Pharmacoeconomic assessment of propofol 2% used for prolonged sedation.

OBJECTIVE: To demonstrate that the use of propofol 2% is comparable to propofol 1% in effectiveness and in the wake-up time used for prolonged sedation. DESIGN: Open-label, case cohort study with a cohort of historical controls, phase IV clinical trial. SETTING: Medical and surgical intensive care unit (ICU) in a community hospital. PATIENTS: Fifty-one consecutive patients (medical, surgical, and trauma) admitted to our ICU requiring mechanical ventilation for >24 hrs. METHODS: All patients received propofol 2% (1-6 mg.kg-1.hr-1, starting with the lowest dose) and morphine chloride (0.5 mg.kg-1.24 hrs-1). A 4-5 level of sedation (Ramsay scale) was recommended. When weaning was indicated clinically, sedation and analgesia were interrupted abruptly, mechanical ventilation was discontinued, and the patient was connected to a T-bridge. OUTCOME MEASUREMENTS: Inability to attain the desired level of sedation with the highest dose rate of proposal, and hypertriglyceridemia >500 mg/dL, were considered therapeutic failure. The time between discontinuation of mechanical ventilation and extubation was measured. Those variables, as well as different items related to ICU cost, were compared between the study group and two historical groups sedated with propofol 1% and midazolam. RESULTS: The duration of sedation was 122.4 +/- 89.2 (sd) hrs for the propofol 2% group. The frequency of hypertriglyceridemia was 3.9% and 20.4% for the propofol 2% and the propofol 1% groups, respectively (p =.016). Therapeutic failure rates were 19.6% and 33.4% for the propofol 2% and propofol 1% groups, respectively (p =.127). The lower frequency of hypertriglyceridemia was associated with a higher number of patients reaching weaning. Weaning time was similar in the two propofol groups, 32.3 hrs ($1,744) for the propofol 2% group vs. 97.9 hrs ($5,287) for the midazolam group. Cost of sedation was $2.68 per hour for the midazolam group and $7.69 per hour for the propofol group. There was a favorable cost-benefit ratio for the propofol group, attributable to the shorter weaning time, although benefit was less than expected because higher doses of propofol 2% than propofol 1% were required during the first 48 hrs (p <.05). CONCLUSIONS: The new propofol 2% preparation is an effective sedative agent and is safe because of the low frequency of associated hypertriglyceridemia. The shorter weaning time associated with the use of propofol 2% as compared with midazolam compensates for its elevated cost. The economic benefit of propofol 2% is less than expected because higher doses of propofol 2% than propofol 1% are required over the first 48 hrs.

Prolonged sedation of critically ill patients with midazolam or propofol: impact on weaning and costs.

OBJECTIVE: To compare the effectiveness of sedation, the time required for weaning, and the costs of prolonged sedation of critically ill mechanically ventilated patients with midazolam and propofol. DESIGN: Open-label, randomized, prospective, phase IV clinical trial. SETTING: Medical and surgical intensive care unit (ICU) in a community hospital. PATIENTS: All ICU admissions (medical, surgical and trauma) requiring mechanical ventilation for > 24 hrs. A total of 108 patients were included in the study. INTERVENTIONS: Patients were randomized to receive midazolam or propofol. The dose range allowed for each drug was 0.1 to 0.5 mg/kg/hr for midazolam and 1 to 6 mg/kg/hr for propofol. The lowest dose that achieved an adequate patient-ventilator synchrony was infused. All patients received 0.5 mg/kg/24 hrs of morphine chloride. MEASUREMENTS AND MAIN RESULTS: The level of sedation was quantified by the Ramsay scale every 2 hrs until weaning from mechanical ventilation was started. If sedation could not be achieved by infusing the highest dose of midazolam or propofol, the case was recorded as a therapeutic failure. In the propofol group, serum triglycerides were determined every 72 hrs. Concentrations of > 500 mg/dL were also recorded as a therapeutic failure. When the patient was ready for weaning according to defined criteria, sedation was interrupted abruptly and the time from interruption of sedation to the first T-bridge trial and to extubation was measured. Cost analysis was performed based on the cost of intensive care in our unit ($54/hr). In the midazolam group (n = 54), 15 (27.8%) patients died; 11 (20.4%) patients had therapeutic failure; and 28 (51.8%) patients were subjected to a T-bridge trial. In the propofol group (n = 54), these proportions were 11 (20.4%), 18 (33.4% [including seven due to inadequate sedation, and 11 due to hypertriglyceridemia]), and 25 (46.2%), respectively. None of these values was significantly different between the two groups. Duration of sedation was 141.7 +/- 89.4 (SD) hrs and 139.7 +/- 84.7 hrs (p = NS), and cost (US dollars) attributed to sedation was $378 +/- 342 and $1,047 +/- 794 (p = .0001) for the midazolam and propofol groups, respectively. In the midazolam group, time from discontinuation of the drug infusion to extubation was 97.9 +/- 54.6 hrs (48.9 +/- 47.2 hrs to the first disconnection, and 49.0 +/- 23.7 hrs to extubation). In the propofol group, time from discontinuation of the drug infusion to extubation was 34.8 +/- 29.4 hrs (4.0 +/- 3.9 hrs to the first disconnection, and 30.8 +/- 29.2 hrs to extubation). The difference between the two groups in the weaning time was 63.1 +/- 12.5 (SEM) hrs (p < .0001). Cost per patient in the midazolam group (including ICU therapy and sedation with midazolam) was $10,828 +/- 5,734. Cost per patient in the propofol group was $9,466 +/- 5,820, $1,362 less than in the midazolam group. CONCLUSIONS: In our population of critically ill patients sedated with midazolam or propofol over prolonged periods, midazolam and propofol were equally effective as sedative agents. However, despite remarkable differences in the cost of sedation with these two agents, the economic profile is more favorable for propofol than for midazolam due to a shorter weaning time associated with propofol administration.