Methanol is a highly toxic alcohol commonly found in automobile windshield washer solvent, gas line antifreeze, copy machine fluid, fuel for small stoves, paint strippers, and as an industrial solvent (Budavari 1996B; Suit 1990). Many new uses for methanol, predominantly as an alternative energy source, have also been proposed. If these new applications are developed, methanol is likely to become even more accessible in the future and therefore, more available for misuse.
As with ethylene glycol, the clinical course of methanol poisoning occurs over a number of hours. While methanol itself is only mildly intoxicating, it is converted to highly toxic metabolites responsible for acidosis, blindness, and potentially death. Because the morbidity for methanol poisoning is related to delay in treatment, real or suspected methanol poisoning creates many challenges for clinicians because laboratory tests, antidotes and intensive care facilities are not always available.
The lethal dose of pure methanol is estimates to be 1-2 mL/kg (Jacobsen 1986); however, permanent blindness and death have been reported with as little as 0.1 mL/kg (6-10 mL in adults) (ATSDR 1993).
In the 2002 Annual Report of the Toxic Exposure Surveillance System (TESS) by the American Association of Poison Control Centers (AAPCC), 2,610 exposures to methanol were reported. There were 18 deaths attributed to methanol and 55 near fatalities (Watson 2002).
Methanol, also known as methyl alcohol and wood alcohol, is a primary alcohol with the chemical formula CH3OH, a molecular weight of 32.04, a specific gravity of 0.81 and a boiling point of 65° C. It is colorless, volatile, flammable, and readily miscible in water (Budavari 1996B). It also has a light odor that is distinctly different from that of ethanol.
Methanol is readily absorbed from the gut, skin, and lungs. Peak serum concentration usually occurs in 30-60 minutes following oral ingestions. Methanol distributes widely in body water with a volume distribution of 0.6 L/kg. Methanol is slowly and erratically metabolized in the liver and follows zero order kinetics. Approximately 3% of a methanol dose is excreted through the lungs or excreted unchanged in the urine. The half-life of methanol is prolonged to 30-50 hours during antidotal therapy (Palatnick 1995).
Mechanism of Toxicity
Like ethylene glycol, methanol is relatively non-toxic; however, it is metabolized to highly toxic compounds that are responsible for the acidosis and blindness characteristic of methanol poisoning.
As in ethylene glycol poisonings, the initial step in the metabolism of methanol involves the enzyme alcohol dehydrogenase (ADH) (see Figure 2). First, methanol is slowly oxidized by ADH to yield formaldehyde. Next,formaldehyde is oxidized by formaldehyde dehydrogenase to yield formic acid (or formate, depending on the pH). This oxidation occurs rapidly so that little formaldehyde accumulates in the serum. FInally, formic acid is metabolized to carbon dioxide and water, which are excreted by the kidneys and lungs.
Figure 2. Metabolic Pathway of Methanol Toxicity (Adapted from Brent 2001)
The accumulation of formic acid is responsible for the presence of metabolic acidosis. Formic acid also inhibits cellular respiration leading to lactic acidosis. The ocular injury caused by methanol may be due to retinal injury, which results from intra-retinal metabolism of methanol and the accumulation of formic acid. Alternatively, it may be caused be the inhibition of normal metabolism in optic nerve calls (Jacobsen 1997).
Initial symptoms of methanol poisoning may appear as soon as 12 hours post-ingestion, but usually develop 24 hours after ingestion. These may resemble ethanol intoxication and consist of drowsiness, confusion, and ataxia, as well as weakness, headache, nausea, vomiting, and abdominal pain. Collectively, these symptoms may mimic an alcohol hangover and are due to mild intoxication, caused by methanol itself.
As methanol metabolism proceeds, a severe anion gap metabolic acidosis will develop. Severe metabolic acidosis in conjunction with visual effects are the hallmark of methanol poisoning. Patients usually describe blurred or misty vision, double vision, or changes in color perception. There my be constricted visual field and, occasionally, total loss of vision. Characteristic visual dysfunctions include pupillary dilation and loss of pupillary reflex (Burkhart 1990; Suit 1990).
Further signs and symptoms may be shallow respiration, cyanosis, tachypnea, coma, seizures, electrolyte disturbances, and various hemodynamic changes including profound hypotension and cardiac arrest. There may be mild to profound loss of memory, confusion, and agitation, which may progress to stupor and coma as the severity of the acidosis increases (Suit 1990). In severe cases, death is possible. Surviving patients can be left with permanent blindness or with other neurological deficits (Jacobsen 1997).
Methanol poisonings can be relatively difficult to diagnose when a specific history of ingestion is not available. Diagnosis requires both clinical and laboratory data; however, there may be an initial lack of clinical data for patients who are unable, or unwilling, to supply a history of ingestion. In such situations, obtaining a patient's history from family or friends can be valuable. In addition, it is often difficult for a clinician to distinguish between poisoning by methanol or by ethylene glycol.
The most direct means of diagnosing methanol poisoning is through the measurement of serum methanol concentration. The decision to perform a serum methanol determination may be based on patient disclosure of methanol ingestion or the presence of a methanol-containing product at the scene of ingestion. Other reasons to suspect methanol poisoning may be based on clinical signs together with laboratory findings such as anion gap metabolic acidosis and an osmolal gap. According to Kearney et al. (1997), only 39% of teaching hospitals were able to perform serum methanol determinations in-house.
An anion gap metabolic acidosis is not immediately seen following ingestion of methanol and may be due to other types of poisoning, including iron, salicylates, and ethylene glycol or disease states such as diabetic ketoacidosis or uremia. The presence of an osmolal gap may further support the diagnosis of methanol poisoning; however, its absence does not rule it out, as the osmolal gap will diminish as methanol metabolism proceeds. Also, other toxins, including other alcohols, will produce an osmolal gap. Finally, the co-ingestion of ethanol my produce a confusing clinical picture as the toxic effects of methanol may be masked or delayed (Jacobsen 1997).
Other diagnostic clues are ophthalmic changes and may include hyperemia of the optic disc or optic disc edema, and eventually, pallor (Jacobsen 1997).
A serum methanol concentration greater than 20 mg/dL soon after ingestion generally indicates the need for antidotal therapy; however, in late-presenting patients, any concentration of methanol in the presence of systemic toxicity should be treated.
As with ethylene glycol, the three primary goals of therapy include treatment of metabolic acidosis, inhibition of the methanol metabolism and enhanced elimination of the unmetabolized compound and existing toxic metabolites.
Gastric decontamination is unlikely to be beneficial because methanol is rapidly and completely absorbed from the gut. Ipecac-induced emesis is contraindicated due to the risk of rapid loss of consciousness. It is doubtful activated charcoal has the ability to absorb significant amounts of methanol; however, it may be useful if a co-ingestant is suspected. Gastric lavage would need to be performed soon after ingestion to be beneficial.
Stabilization of the critical patient must be performed before other therapies can be instituted. Correcting acid/base status should be a priority because serious metabolic acidosis is common and a pH less than 7 is associated with poor prognosis. Sodium bicarbonate should be administered to correct serum pH. Fluid and electrolyte replacement, airway management and the treatment of serious cardiovascular and neurological signs, such as hypotension and seizures, should also be a primary concern.
The elimination of methanol may be enhanced by administering folic acid, a cofactor in the conversion of formic acid to carbon dioxide, and by performing hemodialysis (Jacobson 1997).
Outcomes are excellent when asymptomatic methanol-poisoned patients are treated promptly. Reversal of presenting blindness, in one reported case, was attributed to prompt treatment (Sivilotti 1998). According to one study, poor outcomes were associated with coma or seizures on presentation or acidosis with pH less than 7 (Liu 1997).