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

Abstract

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. Prospective, observational study. Tertiary care, medical intensive care unit. Nine critically ill adults receiving high-dose lorazepam (≥10 mg/hr) infusion. Cumulative lorazepam dose (mg/kg) and the rate of infusion (mg·kg−1·hr−1) 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 (≥15 mmol/L) metabolic acidosis with elevated osmol gap (≥10 mOsm/L), was assessed at that time. 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 mg·kg−1·hr−1 (range, 0.11–0.22), respectively. A significant correlation between high-dose lorazepam infusion rate and serum propylene glycol concentrations was observed (r2 = .557, p = .021). Osmol gap was the strongest predictor of serum propylene glycol concentrations (r2 = .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). 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 ≥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.