Avoiding Fatal Consequences of Adulterated Alcohol Requires Unexpected Treatment

Roxana Tabakman

August 12, 2019

Recently, Costa Rica reported 55 suspected cases of methanol intoxication, resulting in 23 deaths between June and July. This type of tragedy has already been experienced by countries such as Ecuador, Nicaragua, Norway, Czech Republic, India, Indonesia, and Iran, among others.

Colombia still remembers the so-called 'fatal wedding' in the 1960s in Bogotá, where the couple and several guests were affected by drinking adulterated alcohol.

In Nicaragua, in 2006, 788 people were affected (50 died, 15 lost their sight) after ingesting what purported to be guaro (sugar cane liquor), but was in fact a home-made distilled alcohol containing methanol.

A thousand people died from drinking toxic alcohol in the 1960s in Spain and in 2011, six teenagers were hospitalised in Barcelona after drinking methylated spirits mixed with fruit juice at a small party that they had organised.

Appropriate Action

"When there is one case, there are generally many", claim Doctors without Borders and the Oslo University Hospital in the Methanol Poisoning Initiative.

The consumption of beverages adulterated with methanol happens sporadically in countries that sell distilled alcohols like vodka, pisco, tequila or other spirits that may be illegally adulterated for economic reasons, or in countries like Iran, where drinking alcohol is banned.

The effect of treatment reduces when effective medical attention is delayed, and the waiting time for patients to receive effective care influences the mortality rate, which in some cases exceeds 30%, with significant morbidity for the survivors.

When there is little methanol in the drink, the toxicity is not evident as the ethyl [alcohol] itself acts as an antidote. If the proportions exceed the dosage limits, then signs of intoxication appear. The range for causing death is broad and varies if it is consumed with ethyl alcohol.

However, "between 4 and 5 ml of methanol is already enough to cause blindness", Professor Aldo Sergio Saracco told Medscape in Spanish . He's an emergency doctor and toxicologist from the Argentine Toxicology Association and director of the Observatory for Public Health and Consumer Issues, at the Faculty of Medicine at the National University in Cuyo, Mendoza, Argentina.

Drunkenness That Does Not Get Better

A limited knowledge of methanol intoxication contributes to delay in the starting of treatment. At 12 to 24 hours after ingestion, the symptoms and signs are not specific; the person appears in a state of mild drunkenness and drowsiness that is readily confused with ethanol intoxication. "The specific symptoms do not appear immediately", explains Prof Saracco. "The patient shows signs that are similar to being drunk; the normal measures are taken, blood sugar is controlled, the patient is wrapped-up and kept under observation. However as time passes, instead of getting better, the toxic effects of methanol appear."

Between 8 and 36 hours they may experience headaches, stomach pains, vomiting, diarrhoea, rapid breathing and drowsiness, and have pale, cold and damp skin, fixed dilated pupils, slow pulse and low blood pressure. They may see flashing lights or complain of blurred vision or even blindness, and may progress to unconsciousness, convulsions and pulmonary oedema.

"The most common characteristic is blurred vision, with reduced visual acuity, which can progress to blindness. Formic acid, produced from metabolism of methyl alcohol, acts on the optic nerve and the retina. When it damages the optic nerve, the pupil remains dilated and fixed, and then blindness is usually irreversible," he says.

Diagnosis relies on clinical suspicion and analytical interpretation, and it may help to take into account previous consumption of illegal alcohol and the existence of other suspected or confirmed cases. "This is corroborated by the laboratory, with severe blood pH levels not seen in other illnesses apart from methyl or glycol alcohol intoxication," Prof Saracco adds.

Ethyl Therapy to 'Trick' the Liver

The most prominent therapy is the administration of ethyl alcohol. The treatment must be started quickly to avoid the liver metabolising the methyl alcohol into formaldehyde and formic acid, which cause the symptoms.

"With ethyl therapy we are intoxicating the patient, getting them drunk to avoid a greater evil," says Prof Saracco. "The liver has 10 to 20 times more affinity with ethyl alcohol than with methanol, and by administering ethanol orally or intravenously, the methanol that is not metabolised is excreted through the urine." In the most severe cases this may take up to 35 hours.

To saturate the liver, the medicinal alcohol must be administered in specific concentrations, according to the patient’s weight. The dose is 1 ml/kg of absolute alcohol, diluted to 50% for oral use, and to 5% or 10% for intravenous use.  Regular drinkers may require higher doses.

There is another therapy, 4-methylpyrazole also known as fomepizole, which "is the ideal therapy, because it inhibits the two enzymes that metabolise alcohol.  However in many countries, such as Argentina, it is not available, and when it is, it is expensive and, as it is not used frequently, it is not always permanently stocked," he says. This is also the case in the UK where the treatment is available only on special order.

In addition to supportive treatment, patients are usually administered bicarbonate, but this usually merely postpones the symptoms that are only avoided with antidotes. Folic acid is administered as a coadjuvant, which helps to metabolise the methanol to reduce its toxic effect.

In some cases, to remove the methanol and the formic acid, it is necessary to submit the patient to haemodialysis.

Priorities

The majority of occurrences happen in regions with limited resources, where one of the challenges is to use them in the best possible way. For this reason, a group of 22 experts from several countries (United States, Iran, Australia, Norway, United Kingdom, India, Czech Republic, Estonia, France, and Belgium) invited by Dr Hossein Hassanian-Moghaddam, from the Tehran University of Medical Sciences, recently defined the best treatment practices adapted to each situation. The objective was to create a consensus to guide decisions and processes in the case of an occurrence of methanol intoxication (see table).

The discussion was based on a series of cases that had a mortality rate of 5% to 83% (category 1: pH 7 and alert: mortality [5%]; category 2: pH 6.74 - 6.99 and alert: mortality [14%];  category 3: pH < 6.74, and alert, or pH 6 - 74 - 6.99 and coma: mortality [52%]; category 4: pH < 6.75, and coma: mortality [83%]).

Table

Consensus Declarations of Experts on the Focus of an Occurrence of Methanol Intoxication
Action/Definition
Level of recommendation and degree of evidence
Occurrence: Sudden increase in the number of cases in a short period (days or weeks) above the expected number for the population of the area. In the absence of data, consider three victims in 48 to 72 hours. Level 1D
Notify the health systems and actively search for cases. Level 2D
Use awareness level, pH, PCO2 for triage.  Level 1C
Patients with a high probability of methanol intoxication during an occurrence should quickly receive an antidote while further determinations are made. Level 1C
In case the following are available: both fomepizole and ethanol, the most serious patients should receive fomepizole and the less serious patients ethanol.  Level 1D
Fomepizole (15 mg/kg) is recommended for patients with serious intoxication (acidosis, visual disorders or coma). Level 1D
In light of the variable availability and the high price of fomepizole, in choosing between ethanol and fomepizole the focus recommends: "Use what is available". Level 1B
Patients who require antidote treatment also receive optimum treatment with bicarbonate, folic acid and support treatment. Level 1D
Prioritise extracorporeal elimination treatment in patients with altered vision, particularly in selecting patients from the same risk category. Level 1D
When the need exceed the resources, risk category 3 is a priority for extracorporeal elimination treatments. Level 1D
When there is a limitation on resources, the most stable patients can be transferred; patients from categories 1 and 2 should be a priority for transfer. Level 1D
The plan to transfer intoxicated patients to other hospitals in the region must consider the bed capacity, transfer distance, possibility of maintaining an optimum treatment during transfer, experience, availability of extracorporeal elimination and the expected result. Level 1D

Level 1: strong recommendation (95% of experts support the fact that the desirable affects exceed the undesirable affects).
Level 2: weak recommendation (more than 90% of experts disagree).
Level 3: neutral recommendation (more than 50% of the experts, but less than 90% support the fact that it is suitable in the appropriate context).
The level of evidence goes from degree A (high quality) to degree D (very low quality).

Adapted by  Hassanian-Moghaddam H, et al.  Clin Toxicol (Phila) 2019.

Prevention

Even with access to the best treatments, nothing is better than prevention, which depends in part on public policies, and which is not limited to controlling alcoholic beverages.

In the past, people in Argentina with alcoholism would frequently drink methanol as it was sold as methylated spirits. However recently the Ministry of Health managed to stop this and have methylated spirits replaced with denatured ethyl alcohol, incorporating substances that change the taste and smell. This has reduced the problem of intoxication from drinking low-cost alcohol.

Other important new regulations affect the manufacturers of methyl alcohol, which must be strictly registered according to where the product is destined. "It is also important to avoid accidental intoxication, preserving these toxic products in their original packaging", the consensus says, pointing out that a case had occurred in a biochemical laboratory where methanol had been put in a sweetener container, and one of the [staff] members [accidentally] intoxicated themselves.

When all preventive measures fail, treatment must be started immediately, along with measures to identify the origin of the problem and alert other possible victims.

Professor Saracco has declared no relevant financial conflicts of interests.

Translated from Medscape Spanish Edition .

References:

Costa-Pau M. Six minors intoxicated by ingesting methylated spirits. El país. Published 2nd February 2011. Accessed online. Source.
Methanol poisoning at a glance. Accessed online. Source.
Hassanian-Moghaddam H, Zamani N, Roberts DM, Brent J, et al. Consensus statements on the approach to patients in a methanol poisoning outbreak. Clin Toxicol (Phila). 22 Jul 2019:1-8. doi: 10.1080/15563650.2019.1636992. PMID: 31328583. Source.

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