Isopropanol

Source of Exposure

Aftershave Lotions
Antifreeze: in combination with ethylene glycol, ethanol, and methanol
Disinfectants/Cleaners (Windex, etc)/Solvents
Nail Polish Remover
Rubbing Alcohol: isopropanol constitutes approximately 70% of “rubbing alcohol”

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 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
Hypoglycemia (see Hypoglycemia, [[Hypoglycemia]])

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

Required to Rule Out Metabolic Acidosis

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

Required To Detect Ketonemia (see Ketonemia, [[Ketonemia]])

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

Required To Diagnose Ketonuria (see Ketonuria, [[Ketonuria]])

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

Elevated Osmolal Gap (see Metabolic Acidosis-General, [[Metabolic Acidosis-General]]): >10 mmol/L
- Osmotically-Active Solutes
  - Isopropanol
  - Acetone (see Acetone, [[Acetone]])

Isopropanol Level

Diagnostic Early in the Course: but isopropanol may be minimally detectable later in the course, as acetone is formed
- Level >17 mmol/L (100 mg/dL): lethargy
- Level 25-33 mmol/L (150-200 mg/dL): coma
- Level >66-84 mmol/L (>400-500 mg/dL): potentially fatal
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]])
- 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

Treatment

Supportive Care

Supportive Care is Adequate in Most Cases
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)

Alcohol Dehydrogenase Inhibitors (Ethanol, Fomepizole)

Not Effective

Hemodialysis (see Hemodialysis, [[Hemodialysis]])

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]
Isopropanol poisoning. Clin Toxicol (Phila). 2014;52(5):470-478 [MEDLINE]