Epidemiology

• Propylene Glycol is an FDA-Approved Solvent: used in food, drugs, and cosmetics
  • Most cases are subacute poisoning, with toxicity observed after several days of propylene glycol infused as a solvent in PO/IV/topical drug formulations
  • Propylene glycol intoxication is the most common alcohol intoxication in the ICU
• Risk Factors for Propylene Glycol Toxicity
  • Acute Kidney Injury/Chronic Kidney Disease
    • There are even case reports of propylene glycol toxicity occurring during continuous venovenous hemodialysis (CVVHD) [MEDLINE]: in these cases, removal rate during CVVHD might be less than infusion rate of propylene glycol in the infused medication (when the offending medication is used at a high infusion rate)
  • Liver Disease

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Physiology

Properties

• Propylene Glycol is a Colorless, Odorless Liquid
  • Molecular Weight: 76.1 Daltons

Exposure

• Dermal Absorption: may occur through normal skin
• Intravenous Adminstration: via intravenous medications (below)

Propylene Glycol Metabolism

• Renal Excretion: 50% of propylene glycol is excreted unchanged by the kidneys
• Hepatic Metabolism: 50% is metabolized by hepatic alcohol dehydrogenases and aldehyde dehydrogenase to glycolic acid, L-lactate/D-lactate, and glyoxal
  • Lactate is ubsequently converted to pyruvate or acetone

Lipophilic Properties of Propylene Glycol

• Lipophilic Properties: allow propylene glycol to enter the lipid bilayer of renal proximal tubular cells
  • Inside proximal tubular cell, propylene glycol exerts significant cytotoxic effects by disrupting cellular membrane integrity
  • Propylene glycol exerts an osmotic effect, creating osmotic nephrosis -> swelling of proximal renal tubules
  • Swelling and vacuole formation induce renal injury and proximal tubular dysfunction

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Etiology

• Chlordiazepoxide (Librium) (see Chlordiazepoxide)
• Diazepam (Valium) (see Diazepam)
• Digoxin (see Digoxin)
• Esmolol (see Esmolol)
• Etomidate (see Etomidate)
• Hydralazine (see Hydralazine)
• Lorazepam (Ativan) (see Lorazepam): most common etiology in case reports (probably related to higher concentration of propylene glycol in this formulation)
  • Each ml of a standard 2 mg/ml lorazepam solution contains 830 mg of propylene glycol
  • Propylene glycol (associated with prolonged high-dose lorazepam infusion) has been implicated in the development of acute tubular necrosis/lactic acidosis/hyperosmolar states
  • Lorazepam also contains polyethlyene glycol (PEG): PEG (associated with prolonged high-dose lorazepam infusion) has been implicated in the development of acute tubular necrosis/lactic acidosis/hyperosmolar states
  • Toxicity has been reported to occur at infusion rates >18 mg/hr x >4 wks and at >25 mg/hr x hrs-days
  • Predictors of Toxicity (in those requiring intravenous lorazepam at doses >1 mg/kg/day): elevated osmolal gap >12 mOsm/L may identify those at risk for propylene glycol toxicity
• Multivitamin
• Nitroglycerin (see Nitroglycerin)
• Pentobarbital (see Pentobarbital)
• Phenobarbital (see Phenobarbital)
• Phenytoin (Dilantin) (see Phenytoin)
• Sulfamethoxazole-Trimethoprim (Bactrim, Septra) (see Sulfamethoxazole-Trimethoprim): intravenous preparation
  • Each One Milliliter of Sulfamethoxazole-Trimethoprim Contains 400 mg of Propylene Glycol

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Diagnosis

Serum Chemistry/Arterial Blood Gas (ABG)

• Anion Gap Metabolic Acidosis (see Metabolic Acidosis-Elevated Anion Gap)

Serum Osmolality

• Elevated Osmolal Gap (see Metabolic Acidosis-General)

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Clinical Manifestations

Cardiovascular Manifestations

Sinus Bradycardia (see Sinus Bradycardia)

• Epidemiology
  • XXXX

Cardiac Arrhythmias/Cardiac Arrest (see Ventricular Tachycardia)

• Epidemiology
  • XXXX

Hypotension (see Hypotension)

• Epidemiology
  • XXXX

QRS and T-Wave Abnormalities

• Epidemiology
  • XXXX

Hematologic Manifestations

Hemolytic Anemia (see Hemolytic Anemia)

• Physiology
  • *Intravascular Hemolysis

Neurologic Manifestations

Delirium/Central Nervous System Depression/Obtundation-Coma (see Delirium and Obtundation-Coma)

• Epidemiology
  • XXXX

Seizures (see Seizures)

• Epidemiology
  • XXXX

Pulmonary Manifestations

Respiratory Arrest (see Respiratory Failure)

• Epidemiology
  • XXXX

Renal Manifestations

Anion Gap Metabolic Acidosis (AGMA) (see Metabolic Acidosis-Elevated Anion Gap)

• Lactic Acidosis (see Lactic Acidosis): variably present

Elevated Serum Osmolal Gap (see Elevated Serum Osmolal Gap)

• Physiology: propylene glycol is metabolized to L-lactate, D-lactate, and glyoxal
• Clinical: may produce a large osmolal gap (>20 mOsm/L)
  • The absence of an osmolal gap does not exclude the presence of diethylene glycol
  • There are often discrepancies between the degree of osmolal gap and the severity of clinical manifestations

Acute Kidney Injury (AKI) (see Acute Kidney Injury)

• xxxx

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Treatment

• Discontinuation of Offending IV Infusion
• Administration of IVF
• Hemodialysis
• Fomepizole (see Fomepizole): although has been used in ethylene glycol intoxication, there are no reports of efficacy with propylene glycol intoxication

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References

• Propylene glycol toxicity associated with lorazepam infusion in a patient receiving continuous veno-venous hemofiltration with dialysis. Anesth Analg. 2002 Jun;94(6):1583-5 [MEDLINE]