Emergency physicians see toxicology cases every day, and the treatment for these cases is often just symptomatic care and stopping the offending agent. Certain cases, however, require specific antidotes to prevent significant morbidity and even mortality.
Toxicology cases are in many ways just as important as diagnosing sepsis or a ST-elevation myocardial infarction. Toxic alcohol cases fit into this “immediate treatment” category, like a patient we recently saw who drank windshield wiper fluid. She survived without any major morbidity or mortality thanks to early recognition and treatment by the emergency department staff. The early administration of fomepizole in this particular case likely prevented the harmful effects of these toxins.
As Amal Mattu, MD, says, “When other physicians hear hoof beats, they think of horses, but emergency physicians think of lions, tigers, and bears.” As emergency physicians, we are taught to think of the worst things first because we are often the first physicians to see a patient, and we often dictate the direction of their care. Many emergency department cases require prompt recognition and treatment to prevent significant morbidity and mortality.
This patient ingested a potentially toxic dose of methanol, and complications such as optic disk edema, metabolic acidosis, and anoxic brain injury were prevented simply by the prompt administration of antidote based on a thorough history and physical examination. The fomepizole was administered even before the onset of symptoms and laboratory abnormalities.
The patient was a 26-year-old woman with a history of self-reported attention deficit hyperactivity disorder who was brought in clinically intoxicated by EMS. The patient had been arguing with her boyfriend, and was visibly upset. She reported being anxious because of final examinations and other stressors she refused to identify. She argued with her boyfriend, and then ingested four 200 mg ibuprofen tablets and an unknown quantity of isopropyl rubbing alcohol. She later divulged that she also consumed an unknown but substantial amount of windshield washer fluid. The patient denied that this was a suicide attempt; she said she did this “to get a reaction” from her boyfriend. Her past medical history was significant for situational depression after a break-up several years before presentation, for which she was placed on bupropion, which was later discontinued.
She denied headache, dizziness, visual changes, chest pain, nausea, vomiting, diarrhea, hematemesis, and melena. Her vital signs in the ED were blood pressure of 134/76 mm Hg, heart rate of 91 bpm, temperature of 36.7°C, and a respiratory rate of 20 bpm. She had an oxygen saturation of 95% on room air, and her physical examination was unremarkable. She was alert and oriented with an intact neurologic examination, and had no positive findings for optic disk edema, abdominal tenderness, peritoneal signs, or Kussmaul breathing.
Treatment in the emergency department consisted of a fomepizole loading dose of 15 mg/kg over 30 minutes and 10 mg/kg maintenance infusion over the next 12 hours. The patient was also treated with a loading dose of magnesium for QT prolongation on ECG.
She was admitted to the hospitalist service, and eventually was medically cleared after another dose of fomepizole and a discussion with the poison control center. No metabolic acidosis or osmolar gap was appreciated on subsequent laboratory studies likely because fomepizole was promptly administered. No neurologic or ophthalmologic sequelae were appreciated on future physical examinations. The patient was eventually seen by psychiatry, and was diagnosed with poor coping skills. Her physician recommended 24-hour observation with discharge the next day.
Methanol is used in many different formularies across North America because of its low freezing point. It can be found in common items such as antifreeze, glass cleaner, solvents, de-icers, homemade alcohol (moonshine), and windshield wiper fluid. The initial presentation of methanol poisoning is frequently nonspecific with symptoms such as nausea, vomiting, and abdominal pain. (CJEM 2002;4:34.) Fomepizole is currently viewed as efficacious as ethanol in toxic alcohol poisoning without the risk of hepatotoxicity, hypoglycemia, or intoxication. (New Engl J Med 2001;344:424.)
An index of suspicion should always be maintained for methanol toxicity because untreated patients are at risk for blindness from optic nerve toxicity, coma, retinal injury, seizures, cardiopulmonary arrest, and severe metabolic acidosis. Early administration of fomepizole can prevent conversion of methanol to formaldehyde and subsequent conversion to its toxic metabolite, formic acid, by inhibiting alcohol dehydrogenase. (CJEM 2002;4:34.) It is well known that the degree of toxicity correlates with the amount of methanol ingested, but data show that this does not correlate well with presenting methanol levels. The lethal dose of methanol is reported to be 1–2 mL/kg, though ingestion of as little as 0.1 mL/kg has resulted in permanent blindness. (Medline 2009;52:125.)
Some guidelines state that a methanol level of 20 mg/dl could be an arbitrary cutoff for treatment, but few data support this practice. We followed the recommendations of the Central Ohio Poison Center for our patient, which were an initial dosing of 15 mg/kg of fomepizole, followed by 10 mg/kg every 12 hours for 48 hours, and continuation of 15 mg/kg every 12 hours until the methanol level is less than 20 mg/dl. They recommend fomepizole administration for asymptomatic methanol levels of 20–50 mg/dl. They recommend fomepizole and hemodialysis for patients with end-organ damage, elevated osmolal gap, or levels greater than 50 mg/dl.
Our patient's report of how much methanol she ingested and when she ingested it were likely unreliable because of her concomitant ethanol ingestion. Her ethanol intake may have inadvertently provided a temporary protective effect against her methanol ingestion because ethanol also inhibits alcohol dehydrogenase.
The prompt diagnosis of methanol toxicity may have prevented severe end-organ damage in this patient, and emergency physicians should suspect it in any patient where ingestion of antifreeze, glass cleaner, solvents, de-icers, homemade alcohol, or windshield wiper fluid is reported or suspected. The data for treating asymptomatic individuals with levels above is 20 mg/dl are lacking, but this seems to be standard of care given the severe repercussions of not administering the antidote. We recommend administering this medication and treating all toxic alcohol ingestions in cooperation with your local poison control center because practice patterns may vary in different locations.