Basics
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 CNS, heart, and kidneys
Etiology
- Ethylene-glycol-containing products:
- Min. reported lethal dose is 30 mL of 100% ethylene glycol.
Diagnosis
Signs and Symptoms
- Cardiovascular:
- Tachycardia/bradycardia/other dysrhythmias
- Hypertension/hypotension
- CNS:
- Inebriation/irritability
- Ataxia
- Obtundation
- Coma
- Cerebral edema
- Convulsions
- Peripheral nervous system
- Cranial nerve abnormalities
- GI:
- Nausea/vomiting
- Abdominal pain
- Pulmonary:
- Hyperventilation/tachypnea/Kussmaul respiration
- Pulmonary edema
- Renal:
- Acute renal failure
- Crystalluria
- 3 stages (may overlap):
- 1st stage: 1-12 hr after ingestion:
- CNS depression
- GI symptoms
- Worsening acidosis
- Coma
- Convulsions
- Cerebral edema
- Tetany and myoclonus secondary to hypocalcemia
- 2nd stage: 12-36 hr after ingestion:
- Cardiopulmonary symptoms
- When most deaths occur
- 3rd stage: 36-72 hr after ingestion:
- Oliguria
- Flank pain
- Acute renal failure
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
- 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
Diagnosis 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:
- Measured to determine amount of ethanol bolus necessary to attain therapeutic serum concentration, and to determine coingestants
- 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
Treatment
Pre-Hospital
- 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-Check), 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:
- Fomepizole (4-MP, Antizol):
- Initiate before ethylene glycol serum concentration returns, if accidental ingestion greater than a sip or intentional ingestion oraltered mental status associated with unexplained osmol gap or elevated anion gap acidosis.
- Competitive inhibitor of alcohol dehydrogenase
- Disadvantages:
- Blurry vision
- 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
- Ethanol therapy:
- 2nd 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 25 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: Severe acidosis or osmol gap; persistent electrolyte or metabolic acidosis; renal insufficiency; pulmonaryedema; cerebral edema; serum ethylene glycol serum concentration >25 mg/dL
- Continue hemodialysis until ethylene glycol serum concentration approaches 25 mg/dL and metabolic acidosis resolves.
- Correct secondary disorders:
- Ensure adequate urine output via IV fluids.
- Sodium bicarbonate therapy for acidemia with pH < 7.1:
- The goal is to maintain a serum pH in the normal range.
- Monitor/replace calcium:
- Deposition of calcium into tissues can result in hypocalcemia.
- Fomepizole is class C in pregnancy.
- Ethanol is not recommended in pregnancy. Class D/X
Ethanol can cause serious CNS depression and hypoglycemia when administered to children.
Medication
- Activated charcoal: 1 g/kg PO
- Dextrose: D50W 1 ampule: 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/h
- Maintenance dose during hemodialysis: 0.4-0.7 mL/kg/h
- IV: 10% ethanol in D5W:
- Loading dose: 8 mL/kg over 30-60 min
- Maintenance infusion: 1-2 mL/kg/h
- Maintenance infusion during hemodialysis: 2-4 mL/kg/h
- 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 are reduced to <25mg/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 days
- Sodium bicarbonate: 1-2 mEq/kg in D5W IV
- Thiamine: 100 mg (peds: 50 mg) IV or IM per day for 2 days
Follow-Up
Disposition
Admission Criteria
- All patients with significant ethylene glycol ingestion, even if initially asymptomatic
- ICU admission for seriously ill patients, metabolic acidosis, and renal failure
- Transfer to another facility if hemodialysis or fomepizole is indicated but not readily available.
Discharge Criteria
Asymptomatic patient with isolated ethylene glycol ingestion, if serum ethylene glycol serum concentration is undetectable and no metabolic acidosis
Followup Recommendations
Psychiatric referral for suicidal patients.
Pearls and Pitfalls
- An osmol gap <10 mmol/L does not rule out an ethylene glycol exposure.
- Administer fomepizole immediately and confirm exposure with a serum 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.
Additional Reading
- Leikin J, Paloucek F. Ethylene glycol. Fomepizole. Alcohol. In: Leikin JB, Paloucek F, eds. Leikin and Palouceks Poisoning and Toxicology Handbook. 4th ed. Boca Raton, FL: Lexi-Comp; 2008;989: 294-295, 794-795.
- Levine M, Curry SC, Ruha AM, et al. Ethylene glycol elimination kinetics and outcomes in patients managed without hemodialysis. Ann Emerg Med. 2012;59:527-531.
Codes
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)