Toxic alcohol poisoning

Toxic alcohol poisoning is a potentially life-threatening condition caused by the ingestion of toxic alcohols, which are either themselves toxic (e.g., isopropyl alcohol) or have toxic metabolites (e.g., methanol, ethylene glycol). Clinical features are generally nonspecific and include altered mental status, nausea, vomiting, tachypnea, and tachycardia. In particular, methanol poisoning is associated with ophthalmologic pathologies (e.g., blurred vision, blindness), while ethylene glycol poisoning is associated with renal pathologies (e.g., hematuria, flank pain). While toxic alcohol poisoning may be definitively diagnosed with serum toxic alcohol levels, these tests are generally not readily available. It is most often a clinical diagnosis, which may be supported by laboratory findings. An elevated osmolar gap with an anion gap metabolic acidosis suggests methanol or ethylene glycol poisoning. Management of methanol and ethylene glycol poisoning involves treatment with fomepizole, with severe cases requiring hemodialysis. Patients often require admission for further monitoring and treatment.

See also “Alcohol intoxication.”

• Toxic alcohol: a type of alcohol that can cause significant organ damage and/or death when ingested, most often due to toxic metabolites. Examples include ethylene glycol, methanol, isopropyl alcohol, diethylene glycol, and propylene glycol. ^[1]

Approach

• All patients: Provide general management of toxic alcohol poisoning.
• Methanol or ethylene glycol poisoning
  • Antidote: Administer alcohol dehydrogenase inhibitors (e.g., fomepizole).
  • Enhanced elimination
    • Normalize pH with sodium bicarbonate.
    • Consider a nephrology consultation for hemodialysis.
• Isopropyl alcohol poisoning
  • Antidote and enhanced elimination: not routinely required
  • Supportive care: Monitor for symptoms of GI bleeding and hypotension.

General management of toxic alcohol poisoning

• Follow the ABCDE approach in poisoning.
• Call poison control; the US National Poison Help line is 1-800-222-1222.
• Obtain laboratory studies.
  • Routine: BMP, ABG, serum osmolality, urinalysis, serum ethanol
  • Confirmatory: methanol, ethylene glycol, and isopropyl alcohol levels
• Calculate anion gap and osmolar gap .
• Identify and treat toxic co-ingestions (e.g., acetaminophen poisoning, ethanol intoxication).
• Consider treatment of alcohol use disorder.
• Consult psychiatry if there has been a self-harm attempt.

Elevated osmolar gap is classically an early feature of toxic alcohol ingestion. As methanol and ethylene glycol are metabolized, the osmolar gap decreases and a high anion gap metabolic acidosis (HAGMA) develops. Isopropyl alcohol poisoning does not cause HAGMA.

Alcohol dehydrogenase inhibitors ^[2][3]

• Goal: to prevent the conversion of methanol or ethylene glycol to toxic metabolites (e.g., formic acid, glycolic acid, oxalic acid) by competitively inhibiting alcohol dehydrogenase
• Indications
  • Clinical suspicion of methanol or ethylene glycol ingestion AND two of the following:
    • Arterial pH < 7.3
    • Serum bicarbonate < 20 mEq/L
    • Osmolar gap > 10 mOsm/L
    • Presence of urinary oxalate crystals
  • History of methanol or ethylene glycol ingestion AND osmolar gap > 10 mOsm/L
  • Serum methanol or ethylene glycol concentration ≥ 20 mg/dL
• Options
  • Fomepizole (first-line) : a competitive alcohol dehydrogenase inhibitor; safer and easier to administer than ethanol
  • Ethanol (second-line) ^[4]
• Duration: Continue treatment until ethylene glycol or methanol concentrations are < 20 mg/dL.

Normalize pH ^[2][3]

• Goals ^[4]
  • Enhanced elimination of ethylene glycol in urine
  • Prevention of calcium oxalate-induced acute renal failure
• Indication: pH < 7.3
• Treatment: Administer IV sodium bicarbonate bolus and infusion until pH normalizes.

Hemodialysis ^[2][3]

Usually reserved for poisoning with severe features, e.g., severe acidosis, neurological or renal dysfunction

• See “Indications for hemodialysis in methanol poisoning.”
• See “Indications for hemodialysis in ethylene glycol poisoning.”

Background ^[1][4]

Methanol is a slightly sweet-tasting alcohol that is commonly used as a solvent and gasoline additive.

• Sources of exposure
  • Ingested as ethanol substitute by individuals with alcohol use disorder
  • Improper distillation of spirits
  • Self-harm attempts
  • Accidental ingestion
• Mechanism of toxicity: hepatic metabolism of methanol → accumulation of formaldehyde and formic acid → anion gap metabolic acidosis → cellular toxicity

Clinical features ^[1][4]

Can resemble clinical features of alcohol intoxication (e.g., altered mental status, nausea) but may also include:

• Ophthalmologic
  • Optic neuropathy (e.g., blurred vision, scotoma, blindness)
  • Papilledema
  • Peripapillary retinal edema
  • Afferent pupillary defect
• Cardiopulmonary: Kussmaul breathing, tachycardia
• Gastrointestinal: abdominal pain, hemorrhagic gastritis in severe cases

Diagnostics ^[1][4]

• Methanol poisoning is most often diagnosed clinically.
• Peak serum methanol level can confirm the diagnosis, but may not be readily available. ^[4]
  • > 50 mg/dL: poisoning likely
  • < 20 mg/dL: poisoning unlikely
• Routine laboratory studies that support the diagnosis include:
  • Elevated osmolar gap: > 20 mOsm is highly suspicious for toxic alcohol ingestion. ^[4]
  • Anion gap metabolic acidosis (e.g., ↓ pH, ↓ HCO₃^-)

Management

• Begin general management of toxic alcohol poisoning.
• Administer an antidote for toxic alcohol poisoning (e.g., fomepizole ) if indicated.
• Consider leucovorin (off-label) as an adjunct to enhance formic acid clearance. ^[2]

Indications for hemodialysis in methanol poisoning ^[5]

• Presence of neurological symptoms (e.g., seizures, coma, new vision deficits)
• Serum pH ≤ 7.15 or persistent acidosis despite treatment
• Serum anion gap > 24 mmol/L
• Serum methanol level
  • > 70 mg/dL if receiving fomepizole therapy
  • > 60 mg/dL if receiving ethanol therapy
  • > 50 mg/dL if not receiving an ADH antagonist
• Impaired kidney function

Disposition ^[4]

• Admit patients with methanol poisoning for treatment and monitoring.
• Transfer patients who meet criteria for emergency hemodialysis, if hemodialysis is not available on site.
• Admit patients with hemodynamic instability or receiving ethanol therapy to the ICU. ^[1]
• Asymptomatic patients without laboratory abnormalities and a serum methanol level < 20 mg/dL may be discharged.
• Refer to ophthalmology within 24 hours to evaluate for methanol-induced ocular injury.

Background ^[1][4]

Ethylene glycol is a sweet-tasting alcohol that is commonly used as an antifreeze agent.

• Sources of exposure
  • Ingested as ethanol substitute by individuals with alcohol use disorder
  • Self-harm attempts
  • Accidental ingestion
• Mechanism of toxicity
  • Hepatic metabolism of ethylene glycol → accumulation of glycolic acid → anion gap metabolic acidosis
  • Metabolism of glycolic acid → accumulation of oxalic acid → deposition of calcium oxalate crystal in renal tubules → acute kidney injury

Clinical features ^[1][4]

The clinical features of ethylene glycol poisoning are commonly divided into three stages.

• Neurologic stage: first 12 hours after ingestion
  • Clinical features of alcohol intoxication (e.g., altered mental status, ataxia)
  • Seizures
  • Nystagmus
• Cardiopulmonary stage: 12–24 hours after ingestion
  • Tachypnea secondary to metabolic acidosis
  • Tachycardia
  • ARDS and/or circulatory collapse in severe cases
• Renal stage: 24–72 hours after ingestion
  • Flank pain
  • Hematuria
  • Oliguria or anuria
  • Symptoms of hypocalcemia

Diagnostics ^[1][4]

• Ethylene glycol poisoning is most often diagnosed clinically.
• Peak serum ethylene glycol level can confirm the diagnosis, but may not be readily available. ^[4]
  • > 50 mg/dL: poisoning likely
  • < 20 mg/dL: poisoning unlikely
• Routine laboratory studies that support the diagnosis include:
  • Elevated osmolar gap: > 20 mOsm is highly suspicious for toxic alcohol ingestion. ^[4]
  • Anion gap metabolic acidosis (e.g., ↓ pH, ↓ HCO₃^-)
  • Urinalysis: hematuria, proteinuria, calcium oxalate crystalluria

Because antifreeze preparations often have a fluorescent component, the urine of patients who ingest antifreeze may glow under a Woods lamp. ^[4]

Lactate levels may be falsely elevated on point-of-care machines because of interference from glycolic acid. ^[1]

Management

• Begin general management of toxic alcohol poisoning.
• Administer an antidote for toxic alcohol poisoning (e.g., fomepizole ) if indicated.
• Consider adjunctive vitamin supplementation ^[6]
  • Thiamine (off-label)
  • Pyridoxine (off-label)

Indications for hemodialysis in ethylene glycol poisoning ^[7]

Consider hemodialysis in patients with any of the following:

• Dialysis recommended
  • Neurologic symptoms (e.g., coma, seizures)
  • Plasma ethylene glycol concentration of:
    • > 310 mg/dL in patients being treated with ethanol therapy
    • > 62 mg/dL if no antidote is given
  • Osmolar gap
    • > 50 mOsm/L in patients being treated with ethanol therapy
    • > 10 mOsm/L if no antidote is given
  • Plasma glycolate concentration > 12 mmol/L
  • Anion gap > 27 mmol/L
  • Acute kidney injury
• Dialysis suggested
  • Plasma ethylene glycol concentration of:
    • > 310 mg/dL in patients being treated with fomepizole
    • 124–310 mg/dL in patients being treated with ethanol therapy
  • Osmolar gap
    • > 50 mOsm/L in patients being treated with fomepizole
    • 20–50 mOsm/L in patients being treated with ethanol therapy
  • Plasma glycolate concentration 8–12 mmol/L
  • Anion gap 23–27 mmol/L
  • Chronic kidney disease

Disposition ^[4]

• Admit patients with ethylene glycol poisoning for treatment and monitoring.
• Transfer patients who meet criteria for emergency hemodialysis, if hemodialysis is not available on site.
• Admit patients with hemodynamic instability and those receiving ethanol therapy to the ICU. ^[1]
• Asymptomatic patients without laboratory abnormalities and a serum ethylene glycol level < 20 mg/dL may be discharged.

Background ^[1][4]

Isopropyl alcohol is a bitter-tasting alcohol with a fruity odor. It is used as a solvent and is the main component of rubbing alcohol.

• Sources of exposure
  • Disinfectants (e.g., rubbing alcohol)
  • Solvents
  • Antifreeze
• Mechanism of toxicity: : directly toxic; metabolized in the liver to acetone

Clinical features ^[1][4]

Can resemble clinical features of alcohol intoxication (e.g., altered mental status, ataxia) but may also include:

• Gastrointestinal
  • Nausea, vomiting, abdominal pain
  • Fruity, sweet-smelling breath
  • In severe cases, hemorrhagic gastritis and/or hematemesis
• Cardiopulmonary
  • If isopropyl alcohol is aspirated: pulmonary edema, hemorrhagic tracheobronchitis
  • Respiratory depression and/or hypotension in severe poisoning
• Neurological: headache, hypotonia, seizures

Diagnostics ^[1][4]

• Isopropyl alcohol poisoning is most often diagnosed clinically.
• Peak serum isopropyl alcohol levels > 50 mg/dL can confirm the diagnosis, but may not be readily available. ^{[4] [4]}
• Routine laboratory studies that support the diagnosis include:
  • Elevated osmolar gap: > 20 mOsm is suspicious for toxic alcohol ingestion. ^[4]
  • Absence of anion gap metabolic acidosis
  • Ketosis: urine and/or serum ketones

Acetone may interfere with some creatinine assays, causing a falsely elevated creatinine level. ^[4]

Management ^[4]

Antidotes for toxic alcohol poisoning are not required for isopropyl alcohol poisoning.

• All patients: Begin general management of toxic alcohol poisoning.
• Hemorrhagic gastritis: See “Treatment of GI bleeding.”
• Hypotension
  • IV fluid resuscitation
  • Titratable vasopressors: e.g., norepinephrine infusion
• Clinical deterioration: Consult poison control to discuss options; hemodialysis is very rarely indicated. ^[4]

Avoid administering fomepizole, as it will prolong the effects of isopropyl alcohol. ^[4]

Disposition ^[4]

• Admit patients with symptoms of intoxication or altered mental status for monitoring.
• Admit patients with hemodynamic instability to the ICU.
• Asymptomatic patients who do not appear to be intoxicated may be discharged 6 hours after ingestion.