poison Center University of Maryland, School of Pharmacy

  • Barceloux DG, Krenzelok EK, Olson K et al. American Academy of Clinical Toxicology Practice Guidelines on the Treatment of Ethylene Glycol Poisoning. Journal of Toxicology – Clinical Toxicology 1999; 37:537-560.

  • Brent J, McMartin K, Phillips SP et al.  Fomepizole for the treatment of ethylene glycol poisoning.  New England Journal of Medicine 1999; 340:832-838.

  • Brent J, McMartin K, Phillips SP et al.  Fomepizole for the treatment of methanol poisoning.  New England Journal of Medicine 2001; 344:424-429.

  • Brent J. Fomepizole for ethylene glycol and methanol poisoning. New England Journal of Medicine 2009; 360:2216-2223.

  • Lepik KJ, Levy AR, Sobolev BG et al.  Adverse drug events associated with the antidotes for methanol and ethylene glycol poisoning: a comparison of ethanol and fomepizole. Annals of Emergency Medicine 2009; 53:439-450.

 

 

 

 

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