Meg Reitmeyer, M.D.
Clinical Medicine Conference
January 16, 1997
Toxic alcohol ingestions comprise a small but dangerous group of poisonings. In a 1988 report issued by the American Association of Poison Control Centers, there were a total of 20,291 cases of poisoning with toxic alcohols (excluding ethanol). These included 13,045 isopropanol, 1918 methanol and 5328 ethylene glycol ingestions. Of these, 1171 were deliberate. Diagnosis is often confusing as the most common ingestion scenario is in an alcoholic patient seeking an ethanol substitute. Ethanol is often consumed at the same time which prolongs the half-life of all these agents and exacerbates common symptoms.
Metabolic acidosis can be subdivided into the hyperchloremic variety and those with anion gaps. An anion gap reflects the presence of ingested exogenous or overproduction of endogenous organic acids. The anion gap is calculated by subtracting the total of chloride and bicarbonate from the sodium. A "normal" gap is 12-14. Gaps become truly significant when they are over 20. Anion gaps should only be calculated if the patient has an acidosis. The "gap" seen in alkalotic processes is due to changes in surface charges on proteins. A study by Gakow showed that 62% of patients with anion gaps had lactic or ketoacidosis. Another 15% had "gaps" from changes in the serum concentration of total protein, phosphate, potassium and calcium. Patients in renal failure may appear to have a small gap due to the decreased excretion of major cations such as phosphate and sulfate.
A commonly used mnemonic is "MUDPILES." This stands for methanol, uremia, diabetic ketoacidosis, phenformin or paraldehyde, iron or isoniazid, lactate, ethylene glycol and salicylates. All of these things can be readily measured or excluded with simple blood chemistries. Other clinical clues include:
The normal measured serum osmolality is 280-300 mOsm/kg H2O. The serum osmolality is calculated with the equation (sodium X 2) + BUN/3 + glucose/20 + ethanol/4. The BUN, glucose and ethanol are in mg/dl. The limit for the difference between measured and calculated is 10-20 in most textbooks. The list of substances causing an osmolar gap is limited because certain serum levels must be obtained before any substance can contribute to the serum osmolality. These substances include sorbitol, mannitol, glycerin, isoniazid, ethanol, isopropanol, methanol, acetone and ethylene glycol. The presence of ethanol is the most common confounder for calculating the gap to check for the presence of another agent. Please see the table below for the information necessary to make these adjustments.
|
Serum Osm increase per each 1mg/dl |
Concentration (mg/dl) increase per each 1 mOsm/kg H20 |
||
| Methanol | 0.34 | 2.6 | |
| Ethanol | 0.22 | 4.3 | |
| Ethylene glycol | 0.20 | 5.0 | |
| Acetone | 0.18 | 5.5 | |
| Isopropanol | 0.17 | 5.9 |
From Kulig, K. et al. Toxic effects of methanol, ethylene glycol and isopropyl alcohol. Topics in Emergency Medicine. 6 (2): 16.
|
BAL (mg/dl) |
Clinical Findings |
|
<50 |
Limited muscular coordination, driving not seriously impaired |
|
50-100 |
Driving increasingly dangerous, incoordination, impaired sensory function |
|
100-150 |
Mood, personality and behavioral changes; driving is dangerous, marked mental impairment, incoordination, ataxia |
|
150-200 |
Prolonged reaction time; driving is very dangerous |
|
200-300 |
Nausea, vomiting, diplopia, marked ataxia |
|
300-400 |
Hypothermia, dysarthria, amnesia |
|
400-700 |
Coma, respiratory failure, death |
From Smith, M. Ethanol. In Noji, E;, Kelen, G. and Goessel, T. (eds): Manual of Toxicologic Emergencies. Chicago. Year Book Medical Publishers. 1989. Pg. 250.
Although as internists we primarily treat the chronic effects of ethanol consumption, acute ethanol poisoning is a not uncommon problem, especially in the student population. The table above summarizes the expected effects at each level of intoxication. Ethanol can make a significant contribution to an osmolar gap but does not cause a significant anion gap. Treatment is supportive with emphasis on airway protection and observation for gastritis and pancreatitis. Hemodialysis will remove ethanol.
In some series, this is the sixth most common ingestion. The number of ingestions of this substance led to the addition of blue dye to some solutions, hence the nickname of "blue heaven." It can also be absorbed cutaneously. Almost 80% of the drug is converted to acetone which leads to severe "fingerpolish remover" breath. The central nervous system depressant effects of isopropyl alcohol are 2-3 times more than ethanol which is much more potent than methanol or ethylene glycol. Coma may last over 24 hours. Symptoms include weakness, ataxia, abdominal pain, gastritis, hypotension, tachycardia, apnea and hemorrhagic tracheobronchitis. Laboratory analysis reveals a normal glucose in the presence of severe ketonemia and ketonuria. Unlike the other toxic alcohols, isopropanol does not lead to a metabolic acidosis, but it does cause a serum osmolar gap. The presence of acetone in the absence of acidosis should automatically trigger measurement of serum isopropanol. False positive tests have been noted when alcohol swabs used to disinfect the site of venipuncture contaminate the specimen. Treatment is supportive although hemodialysis can remove the toxin if conservative measures fail.
This is found in a variety of forms including windshield wiper fluid, antifreeze, gasoline, Sterno and paint remover. Epidemics have been traced to contaminated batches of bootleg whiskey. It can be absorbed through the skin, gastrointestinal tract and by inhalation. The minimum lethal dose is 80 gm although visual disturbances may occur after 40 gm. This alcohol is especially dangerous due to lag time between ingestion and onset of symptoms. CNS depression is much milder than seen in the other toxic alcohols. Since it takes an average of 24 hours (range 1-72 hours) to develop the initial symptoms (malaise, nausea, weakness, headache), there is adequate time for toxic metabolites to accumulate. The primary metabolite, formic acid, cause a variety of visual disturbance and leads to irreversible blindness in 15% of survivors. Patients complain of "snowfield" vision. Signs include mydriasis, decreased light reflex, retinal edema, hyperemia of the disk and eventually optic atrophy. Pupillary changes may precede the visual disturbances. Other problems include amnesia, confusion, seizures, meningismus, obstipation, pulmonary edema, hypophosphatemia and elevation of creatinine kinase. This alcohol causes more direct gastrointestinal effects including hemorrhagic gastritis and pancreatitis. Cerebral edema is common. Autopsy studies reveal a symmetrical putaminal necrosis, and a Parkinsonian-like syndrome may result. There is no Kussmaul breathing despite the severe acidosis. Survival correlates with the severity and duration of acidosis.
Although usually only considered a part of antifreeze, ethylene glycol and esters which can be converted to it are found in a variety of products including fire extinguishers, inks, air conditioning units, adhesives and solvents. Antifreeze is about 95% ethylene glycol and represents the most common exposure risk. The sweet taste of antifreeze makes it appealing to children and animals, and it also goes well with iced tea or lemonade. There is limited risk from inhalation or cutaneous absorption. At least one case of poisoning of hemodialysis patients has been linked to contaminated water baths. There are three phases to EG poisoning. The first is due to the direct depressant effects on the CNS and lasts 1-12 hours. This is followed by the metabolic phase with potential cardiopulmonary compromise and then renal damage occurs. Symptoms begin to peak in 4-8 hours with nausea, vomiting and progressive mental status changes leading to coma. Neurologic manifestations include nystagmus, ataxia, areflexia, myoclonus and seizures. Ophthalmologic disturbances are rare. The patient may also develop hypocalcemia (due to precipitation of calcium in the kidneys), tachycardia, tachypnea, ARDS, CHF, leukocytosis and CSF pleocytosis. Acute tubular necrosis may be due to direct damage from the alcohol or from the crystalluria. This occurs by 72 hours after ingestion. Flank and costovertebral angle pain are common. Further renal injury may occur due to rhabdomyolysis. Of all the alcohols, EG usually cause the most marked anion gap. There is often a serum osmolar gap as well. Despite common lore (and a habit of showing up on the boards), calcium oxalate crystals appear in the urine only about 50% of the time, and they may not be present if one of the ester solvents is ingested instead of pure ethylene glycol. Several years ago, most antifreeze manufacturers began adding fluorescein to antifreeze so that radiator leaks could be more easily discovered. Shining a Wood's lamp on a fresh urine specimen may lead to the diagnosis.
Methanol Ethanol Isopropanol Ethylene glycol
Characteristic Yes Yes Yes (acetone) No
odor
Metabolic Severe (lactate Mild Absent or Severe
acidosis formation) (lactate) slight (lactate,
(lactate) oxalate,
glycolate)
Ketones Ketobutyric Acetoacetic Acetone ---------
hydroxybutyrate
Anion gap Large No or small Slight Large
Osmolar gap Yes Yes Yes Yes
Compiled from the references by Reitmeyer.
Activated charcoal has little efficacy in these ingestions since alcohol is absorbed so rapidly and thoroughly from the gastrointestinal mucosa. Gastric lavage may be helpful if ingestion occurred just prior to presentation.
The key to management is to prevent conversion of the alcohol to its toxic metabolites and either allow the poison to be eliminated renally or dialyze it off. Ethanol inhibits alcohol dehydrogenase and should be used for poisonings with methanol and ethylene glycol. A therapeutic goal is 100-150 mg/dl. This is accomplished by a loading dose of 0.8 gm/kg followed by an infusion of 130 mg/kg/hr. The blood level should be closely followed. In patients on dialysis, the infusion should be 250-350 mg/kg/hr since ethanol will also be removed in the dialysate. The intravenous route is preferable to prevent gastritis and more easily control absorption, but the oral route may be used. Ethanol therapy should be continued until the methanol or ethylene glycol level is zero.
Sodium bicarbonate should be used to counteract the acidosis and enhance renal excretion of the alcohol. A goal of pH > 7.35 is acceptable. In ethylene glycol poisoning, patients should also receive thiamine (100 mg IV every 6 hours) and pyridoxine (50 mg IV every 6 hours). These vitamins shunt the alcohol degradation pathway to less toxic metabolites. Folic acid (50-75 mg IV every 4 hours) may decrease conversion of methanol to formic acid.
Hemodialysis is effective in removing all of the alcohols. Indications for dialysis include severe symptoms in the patient, intractable anion gap acidosis, levels of methanol or ethylene glycol of > 25 mg/dl or renal compromise. Any patient with visual disturbances from methanol poisoning should be considered for dialysis.
Special thanks to Drs. Mimi Lam and Mike Wilkowski for their input.
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