Economic evaluation of propofol and lorazepam for critically ill patients undergoing mechanical ventilation

Abstract

Objective: The economic implications of sedative choice in the management of patients receiving mechanical ventilation are unclear because of differences in costs and clinical outcomes associated with specific sedatives. Therefore, we aimed to determine the cost-effectiveness of the most commonly used sedatives prescribed for mechanically ventilated critically ill patients.

Design, setting, and patients: Adopting the perspective of a hospital, we developed a probabilistic decision model to determine whether continuous propofol or intermittent lorazepam was associated with greater value when combined with daily awakenings. We also evaluated the comparative value of continuous midazolam in secondary analyses. We assumed that patients were managed in a medical intensive care unit and expected to require ventilation for > or = 48 hrs. Model inputs were derived from primary analysis of randomized controlled trial data, medical literature, Medicare reimbursement rates, pharmacy databases, and institutional data.

Main results: We measured cost-effectiveness as costs per mechanical ventilator-free day within the first 28 days after intubation. Our base-case probabilistic analysis demonstrated that propofol dominated lorazepam in 91% of simulations and, on average, was both $6,378 less costly per patient and associated with more than three additional mechanical ventilator-free days. The model did not reveal clinically meaningful differences between propofol and midazolam on costs or measures of effectiveness.

Conclusion: Propofol has superior value compared with lorazepam when used for sedation among the critically ill who require mechanical ventilation when used in the setting of daily sedative interruption.

Figure 1. Decision Model

This is a simplified version of the decision model used in analyses. In this model, patients ventilated for at least 48 hours could either receive propofol or lorazepam for sedation. Progression through the decision tree over the course of the succeeding 28 days examined was determined by probabilities defined in Table 1.

Figure 2. Scatterplot of probabilistic analyses comparing costs and effects

These scatterplots depict the results of 1,000 simulations during which important clinical variables were allowed to vary simultaneously within predefined distributions (see Methods). In contrast to Figure 4, the axes represent the actual (not incremental) costs and effects of each separate trial. This figure demonstrates near duplication of propofol (blue circles) costs and effects for midazolam (yellow circles), though little overlap of lorazepam with either of these groups—emphasizing the dominance of propofol and midazolam over lorazepam (pink circles).

Figure 3. Scatterplot of probabilistic analyses comparing incremental costs and effects

These scatterplots graph the results of 1,000 simulations during which important clinical variables were allowed to vary simultaneously within predefined distributions (see Methods). The x axis represents the incremental difference in mechanical ventilator-free days by group (propofol – lorazepam in Graph A, midazolam – lorazepam in Graph B, and propofol – midazolam in Graph C). The y axis represents incremental costs calculated in a similar fashion. The clustering of simulation results in the lower right quadrant in Graphs A and B demonstrates the comparative dominance of propofol and midazolam over lorazepam. The clustering of analyses at the intersection of the axes in Graph C suggests that there is little evidence that clinically or economically important differences exist between propofol and midazolam.

Figure 4. Tornado diagram comparing cost differences between lorazepam and propofol

The length of the horizontal bars corresponds to the difference in average costs between lorazepam and propofol groups over the range specified for variables of interest depicted on the y axis. The vertical line transecting the bars represents the cost difference between lorazepam and propofol in the point-estimate (non-probabilistic) base-case analysis. The horizontal line at the top of the figure represents the range of values over which propofol’s cost is less than that of lorazepam. There were fewer mechanical ventilator-free days in all ranges and scenarios with the exception of a propofol to lorazepam ratio of mechanical ventilation duration >1.5 (for example, 6 propofol ventilator days to 4 lorazepam ventilator days). The grey bar and horizontal arrow depict this gain in lorazepam-associated mechanical ventilator-free days.