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Toxicology

Treating Toxic Alcohols Like It’s 1999 (…again)

Sean Boley, MD
Julie Schaefer, MD
Jessica Jones

The management of a toxic alcohol exposure is a common clinical question for the emergency physician. Either as a known ingestion or in the context of an unexplained metabolic acidosis, medical providers of all kinds should be aggressive in the management of these dangerous toxins.  While all toxic alcohols can be inebriating to an extent, their sequelae is variable – from relatively benign (e.g. isopropanol, propylene glycol) to more severe (e.g. methanol and ethylene glycol).  Specifically, exposure to methanol and ethylene glycol can cause severe and life-threatening end-organ dysfunction.  Methanol – commonly known as wood alcohol and found in a multitude of household chemicals such as colognes and windshield wiper fluid – is metabolized via alcohol dehydrogenase (ADH) to formaldehyde and further by aldehyde dehydrogenase (ALDH) to formate. The latter toxic metabolite is responsible for the metabolic acidosis as well as the visual and neurological impairment that aggressive treatment aims to avoid.  Ethylene glycol – a sweet liquid most frequently used as engine coolant – is metabolized via ADH ultimately to glycolate, glyoxylic acid, and oxylate.  These metabolites not only create a metabolic acidosis but also cause renal injury (via accumulation of calcium oxalate crystals) and hypocalcemia1,2.

The initial treatment of a toxic alcohol exposure is aimed at inhibiting the alcohol dehydrogenase enzyme – thereby limiting the generation of the aforementioned toxic metabolites1,2. Historically, this was achieved through the use of ethanol, which has a 67 and 15.5 times greater affinity for ADH than ethylene glycol and methanol, respectively. The affinity of fomepizole for ADH is approximately 10 times that of ethanol3.  There have been no studies directly comparing the safety, efficacy, or cost-effectiveness of fomepizole versus ethanol in the treatment of toxic alcohol ingestion.  A recent prospective observational study performed during a cluster of methanol ingestions in the Czech Republic during the years of 2012-2014 has suggested similar efficacy (mortality and ICU stay) and rate of adverse effects4.  Despite this evidence, fomepizole remains the most commonly administered antidote2.  

Unfortunately, there is currently a national shortage of fomepizole. The FDA has cited several factors contributing to the shortage, including one manufacturer’s recall of fomepizole in March 2015. Other factors include shortages in active ingredients and increased demands for the product. One manufacturer has estimated a tentative release of additional doses in October/November 20155. In the context of this shortage, it is imperative that emergency providers feel comfortable with ethanol dosing regimens. The table below describes ethanol dosage to achieve a serum ethanol concentration of 100-150 mg/dL, which is the minimum ethanol concentration that has been shown to adequately achieve inhibition of ADH in most cases3. It is important to consider that there is significant variability in metabolism of ethanol; therefore this represents a guideline for starting doses. Serum ethanol concentrations must be monitored and doses titrated appropriately. Although some online calculators are available to determine initial ethanol dosing providers should be familiar with this calculation6,7

Another consideration is the fluid burden that may be required to treat larger patients who are chronic drinkers. For example, a chronic drinker weighing 150 kilograms would require an IV bolus of 1.5 liters and a maintenance infusion of 300 mL/hr of 10% ethanol.  In these cases, oral administration of 40% ethanol or central IV infusion of more concentrated ethanol may be prudent.

Given similar efficacies of ethanol and fomepizole, coupled with the recent fomepizole shortage, ethanol is an acceptable antidote for toxic alcohols. Fomepizole has historically been the antidote of choice due to its ease of administration. However, ethanol infusion for the treatment of toxic alcohol ingestions is both manageable, effective, and relatively inexpensive. Therefore, it remains a vital treatment regimen with which emergency physicians should maintain familiarity.

Toxic Alcohol Overdose Treatment with IV Ethanol3,6:

10% ethanol in D5W dosing:

                                                                                             Weight (kg)
  5 7 10 20 30 40 50 70 100 125 150
Loading Dose:
(mL/1st hr)*
40-50 56-70 80-100 160-200 240-300 320-400 400-500 560-700 800-1000 1000-1250 1200-1500
Nondrinker
(mL/hr)
4 6 8 17 25 33 42 56 83 104 125
Average drinker (mL/hr) - - - - - 56 70 105 140 175 210
Chronic Drinker (mL/hr) - - - - - 80 100 150 200 250 300

*If a pediatric non-drinking patient, do not exceed 200mL for loading dose.

Dosing derived as follows:
Loading Dose: 8-10mL/kg, given over 1st hour
Maintenance Infusion
        Nondrinker: 0.8mL/kg/hr
        Average drinker: 1.4 mL/kg/hr
        Chronic drinker: 2.0 mL/kg/hr

Citations:

  1. Wiener, Sage W. "Toxic Alcohols." Goldfrank's Toxicologic Emergencies, 10e. Eds. Robert S. Hoffman, et al. New York, NY: McGraw-Hill, 2015.
  2. Beatty, Lorri, et al. "A systematic review of ethanol and fomepizole use in toxic alcohol ingestions." Emergency medicine international 2013 (2013).
  3. Howland, Mary Ann. "Antidotes in Depth." Goldfrank's Toxicologic Emergencies, 10e. Eds. Robert S. Hoffman, et al. New York, NY: McGraw-Hill, 2015.
  4. Zakharov, Sergey, et al. "Fomepizole versus ethanol in the treatment of acute methanol poisoning: Comparison of clinical effectiveness in a mass poisoning outbreak." Clinical Toxicology ahead-of-print (2015): 1-10.
  5. U.S. Food and Drug Administration. FDA Drug Shortages. Accessed July 18, 2015.  http://www.accessdata.fda.gov/scripts/drugshortages/dsp_ActiveIngredientDetails.cfm?AI=Fomepizole%20Injection&st=c&tab=tabs-1
  6. Phelps SJ, Thompson AJ, and Hagemann TM. Ethanol. Pediatric Injectable Drugs (The Teddy Bear Book). 10th ed. Bethesda, MD: ASHP, 2013. ProQuest ebrary. Web. 17 July 2015.
  7. http://www.micromedexsolutions.com/

 

 
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