Why this poison is interesting

The library's methanol and ethylene glycol pages are built on a single idea: the parent alcohol is nearly harmless, and the danger is a metabolite — formate, glycolate, oxalate — made by alcohol dehydrogenase, arriving after a latent phase, and producing a severe high-anion-gap metabolic acidosis. Everything about their management follows from that: block the enzyme with fomepizole, buy time, dialyse the acid away. Isopropanol is the poison that takes the same first step and produces none of the consequences, and it is on this page precisely because it is the exception that proves how the rest of the class works.

Isopropanol — isopropyl alcohol, rubbing alcohol, the alcohol in most hand sanitiser — is also metabolised by alcohol dehydrogenase. But its product is acetone, and acetone is a ketone, not an organic acid. There is no formate, no glycolate, no oxalate; there is no acid to accumulate. The result is a poisoning that produces ketonemia, ketonuria without hyperglycemia or acidosis and elevated osmol gap² — a combination that exists in almost no other clinical situation and is close to diagnostic. The metabolite of every other toxic alcohol is the emergency. The metabolite of isopropanol is a smell.

Two consequences follow, and both invert the toxic-alcohol teaching. First, there is no latent phase: the toxicity is the parent alcohol's own CNS depression — about twice as potent as ethanol's — and it is present from the moment it is absorbed, not delayed while a metabolite forms. Second, fomepizole is not merely unnecessary but wrong: blocking alcohol dehydrogenase would trap the patient in the CNS-depressant parent alcohol and prevent formation of the harmless acetone. The one intervention that defines management of the other toxic alcohols is contraindicated here.

A poison is a drug whose kinetics have escaped its pharmacology.

The toxic principle

The toxic principle is the intact alcohol acting on the central nervous system, with acetone contributing a secondary, milder and longer-lasting depression. Isopropanol is a larger, more lipophilic alcohol than ethanol and is a correspondingly more potent CNS depressant — roughly twice as potent at the same blood concentration — so the clinical picture is a deeper, faster drunkenness than the same volume of ethanol would produce. Established

Acetone, the metabolite, is itself a CNS depressant and is cleared slowly — by the kidney and, distinctively, by the lungs, which is the source of the acetone (fruity, nail-varnish) smell on the breath and in the urine. But acetone is a ketone: it has no carboxylic acid group, it is not further oxidised to one in any quantity that matters, and it therefore cannot generate the high-anion-gap acidosis that kills methanol and ethylene glycol patients. The laboratory signature — ketonemia, ketonuria without hyperglycemia or acidosis and elevated osmol gap² — is the direct fingerprint of that chemistry. Established

Toxicokinetics

The kinetics are those of a small water-miscible alcohol: rapid and complete absorption, distribution through total body water, a single oxidative clearance route to acetone, and — crucially for management — a small molecule with negligible protein binding that dialyses extremely well. The one asymmetry worth holding is that acetone is cleared far more slowly than isopropanol, so it outlasts the parent and prolongs the sedation.

Isopropanol — a small alcohol cleared to a ketone, and a near-ideal dialysis target
Parameter	Therapeutic	In overdose	Why it changes
Absorption	Rapid and near-complete from the gut within 30–60 minutes; also absorbed dermally and by inhalation	No absorptive ceiling; peak is early	The early peak is why there is no latent phase. What is swallowed is absorbed and acts as an alcohol at once — there is no metabolic delay to a toxic species, because the toxic species is the parent.
Distribution	Distributes through total body water; small volume of distribution (~0.6 L/kg); negligible protein binding	Freely accessible in plasma and tissue water	A small, water-soluble, unbound molecule is the textbook dialysable poison — which is exactly why haemodialysis is so effective when it is needed.
Metabolism	Alcohol dehydrogenase oxidises isopropanol to acetone — a secondary alcohol to a ketone	The metabolite is less toxic than the parent, not more	This is the step that would ordinarily make a toxic alcohol dangerous, and here it detoxifies. Because the product is a ketone, not an aldehyde or acid, there is no onward oxidation to a carboxylic acid — the pathway stops at acetone.
Elimination	Isopropanol cleared mainly by metabolism to acetone; acetone excreted renally and pulmonary (acetone breath), and cleared slowly	Acetone outlasts the parent — half-life of the order of a day	The slow acetone tail is why sedation can persist after the isopropanol itself is gone, and why the acetone smell lingers. The lung as an excretory route is unusual and is the origin of the classic breath finding.
Dialysability	—	Highly dialysable. Haemodialysis removed isopropanol 52 times and acetone 40 times more efficiently than urinary excretion in a measured case¹	Dialysis is the one intervention with a mechanism here, and it clears both the parent and the metabolite. It is reserved for the patient in whom the parent alcohol's CNS and cardiovascular depression is itself life-threatening — coma with hypotension.¹²

Metabolism and the metabolites

The metabolism is a single step that, in every other toxic alcohol, is where the danger is made — and here it is where the danger stops. Alcohol dehydrogenase oxidises the secondary alcohol isopropanol to the ketone acetone, and there the pathway ends. There is no aldehyde dehydrogenase step producing an acid, because a ketone has no hydrogen on the carbonyl carbon to be oxidised further in the way an aldehyde does.

Isopropanol — the alcohol-dehydrogenase step that detoxifies instead of poisoning

Isopropanol (a secondary alcohol)CNS depressant ~2× ethanol; the main toxin
Alcohol dehydrogenaseThe same enzyme that makes formate from methanol and glycolate from ethylene glycol — here it makes a ketone
Acetone (a ketone)Less toxic than the parent; a mild, long-lasting CNS depressant. No carboxylic acid group — the pathway stops here
Renal excretionUrine (acetone, ketonuria)Contributes to the osmolar gap, not the anion gap
Pulmonary excretionBreath (the acetone smell)An unusual excretory route — the lung — and the origin of the classic finding

Elimination and accumulation

Isopropanol is cleared chiefly by conversion to acetone; acetone is then cleared slowly by the kidney and the lung. The important asymmetry is that acetone accumulates and lingers — its half-life is of the order of a day, far longer than the parent alcohol's — so a patient can smell of acetone and remain mildly sedated after the isopropanol concentration has fallen. There is no organ that isopropanol slowly destroys in the way methanol destroys the optic nerve or ethylene glycol the kidney; the accumulation that matters is simply the persistence of two CNS depressants.

The corollary is that the danger of isopropanol is dose and depth, not time. A large ingestion that produces deep coma and hypotension is genuinely life-threatening — the parent alcohol depresses the circulation as well as the brain — and it is these patients, not the metabolic-acidosis patients of the other alcohols, for whom haemodialysis is considered.¹² Inferred

Target organs — and why those

Brain

TargetThe same membrane and receptor effects as ethanol, roughly twice as potent

Why hereThe dominant organ and the seat of the main toxin. Isopropanol is a lipophilic small alcohol and a more potent CNS depressant than ethanol; the coma of a large ingestion is the parent drug's, deepened and prolonged by the slowly cleared acetone.² The brain is targeted because the poison is a sedative alcohol, not because a metabolite reaches it — which is why the depth is immediate rather than delayed. Established

At the bedsideInebriation progressing to stupor and coma, faster and deeper than the same volume of ethanol; recovery as both isopropanol and acetone clear.

Cardiovascular system — at high dose

TargetMyocardial depression and vasodilatation from a high alcohol concentration

Why hereIncluded because it is what turns an isopropanol overdose from unpleasant to fatal. At high concentrations the parent alcohol depresses the myocardium and dilates the vasculature, producing hypotension; the reported fatalities are in patients with deep coma and… hypotension.¹² This is the organ whose failure defines a life-threatening ingestion and the trigger for considering haemodialysis. Inferred

At the bedsideHypotension and cardiovascular collapse in severe poisoning²; its presence, with coma, is the indication that dialysis may be life-saving.¹

Stomach

TargetDirect mucosal irritation by a concentrated alcohol

Why hereIncluded because haematemesis in an alcohol overdose can mislead. Isopropanol is a direct gastric irritant, and severe ingestions produce a haemorrhagic gastritis² — a local chemical injury, not a systemic effect. The organ is targeted by contact, not by circulation, which is why it is an early and upper-gastrointestinal problem. Inferred

At the bedsideVomiting, abdominal pain and, in severe cases, haematemesis from haemorrhagic gastritis.²

Timeline of effects

Isopropanol — immediate, not delayed; the whole point is the absent latent phase

Time

What you seeWhat is happening

0–1 hAbsorption and onset
What you seeInebriation, vomiting, abdominal pain; deepening drowsiness with a large ingestion.²
What is happeningRapid, near-complete absorption. The parent alcohol acts as a CNS depressant immediately — there is no metabolite to wait for, so no latent phase.
1–6 hPeak toxicity
What you seeMaximum CNS depression — stupor to coma; hypotension and cardiovascular collapse in severe cases.²
What is happeningPeak isopropanol concentration with acetone rising. Labs show a large osmolar gap, ketonaemia and ketonuria, a normal anion gap and no acidosis.² The depth of coma and the blood pressure decide severity.
6–24 hIsopropanol falls, acetone lingers
What you seeGradual lightening of coma; persistent acetone breath and mild residual sedation.
What is happeningIsopropanol is converted to acetone; acetone is cleared slowly by kidney and lung and outlasts the parent, prolonging mild sedation and the smell.
RecoveryResolution
What you seeFull recovery is the rule; mortality is low except after deep coma with hypotension.²
What is happeningNo metabolite-driven organ injury develops — the absence of a toxic acid is why there is no late deterioration and no optic or renal sequel.

What the mechanism predicts at the bedside

A large osmolar gap with ketones but no acidosis and a normal glucose is close to diagnostic. The combination ketonemia, ketonuria without hyperglycemia or acidosis and elevated osmol gap² points at isopropanol more specifically than almost any other single lab pattern in toxicology.
Do not give fomepizole or ethanol. They are the treatment for methanol and ethylene glycol and are counterproductive here — the metabolite is harmless and blocking the enzyme prolongs the toxic parent.² This is the one place in the toxic-alcohol group where the reflex antidote is wrong.
Judge severity by depth of coma and blood pressure, not by acid–base. There is no acidosis to track; the dangerous patient is the deeply comatose, hypotensive one, and the fatalities are in that group.¹²
Haemodialysis is for coma with hypotension, and it works. It clears isopropanol and acetone about 50 and 40 times faster than the kidney¹; it is reserved for the life-threatening ingestion, and even then its necessity is debated.² See the dialysis note below.
Expect no latent phase and no late deterioration. Unlike ethylene glycol and methanol, a patient who is not deeply obtunded early is not harbouring a metabolite that will injure an organ hours later.
Look for haematemesis. Severe ingestions cause haemorrhagic gastritis²; upper-GI bleeding in an alcohol overdose may be the isopropanol itself.
Charcoal does not help. Alcohols are poorly adsorbed; it is listed here to be explicit that it is not the answer.
The acetone smell is a clue, not a complication. Acetone on the breath in an obtunded patient with a big osmolar gap and no acidosis is the diagnosis announcing itself.

The antidote, from the poison's side

There is no antidote and none is needed, because the poison is a self-limiting sedative alcohol with a harmless metabolite. The single intervention with a mechanism is extracorporeal removal, and its role is defined narrowly by the depth of the parent alcohol's effect rather than by any metabolic emergency.

Supportive care: The mainstay. Airway protection, ventilation and circulatory support carry the patient through the parent alcohol's CNS and cardiovascular depression while it and the acetone are cleared. Most patients need nothing more.²
Haemodialysis: The one measure with a mechanism, and a good one: it removes isopropanol and acetone about 52 and 40 times more efficiently than the kidney.¹ It is reserved for the patient in whom the parent alcohol is itself life-threatening — deep coma with hypotension — and even in that setting its necessity is genuinely debated, some arguing that supportive care alone suffices.²
Fomepizole and ethanol: Explicitly not indicated, and counterproductive. They block the enzyme that converts isopropanol to harmless acetone, prolonging the toxic parent. Their appearance in the other toxic-alcohol pages is a reason to name their absence here.²
Activated charcoal: Not useful — alcohols are poorly adsorbed. Named so that its uselessness is on the record rather than assumed.
Vasopressors and fluids: For the hypotension of a severe ingestion, on general critical-care grounds — supporting the circulation through the depth of the parent alcohol's effect.

Critical appraisal

The core biochemistry is Established and the page leans on it heavily. That isopropanol is oxidised by alcohol dehydrogenase to acetone, and that acetone is a ketone incapable of generating a high-anion-gap acidosis, is standard and uncontested; the Established badges on the metabolic claims reflect that.
The dialysis question is genuinely unsettled and the page says so. Rosansky's measured case shows dialysis is highly efficient and argues it may be considered life-saving in the comatose patient¹; Trullas's group, reporting a life-threatening case treated successfully, argues hemodialysis is not needed, even in life-threatening situations². The page presents both positions rather than resolving a question the literature has not.
The CNS-potency figure is an approximation. 'About twice as potent as ethanol' is the widely quoted comparative depressant potency and is stated as an order-of-magnitude comparison, not a precise ratio derived from a specific study.
The gastritis and cardiovascular claims are Inferred, not Established. Haemorrhagic gastritis and hypotension are reported clinical features²; the mechanistic attributions — direct mucosal irritation, myocardial depression and vasodilatation — are the standard explanations and are badged as inference rather than as demonstrated causation in poisoned humans.
No lethal dose and no fatal concentration is given. Severity is described by depth of coma and blood pressure¹²; risk assessment and any concentration thresholds belong to TOXBASE and NPIS.
The acetone half-life is stated as an order of magnitude. 'Of the order of a day' reflects that acetone clearance is slow and variable; the page does not attach a precise figure to it.

References

1
Rosansky SJ. Isopropyl alcohol poisoning treated with hemodialysis: kinetics of isopropyl alcohol and acetone removal. Journal of Toxicology — Clinical Toxicology 1982;19(3):265–271. PMID 7131613. A comatose, hypotensive patient after 480 mL ingestion; haemodialysis removed isopropanol 52× and acetone 40× more efficiently than urinary excretion, and is argued to be life-saving in the comatose patient.
2
Trullas JC, Aguilo S, Castro P, Nogue S. Life-threatening isopropyl alcohol intoxication: is hemodialysis really necessary? Veterinary and Human Toxicology 2004 Oct;46(5):282–284. PMID 15487656. Ketonaemia and ketonuria without hyperglycaemia or acidosis and an elevated osmolar gap as the characteristic findings; low mortality except with deep coma and hypotension; a life-threatening case treated successfully, with an argument that dialysis is not always required.

Isopropanol

At a glance