Economic Evaluation of Propofol and Lorazepam for Critically Ill Patients
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 ≥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.

Mechanical ventilation is the most common intervention, delivered daily to tens of thousands of patients, in intensive care units (ICUs) worldwide . The provision of pharmacologic sedation and analgesia to those receiving ventilation is an essential part of quality critical care because adequate sedation can reduce patient anxiety, improve patient-ventilator synchrony, and facilitate overall clinical care .

Current clinical practice guidelines recommend the provision of either intermittent or continuous lorazepam as the primary sedative for patients requiring prolonged ventilation and continuous propofol or midazolam for patients requiring short-term (48-72 hrs) ventilation . Although these and other sedatives have been compared in past studies, few have been assessed rigorously with high-quality, randomized clinical trials that included outcomes such as duration of ventilation and length of hospital stay . To our knowledge, only two randomized clinical trials evaluating sedation regimens have been published that also incorporated daily trials of awakening from sedation, an intervention now widely utilized . Neither of these studies, one comparing midazolam with propofol and the other comparing propofol with intermittent lorazepam, reported a survival advantage to any specific sedative regimen .

Given the lack of mortality differences among these three sedatives, factors such as costs and clinical outcomes, such as frequency of adverse events, duration of mechanical ventilation, and length of stay, could be useful in differentiating the value of these products that are part of the $180 billion spent annually on critical care in the United States. Although propofol may facilitate weaning when compared with lorazepam, it is significantly more costly than lorazepam and is associated with significant hemodynamic and metabolic side effects . Because of these concerns, many practitioners use midazolam because it is perceived to have a considerably shorter half-life than lorazepam and is less expensive than propofol. However, accumulation of midazolam and its active metabolites is likely to occur in critically ill patients, potentially causing prolonged sedation .

Because of the strong association between ICU length of stay and costs, identification of safe and effective sedative options that can also reduce resource utilization during a time of changing population demographics is important for policy makers and clinicians alike . However, we know of no formal economic analyses comparing sedatives in the setting of contemporary critical care practice. Therefore, we performed cost-effectiveness analysis comparing continuous propofol and intermittent lorazepam for the sedation of critically ill adults, with secondary analyses including midazolam.