Basics
Description
- Toxic alcohols discussed here include ethylene glycol, isopropyl alcohol, and methanol.
- Ethylene glycol is a sweet, odorless, colorless liquid, commonly used as automobile antifreeze solution as well as for other uses.
- Isopropyl alcohol is used as rubbing alcohol, as well as in liquid soaps and for other uses.
- Methanol is wood alcohol used in windshield wiper fluid, Sterno, and other products.
General Prevention
Poison proofing homes and giving parents poison prevention advice is the most effective way to prevent toxic alcohol exposures in children.
Risk Factors
Toxicity via dermal absorption can occur in infants or young children with permeable skin.
Pathophysiology
All toxic alcohols have direct effects as intoxicants. More importantly, ethylene glycol and methanol are metabolized to toxic by-products that result in severe morbidity or mortality.
- All toxic alcohols may result in altered mental status or coma similar to ethanol. CNS depression may result in respiratory depression requiring ventilatory support.
- Ethylene glycol is metabolized to oxalic acid and glycolic acid, ultimately forming calcium oxalate crystals, which may precipitate in the renal tubules and cause renal failure.
- Methanol is metabolized to formaldehyde and then formic acid, which may damage the retina and cause visual impairment or blindness.
- The metabolism of ethylene glycol and methanol to their toxic metabolites may be prevented by competitively inhibiting alcohol dehydrogenase with either fomepizole or ethanol.
- Therapy to inhibit alcohol dehydrogenase is used for ethylene glycol and methanol exposure.
- Isopropyl alcohol is metabolized to acetone.
- Inhalational absorption of isopropyl alcohol may rarely occur.
Diagnosis
- Signs and symptoms:
- Inebriation may occur after exposure.
- Isopropyl alcohol may cause severe gastrointestinal irritation or hemorrhage.
History
- Typically, a history of exposure is available.
- In absence of this history, and osmolal gap or anion gap with metabolic acidemia is suggestive of toxic alcohol exposure.
Physical Exam
- Tachycardia and hypotension are the most frequent vital sign abnormalities that occur.
- Hyperpnea or tachypnea often accompanies metabolic acidemia.
- Cardiovascular effects may include hypocalcemic QT prolongation and myocarditis.
- Neurologic abnormalities may include ataxia, CNS depression, coma, dysarthria, focal neurologic changes, hyporeflexia, hypotonia, nystagmus, or seizure.
- Gastrointestinal effects may include gastritis emesis, hematemesis, pain, or pancreatitis.
- Ophthalmologic findings may include blurred vision, diplopia, hazy vision, or nystagmus.
- Constricted visual fields, hyperemic optic disk with retinal edema, and transient or permanent blindness may result from methanol exposure.
- Hematuria, renal insufficiency, or renal failure may occur, particularly from ethylene glycol.
- Fluid and electrolyte abnormalities from ethylene glycol or methanol may include hypokalemia, hypocalcemia, hypomagnesemia, and elevated anion gap metabolic acidosis.
- Acetonemia and ketonemia may result from isopropyl alcohol ingestion.
- Hypoglycemia may be associated with toxic alcohol exposure as well as with ethanol therapy.
- Respiratory irritation from isopropyl alcohol inhalation or respiratory depression from any toxic alcohol ingestion may occur.
Diagnostic Tests & Interpretation
- Check serum electrolytes, BUN, creatinine, and glucose.
- As metabolism occurs, an increased anion gap metabolic acidemia results with ethylene glycol or methanol toxicity.
- Absence of this gap early after ingestion is expected and does not rule out ingestion.
- Elevated anion gap metabolic acidemia supports the diagnosis of ethylene glycol or methanol exposure.
- Acidemia is an indication for use of fomepizole or ethanol as well as potential indication for hemodialysis.
- Fomepizole treatment should not be delayed waiting to determine if acidemia will develop.
- Anion gap metabolic acidemia does not result from isopropyl alcohol poisoning.
- Blood gas analysis should be performed to assess for degree of metabolic acidemia in any patient with low serum bicarbonate.
- Initial use of venous blood gas to screen for abnormality is acceptable.
- Repeated blood gas analysis should occur every 1 " 2 hours if acidemia results.
- Serum level of ethylene glycol, isopropyl alcohol, or methanol should be obtained.
- An ethylene glycol or methanol level greater than 20 mg/dL is an indication for fomepizole or ethanol infusion.
- An ethylene glycol or methanol level greater than 50 mg/dL is an indication for hemodialysis.
- Serum ionized calcium is useful in managing ethylene glycol toxicity.
- Urinalysis with microscopic examination is recommended with ethylene glycol exposure.
- Presence of oxalate crystals corroborates poisoning.
- Absence of crystals does not exclude the possibility of ethylene glycol toxicity.
- Fluorescence of urine is unreliable and is neither sensitive nor specific for exposure.
- A spurious rise in creatinine may occur.
- Proteinuria and hematuria may be present with ethylene glycol or isopropyl alcohol exposure.
- Serum osmolality or osmolarity may be useful in predicting the level of ethylene glycol, isopropyl alcohol, or methanol if rapid laboratory quantification cannot be performed.
- Serum ethanol level should simultaneously be performed to determine quantity of ethanol contribution to osmolal gap.
- An elevated osmolal gap can be used to rule in, but not exclude, toxic alcohol exposure.
- An elevated osmolal gap indicates the presence of unmeasured solute such as ethanol, ethylene glycol, isopropyl alcohol, or methanol.
- Absence of an osmolal gap does not exclude the possibility of toxic alcohol exposure.
- Osmolal gap is calculated as follows: Osmolal gap = (calculated serum osmolality ’ measured osmolality).
- The measured osmolality is determined by the laboratory.
- The calculated osmolality is determined as follows: 2 [Na (mEq/L)] + [BUN (mg/dL)/2.8] + [glucose (mg/dL)/18].
- Normal osmolal gap is less than 15 mEq/L.
- Any patient with increased osmolal gap should be presumed to have toxic alcohol exposure.
- Additional tests may include ECG to detect cardiac conduction disturbance or serum acetaminophen and salicylate levels in patients with intentional ingestion or with presumed intent of self-harm.
- Tests necessary to rule out differential diagnoses should be obtained when appropriate.
Differential Diagnosis
Drugs and disorders that may alter lab values include acetone, diethylene glycol, ethanol, iron, isoniazid, lactic acidemia, mannitol, methanol, propylene glycol, renal failure, salicylates, toluene, and various forms of ketoacidosis.
Imaging
Neuroimaging to rule out intracranial pathology may rarely be indicated.
Treatment
Initial Stabilization
- Prompt evaluation of airway, breathing, circulation, serum glucose, and ECG (A,B,C,D,E) is critical.
- Consultation with a medical toxicologist or poison center is recommended.
General Measures
Supportive care is the most important general principle. The illness is managed with intent of close monitoring and addressing issues as they arise.
- For ingestion less than 1 hour previously, an attempt to aspirate gastric contents with a nasogastric tube is reasonable.
- Treatment for ethylene glycol or methanol exposure should focus on acid-base correction and preventing organ damage.
- Hemodialysis should be considered for the following:
- Any patient with severe metabolic acidemia from ethylene glycol or methanol
- Any patient with evidence of end organ damage, particularly if metabolic acidemia is present
- Any patient with profound hypotension or life-threatening symptoms resulting from isopropyl alcohol toxicity
Nursing
- Protect inebriated patients from falls.
- For the duration of inebriation or therapy with ethanol, vigilance for detection of hypoglycemia should be maintained.
IV Fluids
- IV fluid to maintain adequate blood pressure may be necessary.
- Maintenance IV fluid may be required in patients who are unable to take PO.
- IV fluid may be necessary to aid in prevention of calcium oxalate crystals in the urine.
- IV fluid may be helpful to prevent renal injury if rhabdomyolysis occurs.
- 8.4% sodium bicarbonate may be used in resistant acidosis and should be given via a central line if available.
Medication
- For ethylene glycol or methanol poisoning (but NOT isopropyl alcohol), either fomepizole or ethanol are used to competitively inhibit alcohol dehydrogenase.
- Fomepizole is highly preferable to ethanol for this purpose, as ethanol has many severe, adverse side effects and fomepizole does not.
- Indications for fomepizole or ethanol include the following:
- Serum level of ethylene glycol or methanol greater than 20 mg/dL
- Metabolic acidemia with any quantity of detectable ethylene glycol or methanol
- Use of fomepizole or ethanol will prolong the half-life of ethylene glycol and methanol.
- Without therapy, the ethylene glycol half-life is 3 " 4 hours, and methanol 14 " 20 hours.
- With fomepizole or ethanol, the ethylene glycol half-life is 12 hours, and methanol 30 " 50 hours.
- Some clinicians consider a necessary duration of therapy longer than several days to be an indication for hemodialysis. Successful use of prolonged therapy with fomepizole to avoid hemodialysis has been reported.
- Fomepizole is contraindicated in patients with documented allergic reaction to the drug.
- Ethanol should be used with extreme caution in Asians, as aldehyde dehydrogenase deficiency may result in severe illness and hypotension.
- The loading dose of fomepizole is dose of 15 mg/kg IV.
- Initial maintenance dosing is 10 mg/kg q12h for 4 doses. Because fomepizole induces its own metabolism, the subsequent maintenance dose is increased to 15 mg/kg q12h thereafter.
- Each dose is diluted into normal saline or D5W (<25 mg/mL) and infused over 30 minutes.
- Each time after hemodialysis is performed, a loading dose must be readministered.
- Ethanol is administered as a 10% solution in D5W. This dilution requirement often results in a very large quantity of free water administration.
- The ethanol loading dose is 10 mL/kg (max 200 mL) of a 10% solution infused IV over 1 hour.
- A maintenance dose of 1 " 2 mL/kg of 10% ethanol is then given IV.
- Target blood ethanol level is 100 " 125 mg/dL.
- Patients receiving ethanol should have the ethanol level and serum glucose checked hourly.
- Oral ethanol may be used when IV is not available or if the patient is willing and capable of drinking. This is possibly feasible in adolescents.
- Adjunctive treatment with folate or leucovorin for methanol, and thiamine and pyridoxine for ethylene glycol may be given:
- This continues until methanol or ethylene glycol levels are undetectable.
- Folate or tetrahydrofolate (leucovorin) may hasten the elimination of formic acid resulting from methanol exposure.
- Leucovorin 1 " 2 mg/kg may be administered IV every 6 hours.
- Pyridoxine and thiamine hasten elimination of ethylene glycol metabolites.
Follow-up Recommendations
Disposition
- Asymptomatic patients with undetectable ethylene glycol or methanol levels and no metabolic acidemia may be safely discharged.
- Most exposures for which ethylene glycol or methanol levels cannot be obtained should be followed for 12 " 24 hours to detect development of metabolic acidemia or other symptoms.
- From the hospital, patients with ethylene glycol or methanol level less than 20 mg/dL, no anion gap, no metabolic acidemia, and stable renal function and vision may be discharged.
- Patients with isopropyl alcohol exposure who develop no symptoms or have only mild symptoms may be discharged within 4 " 6 hours.
Admission Criteria
- Any patient requiring therapy with fomepizole, ethanol, or hemodialysis
- Any patient with renal impairment, visual impairment, or other organ effect
- Any patient for whom consequential ingestion is suspected and ethylene glycol or methanol levels are unavailable
Discharge Criteria
- Inpatients who have received therapy with fomepizole, ethanol, or hemodialysis must be medically and metabolically stable for at least 12 " 24 hours prior to discharge.
- Patients with ethylene glycol or methanol exposure who have not developed symptoms or metabolic derangement may be discharged within 24 hours.
Ongoing Care
Prognosis
- For ethylene glycol and methanol exposure, prognosis depends on the degree of toxin metabolism, as well as adequacy of care.
- Speed and adequacy of therapy with fomepizole or ethanol, as well as prompt hemodialysis when indicated is critical.
- For isopropyl alcohol, prognosis depends on severity of intoxication and adequacy of supportive care.
Complications
Blindness, coma, hepatic injury, hypertension or hypotension, myocarditis, temporary or permanent neurologic injury, pancreatitis, renal failure, respiratory depression, rhabdomyolysis, seizure may occur as a result of toxic alcohol exposure.
Patient Monitoring
Symptomatic exposure to ethylene glycol or methanol may warrant intensive care monitoring.
Additional Reading
- Brent J. Fomepizole for the treatment of pediatric ethylene and diethylene glycol, butoxyethanol, and methanol poisonings. Clin Toxicol. 2010;48(5):401 " 406. [View Abstract]
- Howland MA. Antidotes in depth: ethanol. In: Goldfrank LR, Flomenbaum NE, Lewin NA, et al, eds. Goldfrank 's Toxicologic Emergencies. 8th ed. Stamford, CT: Appleton & Lange; 2006.
- Weiner S. Toxic alcohols. In: Goldfrank LR, Flomenbaum NE, Lewin NA, et al, eds. Goldfrank 's Toxicologic Emergencies. 8th ed. Stamford, CT: Appleton & Lange; 2006.
Codes
ICD09
- 982.8 Toxic effect of other nonpetroleum-based solvents
- 980.2 Toxic effect of isopropyl alcohol
- 980.1 Toxic effect of methyl alcohol
ICD10
- T52.8X1A Toxic effect of organic solvents, accidental, init
- T51.2X1A Toxic effect of 2-Propanol, accidental (unintentional), initial encounter
- T51.1X1A Toxic effect of methanol, accidental (unintentional), initial encounter
SNOMED
- 426692001 Ethylene glycol poisoning (disorder)
- 212813006 Toxic effect of isopropyl alcohol
- 212809004 Methyl alcohol causing toxic effect (disorder)