The accuracy and precision of measuring Lorazepam from three liquid preparations.

Objectives: Commercially available lorazepam solution contains both polyethylene glycol (PEG) and propylene glycol. When large doses are administered for deep sedation in the pediatric intensive care unit (PICU), PEG may cause diarrhea, and the accumulation of propylene glycol may result in toxicity. These adverse effects may be avoided by preparing a slurry from crushed lorazepam tablets suspended in water immediately prior to administration. This slurry, which is extemporaneously prepared at bedside by nurses, lacks a suspending agent, and, therefore, the rapid settling of drug particles may produce suspensions that are not homogeneous. Thus, there may be significant inaccuracy and imprecision in dosage measurement. The objective of this study was to compare the accuracy and precision of lorazepam dosage measurement from three liquid preparations: 1) tablet slurry prepared at bedside by a nurse; 2) lorazepam suspension extemporaneously prepared by a pharmacist; and 3) the commercially available lorazepam solution.

Methods: Sixteen PICU nurses measured three doses of lorazepam (0.5 mg, 1.5 mg, 3.5 mg) in triplicate from each of the three liquid preparations using oral syringes. PICU nurses prepared the slurry by mixing crushed lorazepam tablet(s) with water and drawing up the appropriate dose in an oral syringe. Additionally, nurses drew up the appropriate dose from a pharmacist-prepared lorazepam suspension (1 mg/mL) and the commercially available lorazepam solution (2 mg/mL). All samples were analyzed by HPLC and the groups were compared using two-way ANOVA.

Results: Dosage accuracy for the slurry (91.2 ± 7.8%) and suspension (109.2 ± 4.9%) were significantly different from the commercially available solution (101.5 ± 3.1%) (P < .05). Imprecision in dosage measurement, as determined by the relative standard deviation, was greatest for the slurry (8.6%) as compared to the suspension (4.5%) and commercially available solution (3.0%).

Conclusions: Dosage measurement from lorazepam slurry and suspension led to significant deviation from the intended dose. Dosage measurement using the slurry was the least precise among the three preparations.