ETHYLENE GLYCOL DR BABAK MASOUMI ASSISTANT PROFESSOR OF

ETHYLENE GLYCOL DR BABAK MASOUMI ASSISTANT PROFESSOR OF EMERGENCY MEDICINE ESFAHAN UNIVERSITY OFMEIDCAL SCIENCES 2011

ETHYLENE GLYCOL n n Ethylene glycol has many commercial uses as a coolant (antifreeze), preservative, and glycerine substitute; it has also been used in lacquers, cosmetics, polishes, and detergents. It may be ingested as an alcohol substitute by alcoholics, in suicide attempts, and accidentally by children.

Ethylene Glycol / Methanol Ethylene Glycol Methanol

ETHYLENE GLYCOL n Ethylene glycol's toxicity is the result of the formation of two toxic metabolites, formaldehyde and formic acid. n As with methanol, therapeutic strategies are based on prevention of formation of these metabolites or their removal from the body.

Pathophysiology Ethylene glycol is a colorless, odorless, sweet-tasting substance. n It is highly water-soluble and rapidly absorbed when ingested orally, but not when exposure is via the lungs or skin. n Peak blood levels occur within 1 to 4 h of an ingestion. The plasma half-life is 3 to 5 h. n

Pathophysiology n n n Ethylene glycol is metabolized in the liver and kidneys to toxic metabolites—aldehydes, glycolate, oxalate, and lactate—which in turn cause toxicity to the lungs, heart, and kidneys. These metabolites also cause the metabolic acidosis associated with ethylene glycol poisoning. The potentially lethal dose in adults is 2 m. L/kg, although survival has been reported after ingestions ranging from 240 to 2000 m. L.

Ethylene Glycol / Methanol Ethylene Glycol Alcohol dehydrogenase Formaldehyde Glycoaldehyde Aldehyde dehydrogenase Formic acid Folate CO 2 & H 2 O Lactic Dehydrogenase Or Glycolic acid Oxidase Glycolic acid Th Glyoxylic acid B & Oxalic acid 6 A-OH-B ketoadipic acid Glycine and benzoic acid

Clinical Features n Ethylene glycol poisoning often exhibits three distinct clinical phases, the severity and progression of which depends on the amount ingested: 1)The initial phase(CNS depression) 1 to 12 h after ingestion. 2)The second phase(cardiopulmonary phase) develops 12 to 24 h after ingestion. 3)The third phase (nephrotoxicity) occurs 24 to 72 h after ingestion.

The initial phase n n Patients may appear inebriated, with slurred speech and ataxia but without the odor of ethanol on their breath. Hallucinations, coma, seizures, and death may also occur during this initial phase. The optic fundus is usually normal, differentiating the syndrome from methanol poisoning, although nystagmus and ophthalmoplegia may be observed. Lumbar puncture may demonstrate elevated CSF pressure and protein and a few polymorphonuclear cells.

The second phase n n n The second, cardiopulmonary phase develops 12 to 24 h after ingestion. Tachycardia, mild hypertension, and tachypnea are the most common symptoms; Congestive heart failure, acute respiratory distress syndrome, cardiomegaly, and circulatory collapse are also observed. Myositis has also been reported less commonly during this phase.

The third phase n n n Early symptoms consist of flank pain and costovertebral angle tenderness. Oliguric renal failure and acute tubular necrosis ensue. Complete anuria may occur, but most patients recover without renal damage if they receive appropriate therapy. Nephrotoxicity is caused by aldehyde metabolites and oxalic acid. Two forms of urinary calcium oxalate crystals may be identified on microscopic evaluation of the urine.

Clinical Features n n n Hypocalcemia may develop secondary to precipitation of calcium as calcium oxalate and may be severe enough to cause tetany and prolongation of the QT interval. Elevated serum creatine phosphokinase levels may accompany and explain the generalized myalgias experienced by some patients. Leukocytosis is common and should not be considered a manifestation of infection unless clinical signs are present.

Clinical Features n n Tentative diagnosis and initiation of treatment should be based on history and characteristic clinical presentation. As with methanol poisoning, confirmation of a tentative diagnosis depends on identification of the substance in the bloodstream, but treatment should be initiated based on compatible clinical presentation to avoid morbidity resulting from delay.

Clinical Features Serum levels greater than 20 mg/d. L are likely to result in toxicity. Survival has been reported with levels up to 650 mg/d. L, while fatality has been associated with levels >98 mg/d. L. n Serious intoxication has been reported in the absence of an osmolar gap or calcium oxalate crystalluria. n

Treatment n n The management of ethylene glycol poisoning is similar to that of methanol poisoning. Indications for gastric emptying and guidelines for administration of sodium bicarbonate are the same as those given for methanol.

Treatment n n n If the patient is hypocalcemic, 10 m. L of calcium gluconate 10 percent should be given IV. Pyridoxine 100 mg and thiamine 100 mg IM or IV should be administered daily to facilitate metabolism of ethylene glycol by nontoxic pathways. Magnesium has also been shown to be a cofactor in the metabolism of toxic metabolites and should be given if patients are hypomagnesemic, as is often the case with alcoholics.

Treatment n n Laboratory tests that may be useful in evaluating patients suspected of ethylene glycol ingestion include complete blood count; serum electrolytes; acetone; alcohol toxicology panel with ethanol, isopropanol, and methanol determinations; electrolytes; blood urea nitrogen; creatinine; salicylate level; arterial blood gases; urinalysis; serum ethylene glycol level; calcium; creatine phosphokinase (CPK); and magnesium levels. Lactate levels should also be determined if the reason for the severe acidosis is unclear.

Treatment n n Competitive inhibition of alcohol dehydrogenase's breakdown of ethylene glycol with fomepizole or ethanol should be initiated in the ED when overdose is suspected or confirmed. Fomepizole has supplanted ethanol as the initial treatment of choice. Dosing is the same for ethylene glycol as for methanol. Ethanol's affinity for alcohol dehydrogenase is 100 times that of ethylene glycol, resulting in a prolongation of the half-life of ethylene glycol to 17 h.

Treatment n Oral and intravenous dosing guidelines for ethanol are identical to those outlined for methanol, above. Due to ease of administration, greater affinity for alcohol dehydrogenase, and a superior side-effect profile, fomepizole is the drug of choice unless it is not readily available or there is a history of allergy to fomepizole.

As for methanol, fomepizole or ethanol administration and dialysis should be continued until serum blood levels of whichever substance has been ingested are zero and acidosis has resolved.

Indications for Dialysis with Ethylene Glycol Poisoning

Disposition n n Any patient with the serious signs and symptoms associated with ethylene glycol or methanol intoxication, or a history of significant ingestion even in absence of symptoms, should be admitted to an intensive care setting. Because the symptoms of ethylene glycol and methanol intoxication may be delayed, patients who have ingested these substances should be admitted to the hospital for observation and laboratory testing even if they are initially asymptomatic.