Ethylene Glycol Poisoning

[Section Outline]

Description
Etiology

Author:

Kirk L.Cumpston

Description

Peak serum concentration in 1-4 hr
Half-life, 2.5-4.5 hr
<20% excreted unmetabolized by kidneys
Pathophysiology:
- Metabolized by hepatic alcohol dehydrogenase and aldehyde dehydrogenase ultimately to oxalic acid
- Results in aldehyde and acid metabolites
- Directly toxic to kidney
- Ethylene glycol metabolism:
  - Step 1 Ethylene glycol is converted by alcohol dehydrogenase to glycoaldehyde
  - Step 2 Glycoaldehyde is converted by aldehyde dehydrogenase to glycolic acid
  - Step 3 Glycolic acid is converted by lactate dehydrogenase to glyoxylic acid
  - Step 4 Glyoxylic acid is converted to oxalic acid

Etiology

Ethylene-glycol-containing products:
- Antifreeze
- Solvents
Min reported lethal dose is 30 mL of 100% ethylene glycol

[Section Outline]

Signs and Symptoms
Essential Workup
Diagnostic Tests & Interpretation
Differential Diagnosis

Signs and Symptoms

Cardiovascular:
- Tachycardia
- hypotension
CNS/PNS:
- Inebriation/irritability
- Ataxia
- Obtundation
- Cranial nerve abnormalities
GI:
- Nausea/vomiting
- Abdominal pain
Pulmonary:
- Hyperventilation/tachypnea/Kussmaul respiration
Renal:
- Acute renal failure
- Crystalluria

History

Intentional or unintentional ethylene glycol ingestion
No history but a patient with an unexplained high anion gap metabolic acidosis
Elevated unexplained osmol gap

Physical Exam

Tachypnea
Altered mental status

Essential Workup

History of all substances ingested
Drawn simultaneously:
- Arterial blood gas or venous blood gas
- Serum ethylene glycol, methanol, isopropyl alcohol, and ethanol serum concentration
- Electrolytes, BUN/creatinine, glucose
- Measured serum osmolality (by freezing point depression)
- Serum calcium, phosphorus, magnesium

Diagnostic Tests & Interpretation

Lab

Determine the anion gap:
- Anion gap = (Na⁺) − (Cl⁻ + HCO₃⁻)
- Normal anion gap is 8-12
Determine osmol gap:
- Osmol gap = measured osmolality − calculated osmolarity
- Increased osmol gap: >10
- Calculated osmolarity = 2(Na⁺) + glucose/18 + BUN/2.8 + ethanol (mg/dL)/4.6
- Calculated to screen for ethylene glycol ingestion because toxic alcohol serum concentration are not commonly available in timely manner from most clinical labs
- Most useful early in course of ethylene glycol poisoning or with concurrent ethanol ingestion
- With concurrent ethanol ingestion, osmol gap tends to be larger and acidosis tends to be less severe because relatively less ethylene glycol has been converted to acid-producing metabolites
- Normal osmol gap does not rule out ethylene glycol ingestion
- Late presentation after ethylene glycol ingestion may manifest itself with only an elevated anion gap without a significant osmol gap
Ethylene glycol, methanol, isopropyl alcohol serum concentration
Ethanol serum concentration:
- Is helpful to determine if an ethanol co-ingestion is therapeutic (100 mg/dL) and how this will effect assessment of osmols.
Urinalysis:
- Envelope-shaped oxalate crystals: Insensitive but specific finding
- Absence of urine calcium oxalate crystals does not rule out ethylene glycol exposure
- Ketones may be due to isopropyl alcohol ingestion, starvation, or diabetic ketoacidosis

Diagnostic Procedures/Surgery

Wood lamp inspection of urine or gastric contents:

Detects presence of fluorescein, a common antifreeze additive
Insensitive and not specific marker of antifreeze ingestion
Absence of urinary fluorescence does not rule out ethylene glycol exposure

Differential Diagnosis

Increased osmol gap:
- Methanol
- Ethanol
- Diuretics (mannitol, glycerin, propylene glycol, sorbitol)
- Isopropyl alcohol
- Ethylene glycol
- Acetone, ammonia
- Propylene glycol
Elevated anion gap metabolic acidosis: A CAT MUDPILES:
- Alcoholic ketoacidosis
- Cyanide, CO, H₂S, others
- Acetaminophen
- Antiretrovirals (NRTI)
- Toluene
- Methanol, metformin
- Uremia
- Diabetic ketoacidosis
- Paraldehyde, phenformin, propylene glycol
- Iron, INH
- Lactic acidosis
- Ethylene glycol
- Salicylate, acetylsalicylic acid (ASA; aspirin), starvation ketosis

[Section Outline]

Prehospital
Initial Stabilization/Therapy
ED Treatment/Procedures
Medication

Prehospital

Bring containers of all possible substances ingested
Monitor airway and CNS depression
Dermal decontamination of an ethylene glycol chemical spill by removal of clothing and jewelry and irrigation with soap and water

Initial Stabilization/Therapy

ABCs
Supplemental oxygen, cardiac monitor, secured IV line with 0.9% NS
D₅₀W (or Accu-Chek), naloxone, and thiamine for altered mental status

ED Treatment/Procedures

Prevent further ethylene glycol absorption:
- Gastric lavage with nasogastric tube:
  - If <1 hr since ingestion, if patient is in coma, or if history of large ingestion
- Initial dose of activated charcoal for potential coingestants, but unlikely to help if only ethylene glycol:
  - Activated charcoal adsorbs ethylene glycol poorly
  - Prevent ethylene glycol conversion to toxic metabolites with fomepizole, a competitive inhibitor of alcohol dehydrogenase
Fomepizole (4-MP, Antizol):
- Indications
  - Initiate before ethylene glycol serum concentration returns, if accidental ingestion greater than a sip, or intentional ingestion, OR altered mental status associated with unexplained osmol gap or elevated anion gap acidosis, pH <7.3, or renal failure
  - OR serum ethylene glycol >20 mg/dL
- Disadvantages:
  - Transient elevation of LFTs
- Advantages:
  - Easy dosing
  - No need for continuous infusion
  - No inebriation/CNS depression
  - No hypoglycemia, hyponatremia, or hyperosmolality
  - Not necessary to check ethanol serum concentration
  - Reduction in degree of nursing care and monitoring
  - No need for ICU admission
Ethanol therapy:
- Second choice antidote if fomepizole is not available
- Not FDA approved for treatment of ethylene glycol
- Initiate before ethylene glycol serum concentration returns, if potentially toxic ingestion is suspected
- Ethanol: Greater affinity than ethylene glycol for alcohol dehydrogenase:
  - Slows conversion to toxic metabolites
- Indications:
  - History of accidental ethylene glycol ingestion of greater than a sip, or intentional ethylene glycol ingestion
  - Altered mental status associated with unexplained osmol gap or elevated anion gap metabolic acidosis
- Goal: Serum ethanol serum concentration of 100-150 mg/dL
- Continue ethanol therapy until ethylene glycol serum concentration is <20 mg/dL
Administer thiamine, pyridoxine, and magnesium:
- Cofactors in metabolism of ethylene glycol that may promote conversion to nontoxic metabolites
- No human data supporting this theory
Hemodialysis:
- Decreases elimination half-life of ethylene glycol and removes toxic metabolites
- Indications:
  - Metabolic acidosis bicarbonate< 20 mmol/L and serum pH < 7.3 or
  - Elevated osmol gap > 10 mmol/L or
  - Renal injury + metabolic acidosis or
  - Serum ethylene glycol serum concentration >50 mg/dL alone
- Continue hemodialysis until ethylene glycol serum concentration <20 mg/dL and metabolic acidosis resolves
Correct secondary disorders:
- Ensure adequate urine output via IV fluids
- Sodium bicarbonate therapy for acidemia with pH <7.3:
  - The goal is to maintain a serum pH in the normal range (pH 7.35-7.45)
Monitor/replace calcium:
- Deposition of calcium into tissues can result in hypocalcemia

Pregnancy Prophylaxis
Fomepizole is class C in pregnancy Ethanol is not recommended in pregnancy. Class D/X

Pediatric Considerations
Ethanol can cause serious CNS depression and hypoglycemia when administered to children

Medication

Activated charcoal: 1 g/kg PO
Dextrose: D₅₀W 1 amp: 50 mL or 25 g (peds: D₂₅W 2-4 mL/kg) IV
Ethanol:
- PO: 50% ethanol solution (100-proof liquor) via nasogastric tube:
  - Loading dose: 1.5 mL/kg
  - Maintenance dose: 0.2-0.4 mL/kg/hr
  - Maintenance dose during hemodialysis: 0.4-0.8 mL/kg/hr
- IV: 10% ethanol in D₅W:
  - Loading dose: 8 mL/kg over 30-60 min
  - Maintenance infusion: 1-2 mL/kg/hr
  - Maintenance infusion during hemodialysis: 2-4 mL/kg/hr
Fomepizole:
- Loading dose: 15 mg/kg slow infusion over 30 min
- Maintenance dose: 10 mg/kg q12h for 4 doses, then 15 mg/kg q12h until ethylene glycol serum concentration is reduced to <20 mg/dL
- Dosing related to hemodialysis:
  - Do not administer dose at beginning of dialysis if last dose was <6 hr previously
  - Administer next dose if last dose was >6 hr previously
  - Dose q4h during dialysis
  - If time between last dose and end of dialysis was <1 hr from last dose, do not administer new dose
  - If time between last dose and end of dialysis was 1-3 hr from last dose, administer 1/2 of next scheduled dose
  - If time between last dose and end of dialysis was >3 hr from last dose, administer next scheduled dose
Magnesium: 25-50 mg/kg IV 1 dose up to 2 g
Naloxone: 2 mg (peds: 0.1 mg/kg) IV or IM initial dose
Pyridoxine: 100 mg/d for 2 d
Sodium bicarbonate: 1-2 mEq/kg in D₅W IV
Thiamine: 100 mg (peds: 50 mg) IV or IM per d for 2 d

[Section Outline]

Disposition
Follow-up Recommendations

Disposition

Admission Criteria

All patients with significant ethylene glycol ingestion, even if initially asymptomatic
ICU admission for patients with unstable vital signs or mental status. ICU may be required for emergent hemodialysis to treat metabolic acidosis and renal failure
Transfer to another facility if hemodialysis or antidote is indicated but not readily available

Discharge Criteria

Asymptomatic patient with isolated ethylene glycol ingestion, if serum ethylene glycol serum concentration is <20 mg/dL and no metabolic acidosis

Follow-up Recommendations

Psychiatric referral for suicidal patients

An osmol gap <10 mmol/L does not rule out an ethylene glycol exposure
Administer fomepizole immediately and confirm exposure with a serum ethylene glycol concentration for patients with an elevated anion gap and ethylene glycol exposure in the differential diagnosis
If you cannot confirm an ethylene glycol exposure, or do not have hemodialysis capabilities 24/7, or no antidote, transfer the patient to a facility which has all of the above capabilities
Not all patients will have an elevated osmol and anion gap. Early presenters will have an osmol gap only, and late presenters may have an anion gap only
Do not use the absence of urine crystals or fluorescence of the urine to rule out an ethylene glycol exposure
In the setting of metabolic acidosis, maintaining the serum pH in the normal range (7.35-7.45) with a sodium bicarbonate drip may be helpful

KrautJA, MullinsME. Toxic alcohols . N Engl J Med. 2018;378(3):270-280.
LungDD, KearneyTE, BraiselJA, et al. Predictors of death and prolonged renal insufficiency in ethylene glycol poisoning . J Int Care Med. 2015;30(5):270-277.
McMartinK, JacobsenD, HovdaKE. Antidotes for poisoning by alcohols that form toxic metabolites . Br J Clin Pharm. 2015;81(3):505-515.

ICD9

982.8 Toxic effect of other nonpetroleum-based solvents

ICD10

T52.8X1A Toxic effect of organic solvents, accidental, init
T52.8X2A Toxic effect of organic solvents, self-harm, init
T52.8X4A Toxic effect of oth organic solvents, undetermined, init
T52.8X3A Toxic effect of other organic solvents, assault, init encntr

SNOMED

426692001 Ethylene glycol poisoning (disorder)
241769004 Organic solvents causing toxic effect (disorder)

section name header

Basics ⬇

Diagnosis ⬆ ⬇

History

Physical Exam

Lab

Diagnostic Procedures/Surgery

Treatment ⬆ ⬇

Pregnancy Prophylaxis

Pediatric Considerations

Follow-Up ⬆ ⬇

Admission Criteria

Discharge Criteria

Pearls and Pitfalls ⬆ ⬇

Additional Reading ⬆ ⬇

Codes ⬆