Absorption

• Gastrointestinal Absorption: rapidly absorbed following ingestion
• Respiratory Absorption: rapidly absorbed following inhalation
• Dermal Absorption: may occur through normal skin
  • May Result in Toxicity, Especially in Infants

Background on Alcohols and Their Metabolism

Ethylene Glycol (see Ethylene Glycol, [[Ethylene Glycol]])

• 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 (see Methanol, [[Methanol]])

• 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

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]])
  • Epidemiology
    • Observed with Isopropanol Level >400 mg/dL

Endocrinologic Manifestations

• Hypoglycemia (see Hypoglycemia, [[Hypoglycemia]])

Gastrointestinal Manifestations

• Abdominal Pain (see Abdominal Pain, [[Abdominal Pain]])
• Emesis (see Nausea and Vomiting, [[Nausea and Vomiting]])
• Fruity Breath (see Abnormal Breath Odor, [[Abnormal Breath Odor]])
  • Physiology: due to acetone
• Hemorrhagic Gastritis (see Gastritis, [[Gastritis]] and Gastrointestinal Hemorrhage, [[Gastrointestinal Hemorrhage]]): may occur following large ingestion
  • Clinical
    • Hematemesis (see Hematemesis, [[Hematemesis]])

Hematologic Manifestions

• Hemolytic Anemia (see Hemolytic Anemia, [[Hemolytic Anemia]]): may occur

Neurologic Manifestations

• Altered Mental Status (see Altered Mental Status, [[Altered Mental Status]])
  • Obtundation/Coma (see Obtundation-Coma, [[Obtundation-Coma]])
    • 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)
• Dizziness (see Dizziness, [[Dizziness]])
• Headache (see Headache, [[Headache]])
• Myopathy (see Myopathy, [[Myopathy]])

Pulmonary Manifestations

• Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome, [[Acute Respiratory Distress Syndrome]])
  • Epidemiology
    • May Occur Following Large Isopropanol Ingestion
• Hemorrhagic Tracheobronchitis (see Tracheobronchitis, [[Tracheobronchitis]])
• Respiratory Depression
  • Acute Respiratory Failure (see Respiratory Failure, [[Respiratory Failure]])

Renal Manifestations

• Elevated Osmolal Gap (Usually) without Anion Gap Metabolic Acidosis (see Serum Osmolality, [[Serum Osmolality]])
  • Physiology
    • Isopropanol is a Low Molecular Weight Osmotically-Active Substance Which is Metabolized to Acetone
    • Acetone is an Osmotically-Active, Non-Ionized Molecule That is Not an Acid and, Therefore, by Itself, Does Not Result in Metabolic Acidosis
  • Diagnosis
• Ketonemia (see Ketonemia, [[Ketonemia]])
  • 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
• Ketonuria (see Ketonuria, [[Ketonuria]])
  • Physiology: due to ketonemia (see Ketonemia, [[Ketonemia]])
  • Diagnosis
    • Positive Urine Ketones Using the Nitroprusside Reaction: due to presence of acetone
      • Nitroprusside Reaction Detects Acetoacetate and, to a Far Lesser Extent, Acetone
      • Nitroprusside Reaction May Be Negative or Only Weakly Positive

Other Manifestations

• Hypothermia (see Hypothermia, [[Hypothermia]])
• Odor of Rubbing Alcohol