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
- 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
Gastrointestinal Manifestations
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
- 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)
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]