Ethylene Glycol is a Primary Alcohol Which is Metabolized by Alcohol Dehydrogenase and Aldehyde Dehydrogenase to Carboxylic Acids (Namely, Glycolic Acid, Glyoxylic Acid, and Oxalic Acid): these carboxylic acids cause most of the toxic effects
Methanol is a Primary Alcohol Which is Metabolized by Alcohol Dehydrogenase and Aldehyde Dehydrogenase to Carboxylic Acids (Namely, Formic Acid): these carboxylic acids cause most of the toxic effects
Isopropanol
Isopropanol is a Secondary Alcohol Which is Metabolized by Alcohol Dehydrogenase Only to a Ketone (Namely, Acetone), Rather than to an Aldehyde: ketones cannot be oxidized to an aldehyde and therefore, only limited acidosis can result
Isopropanol Metabolism
Hepatic Metabolism: isopropanol is predominantly hepatically metabolized by alcohol dehydrogenase to acetone
Following Ingestion of at Least Several Grams of Isopropanol, the Formation of Acetone Exceeds its Elimination, Leading to Accumulation of Acetone (and Resulting Ketoacidosis)
Acetone is Excreted by Kidneys and Lungs
Renal Metabolism: 20% of isopropanol is excreted unchanged by kidneys
Co-Ingestion with Ethanol
Since the Affinity of Alcohol Dehydrogenase is Far Higher for Ethanol than for Isopropanol, Co-Ingested Ethanol May Result in Slowed Isopropanol Elimination
Half-Life of Isopropanol (Untreated): 2.5-8 hrs
Half-Life of Acetone: >10 hrs
Half-Life of Isopropanol (In Presence of the Alcohol Dehydrogenase Inhibitors, Ethanol or Fomepizole): up to 28 hrs
End Organ Toxicity
General Comments
Toxicity is Similar to Ethanol (Due to Structural Similarity Between These Acohols)
Median Lethal Dose
Untreated Animals: 4-8 g/kg
Humans: 250 mlL (<400 ml of a 70% solution)
However, with Proper Treatment, Many Patients Will Survive a Much Larger Dose
Central Nervous System Depression
The Degree of Central Nervous System Depression with Alcohols is Linearly-Related to their Molecular Weight
Higher Molecular Weight = More Sedative Effects
Isopropanol is About Twice as Potent of a Central Nervous System Depressant as Ethanol
Acetone is Also a Mild Central Nervous System Depressant
Ketoacidosis Occurs Due to the Accumulation of Acetone
Diagnosis
Serum Chemistry
Absence of Anion Gap Metabolic Acidosis: usually
Isopropanol is an Osmotically-Active Alcohol
Isopropanol is Metabolized to Acetone (an Osmotically-Active, Non-Ionized Molecule that is Not an Acid and, Therefore, by Itself, Does Not Directly Result in Metabolic Acidosis)
However, Ketoacidosis May Be Present
Falsely Elevated Serum Creatinine (see Increased Creatinine, [[Increased Creatinine]]): may occur with acetone concentration >100 mg/dL
False-Positive Results: low concentrations of isopropanol may be detected in patients with severe diabetic ketoacidosis (see Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic State, [[Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic State]]) or alcoholic ketoacidosis (see Alcoholic Ketoacidosis, [[Alcoholic Ketoacidosis]]), due to endogenous reduction of acetone to isopropanol
Clinical Manifestations
General Comments
Onset: effects begin within 30 min of ingestion (peak effects occur within 1-2 hrs)
Similar to Ethanol Intoxication
The Absence of Early Symptoms Excludes a Significant (Isolated) Isopropanol Ingestion
Cardiovascular Manifestations
Hypotension/Shock (see Hypotension, [[Hypotension]])
Hemorrhagic Gastritis (see Gastritis, [[Gastritis]] and Gastrointestinal Hemorrhage, [[Gastrointestinal Hemorrhage]]): may occur following large ingestion
Deep Coma is Observed with Isopropanol Level >400 mg/dL
Since Acetone is Less Sedating than Isopropanol, Central Nervous System Depression May Gradually Decrease Throughout the Course (as Isopropanol is Gradually Converted to Acetone)
Physiology: due to metabolism of isopropanol to acetone
Diagnosis
Positive Serum Ketones Using the Nitroprusside Reaction (see Serum Ketones, [[Serum Ketones]])
Nitroprusside Reaction Detects Acetoacetate and, to a Far Lesser Extent, Acetone
When Serum Ketones are Measured at Least 2 hrs After Suspected Ingestion of Isopropanol (and in the Absence of Alcohol Dehydrogenase Inhibitors, Such as Ethanol or Fomepizole), a Low Serum Ketone Concentration Excludes a Significant Isopropanol Ingestion
Absent Serum β-Hydroxybutyrate (see Serum β-Hydroxybutyrate, [[Serum β-Hydroxybutyrate]]): even with large ingestions
In Fact, Ketosis with Detected β-Hydroxybutyrate Suggests that Isopropanol is Not the Etiology of the Ketosis
Intubation/Mechanical Ventilation (see Mechanical Ventilation-General, [[Mechanical Ventilation-General]]): as necessary
Intravenous Fluid Resucitation/Pressors: as necessary
Treatment of Hypoglycemia (see Hypoglycemia, [[Hypoglycemia]]): as necessary
Gastrointestinal Decontamination
Activated Charcoal (see Activated Charcoal, [[Activated Charcoal]]): only useful for possible co-ingested substances
Gastric Lavage (see Gastric Lavage, [[Gastric Lavage]]): effective to shorten coma if performed within 1 hr after a massive ingestion (due to rapid isopropanol absorption)
Effectively Removes Isopropanol and Acetone: with clearance rates >200 mL/min
Indications
Coma with Isopropanol Level >400 mg/dL
Hypotension/Shock (see Hypotension, [[Hypotension]])
Prognosis
Prognosis is Excellent in Isolated Isopropranol Ingestion
Few Cases of Death That Occur are Usually Due to Respiratory Depression or Hypotension/Shock
References
Acute isopropyl alcohol intoxication. Diagnosis and management. Am J Med 1983; 75:680-686
The generation of acetonemia/acetonuria following ingestion of a subtoxic dose of isopropyl alcohol. Am J Emerg Med 1989; 7:38-40
Osmolality. Ann Intern Med. 1991 Feb 15;114(4):337-8 [MEDLINE]
Serum determinations in toxic isopropanol ingestion. Am J Emerg Med 1992; 10:200-202
Poisonings and overdoses in the intensive care unit: general and specific management issues. Crit Care Med 2003; 31:2794-2801
Toxic alcohol ingestions: clinical features, diagnosis, and management. Clin J Am Soc Nephrol. 2008;3(1):208-225 [MEDLINE]
Ethylene glycol, methanol and isopropyl alcohol intoxication. Am J Med Sci. 2010;339(3):276-281 [MEDLINE]
Approach to the evaluation of a patient with an increased serum osmolal gap and high-anion-gap metabolic acidosis. Am J Kidney Dis. 2011;58(3):480-484 [MEDLINE]