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2250058 
Journal Article 
Relationship of continuous infusion lorazepam to serum propylene glycol concentration in critically ill adults 
Arroliga, AC; Shehab, N; McCarthy, K; Gonzales, JP 
2004 
Yes 
Critical Care Medicine
ISSN: 0090-3493
EISSN: 1530-0293 
32 
8 
1709-1714 
English 
15286548 
WOS:000223410800012 
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 (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 (> 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 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 =.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. 
lorazepam; propylene glycol; toxicity; sedation; adults; osmol gap