Abstract
When clinicians treat patients with pesticide poisoning, they often pay attention only to the chief toxic agent and ignore the toxicity of the pesticide’s additives or solvents. Occasionally, however, a solvent (e.g. methanol) may itself be the cause of poisoning. We report a case of acute methanol intoxication that occurred after ingestion of a methomyl pesticide that contained methanol as an additive. A 49-year-old man was brought to the emergency department in an unconscious state after ingestion of 20 ml of a carbamate pesticide (chief ingredient: methomyl; active ingredient: methanol). Upon arrival, he was semicomatose and did not breathe spontaneously; however, his cholinesterase level was within normal limits and cholinergic symptoms were not observed. High anion gap metabolic acidosis was present. His blood ethanol level was 74.8 mg/dL. The urine methanol level was 55.60 mg/dL, and urine ethanol level was 22.0 mg/dL. He was treated with hemodialysis; subsequently, his metabolic acidosis resolved and he returned to normal mental status. We guessed that methanol, as the solvent of the methomyl, had produced the symptoms. When treating pesticide-poisoned patients, clinicians should identify the solvent used in the pesticide, because solvents such as methanol may exacerbate the symptoms of poisoned patients.
Introduction
Methanol is highly toxic to humans.1 –3 If ingested, as little as 10 ml of pure methanol can cause permanent blindness by destruction of the optic nerve; 30 ml is potentially fatal, although the median lethal dose is typically 100 ml (1–2 mL/kg of pure methanol).4,5 Toxic effects take hours to manifest, and effective antidotes can often prevent permanent damage. Methanol is readily available at various concentrations in numerous industrial and household products. It is a common laboratory solvent. The most important use of methanol by far, however, is in making other chemicals. About 40% of methanol is converted to formaldehyde and then into products as diverse as plastics, plywood, paints, explosives, and permanent-press textiles. Methanol is also used as a solvent in the formulation of some pesticides. Exposure to methanol is common at both the workplace and the household, and this compound is often intentionally ingested by alcoholics. However, the incidence of methanol intoxication differs enormously from country to country.6,7 Intentional and/or accidental ingestion of the pesticide in which methanol is an additive may cause methanol intoxication. In some Asian countries, thousands of cases of acute pesticide intoxication occur each year as a result of ingestion of undiluted pesticides, which may be either accidental or deliberate. When these patients arrive at a hospital, the treating physician is likely to pay attention only to the chief toxic agent and ignore the toxicity of additives such as methanol, the usual solvent. Herein, we describe a patient who showed acute methanol intoxication after ingestion of a methomyl pesticide that contained methanol as an additive. The calculated volume of ingested methanol was 20 mL, and the patient arrived at the hospital 12 h after ingestion. In this article, we have summarized the patient’s clinical characteristics.
Case presentation
A 49-year-old man was brought to the emergency department (ED) in an unconscious state after ingestion of 20 ml of a carbamate pesticide (chief ingredient: methomyl; active ingredient: methanol). He ingested it in a suicide attempt about 2.5 h before arrival at the hospital. He was also in a drunken state, because he drank about 152 g of ethanol (1000 ml × 19% × 0.8) before ingesting the pesticide.
The patient came to our attention because of the rapid worsening of toxic symptoms. In the ED, the patient’s blood pressure was 130/90 mm Hg, his pulse rate was 120 beats/min, and his body temperature was 36°C. Upon arrival in the ED, he became semicomatose and spontaneous respiration ceased. Emergency treatment was initiated, including tracheal intubation and mechanical ventilation. Cholinergic symptoms of salivation, sweating, and lacrimation were not observed in the ED. Sequential measurements of blood chemistry, complete blood count, and blood gases are summarized in Table 1. Rhabdomyolysis was detected in the initial laboratory testing. We treated the patient on the basis of a diagnosis of carbamate intoxication. High anion gap metabolic acidosis persisted after bicarbonate was injected intravenously. Hemodialysis (Gambro AK 95S Hemodialysis machines, blood flow 250ml/min, Dialysate flow 500 ml/min) was performed for 4 h. After hemodialysis, the metabolic acidosis improved and his mental status recovered.
Sequential measurements of blood laboratory data
aInitial laboratory results were obtained in the emergency room. Note that the blood chemistry test results are suggestive of rhabdomyolysis.
PT: prothrombin time; INR: international normalized ratio.
The pseudocholinesterase level was 7575 U/L (normal: 3400–14200) and red blood cell cholinesterase level was 12,483 U/L (normal: 11,188–16,698). We thought that his mental status and metabolic acidosis had not been induced by the carbamate and might have been induced by other agents that cause a high anion gap. We measured blood levels of ethanol and formic acid, and the urine methanol level, both because of his drunken state and the fact that the solvent for methomyl was methanol. The blood ethanol level was 74.8 mg/dl and formic acid was not detected by gas chromatography–mass spectrometry in the emergency department. The urine methanol level was 55.60 mg/dl by gas chromatography, and the urine ethanol level was 22.0 mg/dl. After hemodialysis, the blood ethanol level was less than 0.1 mg/dl, and the urine methanol and ethanol levels were 5.5 mg/dl, and 1.4 mg/dl, respectively. On the second day, his respiratory and mental status had recovered and he was successfully extubated. He was discharged without any complications on the seventh day.
Discussion
Methomyl is a widely used carbamate insecticide. Carbamates are cholinesterase inhibitors that are currently used as agricultural and household pesticides. 8 Symptoms of acute carbamate poisoning are similar to the cholinergic crisis that is observed with organophosphate compounds. However, because of transient cholinesterase inhibition and rapid enzyme reactivation, carbamates are generally considered to be less toxic than organophosphate compounds of comparable toxicity. 9 Cholinergic symptoms include salivation, lacrimation, urination, and sweating.
In this case, the patient’s mental status was impaired although he did not show symptoms of cholinergic crisis. We retrospectively checked that the cholinesterase activity was within normal range. This finding suggested that other factors besides methomyl poisoning were affecting our patient’s central nervous system. The suspected culprits were ethanol intoxication and methanol poisoning.
Before his methomyl poisoning, the patient was already in a drunken state. His blood ethanol level was 74.8 mg/dl at the ED. The signs and symptoms of ethanol intoxication can vary widely depending on the patient’s genetics; the type, amount, and rate of ethanol intake; and the frequency and pattern of ethanol use. Among patients who do not abuse ethanol, euphoria and mild deficits in coordination, attention and cognition may be observed with a blood ethanol concentration between 0.01% and 0.10% (<100 mg/dl or 22 mmol/L). When the blood ethanol concentration exceeds 0.30% (300 mg/dl), stupor and loss of consciousness can occur, and some patients may experience coma and respiratory depression; death is possible. 10 We did not think that our patient’s blood ethanol level related well to his impaired mental status and respiratory failure.
The other factor could be methanol poisoning. Methanol is used as a solvent in the formulation of this pesticide. The initial symptoms of methanol intoxication include central nervous system depression, headache, dizziness, nausea, lack of coordination, confusion, and, with sufficiently large doses, unconsciousness, and death.1 –3,5 –7,11,12
Methanol is rapidly and completely absorbed after oral ingestion. A peak serum methanol concentration is reached within 1–2 h. Acute methanol poisoning should be suspected in all patients with metabolic acidosis with an elevated anion gap, neurological deterioration, or vision disturbances.
We calculated that the volume of methanol that our patient had ingested was 20 ml. Metabolic acidosis was the most striking disturbance seen in our patient. It was probably due to the accumulation of formic acid and lactic acid.
In this case, methanol was detected in urine although formic acid in the blood was not measured. We could not check the blood methanol level because of a technical problem. The initial acidosis could have been caused by lactic acidosis.
Our patient ingested ethanol as well as methanol. Because the same alcohol dehydrogenase competitively breaks down both ethanol and methanol, the administration of ethanol during methanol intoxication reduces the velocity of formic acid production. A concentration of 1 g/L ethanol is sufficient to fully block the degradation of methanol. 13 Therefore, in this case, the symptoms of methanol poisoning were attenuated by ethanol ingestion. Hemodialysis was performed because of the patient’s uncorrected metabolic acidosis. 14 In acute methanol poisoning, rapid recognition and early treatment including alcohol dehydrogenase inhibition are crucial. Unfortunately, we did not use the alcohol dehydrogenase inhibition. But, the patient recovered with conservative treatment after hemodialysis. In conclusion, methanol can exacerbate the symptoms of pesticide-poisoned patients, and clinicians treating these cases should identify the solvent used in the pesticide.
Footnotes
Funding
This work was carried out with the support of “the Cooperative Research Program for Agriculture Science & Technology Development (Project No. PJ008246)”, Rural Development Administration, Republic of Korea.