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

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 (greater than or equal to10 mg/hr) infusion. Interventions: 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 (2:15 mmol/L) metabolic acidosis with elevated osmol gap (greater than or equal to10 m0sm/ 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 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 (r(2) = .557, p = .021). Osmol gap was the strongest predictor of serum propylene glycol concentrations (r(2) = .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). Conclusions. 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 greater than or equal to48 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.