Isopropanol


Source of Exposure


Physiology

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

Diagnosis

Serum Chemistry

Arterial Blood Gas (ABG) (see Arterial Blood Gas, [[Arterial Blood Gas]])

Serum Ketones (see Serum Ketones, [[Serum Ketones]])

Urine Ketones (see Urinalysis, [[Urinalysis]])

Serum Osmolality (see Serum Osmolality, [[Serum Osmolality]])

Isopropanol Level


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

Endocrinologic Manifestations

Gastrointestinal Manifestations

Hematologic Manifestions

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

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

Treatment

Supportive Care

Gastrointestinal Decontamination

Alcohol Dehydrogenase Inhibitors (Ethanol, Fomepizole)

Hemodialysis (see Hemodialysis, [[Hemodialysis]])


Prognosis


References