Isopropyl alcohol toxicity

Background

• Main component of rubbing alcohol
• Hallmark is osmolar gap, ketosis, that is without acidosis
  • Metabolized to acetone, not to an acid
• Takes 30-60 min for acetone to appear in blood; 3 hr to appear in urine
• Lethal Dose: 4-8 g/kg or 250 mL in average adult (calculated using volume of pure isopropyl alcohol)
  • Typical store bought rubbing alcohol is 70% isopropyl alcohol by volume, so lethal dose is ~ 350 mL

Pharmacology

• Unlike other toxic alcohols (methanol, ethylene glycol), toxic effects caused by parent agent (IA) rather than metabolite (acetone)
• Metabolized to acetone by alcohol dehydrogenase
• Maximal distribution in ≤ 2 hours
• Lethal dose > 200 mg/dL, although variable literature

Clinical Features

• CNS depression
  • Similar to ETOH intoxication, but longer-lasting
  • Usually peaks in first hour of ingestion
• GI
  • Nausea/vomiting / abdominal pain / hemorrhagic gastritis
• Respiratory depression
  • Fruity breath from acetone
• Hypotension, hypothermia from peripheral vasodilation
• Hypoglycemia (in malnourished patients)

Differential Diagnosis

• Starvation ketoacidosis
• Diabetic Ketoacidosis
• Inborn errors of metabolism
• Salicylate Toxicity
• Acetone ingestion

Sedative/hypnotic toxicity

• Absinthe
• Barbiturates
• Benzodiazepines
  • Flunitrazepam (Rohypnol)
• Chloral hydrate
• Gamma hydroxybutyrate (GHB)
• Baclofen toxicity
• Opioids
  • Lomotil toxicity
  • Loperamide toxicity
• Toxic alcohols
  • Ethanol
  • Ethylene glycol
  • Isopropyl alcohol
  • Methanol
• Xylazine toxicity

Evaluation

Work-Up

• Fingerstick glucose
• Complete metabolic panel
• Serum ketones
• Serum Osmolality
• Urinalysis
• VBG
• Aspirin/Tylenol levels
• ECG
• Serum isopropyl alcohol level (if available)
• Total CK

Evaluation

• Osmolal gap > 10; see Osmolal or Osmolar Gap
• Absence of anion gap
• Absence of metabolic acidosis
• Absence of serum beta hydroxybutyrate
• Presence of serum and urine ketones
  • Consider other diagnosis if absent 2hr after ingestion
• Creatinine may be falsely elevated due to acetone interference with laboratory measurement of Cr

Toxic Alcohols Anion/Osmolar Gaps

Substance	Osmolar gap	Metabolic acidosis	Anion gap	Ketones	Ca Oxalate crystals	Reduced vision	Management
Ethanol	+	+/- (if ketoacidosis)	+/- (if ketoacidosis)	+/-	-	-	Mainly supportive
Ethylene glycol	+ (early)*	+	+	-	+	-	Fomepizole, Thiamine, Pyridoxine, +/- Dialysis
Methanol	+ (early)*	+	+	-	-	+	Fomepizole or ethanol, Folinic acid/Folic acid, +/- Dialysis
Isopropyl alcohol	+	-	-	+ (acetonemia without acidosis)	-	-	Mainly supportive, +/- Dialysis if severe
Propylene glycol	+	+	+ (lactic acidosis)	-	-	-	D/C offending agent (e.g. IV lorazepam/diazepam), supportive, +/- Dialysis

• Osmolar gap → Anion gap transition: For all toxic alcohols, the osmolar gap is elevated early (parent compound present) and decreases over time as the alcohol is metabolized into organic acid metabolites, which then produce an anion gap metabolic acidosis. A normal osmolar gap does NOT exclude toxic alcohol ingestion if presentation is delayed.

Key distinguishing features

• Isopropyl alcohol: The only toxic alcohol that causes ketosis without metabolic acidosis (metabolized to acetone, not an organic acid)
• Ethylene glycol: Ca oxalate crystals in urine + anion gap metabolic acidosis + renal failure
• Methanol: Visual disturbances (blurred vision, "snowfield" vision, blindness) + anion gap metabolic acidosis + optic disc hyperemia on fundoscopy

Management

• Treatment is supportive.
• No role for fomepizole or ethanol
  • Blockade of alcohol dehydrogenase (ADH) will prolong intoxication
• Hemodialysis indications:
  • Hypotension
  • Comatose
  • Consider if IA serum level >200mg/dL

Disposition

• Generally may be discharged once clinically sober.

See Also

• Toxic alcohols
• In-Training Exam Review