Toxic Alcohol Poisoning

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Chapter 80 Toxic Alcohol Poisoning

Aaron B. Skolnik, MD , Susan R. Wilcox, MD

1 What are the compounds commonly referred to as the toxic alcohols?

Typically, the term toxic alcohols includes isopropanol, methanol, and ethylene glycol. Ethanol, of course, may also be toxic.

2 What household or commercial products commonly contain toxic alcohols?

image Isopropanol (or isopropyl alcohol) is most commonly sold as rubbing alcohol, in a 70% solution. It can also be found in antifreezes, glass cleaners, jewelry cleaner, stain removers, deicers, household disinfectants, and hand sanitizers.

image Methanol can be found in windshield washer fluid, antifreeze, copy machine fluid, canned fuel (Sterno), and some solvents. Perhaps most famously, methanol is a frequent contaminant in illicitly distilled alcoholic beverages—hence the term moonshine blindness, originating from methanol retinal toxicity.

image Ethylene glycol is often the main ingredient in automobile antifreeze and is sometimes used as a solvent.

3 What are potentially lethal doses of isopropanol, methanol, and ethylene glycol?

image Isopropanol ingestion of 150 to 250 mL can be lethal because of central nervous system (CNS) and myocardial depression.

image The reported lethal dose of methanol is 1.2 mL/kg; however, as little as 30 mL (6 teaspoons) may cause permanent vision impairment.

image The lethal dose of ethylene glycol in untreated patients varies, but 100 mL is a common conservative approximation.

4 What are the mechanisms of toxicity for isopropanol?

Isopropanol is estimated to be twice as intoxicating by volume as ethanol. It is a CNS depressant and may cause peripheral vasodilation, myocardial depression, and subsequent shock at high doses. It is metabolized by alcohol dehydrogenase (ADH) to acetone, which appears to contribute to further CNS depression. Isopropanol is extremely irritating to the gastric mucosa and classically causes severe gastritis, which may be hemorrhagic.

5 What are the mechanisms of toxicity for methanol?

Methanol is first metabolized by ADH to formaldehyde, which is then rapidly converted to formic acid by aldehyde dehydrogenase. Formic acid inhibits mitochondrial electron transport, leading to acidemia and production of reactive species. It also depletes glutathione, which is an endogenous antioxidant. The combination of these effects leaves cells that are under significant oxidative stress such as those in the retina and putamen, exposed to oxidant cytotoxicity.

6 What are the mechanisms of toxicity for ethylene glycol?

Ethylene glycol is metabolized to toxic glycolic acid, glyoxylic acid, oxalic acid, and several other minor metabolites. Oxalic acid precipitates with calcium into calcium oxalate crystals. In addition to causing hypocalcemia, deposition of oxalate in the renal tubules and other tissues causes cell death. The resulting metabolic acidosis, renal failure, pulmonary edema, and cerebral injury contribute to mortality in these patients.

7 What are the signs and symptoms of toxic alcohol poisoning?

CNS depression is the common element in toxic alcohol poisoning, ranging from typically mild in the case of methanol to profound intoxication in the case of isopropanol or ethylene glycol poisoning. Patients who ingest any of these substances may ultimately have coma, shock, and death. Each of the toxic alcohols has key clinical features that distinguish one from the other. Isopropanol-intoxicated patients typically have prominent gastrointestinal symptoms and may present with severe abdominal pain, vomiting, or hematemesis. Because acetone is the metabolite of this alcohol, ketosis without acidosis develops, and patients have fruity breath odor.

Retinal toxicity is the hallmark of methanol poisoning and may develop many hours after ingestion. Visual complaints may vary, with complete vision loss, afferent pupillary defects, and optic disc hyperemia on funduscopic examination being late findings.

Ethylene glycol toxicity usually begins with CNS depression. Hypocalcemia may cause tetany or myoclonus. Untreated, patients may progress to seizure, pulmonary edema, and ultimately renal failure, cerebral edema, and death.

8 What is the osmolal gap, and how is it used in diagnosing toxic alcohol poisoning?

The osmolal gap (OG) is the difference between the calculated serum osmolality (oc) and the measured serum osmolality (om). This value approximates the quantity of unmeasured osmoles in the serum. To calculate the serum osmolality:

image

The osmolal gap:

image

An osmolal gap greater than 20 mOsm/L should always raise suspicion for ingestion of exogenous osmoles. All of the toxic alcohols discussed in this chapter increase the serum osmolality, and serum levels of these compounds may be approximated by calculating the osmolal gap and using conversion factors based on their molecular weight. As the parent compounds are metabolized, the osmolal gap closes. In the case of methanol and ethylene glycol poisoning, the acid products of metabolism accumulate, which causes the anion gap to rise as the osmolal gap decreases. In isopropanol poisoning, the osmolal gap simply closes, as acetone is not a strong acid.

9 What is the value of obtaining serum levels for the toxic alcohols?

Generally, the value of serum levels is in confirming the diagnosis of toxic alcohol poisoning. However, serum levels are not readily available at most hospitals and often result hours to days after the patient’s initial evaluation. There are also no absolute values that determine when to start or end therapy for toxic alcohol–poisoned patients. When in doubt, basing treatment decisions on the clinical status of the patient is the right way to proceed, as in most of toxicology.

10 How does fomepizole work, and when should it be given?

Fomepizole (4-methylpyrazole) is a competitive ADH inhibitor. It is used to block metabolism of ethylene glycol and methanol to their toxic metabolites. It should be given when a known or suspected toxic ethylene glycol or methanol ingestion has occurred and the patient has metabolic acidosis and elevated osmolar gap. Because the drug is given every 12 hours, empiric treatment with a single dose allows sufficient time to evaluate the patient, perhaps obtain access and begin hemodialysis, and/or obtain serum levels of the toxins. Many sources recommend giving fomepizole on the basis of a serum ethylene glycol or methanol concentration greater than 20 mg/dL. The loading dose of fomepizole is 15 mg/kg infused intravenously over 30 minutes. If dialysis is initiated, fomepizole will also be dialyzed from the serum, and the dosing interval is decreased to every 4 hours.

11 Can ethanol be used as an antidote to toxic alcohols?

Ethanol can be used, much like fomepizole, as a competitive substrate for ADH to allow time for clearance or extracorporeal removal of methanol or ethylene glycol. Ethanol was widely used in this fashion until the introduction of fomepizole. However, because ethanol retains its intoxicating properties when used in this fashion, the risk of CNS depression and adverse events is higher than with fomepizole use. Fomepizole has been recommended as the first-line ADH-inhibiting agent in toxic alcohol poisoning, and ethanol use should be reserved for when fomepizole is unavailable or the patient is severely allergic.

12 When is hemodialysis indicated for toxic alcohol poisoning?

Patients poisoned with toxic alcohols may meet conventional indications for hemodialysis, such as severe metabolic acidosis or uremia, and this treatment should not be withheld. Those poisoned with isopropanol rarely require dialysis, though it has been suggested in patients who have hypotension or extremely high serum levels.

For patients who have ingested methanol, any vision disturbance is an indication for dialysis. Other methanol-poisoned patients with severe metabolic acidosis unresponsive to medical therapy or methanol levels greater than 50 mg/dL should also undergo dialysis.

Ethylene glycol–poisoned patients should undergo dialysis on the basis of the severity of their metabolic acidosis and their renal function. If oliguric or anuric renal failure develops, hemodialysis must be initiated as ethylene glycol elimination in the presence of fomepizole depends exclusively on renal clearance.

13 What are some common errors in the management of patients poisoned by toxic alcohols?

The most common error is delay to diagnosis. This disease remains relatively uncommon and may not be considered until late in the clinical course. Also, as the ingestant is being metabolized, the osmolal gap will be closing, while the anion gap is opening. Therefore poisoned patients may be evaluated at a time when osmolal and anion gaps are normal or near normal. To avoid this mistake, patients with suspected toxic alcohol poisoning should undergo serial laboratory testing before dismissing the diagnosis from the differential. Delay to inhibiting ADH is another common mistake. When methanol or ethylene glycol ingestion is being considered, giving one empiric dose of fomepizole may prevent further harm to the patient for hours while the diagnosis is being formally made. Clinicians must also remember that both ethanol and fomepizole are removed via hemodialysis, and these should be replaced to maintain ADH inhibition. Finally, patients poisoned with methanol should undergo formal ophthalmologic evaluation initially and after treatment.

Key Points Toxic Alcohol Poisoningimage

1. Toxic alcohols are commonly found in numerous household products, with methanol commonly being a component of windshield washer fluid and ethylene glycol being a main ingredient in antifreeze.

2. Ingestion of toxic alcohols frequently starts with CNS depression, often associated with myocardial depression. Isopropanol may lead to hemorrhagic gastritis, methanol to visual disturbances, and ethylene glycol to renal failure, as well as eventual coma and death.

3. Toxic alcohol ingestions present with an elevated osmolal gap that closes with metabolism but develops an increasing anion gap in the case of methanol and ethylene glycol poisoning.

4. Fomepizole, a competitive ADH inhibitor, should be administered when toxic alcohol poisoning is suspected.

5. Patients with toxic alcohol poisonings and any vision disturbance, severe metabolic acidosis, or renal failure should undergo urgent hemodialysis.

Bibliography

1 Brent J. Fomepizole for the treatment of pediatric ethylene and diethylene glycol, butoxyethanol, and methanol poisonings. Clin Toxicol (Phila). 2010;48:401–406.

2 Brent J., McMartin K., Phillips S., et al. Methylpyrazole for Toxic Alcohols Study Group. Fomepizole for the treatment of ethylene glycol poisoning. N Engl J Med. 1999;340:832–838.

3 Glaser D.S. Utility of the serum osmol gap in the diagnosis of methanol or ethylene glycol ingestion. Ann Emerg Med. 1996;27:343–346.

4 Jammalamadaka D., Raissi S. Ethylene glycol, methanol and isopropyl alcohol intoxication. Am J Med Sci. 2010;339:276–281.

5 Kraut J.A., Kurtz I. Toxic alcohol ingestions: clinical features, diagnosis, and management. Clin J Am Soc Nephrol. 2008;3:208–225.

6 Mégarbane B., Borron S.W., Baud F.J. Current recommendations for treatment of severe toxic alcohol poisonings. Intensive Care Med. 2005;31:189–195.

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