Propylene Glycol Intoxication

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

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

Etiology

  • Chlordiazepoxide (Librium) (see Chlordiazepoxide, [[Chlordiazepoxide]])
  • Diazepam (Valium) (see Diazepam, [[Diazepam]])
  • Digoxin (see Digoxin, [[Digoxin]])
  • Esmolol (see Esmolol, [[Esmolol]])
  • Etomidate (see Etomidate, [[Etomidate]])
  • Hydralazine (see Hydralazine, [[Hydralazine]])
  • Lorazepam (Ativan) (see Lorazepam, [[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, [[Nitroglycerin]])
  • Pentobarbital (see Pentobarbital, [[Pentobarbital]])
  • Phenobarbital (see Phenobarbital, [[Phenobarbital]])
  • Phenytoin (Dilantin) (see Phenytoin, [[Phenytoin]])
  • Sulfamethoxazole-Trimethoprim (Bactrim, Septra) (see Sulfamethoxazole-Trimethoprim, [[Sulfamethoxazole-Trimethoprim]])
    • Each ml of trimethoprim-sulfamethoxazole contains 400 mg of propylene glycol

Diagnosis

Serum Chemistry/Arterial Blood Gas (ABG)

Serum Osmolality


Clinical Manifestations

Cardiac Manifestations

Hematologic Manifestations

Neurologic Manifestations

  • Delirium/Central Nervous System Depression/Obtundation-Coma (see Delirium, [[Delirium]] and Obtundation-Coma, [[Obtundation-Coma]])
  • Seizures (see Seizures, [[Seizures]])

Pulmonary Manifestations

Renal Manifestations

Anion Gap Metabolic Acidosis (AGMA) (see Metabolic Acidosis-Elevated Anion Gap, [[Metabolic Acidosis-Elevated Anion Gap]]):

  • Lactic Acidosis (see Lactic Acidosis, [[Lactic Acidosis]]): variably present

Elevated Osmolal Gap (see xxxx, [[xxxx]])

  • 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, [[Acute Kidney Injury]])

  • xxxx

Treatment

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

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]