Assessing Propylene Glycol Toxicity in Alcohol Withdrawal Patients Receiving Intravenous Benzodiazepines: A One-Compartment Pharmacokinetic Model

Eur J Drug Metab Pharmacokinet. 2018 Aug;43(4):423-430. doi: 10.1007/s13318-018-0462-1.


Background and objectives: While some case reports indicate that high doses of propylene glycol (PG) may result in metabolic acidosis, there has been no large-scale study that evaluated the risk of metabolic acidosis in patients receiving PG-containing benzodiazepines for acute alcohol withdrawal. This study was undertaken to evaluate the potential toxicity of PG in patients with acute alcohol withdrawal treated with intermittent intravenous bolus doses of diazepam and/or lorazepam.

Methods: This is a retrospective case study using data collected from 18 randomly selected patients receiving one or both of these medications per a modified Clinical Institute Withdrawal Assessment for Alcohol (CIWA) Class 3 protocol. Plasma levels of PG were estimated using a one-compartment pharmacokinetic model.

Results: Only two patients had an elevated anion gap compared to their baseline value with one also experiencing a significant increase in serum creatinine. No increases in serum osmolarity were noted. Analysis showed that the benzodiazepine dose received was a good predictor of the estimated PG concentration (r = 0.6), but was poorly correlated with the anion gap. No significant correlation was found with the creatinine clearance or serum creatinine. Patients receiving several daily doses were at higher risk of developing an anion gap (r = 0.33), but the estimated maximum PG concentration did not correlate with the anion gap or serum concentration.

Conclusion: It does not appear that intermittent bolus administration of intravenous benzodiazepines for alcohol withdrawal influenced renal function or anion gap regardless of number of administered doses, amount of PG received, or the estimated PG concentration.

MeSH terms

  • Acid-Base Equilibrium / drug effects
  • Acidosis / chemically induced*
  • Alcoholism / complications
  • Benzodiazepines / administration & dosage
  • Benzodiazepines / therapeutic use
  • Diazepam / administration & dosage
  • Diazepam / therapeutic use
  • Female
  • Humans
  • Injections, Intravenous
  • Lorazepam / administration & dosage
  • Lorazepam / therapeutic use
  • Male
  • Middle Aged
  • Models, Biological
  • Propylene Glycol / adverse effects*
  • Propylene Glycol / blood
  • Propylene Glycol / pharmacokinetics*
  • Propylene Glycol / pharmacology
  • Renal Insufficiency / chemically induced
  • Retrospective Studies
  • Substance Withdrawal Syndrome / drug therapy*


  • Benzodiazepines
  • Propylene Glycol
  • Lorazepam
  • Diazepam