Propylene glycol-associated renal toxicity from lorazepam infusion

Pharmacotherapy. 2003 Sep;23(9):1094-9. doi: 10.1592/phco.23.10.1094.32762.

Abstract

Objectives: Using data from patients who developed elevations in serum creatinine concentrations while receiving continuous-infusion lorazepam, we sought to determine the correlations between the magnitude of serum creatinine concentration rise and each of the following variables: serum propylene glycol level, cumulative lorazepam dose, and duration of lorazepam administration. An additional objective was to identify clinical markers for propylene glycol toxicity.

Design: Retrospective chart review.

Setting: Medical-surgical intensive care unit and burn unit at a university hospital.

Patients: Eight patients who developed elevations in serum creatinine concentrations while receiving continuous-infusion lorazepam (range 2-28 mg/hr).

Measurements and main results: The mean cumulative dose of lorazepam was 4305 mg (range 1200-10,920 mg), and the mean propylene glycol level determined at the time of peak serum creatinine concentration was 1103 microg/ml (range 186-3450 microg/ml). Serum creatinine concentrations increased in all eight patients during lorazepam infusion and decreased in seven within 3 days after stopping infusion. A weak-to-moderate correlation existed between the magnitude of the rise in serum creatinine concentration and propylene glycol level (r=0.53). A weak-to-moderate correlation also was identified between cumulative lorazepam dose and magnitude of serum creatinine concentration rise (r=0.43), and a strong-to-moderate correlation was found between duration of lorazepam infusion and magnitude of serum creatinine concentration rise (r=0.60). Propylene glycol levels were strongly correlated with both serum osmolality and osmol gap.

Conclusion: The patients' increased serum creatinine concentrations are likely to have resulted from exposure to propylene glycol as a result of lorazepam infusion. Serum osmolality and osmol gap may be useful markers for propylene glycol toxicity.

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Biomarkers / chemistry
  • Conscious Sedation / methods
  • Creatinine / blood
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Humans
  • Infusions, Intravenous
  • Kidney / drug effects
  • Kidney / physiopathology
  • Lorazepam / administration & dosage*
  • Lorazepam / adverse effects*
  • Lorazepam / pharmacokinetics
  • Male
  • Middle Aged
  • Osmolar Concentration
  • Propylene Glycol / blood*
  • Propylene Glycol / toxicity*
  • Retrospective Studies

Substances

  • Biomarkers
  • Propylene Glycol
  • Creatinine
  • Lorazepam