Critical Care Medicine

Ethanol, methanol, ethylene Glycol, Ethyl alcohol (EtOH, alcohol, spirits), Ethylene glycol (EG, antifreeze poisoning), methanol (MetOH, wood or methyl alcohol), isopropanol (IPA, rubbing alcohol), toxic alcohols (MetOH, EG, IPA)

Ethanol, Methanol and Ethylene Glycol

Also known as: Ethyl alcohol (EtOH, alcohol, spirits), ethylene glycol (EG, antifreeze poisoning), methanol (MetOH, wood or methyl alcohol), isopropanol (IPA, rubbing alcohol), toxic alcohols (MetOH, EG, IPA)

Related: Propylene glycol, glycol ethers, cellosolves, benzyl alcohol

1. Description of the problem

What every clinician needs to know

Ethanol is the active ingredient in 'spirited' or alcoholic beverages. Ethanol content is typically described in terms of ethanol per volume, with 50% being equal to 100 proof. Each 'drink' contains approximately 15 grams of ethanol. A 'drink' can be a "shot" of 40% liquor, a glass of 12% wine, or a bottle of 5% beer.

“Toxic alcohols” refers to ethylene glycol (EG), methanol (MetOH) and isopropanol (IPA). Sources include de-icing and windshield-washer fluids (MetOH), automotive antifreeze (EG), and rubbing alcohol (IPA). The term 'toxic alcohols' is misleading since all require in vivo metabolism via alcohol dehydrogenase (ADH) to produce toxic metabolites.

Clinical features

All alcohols, including toxic alcohols, can result in inebriation, gastroenteritis, and CNS depression. Massive ingestions can result in coma with cardiopulmonary collapse. Ethylene glycol and methanol can result in severe metabolic acidosis. Ethylene glycol can result in cranial nerve palsies, cardiac dysfunction, and renal failure. Methanol is associated with visual symptoms. Isopropanol is associated with profound CNS depression and gastritis.

Key management points

The management of ethanol intoxication is supportive, with focus on controlling the airway, emesis, and ketosis. The management of ethylene glycol and methanol poisoning involves inhibition of ADH to prevent formation of toxic metabolites, correcting metabolic acidosis, and possibly hemodialysis (HD). Isopropanol management is supportive.

2. Emergency Management

Patients should be immediately stabilized based upon a primary survey. Blood glucose should be checked and corrected. Abnormal vital signs should be addressed and dehydration corrected. A detailed history should be obtained from all sources. Traumatic injuries should be ruled out in patients with altered sensorium. Appropriate laboratory tests should be drawn immediately. When treating toxic alcohol poisoning, acidosis should be corrected. Fomepizole or ethanol should be used to prevent formation of toxic metabolites. The need for HD should be considered early during initial patient evaluation. All patients with alcohol-related toxicities should be discussed with a medical toxicologist or your local poison control center (800-222-1222).

Management points not to be missed

Maintain airway.

Draw blood and order all appropriate laboratory tests simultaneously.

Fluid resuscitation and correction of electrolytes

Sodium bicarbonate to normalize serum pH

Fomepizole (or ethanol) to prevent formation of toxic metabolites

Hemodialysis for significant toxicity

Observe for ethanol withdrawal; treat with benzodiazepines.

3. Diagnosis

Diagnostic criteria

Correct, early diagnosis usually begins with a history of ingestion or clinical evidence of intoxication. A serum ethanol concentration can confirm inebriation but does not not rule out other acute conditions. Toxic alcohol concentrations are not routinely available in most centers. This diagnosis is suggested by the presence of an osmol gap, anion gap acidosis, or both. An elevated acetone concentration will develop within hours of a large IPA ingestion.

The following tests should be obtained: electrolytes, renal function, glucose, measured (serum) osmolality, and ethanol. All samples must be drawn at the same time to ensure accuracy of the calculated serum osmolality An ABG should be drawn if clinical toxicity is evident. Other ingestions should be ruled out. Further testing is based on examination and history.

Indirect determination of an alcohol's concentration can be made by multiplying the unexplained osmol gap by a conversion factor. This will provide an estimate of that alcohol's concentration, assuming that it alone accounts for the unexplained osmol gap. Table I gives conversion factors.

Table I.

Conversion Factors
Alcohol Molecular weight Conversion Factor
Methanol 32 3.2
Ethanol 46 4.6
Acetone 58 5.8
Isopropanol 60 6.0
Ethylene Glycol 62 6.2
Propylene Glycol 76 7.6

Normal lab values

For medical purposes ethanol is measure in serum (or plasma). A 'normal' serum ethanol concentration is zero but often reported as 'negative' or < 10 mg/dL. Whole blood ethanol concentrations are ~ 16% less than serum ethanol concentrations. This subtle difference can be important in some cases where hospital records are used for legal purposes. Normal anion gap is < 14; > 25 suggests severe poisoning. Normal osmol gap is approximately -10 to 10 mOsml/L.

How do I know this is what the patient has

An atraumatic patient who presents with altered sensorium or clinical inebriation is suggestive of ethanol intoxication, though other conditions may be involved. A comatose patient with an osmol gap and anion gap acidosis is suggestive of toxic alcohol poisoing. Acute kidney injury and calcium oxalate crystals suggest EG; visual symptoms suggest MetOH.

Differential diagnosis

A patient suspected of an ethanol or toxic alcohol ingestion should be evaluated for all of the following: hypoglycemia, alcoholic ketoacidosis, trauma, and other ingestions. Focal neurologic findings in a clinically intoxicated patient mandate further testing (e.g. CT scan of the head). Seizure, including post-ictal state, should be considered in patients with altered sensorium.

Confirmatory tests

Confirmatory testing involves documenting a blood (serum) concentration. A comprehensive urine drug test utilizing GCMS mayconfirm the presence of ethanol, methanol, or isopropanol but will not provide a concentration.

4. Specific Treatment

All patients with alcohol intoxication are at risk for dehydration and electrolyte abnormalities, which should be corrected. Consider replacing thiamine, folate and magnesium in malnourished patients. Oral administration should be used for most patients. Higher doses of thiamine are recommended if Wernicke's encephalopathy is a concern.

Gastrointestinal decontamination is not indicated for alcohol toxicity.

Ethylene glycol and methanol intoxication should be treated with fomepizole or ethanol to inhibit ADH.

Co-factor therapy can be used to assist with the enhancement of non-toxic metabolites. Folate should be used for MetOH toxicity, thiamine and pyridoxime for EG.

All patients with ethanol abuse are at risk for potential withdrawal. Treatment involves the use of scheduled oral benzodiazepines, with intravenous doses used, as needed, for worsening signs/symptoms. Severe withdrawal often requires large, repeated doses of IV GABA-agonists.

Drugs and dosages

Fomepizole's dose is 15 mg/kg IV, then 10 mg/kg IV q12h for four doses, then increased back to 15 mg/kg IV q12h. Fomepizole is given q4h during hemodialysis; specific dosing during HD should be discussed with a poison control center or a medical toxicologist.

Ethanol administration (using 20% EtOH solution for oral or 10% EtOH solution for IV administration): loading dose 0.8 grams/kg over one hour; then 80-150 mg/kg/hr infusion. Frequent serum alcohol concentration should be checked to help adjust dosing.

Fomepizole or ethanol should be continued until the toxic alcohol concentration is < 25 mg/dL and serum pH has normalized.

Co-factor therapy should be used for significant ingestions. For MetOH toxicity: folate 50 mg IV q4h for 24 hours. For EG toxicity: thiamine 100 mg IV q6h for 24 hours, and pyridoxime 50 mg IV q6h for 24 hours.

Patients at risk for ethanol withdrawal should be started on a long-acting benzodiazepine, given orally and titrated based on symptoms. A typical starting dose is diazepam 10 mg PO q6h. Additional doses, as needed for worsening withdrawal, can be given IV. Severe ethanol withdrawal should be treated with escalating IV doses of a benzodiazepine or barbiturate in a 'front-loading' technique.

The routine use of adjunctive agents to correct abnormal vital signs is not recommend. The use of beta-blockers to control EtOH withdrawal-induced tachycardia or hypertension neither addresses the underlying pathophysiology nor lowers the risk of seizures. Non-emergent hypertension should be treated with benzodiazepines. Persistent hypertension despite resolution of withdrawal symptoms suggests underlying hypertension. Patients with an established history of hypertension should be restarted on their antihypertensive agent(s).

Ethanol withdrawal is best treated by experienced staff. Patients in, or at risk for, severe withdrawal should be monitored and treated in an intensive care unit. Optimal management may be aided by the use of an assessment tool such as the CIWAS-Ar.

Refractory cases

Hemodialysis may be required for toxic alcohol poisoning with any of the following: significantly elevated concentration, renal insufficiency, or severe acidosis / electrolyte disturbances not corrected with medical management.

Hemodialysis should be continued until a pre-cartridge blood sample contains < 25 mg/dL of the toxic alcohol. This may require more than the 'typical' four-hour run of HD. Arrangements should be made to prevent any interruption of treatment.

5. Disease monitoring, follow-up and disposition

Expected response to treatment

Patients who receive treatment for toxic alcohol poisoning before developing severe acidosis or end-organ damage should make a rapid, complete recovery with optimal therapy. Mild dysfunction (e.g. acidosis, acute kidney injury, visual symptoms) should resolve quickly with treatment.

Incorrect diagnosis

Several small studies have identified the average rate of EtOH metabolism to be approximately 20 mg/dL/hr. Although true for some patients, assuming that a chronic alcoholic metabolizes EtOH at a greater rate, this is difficult to quantify for individual patients. Repeating EtOH concentrations towards this end is not recommended. Disposition decisions, including discharge and informed consent capacity, for patients inebriated from EtOH should be based on the resolution of objective, clinical intoxication.


All patients with substance abuse issues should receive a social work consult. Intentional ingestions warrant psychiatric evaluation. Patients with renal failure following EG ingestion should be seen by nephrology for outpatient dialysis, though recovery is expected within weeks to months.


Chronic ethanol use leads to down-regulation of GABA receptors and up-regulation of NMDA receptors. This explains the toleranceseen after chronic abuse and why some patients may not manifest signs of inebriation despite elevated serum concentrations.

Abrupt cessation of ethanol use leads to depressed GABA receptor activity and enhanced NMDA receptor activity. These combined effects lead to the clinical manifestations of CNS, neuromuscular, and autonomic hyperactivity.

Toxic alcohols (including EG, MetOH, IPA) are osmotically active compounds with limited inherent toxicity. They undergo endogenous metabolism via ADH to form toxic metabolites, which are responsible for clinical pathology.

Ethanol enhances GABA activity within the CNS, leading to neurologic and respiratory depression. Clinical effects are due to enhanced GABA-mediated chloride channel activity resulting in increased chloride entry into cells and lowering of the membrane potential. In addition, ethanol inhibits NMDA glutamate channels, receptors that normally result in CNS stimulation. The end result is CNS and neuromuscular depression.

Ethylene glycol is first converted to glycoaldehyde via ADH. Additional metabolism, including aldehyde dehydrogenase, subsequently forms glycolic, glyoxylic, and oxalic acids. Oxalic acid complexes with calcium to form calcium oxalate crystals. These crystals can precipitate in tissue, leading to organ dysfunction. Formation of crystals in renal tubules explains the nephrotoxicity commonly encountered with EG poisoning.

Methanol is converted to formaldehyde via ADH. Aldehyde dehydrogenase then forms formic acid, which is converted to formate, a mitochondrial toxin that interferes with oxidative phosphorylation. Retinal and optic nerve cells are particularly sensitive to this toxicity, explaining the frequently encountered ocular pathology.

Isopropanol is metabolized by ADH to acetone. Both compounds are capable of significant CNS depression and, in general, result in limited systemic toxicity. Acetone is a ketone, which unlike other toxic alcohols' metabolites does not result in an anion gap, metabolic acidosis.


According to AAPCC 2008 data, all alcohols accounted for 3.5% (86,588) of all calls to US poison control centers. Ethylene glycol was involved in 36 reported deaths, MetOH in 12. Fomepizole was used 1,679 times. There were 21,108 calls concerning IPA-containing products, with 4 reported deaths.AAPCC data only includes those cases reported to a poison center. The full extent of morbidity and mortality associated with ethanol and toxic alcohol poisonings is unknown.


With early, optimal treatment most patients will recover without permanent sequelae. Acute kidney failure, including the need for hemodialysis, should recover within weeks to months. Methanol-induced blindness may be permanent.

Special considerations for nursing and allied health professionals.

Patient with significant acidosis should have an arterial line placed. Any degree of acute kidney injury warrants a bladder catheter and strict volume records. All patient should be questioned about ethanol abuse. Ethanol withdrawal should be monitored for or prevented with prophylactic use of benzodiazepines.

What's the evidence?

Note: many references cover several of these subsections.

Description of the problem

Brent, J. "Current management of ethylene glycol poisoning". Drugs. vol. 61. 2001. pp. 979-88.

(Great overview of the pathophysiology, stabilization and treatment of EG poisoning.)

Pitzele, HZ, Tolia, VM. "Twenty per hour: altered mental state due to ethanol abuse and withdrawal". Emergency Medicine Clinics of North America. vol. 28. 2010. pp. 683-705.

(Overview of ethanol abuse epidemiology, pathophysiology and treatment. Ethanol withdrawal is also discussed.)


Kraut, JA, Kurtz, I. "Toxic alcohol ingestions: clinical features, diagnosis, and management". Clinical Journal of the American Society of Nephrology. vol. 3. 2008. pp. 208-25.

(Concise overview of diagnosis, clinical findings and management of toxic alcohol poisonings.)

Perper, JA, Twerski, A, Wienand, JW. "Tolerance at high blood alcohol concentrations: a study of 110 cases and review of the literature". Journal of Forensic Sciences. vol. 31. 1986. pp. 212-21.

(Concludes that clinical evidence of ethanol inebriation does not correlate well with blood alcohol concentrations.)

Specific Treatment

Amato, l, Minozzi, S, Vecchi, S, Davoli, M. "Benzodiazepines for alcohol withdrawal". Cochrane Database of Systematic Reviews. vol. 17. 2010. pp. CD005063.

(A good overall review of the treatment of ethanol withdrawal.)

Barceloux, DG, Bond, GR, Krenzelok, EP, Cooper, H, Vale, JA. "American Academy of Clinical Toxicology practice guidelines on the treatment of methanol poisoning". Journal of Toxicology Clinical Toxicology. vol. 40. 2002. pp. 415-46.

Barceloux, DG, Krenzelok, EP, Olsen, K, Watson, W. "American Academy of Clinical Toxicology practice guidelines on the treatment of ethylene glycol poisoning". Journal of Toxicol Clinical Toxicology. vol. 37. 1999. pp. 537-60.

Jacobsen, D, McMartin, KE. "Antidotes for methanol and ethylene glycol poisoning". Clinical Toxicology. vol. 35. 1997. pp. 127-43.

(Nice overview of therapeutic options.)

Lepik, KJ, Levy, AR, Sobolev, BG, Purssell, RA, DeWitt, CR, Erhardt, GD, Kennedy, JR, Daws, DE, Brignall, JL. "Adverse drug events associated with the antidote for methanol and ethylene glycol poisoning: a comparison of ethanol and fomepizole". Annals of Emergency Medicine. vol. 53. 2009. pp. 439-50.

(Comparison of fomepizole and ethanol for the treatment of toxic alcohol poisonings.)

Brent, J, McMartin, K, Phillips, S, Aaron, C, Kulig, K. "Fomepizole for the treatment of methanol poisoning". New England Journal of Medicine. vol. 344. 2001. pp. 424429.

(The sentinel paper describing the use of fomepizole for methanol toxicity.)

Brent, J, McMartin, K, Phillips, S, Burkhart, K, Donovan, JW, Wells, M, Kulig, K. "Fomepizole for the treatment of ethylene glycol poisoning". New England Journal of Medicine. vol. 340. 1999. pp. 832-8.

(The sentinel paper describing the use of fomepizole for ethylene glycol toxicity.)

Sullivan, JT, Swift, RM, Lewis, DC. "Benzodiazepine requirements during alcohol withdrawal syndrome: clinical implications of using a standardized withdrawal scale". Journal of Clinical Psychopharmacology. vol. 11. 1991. pp. 291-5.

(Use of CIWA-Ar for ethanol withdrawal and required benzodiazepine doses.)

Disease monitoring, follow-up and disposition

Sullivan, JT, Sykora, K, Schneiderman, J, Naranjo, CA, Sellers, EM. "Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar)". British Journal of Addiction. vol. 84. 1989. pp. 1353-1357.

(Overview of the CIWA scale.)

Jones, AW. "Evidence-based survey of the elimination rates of ethanol from blood with applications in forensic casework". Forensic Science International. vol. 200. 2010. pp. 1-20.

(General review of the rate of ethanol metabolism.)

Jones, AW, Andersson, L. "Influence of age, gender, and blood-alcohol concentration on the disappearance rate of alcohol from blood in drinking drivers". Journal of Forensic Science. vol. 41. 1996. pp. 922-6.

(Concise prospective study evaluating the rate of ethanol metabolism in drinking drivers.)


Dopico, AM, Lovinger, DM. "Acute alcohol action and desensitization of ligand-gated ion channels". Pharmacological Reviews. vol. 61. 2009. pp. 98-114.

(Discusses the effects of ethanol on various receptor subtypes.)

Pizon, AF, Becker, CE, Bikin, D. "The clinical significance of variations in ethanol toxicokinetics". Journal of Medical Toxicology. vol. 3. 2007. pp. 63-72.

(In-depth review of ethanol kinetics.)

Tabarkoff, B, Cornell, N, Hoffman, PL. "Alcohol tolerance". Annals of Emergency Medicine. vol. 15. 1986. pp. 1005-12.

(Overview of the development of tolerance for ethanol.)

McKellar, MJ, Hidajat, RR, Elder, MJ. "Acute ocular methanol toxicity: clinical and electrophysical features". Australian and New Zealand Journal of Ophthalmology. vol. 25. 1997. pp. 225-30.

(Clinical review of methanol's ocular pathophysiology in two cases of human poisoning.)

McMartin, K. "Are calcium oxalate crystals involved in the mechanism of acute renal failure in ethylene glycol poisoning?". Clinical Toxicology. vol. 47. 2009. pp. 859-69.

(Review of the pathophysiology of ethylene glycol-induced acute kidney injury.)



Kalkan, S, Cevik, AA, Cavdar, C, Aygoren, O, Akgun, A, Ergun, N, Tuncok, Y. "Acute methanol poisonings reproted to the drug and poison information center in Izmir, Turkey". Veterinary and Human Toxicology. vol. 45. 2003. pp. 334-7.

(Retrospective review of 113 cases of methanol toxicity; clinical signs and outcomes are reported.)

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