Ethylene glycol toxicity: Difference between revisions

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== Background ==
==Background==
*Characteristics
*Component of antifreeze, automobile coolants, de-icing agents, industrial solvents and hydraulic brake fluid.
**Component of antifreeze
**Fluoresces yellow/green under Wood's lamp (neither Sn nor Sp)
***Fluoresces yellow/green under Wood's lamp (neither Sn nor Sp)
*Sweet taste
**Sweet taste
**Lethal dose = 1g/kg
***Volume depends on percentage of ethylene glycol in solution, typically 0.6 g/mL
***60 kg patient lethal dose ~ 100 mL
*Parent compound causes inebriation; metabolite (glycolic acid) causes toxicity
*Parent compound causes inebriation; metabolite (glycolic acid) causes toxicity


== Clinical Features ==
==Pharmacology<ref>Kraut JF, Kurtz I. Clin J Am Soc Nephrol 2008. PMID: 18045860</ref>==
*Peak serum concentration 1-4 hours, elimination half-life ~9 hours
*Ethanol coingestion roughly doubles ethylene glycol half-life
*Minimum lethal dose 1-1.5 mL/kg
**Volume depends on percentage of ethylene glycol in solution, typically 0.6 g/mL
**60 kg patient lethal dose ~ 100 mL
*Metabolites (eg. oxalate acid, glycolic acid) cause toxicity, but do NOT cause osmolal gap
 
[[File:toxic alcohol ingestion - ethylene glycol.JPG|thumbnail]]
 
==Clinical Features==
===Stage 1 - CNS===
===Stage 1 - CNS===
*30min-12hr after ingestion
*30min-12hr after ingestion
*Appears intoxicated (slurred speech, [[ataxia]], stupor, [[seizure]], [[coma]])
*Appears intoxicated ([[nausea/vomiting]], slurred speech, [[nystagmus]], [[ataxia]], stupor, [[seizure]], [[coma]])


===Stage 2 - Cardiopulmonary===
===Stage 2 - Cardiopulmonary===
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*Most deaths occur during this stage
*Most deaths occur during this stage
**[[Hypertension]], [[tachycardia]], [[CHF]]
**[[Hypertension]], [[tachycardia]], [[CHF]]
**[[ARDS]], pulmonary infiltrates
**[[ARDS]], pulmonary infiltrates, hypoxia
**[[Hyperventilation]] (compensation for severe metabolic acidosis)
**[[Hypocalcemia]] (chelation by oxalate)
**[[Hypocalcemia]] (chelation by oxalate)
**[[Myositis]] & CK elevation
**[[Myositis]] & CK elevation
**Arrhythmias, prolonged QT
**Multi-organ system failure


===Stage 3 - Renal===
===Stage 3 - Renal===
*24-72hr after ingestion
*24-72hr after ingestion
**[[Flank pain]], CVA tenderness
**[[Flank pain]], CVA tenderness
**[[Hematuria]], proteinuria, calcium oxalate crystals (50%)
**[[Hematuria]], [[proteinuria]], calcium oxalate crystals (50%)
**Oliguria or anuria


==Differential Diagnosis==
==Differential Diagnosis==
{{Sedatve/hypnotic toxicity types}}
{{Sedatve/hypnotic toxicity types}}


== Diagnosis ==
==Evaluation==
*Chemistry
===Chemistry===
**Anion gap acidosis
May see:
***Will not be present immediately after exposure (only metabolite causes acidosis)
*Anion gap acidosis
**Renal failure
**Will not be present immediately after exposure (only metabolite causes acidosis)
*Serum Osm
*[[Hypocalcemia]] secondary to formation of calcium oxalate crystals
**Osm gap
*Renal failure
***Calculated serum osm - measured serum osm
*Glucose - may be low in setting of decreased caloric intake
****Calculated serum osm = 2Na + BUN/2.8 + glucose/18 + ethanol/4.2)
 
***Normal < 10
===Serum osmolality===
***>50 highly suggestive of toxic alcohol poisoning)
Osm gap:
***Note: Cannot rule out toxic ingestion with a "normal" osmol gap
*Calculated serum osm - measured serum osm
****Only parent alcohol is osmotically active
*Calculated serum osm = 2Na + BUN/2.8 + glucose/18 + ethanol/4.2)
*****Delayed presentation may mean that much of it is already metabolized
*Normal < 10
*Glucose
*>50 highly suggestive of toxic alcohol poisoning
*Alcohol levels
Note: Cannot rule out toxic ingestion with a "normal" osmol gap
*UA
*Only parent alcohol is osmotically active
**Hematuria, proteinuria, pyuria
*Delayed presentation may mean that much of it is already metabolized
**Calcium oxalate crystals (late finding; only seen in 50%)
 
**Urinary fluorescence (may be seen 6 hours after ingestion)
===Alcohol levels===
*Total CK
May be useful however even if elevated, patients can still have ingested a toxic alcohol
*VBG
===Urinalysis===
*ECG
*Hematuria, proteinuria, pyuria
**QT prolongation ~ hypocalcemia
*Calcium oxalate crystals (late finding; only seen in 50%)
*APAP/ASA levels
*Urinary fluorescence (may be seen 6 hours after ingestion), but lacks sensitivity and specificity
 
===Total CK===
Useful to assess for signs of [[rhabdomyolysis]] especially if the patient was found laying down
===Venous blood gas===
Needed to assess degree of acidosis. An ABG is not necessary since pH can be approximated with a clinical degree via a VBG
===[[ECG]]===
*[[QT prolongation]] ~ [[hypocalcemia]]
===Acetaminophen or Aspirin levels===
*Useful to discern the cause of the anion gap as well as assess for other toxic ingestion
 
{{Toxic Alcohols Anion/Osmolar Gaps}}
 
==Management==
===ADH enzyme blockade===
'''Fomepizole:'''
*Indications:
**Ethylene glycol level >20mg/dL
**Suspected significant ethylene glycol ingestion with ETOH level <100mg/dL
**Coma or altered mental status in patient with unclear history and osm gap >10
**Coma or altered mental status in patient with unclear history and unexplained met acidosis and ETOH level <100
*Dosing
**15mg/kg IV over 30min; follow by 10mg/kg q12hr until level <20 or acidosis resolves
'''Ethanol:'''
*Ethanol drips are rarely used
*BAL of 100-150 completely saturates alcohol dehydrogenase
*Dosing:
**IV: load 800mg/kg; then give 100mg/kg/hr
**Oral: 3-4 1-oz "shots" of 80-proof liquor); then give 1-2 "shots" per hour
===Correction of metabolic acidosis===
*Acidemia leads to protonation of oxalate which increases penetration to end organ tissues and causes more damage
*Bicarbonate infusion is an option however the patient will need to compensate with an increased respiratory rate (or mechanical ventilation which is frequently unsafe in severely acidotic patients) - otherwise a concomitant respiratory acidosis will ensue
*[[Bicarbonate]] 1-2mEq/kg IV bolus to attain pH = 7.45-7.50
**Follow by infusion of 150mEq/L in D5 @ 1.5-2 times maintenance fluid rate
*Monitor for worsening [[hypocalcemia]]
**Must correct hypocalcemia, but be cautious of increased calcium oxalate crystal production
 
===Dialysis===
*Indications:
**Refractory metabolic acidosis (pH <7.25) with AG >30 and base deficit < -15
**Renal insufficiency (serum Cr >3.0 mg/dL or increase in Cr by 1.0 mg/dL)
**Deteriorating vital signs despite aggressive supportive care
**Electrolyte abnormalities refractory to conventional therapy
**Ethylene glycol level >50mg/dL (controversial)
**Glycolic acid level > 8 mmol/L (glycolic acid is metabolite that causes anion gap acidosis)
 
===Decrease oxalate production===
*[[Thiamine]] 100mg IV q6hr x2d
**May promote glyoxalate conversion to alpha-hydroxy-beta-ketoadipate
*[[Pyridoxine]] 50mg q6hr x2d
**May inhibit metabolism of glyoxalate to oxalate
*[[Magnesium]] 2gm IV x1


== Treatment ==
==Disposition==
*ADH enzyme blockade
*Consult nephrology
**Fomepizole
*Admit ICU
***Indications:
****Ethylene glycol level >20mg/dL
****Suspected significant ethylene glycol ingestion w/ ETOH level <100mg/dL
****Coma or AMS in pt w/ unclear history and osm gap >10
****Coma or AMS in pt w/ unclear history and unexplained met acidosis and ETOH level <100
***Dosing
****15mg/kg IV over 30min; follow by 10mg/kg q12hr until level <20 or acidosis resolves
**Ethanol
***BAL of 100-150 completely saturates alcohol dehydrogenase
***IV: load 800mg/kg; then give 100mg/kg/hr
***Oral: 3-4 1-oz "shots" of 80-proof liquor); then give 1-2 "shots" per hour
*Correction of metabolic acidosis with bicarbonate
** Bicarbonate 1-2mEq/kg IV bolus to attain pH = 7.45-7.50
*** Follow by infusion of 150mEq/L in D5 @ 1.5-2 times maintenance fluid rate
** Monitor for worsening hypocalcemia
*Dialysis
**Indications:
***Refractory metabolic acidosis (pH <7.25) w/ AG >30
***Renal insufficiency
***Deteriorating vital signs despite aggressive supportive care
***Electrolyte abnormalities refractory to conventional therapy
***Ethylene glycol level >50mg/dL (controversial)
*Decrease oxalate production
**Thiamine 100mg IV q6hr x2d
**Pyridoxine 50mg q6hr x2d
**Magnesium 2gm IV x1


==See Also==
==See Also==
*[[Methanol Toxicity]]
*[[Sedative/hypnotic toxicity]]
*[[Toxic alcohols]]
*[[In-Training Exam Review]]


== References ==
==References==
<references/>


[[Category:Tox]]
[[Category:Toxicology]]

Revision as of 20:29, 9 March 2021

Background

  • Component of antifreeze, automobile coolants, de-icing agents, industrial solvents and hydraulic brake fluid.
    • Fluoresces yellow/green under Wood's lamp (neither Sn nor Sp)
  • Sweet taste
  • Parent compound causes inebriation; metabolite (glycolic acid) causes toxicity

Pharmacology[1]

  • Peak serum concentration 1-4 hours, elimination half-life ~9 hours
  • Ethanol coingestion roughly doubles ethylene glycol half-life
  • Minimum lethal dose 1-1.5 mL/kg
    • Volume depends on percentage of ethylene glycol in solution, typically 0.6 g/mL
    • 60 kg patient lethal dose ~ 100 mL
  • Metabolites (eg. oxalate acid, glycolic acid) cause toxicity, but do NOT cause osmolal gap
Toxic alcohol ingestion - ethylene glycol.JPG

Clinical Features

Stage 1 - CNS

Stage 2 - Cardiopulmonary

Stage 3 - Renal

Differential Diagnosis

Sedative/hypnotic toxicity

Evaluation

Chemistry

May see:

  • Anion gap acidosis
    • Will not be present immediately after exposure (only metabolite causes acidosis)
  • Hypocalcemia secondary to formation of calcium oxalate crystals
  • Renal failure
  • Glucose - may be low in setting of decreased caloric intake

Serum osmolality

Osm gap:

  • Calculated serum osm - measured serum osm
  • Calculated serum osm = 2Na + BUN/2.8 + glucose/18 + ethanol/4.2)
  • Normal < 10
  • >50 highly suggestive of toxic alcohol poisoning

Note: Cannot rule out toxic ingestion with a "normal" osmol gap

  • Only parent alcohol is osmotically active
  • Delayed presentation may mean that much of it is already metabolized

Alcohol levels

May be useful however even if elevated, patients can still have ingested a toxic alcohol

Urinalysis

  • Hematuria, proteinuria, pyuria
  • Calcium oxalate crystals (late finding; only seen in 50%)
  • Urinary fluorescence (may be seen 6 hours after ingestion), but lacks sensitivity and specificity

Total CK

Useful to assess for signs of rhabdomyolysis especially if the patient was found laying down

Venous blood gas

Needed to assess degree of acidosis. An ABG is not necessary since pH can be approximated with a clinical degree via a VBG

ECG

Acetaminophen or Aspirin levels

  • Useful to discern the cause of the anion gap as well as assess for other toxic ingestion

Toxic Alcohols Anion/Osmolar Gaps

Osmolar gap Anion gap Management
Ethanol + + if ketoacidosis Mainly supportive
Ethylene glycol + + Fomepizole, Thiamine, Pyridoxine, +/- Dialysis
Methanol + + Fomepizole or ethanol, Folinic acid, +/- Dialysis
Isopropyl alcohol + - Mainly supportive

Management

ADH enzyme blockade

Fomepizole:

  • Indications:
    • Ethylene glycol level >20mg/dL
    • Suspected significant ethylene glycol ingestion with ETOH level <100mg/dL
    • Coma or altered mental status in patient with unclear history and osm gap >10
    • Coma or altered mental status in patient with unclear history and unexplained met acidosis and ETOH level <100
  • Dosing
    • 15mg/kg IV over 30min; follow by 10mg/kg q12hr until level <20 or acidosis resolves

Ethanol:

  • Ethanol drips are rarely used
  • BAL of 100-150 completely saturates alcohol dehydrogenase
  • Dosing:
    • IV: load 800mg/kg; then give 100mg/kg/hr
    • Oral: 3-4 1-oz "shots" of 80-proof liquor); then give 1-2 "shots" per hour

Correction of metabolic acidosis

  • Acidemia leads to protonation of oxalate which increases penetration to end organ tissues and causes more damage
  • Bicarbonate infusion is an option however the patient will need to compensate with an increased respiratory rate (or mechanical ventilation which is frequently unsafe in severely acidotic patients) - otherwise a concomitant respiratory acidosis will ensue
  • Bicarbonate 1-2mEq/kg IV bolus to attain pH = 7.45-7.50
    • Follow by infusion of 150mEq/L in D5 @ 1.5-2 times maintenance fluid rate
  • Monitor for worsening hypocalcemia
    • Must correct hypocalcemia, but be cautious of increased calcium oxalate crystal production

Dialysis

  • Indications:
    • Refractory metabolic acidosis (pH <7.25) with AG >30 and base deficit < -15
    • Renal insufficiency (serum Cr >3.0 mg/dL or increase in Cr by 1.0 mg/dL)
    • Deteriorating vital signs despite aggressive supportive care
    • Electrolyte abnormalities refractory to conventional therapy
    • Ethylene glycol level >50mg/dL (controversial)
    • Glycolic acid level > 8 mmol/L (glycolic acid is metabolite that causes anion gap acidosis)

Decrease oxalate production

  • Thiamine 100mg IV q6hr x2d
    • May promote glyoxalate conversion to alpha-hydroxy-beta-ketoadipate
  • Pyridoxine 50mg q6hr x2d
    • May inhibit metabolism of glyoxalate to oxalate
  • Magnesium 2gm IV x1

Disposition

  • Consult nephrology
  • Admit ICU

See Also

References

  1. Kraut JF, Kurtz I. Clin J Am Soc Nephrol 2008. PMID: 18045860