Gastrointestinal Absorption: rapid absorption from gastrointestinal tract -> peak Levels occur about 2 hrs after ingestion
Toxicity: as little as 0.1 mL/kg ingestion (one swallow) may result in a potentially toxic blood level
Background on Alcohols and Their Metabolism
Ethylene Glycol
Ethylene Glycol is a Primary Alcohol Which is Metabolized by Alcohol Dehydrogenase and Aldehyde Dehydrogenase to Carboxylic Acids (Namely, Glycolic Acid, Glyoxylic Acid, and Oxalic Acid): these carboxylic acids cause most of the toxic effects
Methanol is a Primary Alcohol Which is Metabolized by Alcohol Dehydrogenase and Aldehyde Dehydrogenase to Carboxylic Acids (Namely, Formic Acid): these carboxylic acids cause most of the toxic effects
Isopropanol is a Secondary Alcohol Which is Metabolized by Alcohol Dehydrogenase Only to a Ketone (Namely, Acetone), Rather than to an Aldehyde: ketones cannot be oxidized to an aldehyde and therefore, only limited acidosis can result
Ethylene Glycol Metabolism
Ethylene Glycol is Hepatically Metabolized by Alcohol Dehydrogenase and Aldehyde Dehydrogenase: resulting in the formation of several toxic metabolites (glycolic acid and oxalate are the two compounds most responsible for the metabolic acidosis and renal damage)
Glycoaldehyde
Oxalate: precipitates as calcium oxalate crystals in brain, heart, kidney, pancreas, lung, and urine
Glyoxylic Acid: rapidly oxidized to oxalate
Glycolic Acid: as much as 20% is excreted unchanged in urine
Kinetics
Absence of Treatment: half-life of approximately 3-8 hrs
Treatment with Alcohol Dehydrogenase Inhibitor (Ethanol, Fomepizole): elimination becomes almost entirely renal (with half-life of approximately 14 hrs with normal renal function)
End Organ Toxicity
Central Nervous System Toxicity: due to calcium oxalate crystal precipitation
Elevated Anion Gap Metabolic Acidosis: due to glycolic acid (and oxalate)
Renal Interstitial and Tubular Damage: due to glycolic acid-induced tubular damage and calcium oxalate crystal precipitation (to a lesser extent)
Hypocalcemia: due to calcium oxalate formation
Diagnosis
Complete Blood Count (CBC)
Leukocytosis (see Leukocytosis, [[Leukocytosis]]): seen in most cases
Serum Chemistry
Hypocalcemia (see Hypocalcemia, [[Hypocalcemia]]): seen in 33% of cases
Due to calcium oxalate crystal precipitation in tissues)
Note: the serum osmolal gap estimates the molar quantity of uncharged molecules and consequently, increases only in the presence of the parent alcohol ethylene glycol
The toxic ethylene glycol metabolites (glycolate/glyoxylate/oxalate), exist primarily in a dissociated/charged form at physiologic pH: as these anions are accompanied by a cation (mostly sodium), they do not contribute to the serum osmolal gap since they are accounted for in the serum sodium term in the formula for the serum osmolal gap
Lactic Acidosis
Lactate: may be elevated in some cases
However, the degree of lactate elevation is usually not sufficient to explain the degree of metabolic acidosis that is present
Altered Mental Status with Central Nervous System Depression (see Delirium, [[Delirium]] and Obtundation-Coma, [[Obtundation-Coma]]))
Timing: occurs within 4-12 hrs post-ingestion (symptoms associated with toxic metabolites usually predominate, but may be delayed in cases where patient has ingested large amounts of ethanol, which inhibits ethylene glycol metabolism)
Mechanism of Central Nervous System Depression: probably related to calcium oxalate deposition -> cerebral damage
Hyporeflexia (see Hyporeflexia, [[Hyporeflexia]]): may occur in severe cases
Hypotonia: may occur in severe cases
Meningismus (see Meningismus, [[Meningismus]]): may occur in severe cases
Myoclonus (see Myoclonus, [[Myoclonus]]): may occur
Nystagmus (see Nystagmus, [[Nystagmus]]): may occur
Ophthalmoplegia (see Ophthalmoplegia, [[Ophthalmoplegia]]): may occur
Optic Fundus: usually normal (although some cases may manifest papilledema, mimicking methanol intoxication)
Seizures (see Seizures, [[Seizures]]): may occur in severe cases
Transient Inebriation/Euphoria: occurs within min-several hrs (similar to ethanol intoxication)
Renal Manifestations
Anion Gap Metabolic Acidosis (AGMA) (see Metabolic Acidosis-Elevated Anion Gap, [[Metabolic Acidosis-Elevated Anion Gap]]): occurs within 4-12 hrs post-ingestion
Elevated Osmolal Gap (see Serum Osmolality, [[Serum Osmolality]])
Physiology: presence of osmotically-active solute, ethylene glycol
Since the serum osmolal gap estimates the molar quantity of uncharged molecules, the osmolal gap is increased due to the presence of ethylene glycol itself
The toxic ethylene glycol metabolites glycolate/glyoxylate/oxalate exist primarily in a dissociated (charged) form at physiologic pH -> as these anions are accompanied by a cation (mostly sodium), they do not contribute to the serum osmolal gap since they are accounted for in the serum sodium term in the serum osmolal gap formula
Clinical: may produce a large osmolal gap (>20 mOsm/L)
An elevated osmolal gap may appear before the development of metabolic acidosis in cases with concomitant ethanol and ethylene glycol ingestion
A normal osmolal gap does not exclude ethylene glycol intoxication and a small osmolal gap can be seen with high ethylene glycol levels (the sensitivity/specificity of osmolal gap depends on timing of ingestion)
There are often discrepancies between the degree of osmolal gap and the severity of clinical manifestations
Other Manifestations
Nausea/Vomiting (see Nausea and Vomiting, [[Nausea and Vomiting]]): may occur
Stage 2-Cardiopulmonary
General Comments
Timing: occurs within 12-24 hrs post-ingestion (most deaths occur in this stage)
Mild Hypertension (see Hypertension, [[Hypertension]])
Other Manifesttaions
Severe Metabolic Acidosis with Compensatory Hyperventilation (see Metabolic Acidosis-Elevated Anion Gap, [[Metabolic Acidosis-Elevated Anion Gap]]): occurs in severe cases
Multi-Organ Failure
Stage 3-Renal
General Comments
Timing: occurs within 24-72 hrs post-ingestion
Cardiovascular Manifestations
Hypotension/Cardiovascular Collapse (see Hypotension, [[Hypotension]])
Gastrointestinal Manifestations
Faint Sweet Odor on Breath
Hepatotoxicity (see xxxx, [[xxxx]]): serious hepatic damage rarely occurs
However, Earlier Initiation of Hemodialysis Worsens Outcome [MEDLINE]: however, this was retrospective study and there was likely sample bias (as sicker patients were more likely to undergo hemodialysis)
Management with Alcohol Dehydrogenase Inhibitor Monotherapy (Without Hemodialysis): patients who present with normal/near-normal initial pH and renal function likely can be safely managed without hemodialysis
Mechanism: competes with both methanol and ethylene glycol for alcohol dehydrogenase (alcohol dehydrogenase enzyme has higher affinity for ethanol and becomes saturated at an ethanol level between 13-30 mg/dL), preventing formation of toxic metabolites
The half-life of ethylene glycol is prolonged to about 17 hrs in the presence of ethanol infusion
Administration: load with 10% ethanol at 10 mL/kg IV, then infuse 10% ethanol at 1.5 mL/kg/hr IV drip -> titrate to keep ethanol level between 100-200 mg/dl
Concomitant Hemodialysis and Ethanol Infusion: when hemodialysis is used with ethanol infusion, increase the ethanol drip rate to account for its loss with hemodialysis -> administer 3 mL/kg/hr IV drip instead
Monitor: monitor ethanol and ethylene glycol levels during therapy
Concomitant Hemodialysis and Ethanol Infusion: when hemodialysis is used with ethanol infusion, increase the ethanol drip rate to account for its loss with hemodialysis -> administer 3 mL/kg/hr IV drip instead
Charcoal Hemoperfusion (see Hemoperfusion, [[Hemoperfusion]])
General Indications for Charcoal Hemoperfusion: intoxication with compounds with high molecular weight, high protein binding, and large volume of distribution -> these compounds would normally be poorly removed by hemodialysis
Not Beneficial in Ethylene Glycol Intoxication
In addition, it has a higher risk of complications, since blood is in contact with activated charcoal or resin
Fomepizole for the treatment of ethylene glycol poisoning. N Engl J Med 1999; 340:832-838
Methylpyrazole for Toxic Alcohols Study Group. Fomepizole for the treatment of ethylene glycol poisoning. N Engl J Med 1999; 340:832-838
Ethylene glycol intoxication: pathophysiology, diagnosis, and emergency management. ANNA J 1999; 26:295-300, 355
American Academy of Clinical Toxicology practice guidelines on the treatment of ethylene glycol poisoning. Ad Hoc Committee. J Toxicol Clin Toxicol 1999; 37:537-560
Poisonings and overdoses in the intensive care unit: general and specific management issues. Crit Care Med 2003; 31:2794-2801
Predictors of Death and Prolonged Renal Insufficiency in Ethylene Glycol Poisoning. Crit Care Med. 2003 Dec;31(12):2794-801 [MEDLINE]