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Dexmedetomidine versus standard care sedation with propofol or midazolam in intensive care: an economic evaluation.

ABSTRACT: Dexmedetomidine was shown in two European randomized double-blind double-dummy trials (PRODEX and MIDEX) to be non-inferior to propofol and midazolam in maintaining target sedation levels in mechanically ventilated intensive care unit (ICU) patients. Additionally, dexmedetomidine shortened the time to extubation versus both standard sedatives, suggesting that it may reduce ICU resource needs and thus lower ICU costs. Considering resource utilization data from these two trials, we performed a secondary, cost-minimization analysis assessing the economics of dexmedetomidine versus standard care sedation.The total ICU costs associated with each study sedative were calculated on the basis of total study sedative consumption and the number of days patients remained intubated, required non-invasive ventilation, or required ICU care without mechanical ventilation. The daily unit costs for these three consecutive ICU periods were set to decline toward discharge, reflecting the observed reduction in mean daily Therapeutic Intervention Scoring System (TISS) points between the periods. A number of additional sensitivity analyses were performed, including one in which the total ICU costs were based on the cumulative sum of daily TISS points over the ICU period, and two further scenarios, with declining direct variable daily costs only.Based on pooled data from both trials, sedation with dexmedetomidine resulted in lower total ICU costs than using the standard sedatives, with a difference of €2,656 in the median (interquartile range) total ICU costs-€11,864 (€7,070 to €23,457) versus €14,520 (€7,871 to €26,254)-and €1,649 in the mean total ICU costs. The median (mean) total ICU costs with dexmedetomidine compared with those of propofol or midazolam were €1,292 (€747) and €3,573 (€2,536) lower, respectively. The result was robust, indicating lower costs with dexmedetomidine in all sensitivity analyses, including those in which only direct variable ICU costs were considered. The likelihood of dexmedetomidine resulting in lower total ICU costs compared with pooled standard care was 91.0% (72.4% versus propofol and 98.0% versus midazolam).From an economic point of view, dexmedetomidine appears to be a preferable option compared with standard sedatives for providing light to moderate ICU sedation exceeding 24 hours. The savings potential results primarily from shorter time to extubation.ClinicalTrials.gov NCT00479661 (PRODEX), NCT00481312 (MIDEX).

SUBMITTER: Turunen H

PROVIDER: S-EPMC4391080 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Dexmedetomidine versus standard care sedation with propofol or midazolam in intensive care: an economic evaluation.

Turunen Heidi H Jakob Stephan M SM Ruokonen Esko E Kaukonen Kirsi-Maija KM Sarapohja Toni T Apajasalo Marjo M Takala Jukka J

Critical care (London, England) 20150219

<h4>Introduction</h4>Dexmedetomidine was shown in two European randomized double-blind double-dummy trials (PRODEX and MIDEX) to be non-inferior to propofol and midazolam in maintaining target sedation levels in mechanically ventilated intensive care unit (ICU) patients. Additionally, dexmedetomidine shortened the time to extubation versus both standard sedatives, suggesting that it may reduce ICU resource needs and thus lower ICU costs. Considering resource utilization data from these two trial ...[more]

PMID: 25887576

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Project description:Objective: Compare the duration of mechanical ventilation between patients receiving sedation with continuous infusions of propofol alone or combination with the use of dexmedetomidine and propofol. Design: Retrospective, propensity matched (1:1) cohort study, employing eight variables chosen a priori for matching. Timing of exposure to dexmedetomidine initiation was incorporated into a matching algorithm. Setting: Level 1, university-based, 32-bed, adult, mixed trauma and surgical intensive care unit (SICU). Continuous sedation was delivered according to a protocol methodology with daily sedation vacation and spontaneous breathing trials. Choice of sedation agent was physician directed. Patients: Between 2010 and 2014, 149 SICU patients receiving mechanical ventilation for >24 h received dexmedetomidine with propofol. Propensity matching resulted in 143 pair cohorts. Interventions: Dexmedetomidine with propofol or propofol alone. Measurements and Main Results: There was no statistical difference in SICU length of stay (LOS), with a median absolute difference of 5.3 h for propofol alone group (p = 0.43). The SICU mortality was not statistically different (RR = 1.002, p = 0.88). Examining a 14-day period post-treatment with dexmedetomidine, on any given day (excluding days 1 and 14), dexmedetomidine with propofol-treated patients had a 0.5% to 22.5% greater likelihood of being delirious (CAM-ICU positive). In addition, dexmedetomidine with propofol-treated patients had a 4.5% to 18.8% higher likelihood of being above the target sedation score (more agitated) compared to propofol-alone patients. Conclusions: In this propensity matched cohort study, adjunct use of dexmedetomidine to propofol did not show a statistically significant reduction with respect to mechanical ventilation (MV) duration, SICU LOS, or SICU mortality, despite a trend toward receiving fewer hours of propofol. There was no evidence that dexmedetomidine with propofol improved sedation scores or reduced delirium.

Project description:Dexmedetomidine as a sole agent showed limited use for painful procedures due to its insufficient sedative/analgesic effect, pronounced hemodynamic instability and prolonged recovery. The aim of this study was to compare the effects of dexmedetomidine-ketamine (DK) versus dexmedetomidine-midazolam-fentanyl (DMF) combination on the quality of sedation/analgesia and recovery profiles for monitored anesthesia care (MAC).Fifty six patients undergoing chemoport insertion were randomly assigned to group DK or DMF. All patients received 1 μg.kg(-1) dexmedetomidine over 10 min followed by 0.2-1.0 μg.kg(-1)h(-1) in order to maintain 3 or 4 of modified Observer's Assessment of Analgesia and Sedation score checked every 3 min. At the start of dexmedetomidine infusion, patients in group DK or DMF received 0.5 mg.kg(-1) ketamine or 0.05 mg.kg(-1) midazolam + 0.5 μg.kg(-1) fentanyl intravenously, respectively. When required, rescue sedatives (0.5 mg.kg-1 of ketamine or 0.05 mg.kg-1 of midazolam) and analgesics (0.5 mg.kg-1 of ketamine or 0.5 μg.kg-1 of fentanyl) were given to the patients in DK or DMF group, respectively. The primary outcome of this study was the recovery parameters (time to spontaneous eye opening and the length of the recovery room stay). The secondary outcomes were parameters indicating quality of sedation/analgesia, cardiorespiratory variables, and satisfaction scores.There were no significant differences in the onset time, time to spontaneous eye opening, recovery room stay, the incidences of inadequate analgesia, hypotension and bradycardia between the two groups. Despite lower infusion rate of dexmedetomidine, more patients in the DMF group had bispectral index (BIS) < 60 than in the DK group and vice versa for need of rescue sedatives. The satisfaction scores of patients, surgeon, and anesthesiologist in the DMF group were significantly better than the DK group.The DK and DMF groups showed comparable recovery time, onset time, cardiorespiratory variables, and analgesia. However, the DMF group showed a better sedation quality and satisfaction scores despite the lower infusion rate of dexmedetomidine, and a higher incidence of BIS < 60 than the DK group.Clinical Trial Registry of Korea KCT0000951 , registered 12/12/2013.

Project description:BackgroundGuidelines currently recommend targeting light sedation with dexmedetomidine or propofol for adults receiving mechanical ventilation. Differences exist between these sedatives in arousability, immunity, and inflammation. Whether they affect outcomes differentially in mechanically ventilated adults with sepsis undergoing light sedation is unknown.MethodsIn a multicenter, double-blind trial, we randomly assigned mechanically ventilated adults with sepsis to receive dexmedetomidine (0.2 to 1.5 μg per kilogram of body weight per hour) or propofol (5 to 50 μg per kilogram per minute), with doses adjusted by bedside nurses to achieve target sedation goals set by clinicians according to the Richmond Agitation-Sedation Scale (RASS, on which scores range from -5 [unresponsive] to +4 [combative]). The primary end point was days alive without delirium or coma during the 14-day intervention period. Secondary end points were ventilator-free days at 28 days, death at 90 days, and age-adjusted total score on the Telephone Interview for Cognitive Status questionnaire (TICS-T; scores range from 0 to 100, with a mean of 50±10 and lower scores indicating worse cognition) at 6 months.ResultsOf 432 patients who underwent randomization, 422 were assigned to receive a trial drug and were included in the analyses - 214 patients received dexmedetomidine at a median dose of 0.27 μg per kilogram per hour, and 208 received propofol at a median dose of 10.21 μg per kilogram per minute. The median duration of receipt of the trial drugs was 3.0 days (interquartile range, 2.0 to 6.0), and the median RASS score was -2.0 (interquartile range, -3.0 to -1.0). We found no difference between dexmedetomidine and propofol in the number of days alive without delirium or coma (adjusted median, 10.7 vs. 10.8 days; odds ratio, 0.96; 95% confidence interval [CI], 0.74 to 1.26), ventilator-free days (adjusted median, 23.7 vs. 24.0 days; odds ratio, 0.98; 95% CI, 0.63 to 1.51), death at 90 days (38% vs. 39%; hazard ratio, 1.06; 95% CI, 0.74 to 1.52), or TICS-T score at 6 months (adjusted median score, 40.9 vs. 41.4; odds ratio, 0.94; 95% CI, 0.66 to 1.33). Safety end points were similar in the two groups.ConclusionsAmong mechanically ventilated adults with sepsis who were being treated with recommended light-sedation approaches, outcomes in patients who received dexmedetomidine did not differ from outcomes in those who received propofol. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01739933.).

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Dexmedetomidine versus standard care sedation with propofol or midazolam in intensive care: an economic evaluation.

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Dexmedetomidine versus standard care sedation with propofol or midazolam in intensive care: an economic evaluation.

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