Ethylene Glycol Poisoning

by Dr. Brian Feng

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The Case

HPI

53 year-old M with unknown PMH BIBEMS for weakness. Family found him altered at his apartment. The patient was drowsy and difficult to interview.

Physical Exam

• Vitals: T 98.6F, HR 92, RR 18, BP 177/105, O2 sat 98% on RA
• General: NAD, A&Ox1, follow simple commands, speaks in short sentences, very drowsy
• HEENT: PERRL, EOMI, face symmetric, dry oral mucosa
• CVS: S1, S2, RRR, no murmur
• Pulm: CTAB, r mastectomy scar/well healing
• Abd: Soft, nt, nd, no guarding or rebound. BS+
• Neuro: Moves all 4 extremities equally. Difficult to assess further neuro exam due to drowsiness

Studies

ECG
Normal Sinus rhythm, normal intervals, no ischemic changes

Labs

CBC: 8>14/42<354

Chem: 148/4.3/95/5/26/2.1<187

Anion gap: 48

ABG: pH: 6.83, pCO2: 13.6, pO2: 147.5, HCO3: 2.4

Lactate: 13.7

Serum Ketones: negative

Expected Osmolality: 317

Measured Osmolality: 345

OsM gap: 28

Ethylene Glycol Level: 44

Etoh: <10

ASA: <0.3

APAP: <15.0

Imaging

CTH: no acute findings

CXR: no acute findings

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Ethylene Glycol Poisoning 

Differential diagnosis for anion gap metabolic acidosis

• M – methanol
• U – uremia
• D – DKA, AKA, SKA
• P – paraldehyde (metformin)
• I – INH/Iron
• L – lactate
• E – ethylene glycol
• S – salicylates

Labs to consider sending for AG metabolic acidosis

• K – ketones
• L – Lactate
• U – Urea
• T – Toxic alcohol (ethylene glycol, methanol)
• S – Salicylates

If toxic alcohol is a part of the differential, order the serum osmolality, and calculate the Osm Gap

Toxic alcohol levels generally needs to be sent out, and could take days to come back

Clues for ethylene glycol ingestion:

• Osmol gap
• Lactate gap
• Anion gap
• Hypocalcemia
• Renal failure
• Calcium-oxylate crystals

The Osmolar Gap

Osmlar active agents in the serum includes glucose, Na/Cl, BUN, and ethanol. If there is a difference in the measured osm and calculated osm, it means that there must be another substance in the serum that is causing a elevated measured osm level.

Elevated Osm gap can be caused by:

• Sugars (mannitol)
• Lipids (hypertriglyceridemia)
• Proteins (hypergammaglobinemia)
• Toxic Alcohols

However, osmol gap is not without it’s limitations…

• Normal osmol gap is between -14 to +10
• If a patient at baseline has a osmol gap of -14, and now has a osmol gap of 10, he/she has a elevated Osm Gap, even though it is considered normal by textbook definition
• Sick patients in the hospital can have baseline osmol gap between +10 to +20

Metabolism of ethylene glycol

• The osmol gap and anion gap have an inverse relationship
• Over time, as ethylene glycol (osm active) gets metabolized to glycolic acid (acid metabolite), the osmol gap will decrease while the anion gap increases

Lactate Gap

• Glycolic acid is structurally very similar to lactic acid, and can be misread by the POC testing in the ED, and give a falsely elevated lactic acid level
• Some hospitals will have labs that can differentiate gycolic acid from lactic acid, and will produce a lower lactic acid level than the POC testing in the ED, leading to what is called a Lactate Gap

Hypocalcemia

• Oxylate (one of ethylene glycol’s metabolytes) binds to Ca2+, leading to hypocalcemia
• This also leads to deposit of Ca-Ox crystals in the kidneys, eventually leading to renal failure
• Ca-ox crystals is also deposited in the brain

Treatments

Ethanol & Fomepizole

• Both are competitive inhibitors of alcohol dehydrogenase
• In a late presentation of ethylene glycol poisoning, where ethylene glycol has already been metabolized by ADH to its metabolites, there may be little value
• Ethanol is difficult to dose and has more adverse side effects

Fomepizole

Indications:

• Ethylene glycol level >25
• Large osmol gap w/ suspicion of toxic alcohol ingestion
• Significant unexplained anion gap metabolic acidosis
• History indication ethylene glycol ingestion

Dose

• Loading: 15mg/kg
• 10mg/kg q12h for the first 48 hours, after which the dose is increased to 15mg/kg q12h
• Is dialyzable, so an additional dose during HD, and then reloaded post dialysis.

Hemodialysis

Indications

• End organ manifestations of toxicity
• High osmol gap w/o clear cause
• Severe acid/base abnormalities
• Ethylene glycol concentration >25 mg/dL
• Late presentation of ethylene glycol

Thiamine & pyridoxine

• Enhance the elimination of glycolic acid (a toxic metabolite)

Dose

• Thiamine: 100mg IV
• Pyridoxine: 100mg IV

Sodium Bicarbonate

• Initiate if serum pH <7.30 (this is physician dependent)
• Enhances elimination of glycolic acid
• As an immediate temporizing measure, reversing life threatening acidemia

Dose

• 150mEq NaCO3/1L 0.45NS at 100ml/hr to 200ml/hr

NG suction

• May consider within the first 30 minutes of ingestion

Activated charcoal

• Does bind to ethylene glycol, but minimal utility as toxic alcohols are rapidly absorbed by the GI tract. Also in a altered patient, there is risk of aspiration

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References:

1. Hoffman RS, Smilkstein MJ, Howland MA, Goldfrank LR. Osmol gaps revisited: normal values and limitations. J Toxicol Clin Toxicol 1993; 31:81.
2. Fraser AD. Clinical toxicologic implications of ethylene glycol and glycolic acid poisoning. Ther Drug Monit 2002; 24:232.
3. Porter WH, Crellin M, Rutter PW, Oeltgen P. Interference by glycolic acid in the Beckman synchron method for lactate: a useful clue for unsuspected ethylene glycol intoxication. Clin Chem 2000; 46:874.
4. Boyer EW, Mejia M, Woolf A, Shannon M. Severe ethylene glycol ingestion treated without hemodialysis. Pediatrics 2001; 107:172.
5. Purssell RA, Lynd LD, Koga Y. The use of the osmole gap as a screening test for the presence of exogenous substances. Toxicol Rev 2004; 23:189.