Isopropyl alcohol (isoglycol) is commonly used as a disinfectant, antifreeze and solvent. Isopropyl alcohol poisoning is often caused by ethanol substitutes or self-harm. Isopropyl alcohol ingestion manifests primarily as CNS depression, with toxicity and treatment similar to that of ethanol. Isopropyl alcohol toxicity alone is rarely fatal, but it can have serious effects due to cardiovascular depression after ingestion and aggravation of shock. Supportive treatment can prevent the death of most patients. It is important to distinguish isopropyl alcohol poisoning from methanol and ethylene glycol. Isopropyl alcohol does not cause increased anion gap acidosis, retinal toxicity (methanol), or renal failure (ethylene glycol).
Pharmacology and Toxicology
Isopropyl alcohol is a sedative-hypnotic drug whose toxicity is very similar to that of ethanol. The exact mechanism of action of isopropyl alcohol in the CNS remains uncertain. Currently, changes in membrane fluidity or function and interactions with neurotransmitter receptors are mostly considered. There is a linear relationship between the molecular weight of an alcohol and its sedative effect: as size increases, so does the sedative effect. The LD50 for animals is between 4-8g/kg. Many publications incorrectly estimate the human lethal dose to be 250 mL (< mL of a 70% solution).
Isopropyl alcohol is metabolized to acetone by enzymes of the alcohol dehydrogenase family. Acetone production begins after ingesting just a few grams, and its elimination is slower than its formation, which results in the accumulation of acetone. Acetone itself is a mild CNS depressant but may exacerbate CNS depression caused by isopropyl alcohol. This is also why isopropyl alcohol creates ketosis.
Isopropyl alcohol is metabolized into ketones (alcohol dehydrogenase) rather than aldehydes. Ketones cannot be oxidized to carboxylic acids. Therefore, isopropyl alcohol rarely causes acidosis and is significantly less toxic than methanol or ethylene glycol.
Dynamics
Like ethanol, isopropyl alcohol is rapidly and completely absorbed after oral administration. Peak serum concentrations and clinical effects occur approximately 1-2 hours after ingestion. After dermal exposure, especially in infants, there may be substantial absorption.
Isopropyl alcohol is mainly metabolized to acetone by alcohol dehydrogenases, but the affinity of this enzyme family for isopropyl alcohol is about one order of magnitude lower than that of ethanol. Therefore, small amounts of ethanol effectively block the metabolism of isopropyl alcohol and slow its clearance. In the absence of alcohol dehydrogenase (ADH) inhibition, the serum elimination half-life is approximately 2.5-8 hours. Acetone is eliminated slowly and has a variable half-life of over 10 hours. When ADH inhibitors (such as ethanol or fomepizole) are present, the clearance of isopropyl alcohol is significantly reduced, with a serum elimination half-life of 28 hours in one case report. Isopropyl alcohol and acetone are rapidly cleared by hemodialysis with clearance rates exceeding 200 mL/min.
Clinical manifestations
Isopropyl alcohol exhibits varying degrees of CNS depression, ranging from intoxication, sedation, stupor and coma. This occurs primarily with isopropyl alcohol shortly after exposure, with a peak within the first 1 hour after ingestion. Steady improvement in the patient’s level of consciousness is an expected clinical course. Notably, cross-tolerance in chronic alcohol reduces the magnitude and duration of these effects.
In taking a medical history, it is important to identify intake. In addition to determining the timing and amount of isopropyl alcohol ingested, clinicians should try to quantify any ethanol mixture and try to understand whether it is recreational or self-harm. Patients who ingest large amounts of concentrated isopropyl alcohol may complain of nausea, vomiting, and abdominal pain.
Physical examination
A change in mental status may be seen, similar to ethanol intoxication. Any patient with an altered mental status should be evaluated for response. Alcoholic breath is usually detectable, and fruity breath often indicates acetone accumulation. After large amounts of ingestion, shock such as hematemesis, pulmonary edema and hemorrhagic tracheobronchitis may occur.
Differential diagnosis
In patients suspected of having isopropyl alcohol poisoning, it is important to rule out the possibility of methanol or ethylene glycol ingestion. The early clinical course of all toxic alcohols is very similar, but there are differences in treatment. The lack of high anion gap metabolic acidosis 4-6h after ingestion allows clinicians to differentiate isopropyl alcohol from methanol or ethylene glycol poisoning in most cases. However, the presence of ethanol or the use of methanesulfonic acid delays the onset of methanol and glycol acidosis, making the diagnosis unclear.
Starvation, alcohol, and diabetic forms of ketoacidosis may also be accompanied by a neurotic state and ketosis. The presence of metabolic acidosis helps separate these entities from isopropyl alcohol overdose. The production of ketone bodies other than acetone through these metabolic states, particularly the presence of beta-hydroxybutyrate, demonstrates that ketosis is not caused by isopropyl alcohol. Less common causes of ketosis include inborn errors of metabolism such as branched-chain ketonuria and propionic acidemia, salicylic acid peroxidation, and ingestion of acetone itself.
Laboratory Assessment
The following tests should be obtained in all poisoned patients:
●Finger blood sugar to rule out hypoglycemia as the cause of mental status changes
● Acetaminophen and salicylic acid levels to rule out these common combinations
●Electrocardiogram (ECG) can rule out conduction system poisoning caused by drugs that affect the QRS or QTc interval
●Pregnancy test for women of childbearing age
Serum isopropyl alcohol and acetone levels:
Serum concentrations of isopropyl alcohol and acetone can be quantified directly using gas chromatography. The main use of this test is to confirm the diagnosis, as treatment is largely supportive. But the law is not widespread. If there is a cause for the patient’s altered mental statusIn times of uncertainty, and in the presence of another toxic alcohol, it is important to confirm the diagnosis. A serum concentration of at least 100 mg/dL (17 mmol/L) is required to cause a decreased level of consciousness. Due to the endogenous reduction of acetone to isopropanol, low concentrations of isopropyl alcohol may be detected in the serum of patients with severe diabetes or alcoholic ketoacidosis, and even mortality may be erroneously related to isopropanol exposure.
Osmotic pressure difference:
When quantitative serum testing for toxic alcohols is not readily available, osmotic pressure differences can provide important diagnostic information. By comparing measured plasma osmolarity with calculated values, clinicians can infer the presence of osmotically active electrically neutral substances in serum at concentrations above 10 mmol/L (at least 60 mg/dL), and that both isopropyl alcohol and acetone increase the osmotic pressure difference. Plasma osmolality gaps cannot differentiate between isopropyl alcohol, methanol, and ethylene glycol poisoning and therefore cannot be used to exclude the diagnosis. Unlike methanol and ethylene glycol poisoning, neither metabolic acidosis nor an increase in the anion gap is expected after isopropyl alcohol ingestion.
Serum and urine ketones:
Low concentrations of serum ketones are not indicative of isopropyl alcohol exposure, especially if beta-hydroxybutyrate concentration is measured. Acetone is the major ketone produced by the metabolism of isopropyl alcohol, and serum β-hydroxybutyrate concentrations remain low even after large amounts of ingestion. Acetone concentrations >100 mg/dL may increase serum creatinine.
Other checks:
If the patient does not improve steadily over several hours of observation, other causes of the disturbance of consciousness must be sought. Additional tests such as head CT, lumbar puncture, and creatine kinase may be needed.
Treatment
Starting with assessment and stabilization of the airway, breathing, and circulation, advanced cardiac life support measures must be provided. Clinicians should consider endotracheal intubation if there are questions about the patient’s ability to protect the airway and avoid aspiration.
Closely observe the signs of poisoning (such as stupor, hypotension) and establish intravenous access. Intravenous crystalloids are usually sufficient to correct any hypotension due to vasodilation, and vasopressors are occasionally required. Hypoglycemia should be corrected. As with ethanol overdose, most symptomatic patients recover within hours of ingestion.
In the vast majority of cases of isolated isopropyl alcohol poisoning, gastrointestinal decontamination is ineffective. Its rapid absorption and low toxicity after oral ingestion make this intervention unnecessary. Gastrointestinal decompression may be considered if it can be accomplished within one hour of mass ingestion as it may shorten the duration of coma, but it is not a critical intervention.
Alcohol dehydrogenase (ADH) inhibition: Because acetone is less toxic than isopropyl alcohol, there is no indication of ADH inhibition by aspirin or ethanol following isopropyl alcohol exposure.
Large-scale ingestion: Patients with rare large intentional ingestions and hemodynamic instability should be given vasoactive drugs. Serum isopropanol concentrations in such patients typically exceed 500 mg/dL (80 mmol/L), and plasma osmolarity typically exceeds 100 mosmol/L.
Hemodialysis should be considered in patients who remain hemodynamically unstable despite aggressive fluid resuscitation. It should be emphasized, however, that hemodialysis is rarely needed and the risks outweigh the benefits.
Disposal
Symptoms often appear quickly in patients who inadvertently ingest isopropyl alcohol rapidly. If isopropyl alcohol is known to be the only substance ingested, the patient can be discharged from the hospital 2 hours after symptoms subside. Patients who ingest it recreationally or as a substitute for ethanol should have their intake assessed and managed accordingly. Persons who intentionally ingest or cause harm should receive psychiatric evaluation.
