Relationship of continuous infusion lorazepam to serum propylene glycol concentration in critically ill adults

Crit Care Med. 2004 Aug;32(8):1709-14. doi: 10.1097/01.ccm.0000134831.40466.39.


Objectives: The primary objective was to evaluate the relationship between high-dose lorazepam and serum propylene glycol concentrations. Secondary objectives were a) to document the occurrence of propylene glycol accumulation associated with continuous high-dose lorazepam infusion; b) to assess the relationship between lorazepam dose, serum propylene glycol concentrations, and propylene glycol accumulation; and c) to assess the relationship between the osmol gap and serum propylene glycol concentrations.

Design: Prospective, observational study.

Setting: Tertiary care, medical intensive care unit.

Patients: Nine critically ill adults receiving high-dose lorazepam (> or =10 mg/hr) infusion.

Interventions: Cumulative lorazepam dose (mg/kg) and the rate of infusion ( were monitored from initiation of lorazepam infusion until 24 hrs after discontinuation of the high-dose lorazepam infusion. Serum osmolarity was collected at 48 hrs into the high-dose lorazepam infusion and daily thereafter. Serum propylene glycol concentrations were drawn at 48 hrs into the high-dose lorazepam infusion, and the presence of propylene glycol accumulation, as evidenced by a high anion gap (> or =15 mmol/L) metabolic acidosis with elevated osmol gap (> or =10 mOsm/L), was assessed at that time.

Measurements and main results: The mean cumulative high-dose lorazepam received and mean high-dose lorazepam infusion rate were 8.1 mg/kg (range, 5.1-11.7) and 0.16 (-1)(range, 0.11-0.22), respectively. A significant correlation between high-dose lorazepam infusion rate and serum propylene glycol concentrations was observed (r =.557, p =.021). Osmol gap was the strongest predictor of serum propylene glycol concentrations (r =.804, p =.001). Propylene glycol accumulation was observed in six of nine patients at 48 hrs. No significant correlation between duration of lorazepam infusion and serum propylene glycol concentrations was observed (p =.637).

Conclusion: Propylene glycol accumulation, as reflected by a hyperosmolar anion gap metabolic acidosis, was observed in critically ill adults receiving continuous high-dose lorazepam infusion for > or =48 hrs. Study findings suggest that in critically ill adults with normal renal function, serum propylene glycol concentrations may be predicted by the high-dose lorazepam infusion rate and osmol gap.

Publication types

  • Clinical Trial

MeSH terms

  • Acid-Base Equilibrium / drug effects
  • Acidosis / metabolism
  • Adult
  • Critical Illness / therapy*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Hypnotics and Sedatives / administration & dosage*
  • Infusions, Intravenous
  • Lorazepam / administration & dosage*
  • Male
  • Middle Aged
  • Osmolar Concentration
  • Propylene Glycol / blood*
  • Prospective Studies
  • Solvents / analysis*


  • Hypnotics and Sedatives
  • Solvents
  • Propylene Glycol
  • Lorazepam