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Midazolam versus propofol for long-term sedation in the ICU: a randomized prospective comparison |
Weinbroum A A, Halpern P, Rudick V, Sorkine P, Freedman M, Geller E |
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Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. Health technology Midazolam and propofol for long-term sedation in intensive care units (ICUs). A loading dose of midazolam and propofol was administered (0.11 +/- 0.02 mg/kg and 1.3 +/- 0.2 mg/kg, respectively). Midazolam was given in a concentration of 30 mg x 100 ml?-1 saline and propofol was given undiluted in the original 1 % concentration.
Economic study type Cost-effectiveness analysis.
Study population Male and female critically ill, mechanically ventilated patients.
Setting Hospital. The economic study was carried out in California, USA.
Dates to which data relate The main effectiveness data were mainly derived from a single study conducted in 1997. Resource and cost data were obtained from 1997 sources. The price years were not stated.
Source of effectiveness data The estimate of mean duration of sedation, number of patient agitated between 30 and 60 minutes after sedation was discontinued, greater than 20% decrease in systolic blood pressure after the loading dose, 25% decrease in spontaneous minute volume, daily dose adjustment, nurse-rated quality of sedation, resumption of spontaneous respiration, recovery rate and number of amnesia cases were obtained from a single study.
Link between effectiveness and cost data The costing was prospectively undertaken on the same patient sample as that used in the effectiveness analysis.
Study sample A cohort of 67 critically ill, mechanically ventilated patients was included in the analysis. These patients were randomly assigned to receive midazolam (36; 12 male, age: 51 +/- 6 years, duration of stay in ICU: 31 +/- 7 days) or propofol (31; 10 male, age:56 +/- 3, duration of stay in ICU: 21 +/- 4). Only 18 patients in the midazolam group were tested for amnesia. Power calculations to determine the sample size were not undertaken.
Study design The study was a randomized controlled trial. The duration of follow-up was not clearly reported. However, it is likely to have been for 3 hours after the infusion of the sedative drug. Loss to follow-up was not reported.
Analysis of effectiveness The analysis of effectiveness was based on treatment completers only. The primary health outcomes were mean duration of sedation, number of patients agitated between 30 and 60 minutes after sedation was discontinued, greater than 20% decrease in systolic blood pressure after the loading dose, 25% decrease in spontaneous minute volume, daily dose adjustment, nurse-rated quality of sedation, resumption of spontaneous respiration, recovery rate and number of amnesia cases. Patient group comparability was not demonstrated.
Effectiveness results The mean duration of sedation was 141 for midazolam and 99 hours for propofol, (p<0.02). Twenty-seven midazolam patients (18%) and 35 (10%) propofol patients were agitated between 30 and 60 minutes after sedation was discontinued, (p<0.02). Overall, 68% of propofol patients versus 31% of midazolam patients had a greater than 20% decrease in systolic blood pressure after the loading dose, (p< 0.001). Overall, 26% versus 45% showed a 25% decrease in spontaneous minute volume (p<0.01). There were 2.1 (+/- 0.1) versus 1.4 (+/-0.1) daily dose adjustments (p<0.001). Nurse-rated quality of sedation was 8.2 (+/- 0.1) with midazolam versus 7.3 (+/- 0.1) with propofol, on a 10-cm linear visual analog scale, (p<0.001). Twenty midazolam and 19 propofol patients were successfully weaned off synchronous intermittent mandatory ventilation to continuous positive airway pressure on the first attempt, within 3.2 (+/- 1.0) and 2.0 (+/- 1.7) hours, respectively. Among the 18 midazolam patients tested for amnesia, none was able to recall the drawing shown to them while under the effect of the drug nor could they recall any event occurring during the study period. Among the 17 propofol patients tested for amnesia, 12 recalled the drawings and could remember sporadic events from the study period. Recovery from sedation was 1.8 (+/- 0.4) hours for propofol and 2.8 +/- 0.4 hours for midazolam, (p<0.02).
Clinical conclusions Both drugs afford reliable, safe and controllable long-term sedation in ICU patients and rapid weaning from mechanical ventilation. Midazolam depresses respiration, allows better maintenance of sedation and yields complete amnesia while propofol causes more cardiovascular depression during induction.
Measure of benefits used in the economic analysis No summary benefit measure was used in the analysis and as such the benefits are considered to be the same as the outcome measures.
Direct costs Drug costs were included in the analysis. The quantities were reported separately from the prices. The quantity/cost boundary adopted was the ICU. Discounting was not undertaken. The price year was not clearly stated.
Statistical analysis of costs Sensitivity analysis No sensitivity analysis was performed.
Estimated benefits used in the economic analysis The mean duration of sedation was 141 for midazolam and 99 hours for propofol, (p<0.02). Twenty-seven midazolam patients (18%) and 35 (10%) propofol patients were agitated between 30 and 60 minutes after sedation was discontinued, (p<0.02). Overall, 68% of propofol patients versus 31% of midazolam patients had a greater than 20% decrease in systolic blood pressure after the loading dose, (p< 0.001). Overall, 26% versus 45% showed a 25% decrease in spontaneous minute volume (p<0.01). There were 2.1 (+/- 0.1) versus 1.4 (+/-0.1) daily dose adjustments (p<0.001). Nurse-rated quality of sedation was 8.2 (+/- 0.1) with midazolam versus 7.3 (+/- 0.1) with propofol, on a 10-cm linear visual analog scale, (p<0.001). Twenty midazolam and 19 propofol patients were successfully weaned off synchronous intermittent mandatory ventilation to continuous positive airway pressure on the first attempt, within 3.2 (+/- 1.0) and 2.0 (+/- 1.7) hours, respectively. Among the 18 midazolam patients tested for amnesia, none was able to recall the drawing shown to them while under the effect of the drug nor could they recall any event occurring during the study period. Among the 17 propofol patients tested for amnesia, 12 recalled the drawings and could remember sporadic events from the study period. Recovery from sedation was 1.8 (+/- 0.4) hours for propofol and 2.8 +/- 0.4 hours for midazolam, (p<0.02).
Cost results Hourly drug costs were $1.19 (+/- 0.2) in the midazolam group and $6.24 (+/- 0.9) in the propofol group, (p< 0.001).
Synthesis of costs and benefits Costs and benefits were not combined. The drug cost per patient was $164 (+/- 37) in the midazolam group and $662 (+/- 150) in the propofol group, (p<0.001).
Authors' conclusions Both drugs afford reliable, safe and controllable long-term sedation in ICU patients and rapid weaning from mechanical ventilation. Midazolam depresses respiration, allows better maintenance of sedation and yielded compete amnesia at a lower cost while propofol causes more cardiovascular depression during induction.
CRD COMMENTARY - Selection of comparators The reason for the choice of comparator is clear. Midazolam has been successfully used for prolonged sedation due to its relatively short elimination half-life, lack of accumulation of active metabolites and induction of amnesia. Propofol is a rapidly acting general anesthetic agent and recovery is also fast. You, as a user of this database, should consider whether these are widely used health technologies in your own setting.
Validity of estimate of measure of benefit No summary benefit measure was used in the analysis and as such a cost and outcomes study was performed. The data do not appear to have been used selectively
Validity of estimate of costs Resource quantities were reported separately from the prices. Adequate details of methods of quantity/cost estimation were given and important cost items do not appear to have been omitted.
Other issues The authors' conclusions are likely to be justified given the uncertainties in the data. The issue of generalisability to other settings or countries was not specifically addressed. However, appropriate comparisons were made with other studies, particularly in relation to general results, the use of additional analgesics and employing various dosing methods. Results do not appear to have been presented selectively. However, as noted by the authors, as the study was not blinded, a theoretical bias by the nurses may have been present although the authors claim that the random use of a high number of nursing staff makes this unlikely.
Implications of the study Further research is required within the context of a blinded trial.
Source of funding Partially supported by a research grant from F Hoffmann La Roche, Basle, Switzerland.
Bibliographic details Weinbroum A A, Halpern P, Rudick V, Sorkine P, Freedman M, Geller E. Midazolam versus propofol for long-term sedation in the ICU: a randomized prospective comparison. Intensive Care Medicine 1997; 23(12): 1258-1263 Indexing Status Subject indexing assigned by NLM MeSH Adult; Critical Illness; Female; Humans; Hypnotics and Sedatives /adverse effects /economics /therapeutic use; Intensive Care Units; Male; Midazolam /adverse effects /economics /therapeutic use; Middle Aged; Propofol /adverse effects /economics /therapeutic use; Prospective Studies; Respiration, Artificial; Treatment Outcome; Ventilator Weaning AccessionNumber 21998000162 Date bibliographic record published 31/05/1999 Date abstract record published 31/05/1999 |
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