Methanol poisoning results from accidental or voluntary ingestion of methyl alcohol, a compound used in the chemical industry and as fuel. Methanol is in no case suitable for consumption.
Presentation
Methanol causes inebriation similar to ethanol and patients may merely appear drunk, lose their inhibitions and become ataxic. At the same time, gastrointestinal symptoms manifest. MP patients typically suffer from nausea, vomiting, diarrhea and abdominal pain. If they are examined that early, tachypnea, tachycardia, and hypertension may already be detected. They result from metabolic acidosis. In severe cases, fatal respiratory or cardiac failure may occur.
The stage described above is usually followed by a latency period of several hours, generally 12 to 24 hours. Only then, neurological symptoms can be observed. The more methanol has been ingested, the earlier additional symptoms set in. Simultaneous consumption of ethanol delays onset of further deficits since both alcohols are competitive substrates for alcohol dehydrogenase.
Progressive vision loss is characteristic for MP and patients may claim blurred vision, scotomas, scintillations, visual field restriction and eventually complete blindness. Seizures may be registered. Patients show increasingly reduced levels of awareness and may fall into a coma.
Workup
Diagnosis of MP is based on anamnestic data, clinical presentation and laboratory analysis of blood samples.
Patients may have a history of alcohol abuse, or report having drunk the night before, but due to the high toxicity of methanol metabolites, MP may result from consuming minor quantities of spirits. Patients have to be queried accordingly, they may not relate alcohol intake and symptoms. Simultaneous admission of several patients with similar symptoms should raise suspicion of MP, particularly if all patients attended the same event.
High anion gap metabolic acidosis and base deficit are characteristic findings in MP patients. Serum bicarbonate concentrations are below reference ranges, concentrations of lactate and ketones are increased.
Evaluation of serum levels of methanol, ethanol and formate may be helpful in assessing the severity of the disease.
Because a major share of MP patients develops pancreatitis, serum amylase concentrations should also be measured.
MP patients should undergo a thorough ophthalmologic examination and possible electroretinography to assess vision, visual fields, and retinal function. Optic disc hyperemia and blunted pupillary reflexes are commonly observed, but retinal lesions can generally not be detected. However, MP does cause loss of retinal sensitivity and results in decreased signal amplitudes as measured by electroretinography.
Because basal ganglia may also be compromised, brain imaging - either by magnetic resonance imaging or by computed tomography - should be carried out. Common findings are hemorrhages and necroses of the putamen, but white matter lesions and cerebral edema have also been observed [10]. Of note, anomalies may not be detectable until several days after symptom onset.
Treatment
MP treatment consists in preventing further increases of toxic metabolite concentrations, preventing damage by circulating metabolites and compensating for already manifest symptoms. The following therapeutic measures may be applied to this end:
- Application of fomepizole and/or ethanol. Both are substrates of alcohol dehydrogenase, but have a higher affinity than methanol, and are thus competitive antagonists of methanol oxidation by this enzyme. Fomepizole is preferred over ethanol because the latter causes side effects corresponding to ethanol intoxication. However, fomepizole stocks are generally limited, if the drug is available at all. It is also very expensive.
- Administration of bicarbonate to counteract metabolic acidosis. This measure may also relieve neurological symptoms.
- Hemodialysis aims at removing methanol and its metabolites from circulation. Hemodialysis is indicated in moderate to severe cases, i.e., if patients don't respond to the aforementioned measures and/or present neurological symptoms.
- Fluid therapy is indicated in case of dehydration.
Besides drug therapy, patients may suffer from respiratory depression and require mechanical ventilation.
Prognosis
MP is associated with high mortality rates; survivors may suffer from permanent sequelae due to the optic nerve and central nervous system lesions. Although treatment protocols are well established, diagnosis is often delayed because of initial, non-specific symptoms and failure to relate recent alcohol consumption to the patient's condition. Most patients do not know they ingested methanol and may not even report having had a drink the night before.
Severe metabolic acidosis (pH < 6.90, base deficit > 28 mmol/l), respiratory arrest and coma have been identified as unfavorable prognostic parameters [5]. A severity of symptoms and thus, the likelihood of a poor outcome, correlate with the amount of ingested methanol and are inversely related to the quantity of consumed ethanol.
A dose of 6 g methanol per kg body weight is lethal, but fatalities have also been registered after consumption of doses as low as 200 mg/kg.
Etiology
Methanol is a chemical whose formula is CH3OH, i.e., a molecule of methanol consists of a single carbon atom which forms four bonds. Three bonds are saturated with hydrogen atoms, the fourth with a hydroxyl group. At room temperature, methanol is a clear, colorless liquid. Its boiling point is approximately 65 °C.
Thus, methanol shares many properties with ethanol, the second simplest alcohol compound. Its formula is CH3-CH2OH, i.e., one of those hydrogen atoms bound to the single carbon atom in methanol is replaced with a methyl group. At room temperature, ethanol is also clear and colorless. It's less volatile than methanol because its boiling point is at 78 °C. Although methanol tastes sweeter than ethanol, this difference may not be noted in alcoholic beverages that contain other ingredients.
The above-described similarities bear the risk of confusion and have been taken advantage of by unscrupulous people who dilute alcoholic drinks with methanol in order to maximize their profit [1]. Because such non-drinkable mixtures are generally sold to many people, MP generally affects many patients at the same time. Thus, "outbreaks" are reported. Of note, the aforementioned measure of ethanol dilution has also been taken by alcoholics in need of their addictive drug [2].
Epidemiology
MP is mainly reported in developing countries [1]. However, repeated outbreaks in industrialized nations illustrate the necessity of awareness in these geographical regions, too. In recent years, outbreaks have been observed in the Czech Republic, Estonia and Norway [3] [4] [5]. In sum, a total of 326 cases of MP were confirmed during these three outbreaks. 118 patients died either outside the hospital or while being hospitalized; this corresponds to a mortality rate of 36%.
Isolated cases corresponding to intended suicide are rare but have been described [6].
The following patient groups are considered to have an increased risk of MP:
- People living in or traveling to developing countries. Here, methanol is frequently used as a cheap substitute of ethanol. With regards to the local population, people of low socioeconomic status, frequently living in rural areas, are most likely to consume methanol-containing beverages. Travelers are advised not to drink any home-made spirits; they may, however, not be able to recognize which drinks are prepared with such alcohols. In South-East Asia, a tourist presented MP after consuming a drink at a public bar [7].
- Alcoholics may choose to consume methanol-containing drinks if they are unable to procure potable alcohol.
- Children may accidentally ingest household products that contain methanol.
- Employees of methanol-processing plants or laboratories may be exposed to the alcohol, which is readily absorbed through the skin.
Pathophysiology
Methanol itself has a low toxicity; detrimental effects seen in MP patients are mediated by its metabolites.
Methanol is almost exclusively ingested per os and is easily absorbed through the mucous membranes lining the gastrointestinal tract; in rare cases, employees of methanol-processing installations may be in direct contact with methanol and absorb the alcohol through the skin. Absorbed methanol is then transported to the liver, where the enzyme alcohol dehydrogenase catalyzes its oxidation to formaldehyde. Subsequent conversion of formaldehyde to formic acid is mediated by formaldehyde dehydrogenase [8].
The time-limiting step in methanol metabolism is the oxidation of methanol and because it takes hours until significant amounts of formaldehyde are generated, symptom onset after methanol intoxication occurs in a delayed manner. Once formaldehyde is available, formic acid is produced rapidly. Both formaldehyde and formic acid are highly toxic, but, as has been explained, the half-life of formaldehyde is much shorter.
Further metabolization of formic acid does occur - it is indeed degraded to carbon dioxide and water by the enzyme 10-formyl tetrahydrofolate synthetase - but this process is slow. Consequently, formic acid accumulates in the body of a patient who ingested methanol, and this compound accounts for symptoms characteristic for MP. There is a direct correlation between formic acid concentrations, morbidity, and mortality of MP.
Formic acid primarily causes high anion gap metabolic acidosis. It is also neurotoxic and provokes optic nerve demyelination and atrophy, which results in visual impairment or even complete blindness. Interference with the mitochondrial electron transport chain and disruption of ATP-dependent processes is assumed to account for nerve lesions [9]. Further damage to the central nervous system, mainly to basal ganglia, occurs in MP patients and may be mediated by similar mechanisms.
Prevention
In many countries, methanol is only sold to factories and laboratories that hold an appropriate license [6]. This way, neither people who'd like to use methanol as an inexpensive substitute of ethanol nor those who are ignorant of the compound's toxicity can easily procure methanol. However, individuals may still steal and resell the alcohol. Thus, it is of utmost importance to educate people about the risks associated with methanol consumption. This applies to teenagers as well as adults, to people of low socioeconomic status, alcoholics and employees of institutions that work with methanol.
Unambiguous labeling of methanol-containing receptacle prevents confusion. Any corresponding industrial and laboratory equipment should be maintained in good condition. This also applies to entrance barriers. Safety measures should be taken when transporting methanol.
Summary
Methanol is a compound that may also be referred to as methyl alcohol or, colloquially, as wood alcohol or wood spirit. Today, it is mainly used in the chemical industry. Here it serves as a base material for the synthesis of formaldehyde, formic acid, and acetic acid. These compounds are utilized in a plethora of production processes carried out in the automotive and construction sector as well as in the wood industry. Methanol itself may be used as a solvent and in this form, it may be encountered in paints, varnishes, thinners and similar products. Because its melting point is much lower than that of water, methanol is also added to deicing and windscreen washing fluids.
The latter may be accidentally ingested and cause methanol poisoning (MP), although ethylene glycol poisoning will dominate the clinical picture in such cases. MP more commonly occurs due to a substitution of potable alcohol with methanol. This may occur in an intent to stretch alcoholic beverages and to maximize profit or to mix a drink that provokes inebriation if ethanol cannot be procured. Accidental ingestion of household products by children and intended suicide have also been related to MP.
Initially, MP patients show symptoms of inebriation, i.e., speech disorders, loss of inhibition and ataxia. Nausea, vomiting, and diarrhea are common. In severe cases, respiratory arrest may lead to death within hours after consumption of methanol-containing beverages, but in most cases, patients pass through a latency period of several hours before manifesting neurological symptoms like visual impairment, seizures, and loss of consciousness. A "blind drunk" is highly suspicious for MP.
Diagnosis is confirmed after interpretation of blood sample analyses. These reveal severe metabolic acidosis, increased concentrations of methanol, ethanol and formate, and possibly elevations of amylase concentrations. Ophthalmologic examination and neuroimaging complete MP workup.
Administration of fomepizole and/or ethanol, hemodialysis, mechanical ventilation and therapy of acid-base and electrolyte imbalances are the mainstays of therapy. Despite well-established protocols, MP is often diagnosed belatedly and mortality rates of more than 30% are commonly observed.
Patient Information
Methanol is an alcohol that shares many properties with ethanol, which is the chemical compound corresponding to potable alcohol. At room temperature, methanol is a clear, colorless and liquid. It tastes somewhat sweeter than ethanol, though. If sufficient quantities are consumed, both compounds provoke inebriation, e.g., the affected individual appears drunk, loses their inhibitions, shows speech and walking difficulties. Nausea, vomiting, and diarrhea are common.
However, ingestion of methanol causes additional, severe symptoms, which is why methanol is in no case suitable for consumption and accidental intake of this compound is referred to as methanol poisoning. The aforementioned, additional manifestations are life-threatening respiratory depression, cardiac failure, visual impairment or blindness and central nervous system damage. Up to a third of all patients diagnosed with methanol poisoning die from this condition.
MP more commonly occurs due to a substitution of potable alcohol with methanol. This may occur in an intent to stretch alcoholic beverages - a custom that is mainly observed in developing countries, but that has been described in industrialized nations, too. Alcoholics may be tempted to consume methanol instead of ethanol if they can't procure their addictive substance. Accidental ingestion of methanol-containing household products by children and intended suicide have also been related to MP.
In order to avoid involuntary ingestion of methanol, travelers are strongly advised not to drink home-made spirits they may be offered abroad.
References
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- Sharma P, Sharma R. Toxic optic neuropathy. Indian J Ophthalmol. 2011; 59(2):137-141.
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