Efficacy and cost analysis of intravenous conscious sedation for long oral surgery procedures.

The aim of this study was to determine what is considered a long oral surgery and conduct a cost-effective analysis of sedative agents used for intravenous sedation (IVS) and sedation protocols for such procedures. Pubmed and Google Scholar databases were used to identify human studies employing IVS for extractions and implant-related surgeries, between 2003 and July/2023. Sedation protocols and procedure lengths were documented. Sedative satisfaction, operator satisfaction, and sedation assessment were also recorded. Cost estimation was based on The British National Formulary (BNF). To assess bias, the Cochrane Risk of Bias tools were employed. This review identified 29 randomised control trials (RCT), six cohorts, 14 case-series, and one case-control study. The study defined long procedures with an average duration of 31.33 minutes for extractions and 79.37 minutes for implant-related surgeries. Sedative agents identified were midazolam, dexmedetomidine, propofol, and remimazolam. Cost analysis revealed midazolam as the most cost-effective option (<10 pence per procedure per patient) and propofol the most expensive option (approximately £46.39). Bias analysis indicated varying degrees of bias in the included studies. Due to diverse outcome reporting, a comparative network approach was employed and revealed benefits of using dexmedetomidine, propofol, and remimazolam over midazolam. Midazolam, dexmedetomidine, propofol, and remimazolam demonstrated safety and efficacy as sedative agents for conscious IVS in extended procedures like extractions or implant-related surgeries. While midazolam is the most cost-effective option, dexmedetomidine, propofol, and remimazolam offer subjective and clinical benefits. The relatively higher cost of propofol may impede its widespread use. Dexmedetomidine and remimazolam stand out as closely priced options, necessitating further clinical investigations for comparative efficacy assessment.

Clinical and economic impact of the use of dexmedetomidine for sedation in the intensive care unit compared to propofol.

Background Despite the advantages of dexmedetomidine (DEX) over propofol (PRO) including minimal respiratory depression and the potential for preventing and/or treating intensive care unit (ICU) delirium, PRO has been the preferred agent due to its lower cost. However, the acquisition cost of DEX has considerably decreased as a generic version of DEX has recently become available. Objective To evaluate clinical and economic outcomes of DEX-based sedation compared to PRO in the ICU. Setting A retrospective cohort study of 86 ICU patients who received either DEX or PRO for a period ≥ 12 h. Method Patients were matched by age, sex, and Sequential Organ Failure Assessment scores in a 1:1 ratio. Main outcome measure Clinical outcomes included the duration of mechanical ventilation (MV), ICU and hospital length of stay (LOS), and requirements of concomitant sedatives and opioids. Economic outcomes included the ICU and hospital costs as well as the cost of sedatives or combined sedatives and opioids per patient. Results There were no significant differences in ICU and hospital LOS and time on MV in both groups (median ICU LOS 7 [DEX] vs. 9 [PRO] days, p = 0.07; median hospital LOS 12 [DEX] vs. 14 [PRO] days, p = 0.261; median time of MV 144 [DEX] vs. 158 [PRO] hours, p = 0.176). DEX-based sedation compared to PRO was associated with similar ICU and hospital costs (US$ 67,561 vs. 78,429, p = 0.39; US$ 71,923 vs. 71,084, p = 0.1). Conclusion The clinical outcomes and economic impact associated with DEX- and PRO-based sedation were similar.

Managing the Rising Costs and High Drug Expenditures in Critical Care Pharmacy Practice.

Pharmaceutical costs for patients in the intensive care unit (ICU) constitute a large portion of hospital drug budgets. Unfortunately, prices for medications commonly used in the ICU are on the rise for a variety of reasons. In particular, the U.S. Food and Drug Administration's Unapproved Drugs Initiative, generic manufacturers cornering the marketplace, drug shortages, and regulatory device changes are major drivers of pharmaceutical price escalation affecting costs in the ICU. Furthermore, traditional high acquisition cost items still pose challenges to controlling costs. To offer strategies to mitigate the rising costs of pharmaceuticals in the ICU setting, we searched the PubMed/Medline and International Pharmaceutical Abstracts databases and other related sources to identify published cost-saving protocols concerning specific medications that are affected by rising prices or have traditional high acquisition costs. In the absence of specific protocols, we offer possible cost-saving initiatives based on published literature regarding specific agents or based on our own diverse set of experiences. Finally, we review suggested clinical and operational activities at an institutional level to address these rising drug costs in the ICU setting.

Pharmacy-Driven Dexmedetomidine Stewardship and Appropriate Use Guidelines in a Community Hospital Setting.

BACKGROUND: Dexmedetomidine is a widely utilized agent in the intensive care unit (ICU) because it does not suppress respiratory drive and may be associated with less delirium than midazolam or propofol. Cost of dexmedetomidine therapy and debate as to the proper duration of use has brought its use to the forefront of discussion. OBJECTIVE: To validate the efficacy and cost savings associated with pharmacy-driven dexmedetomidine appropriate use guidelines and stewardship in mechanically ventilated patients. METHODS: This was a retrospective cohort study of adult patients who received dexmedetomidine for ICU sedation while on mechanical ventilation at a 433-bed not-for-profit community hospital. Included patients were divided into pre-enactment (PRE) and postenactment (POST) of dexmedetomidine guideline groups. RESULTS: A total of 100 patients (50 PRE and 50 POST) were included in the analysis. A significant difference in duration of mechanical ventilation (11.1 vs 6.2 days, P = 0.006) and incidence of reintubation (36% vs 18% of patients, P = 0.043) was seen in the POST group. Aggregate use of dexmedetomidine 200-µg vials (37.1 vs 18.4 vials, P = 0.010) and infusion days (5.4 vs 2.5 days, P = 0.006) were significantly lower in the POST group. Dexmedetomidine acquisition cost savings were calculated at $374 456.15 in the POST group. There was no difference between the PRE and POST groups with regard to ICU length of stay, expected mortality, and observed mortality. CONCLUSIONS: Pharmacy-driven dexmedetomidine appropriate use guidelines decreased the use of dexmedetomidine and increased cost savings at a community hospital without adversely affecting clinical outcomes.

Dexmedetomidine for the Treatment of Hyperactive Delirium Refractory to Haloperidol in Nonintubated ICU Patients: A Nonrandomized Controlled Trial.

OBJECTIVES: To evaluate the clinical effectiveness, safety, and cost of dexmedetomidine for the treatment of agitated delirium refractory to haloperidol in nonintubated critically ill patients. DESIGN: Nonrandomized, controlled trial. SETTING: Intensive care department of a tertiary care nonprofit hospital. PATIENTS: All consecutive admissions to a medical-surgical ICU with a diagnosis of agitated delirium. INTERVENTIONS: Initial haloperidol titration: all patients received IV bolus doses of haloperidol until agitation was controlled (Richmond Agitation Sedation Scale scoring range, 0 to -2) or reaching the maximum daily dose. Group comparison: patient responders to haloperidol (control group) were compared with nonresponders (dexmedetomidine group). MEASUREMENTS AND MAIN RESULTS: A total of 132 nonintubated patients were treated with haloperidol in the initial haloperidol titration phase. Forty-six patients (34.8%; 95% CI, 26.0-43.1%) did not respond to haloperidol, and 86 patients (65.2%; 95% CI, 56.3-73.0%) were responders. During the group comparison phase, dexmedetomidine achieved a higher percentage of time in satisfactory sedation levels than did haloperidol (92.7% [95% CI, 84.5-99.8%] vs 59.3% [95% CI, 48.6-69.3%], respectively; p = 0.0001). Haloperidol was associated with 10 cases (11.6% [95% CI, 6.5-21.2%]) of oversedation and two (2.0% [0.4-8%]) of corrected QT lengthening. Direct cost of dexmedetomidine was 17 times greater than haloperidol, but it achieved a mean savings of $4,370 per patient due to the reduction in length of ICU stay. CONCLUSIONS: In the study conditions, dexmedetomidine shows to be useful as a rescue drug for treating agitation due to delirium in nonintubated patients in whom haloperidol has failed, and it seems to have a better effectiveness, safety, and cost-benefit profile than does haloperidol.

Comparison of Dexmedetomidine Versus Propofol on Hospital Costs and Length of Stay.

OBJECTIVE: The objective of this evaluation was to compare total hospital costs and length of stay of critically ill patients who received dexmedetomidine versus propofol for sedation in the intensive care unit (ICU). METHODS: This was a retrospective quality improvement evaluation at a tertiary care, academic medical center in the United States. Data were retrieved for patients discharged between April 2012 and June 2013. Patients were included if they were admitted to the ICU, were 18 years of age or older, and received dexmedetomidine or propofol for sedation. Multivariate regression models were developed to determine the association between sedative type and hospital costs, ICU length of stay, and hospital length of stay. RESULTS: The final cohort included 3294 patients. Of these, 2685 received propofol and 609 received dexmedetomidine. The median hospital cost was US$31 041 (interquartile range [IQR] US$17 963-US$57 826) in the propofol group and US$46 716 (IQR US$31 247 to US$85 490) in the dexmedetomidine group (P < .001). The median ICU length of stay was 2 days (IQR 1-6 days) and 4 days (IQR 2-9 days) in the propofol and dexmedetomidine groups, respectively (P < .001). Overall, hospital length of stay was 8 days (IQR 4-15 days) and 9 days (IQR 5-18 days) in the 2 groups, respectively (P < .001). In the multivariate analyses, dexmedetomidine use was associated with increased costs, ICU length of stay, and hospital length of stay (P < .001 for each outcome). CONCLUSIONS: In this academic medical center, dexmedetomidine use was associated with higher costs when compared to propofol for sedation in the ICU. Also, use of dexmedetomidine was associated with increased lengths of ICU and hospital stay. Future prospective trials are needed to confirm these findings.

Limiting the accessibility of cost-prohibitive drugs reduces overall anesthetic drug costs: a retrospective before and after analysis.

PURPOSE: Cost effectiveness is becoming increasingly important in today's healthcare environment. Remifentanil, dexmedetomidine, and desflurane are costly agents that often have suitable alternatives to their use. We sought to identify changes in cost and outcomes following interventions that limited the availability of these drugs. METHODS: We calculated anesthetic drug costs for all operating room procedures performed before and after the accessibility interventions. We retrospectively compared drug costs per case and the frequency of agent use before and after the interventions. In addition, we analyzed the incidence of adverse outcomes, including delayed out-of-room times, postoperative nausea and vomiting (PONV), unplanned intubations, use of naloxone, and reintubations. Wilcoxon-Mann-Whitney and Chi square analyses were used to quantify differences in cost, use, and outcomes between cohorts. RESULTS: Of the 27,233 cases we identified, 24,201 cases were analyzed. The mean anesthetic drug costs per case were significantly lower after the interventions vs before at ($21.44 vs $32.39, respectively), a cost savings of $10.95 (95% confidence interval, $9.86 to $12.04; P < 0.001). Additionally, a comparison of data after vs before the interventions revealed the following results: remifentanil use was significantly lower (3.5% vs 9.2% of cases; P < 0.001). Dexmedetomidine use did not differ significantly (0.4% vs 0.5% of cases; P = 0.07), and desflurane use was significantly lower (0.6% vs 20.2% of cases; P < 0.001). There was no significant relationship between the interventions and the frequency of delayed out-of-room times (15.5% vs 15.9%; P = 0.41), unplanned intubations (0.02% vs 0.03%; P = 0.60), and reintubations (0.01% vs 0.03%; P = 0.28). Postoperative nausea and vomiting decreased significantly after the interventions (22.8% vs 24.4%; P = 0.003), and naloxone use showed a significant increase (0.22% vs 0.11% of cases; P = 0.04). CONCLUSIONS: Reducing the accessibility of these cost-prohibitive agents resulted in significant anesthetic drug cost savings and decreased utilization of remifentanil and desflurane. The interventions had no significant effect on patient recovery time, incidence of unplanned intubations, or incidence of reintubation, but they were associated with a decrease in PONV and an increase in naloxone use.

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

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT00479661 (PRODEX), NCT00481312 (MIDEX).

Cost effectiveness of a benzodiazepine vs a nonbenzodiazepine-based sedation regimen for mechanically ventilated, critically ill adults.

PURPOSE: Nonbenzodiazepine sedation (eg, dexmedetomidine or propofol) may be more cost effective than benzodiazepine (BZ) sedation despite its higher acquisition cost. MATERIALS AND METHODS: A cost effectiveness (CE) analysis of noncardiac surgery, critically ill adults requiring at least 1 day of mechanical ventilation (MV) and administered either BZ or non-BZ sedation, that cycled health states and costs daily using a Markov model accounting for daily MV use until intensive care unit (ICU) discharge, was conducted from a third-party perspective. Transition probabilities were obtained from a published meta-analysis, and costs were estimated from best evidence. Sensitivity analyses were run for all extubation and discharge probabilities, for different cost estimates and for the specific non-BZ administered. RESULTS: When non-BZ rather than BZ sedation was used, the incremental cost-effectiveness ratio to avert 1 ICU day while MV or while either MV or non-MV was $3406 and $3136, respectively. The base-case analysis revealed that non-BZ sedation (vs BZ sedation) resulted in higher drug costs ($1327 vs $65) but lower total ICU costs (percent accounted for MV need): $35380 (71.0%) vs $45394 (70.6%). Sensitivity analysis revealed that BZ sedation would only be less costly if the daily rate of extubation was at least 16%, and the daily rate of ICU discharge without MV was at least 77%. The incremental CE ratio to avert 1 ICU day while MV or non-MV was similar between the dexmedetomidine and propofol non-BZ options. CONCLUSIONS: Among MV adults, non-BZ sedation has a more favorable CE ratio than BZ sedation over most cost estimates.

Clinical and economic impact of substituting dexmedetomidine for propofol due to a US drug shortage: examination of coronary artery bypass graft patients at an urban medical centre.

BACKGROUND: Propofol has reduced healthcare costs in coronary artery bypass graft (CABG) surgery patients by decreasing post-operative duration of mechanical ventilation. However, the US shortage of propofol necessitated the use of alternative agents. OBJECTIVE: This study sought to evaluate clinical and economic implications of substituting dexmedetomidine for propofol in patients undergoing CABG surgery. METHODS: This was a retrospective cohort study. Patients undergoing isolated, elective CABG surgery and sedated with either propofol or dexmedetomidine during the study period were included. The cohorts were matched 1:1 based on important characteristics. The primary outcome was the number of patients achieving a post-operative duration of mechanical ventilation ≤6 h. Secondary outcomes were post-operative intensive care unit (ICU) length of stay (LOS) ≤48 h, total post-operative LOS ≤5 days, the need for adjunctive opioid therapy and associated cost savings. Variables recorded included patient demographics, co-morbid medical conditions, health risks, sedation drug doses, post-operative medical complications and sedation-related adverse events. Univariate and multivariate analyses were completed to examine the relationship between these covariates and post-operative LOS. The cost analysis consisted of examination of the net financial benefit (or cost) of choosing dexmedetomidine versus propofol in the study population, with utilisation observed in the study converted to costs using institutional data from the Premier database. RESULTS: Eighty-four patients were included, with 42 patients per cohort. Mechanical ventilation duration ≤6 h was achieved in 24 (57.1 %) versus 7 (16.7 %) in the dexmedetomidine and propofol cohorts, respectively (p < 0.001). More patients treated with dexmedetomidine achieved ICU LOS ≤48 h (p < 0.05) and total hospital LOS ≤5 days (p < 0.05), as compared with the propofol group. Multivariate analysis revealed that having one or more post-operative medical complication was the most significant predictor of increased post-operative LOS, whereas choosing dexmedetomidine was also significant in terms of reduced post-operative LOS. The estimated net financial benefit of choosing dexmedetomidine versus propofol was US$2,613 per patient (year 2012 value). CONCLUSIONS: Findings suggest that use of dexmedetomidine as an alternative to propofol for sedation of CABG patients post-operatively contributes to reduced mechanical ventilation time, ICU LOS and post-operative LOS. Higher drug costs resulting from the propofol shortage were offset by savings in post-operative room and board costs. Additional savings may be possible by preventing medical complications to the extent possible.

[Dexmedetomidine]. / Dexmedetomidin.

Dexmedetomidine is a highly selective α2-receptor agonist with sedative, analgetic and anxiolytic effects. It is chemically related to clonidine and has been an authorized drug in Europe since September 2011. Dexmedetomidine enables a level of sedation in which mechanically ventilated patients may be woken by verbal stimulation (Richmond agitation sedation scale RASS 0--3). In this respect dexmedetomidine achieves the same desired effect as propofol and midazolam; however, in direct comparison to a sedation regime with benzodiazepines, dexmedetomidine reduces the prevalence, duration and severity of delirium in intensive care. Patients sedated by dexmedetomidine can statistically be extubated earlier and an influence on duration of stay in the intensive care unit (ICU) has not been shown. Daily therapy costs are approximately 5 times higher than those of propofol but an objective standpoint in relation to clinical cost efficiency is unattainable.

A cost-minimization analysis of dexmedetomidine compared with midazolam for long-term sedation in the intensive care unit.

OBJECTIVE: To compare the intensive care unit costs and determine factors influencing these costs in mechanically ventilated patients randomized to dexmedetomidine or midazolam by continuous infusion. DESIGN: Cost minimization analysis of a double-blind, multicenter clinical trial randomizing patients 2:1 to receive dexmedetomidine or midazolam from the institutional perspective. SETTING: Sixty-eight intensive care units in the United States, Australia, New Zealand, Brazil, and Argentina. PATIENTS: A total of 366 intubated intensive care unit patients anticipated to require sedation for >24 hrs. MEASUREMENTS AND MAIN RESULTS: Intensive care unit resource use was compared within the two treatment arms, using the U.S. representative costs for these resources. The analyses characterized patient costs from start of study drug until intensive care unit discharge including costs associated with the intensive care unit stay, costs during mechanical ventilation, study drug acquisition cost, and costs of treating adverse drug reactions probably or possibly related to study drugs. Blinded to treatment group, costs were calculated using Medicare reimbursement schedules, average IMS drug costs, expert opinion, and peer-reviewed literature. Censored lengths of intensive care unit stay and mechanical ventilation were imputed, using a nonparametric adjustment algorithm. Crude and multivariate median regressions were performed to relate intensive care unit cost and treatment. Including drug acquisition cost, sedation with dexmedetomidine was associated with a median total intensive care unit cost savings of $9679 (confidence interval, $2314-$17,045) compared with midazolam. The primary cost drivers were reduced costs of intensive care unit stay (median savings, $6584, 95% confidence interval, $727-$12,440) and reduced costs of mechanical ventilation (median savings, $2958, 95% confidence interval, $698-$5219). CONCLUSIONS: Continuous sedation with dexmedetomidine results in significantly lower total intensive care unit costs compared with midazolam infusion for intensive care unit sedation, primarily due to decreased intensive care unit stay costs and reduced mechanical ventilation costs.

Impact of dexmedetomidine on analgesic requirements in patients after cardiac surgery in a fast-track recovery room setting.

STUDY OBJECTIVE: To compare postoperative opioid requirements in patients who received dexmedetomidine versus propofol after cardiac surgery. DESIGN: Retrospective cohort study. SETTING: Large, community teaching hospital that uses a fast-track cardiovascular recovery unit (CVRU) model. PATIENTS: One hundred adults who underwent coronary artery bypass graft surgery and/or valvular surgery, and who received either dexmedetomidine (50 patients) or propofol (50 patients) for perioperative sedation. MEASUREMENTS AND MAIN RESULTS: Patients were matched according to surgery type and left ventricular ejection fraction. Opioid requirements were assessed over two time intervals: from arrival in the CVRU to discontinuation of the sedative infusion, and from CVRU arrival to CVRU discharge, up to a maximum of 72 hours if admission to the intensive care unit was necessary. All postoperative opioid doses were converted to morphine equivalents. Length of mechanical ventilation, quality of sedation, adverse drug events, and sedation-related costs were determined. Opioid requirements were significantly lower during the sedative infusion period for dexmedetomidine-treated patients than for propofol-treated patients (median [range] 0 [0-10 mg] vs 4 mg [0-33 mg], p<0.001), but not through the entire CVRU admission (median [range] 26 mg [0-119 mg] vs 30 mg (0-100 mg], p=0.284). The proportion of patients who did not require opioids during the infusion was significantly higher in the dexmedetomidine group compared with the propofol group (32 [64%] vs 13 [26%], p<0.001). No significant differences were noted between the groups for length of mechanical ventilation, quality of sedation, or adverse events. Sedation-related costs were significantly higher (approximately $50/patient higher) with dexmedetomidine (p<0.001). CONCLUSION: Dexmedetomidine resulted in lower opioid requirements in patients after cardiac surgery versus those receiving propofol, but this did not result in shorter durations of mechanical ventilation, using a fast-track CVRU model.

An updated focused review of dexmedetomidine in adults.

OBJECTIVE: To evaluate recent comparative studies regarding the safety and efficacy of dexmedetomidine in adults. DATA SOURCES: Articles evaluating safety and efficacy of dexmedetomidine were identified from an English-language MEDLINE search (1996-July 2009), with a focus on data published since our previous review in 2007 to the present. MeSH terms included dexmedetomidine, medetomidine, alpha2-agonist, and sedation. References from selected articles were also reviewed for additional material. STUDY SELECTION AND DATA EXTRACTION: Experimental and observational English-language studies that focused on the efficacy, safety, and pharmacoeconomics of dexmedetomidine in humans were selected. DATA SYNTHESIS: Dexmedetomidine is an 2-agonist used for sedation during procedures and in critical illness. Compared with placebo, use of dexmedetomidine during procedures was associated with decreased use of rescue midazolam and a similar degree of sedation compared with various agents used during surgery or for procedures. Use of long-term (>24 h) dexmedetomidine sedation is comparable to sedation with benzodiazepines in critically ill patients. In a Phase 4 study, dexmedetomidine was safe in dosages up to 1.4 microg/kg/hour for greater than 24 hours and did not produce rebound tachycardia or hypertension when abruptly discontinued. One small randomized controlled trial demonstrated decreased incidence of delirium, the primary endpoint, with dexmedetomidine compared with midazolam or propofol for sedation after cardiac valve surgery. Many, but not all, studies suggest that dexmedetomidine has a promising role in prevention and treatment of delirium in critically ill patients when delirium was studied as a secondary endpoint. CONCLUSIONS: Dexmedetomidine is an alternative for procedural sedation and can be used long-term (>24 h) in critically ill patients, in dosages up to 1.5 microg/kg/hour. More studies are needed to better define the role of dexmedetomidine in preventing and treating delirium.

Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial.

CONTEXT: Lorazepam is currently recommended for sustained sedation of mechanically ventilated intensive care unit (ICU) patients, but this and other benzodiazepine drugs may contribute to acute brain dysfunction, ie, delirium and coma, associated with prolonged hospital stays, costs, and increased mortality. Dexmedetomidine induces sedation via different central nervous system receptors than the benzodiazepine drugs and may lower the risk of acute brain dysfunction. OBJECTIVE: To determine whether dexmedetomidine reduces the duration of delirium and coma in mechanically ventilated ICU patients while providing adequate sedation as compared with lorazepam. DESIGN, SETTING, PATIENTS, AND INTERVENTION: Double-blind, randomized controlled trial of 106 adult mechanically ventilated medical and surgical ICU patients at 2 tertiary care centers between August 2004 and April 2006. Patients were sedated with dexmedetomidine or lorazepam for as many as 120 hours. Study drugs were titrated to achieve the desired level of sedation, measured using the Richmond Agitation-Sedation Scale (RASS). Patients were monitored twice daily for delirium using the Confusion Assessment Method for the ICU (CAM-ICU). MAIN OUTCOME MEASURES: Days alive without delirium or coma and percentage of days spent within 1 RASS point of the sedation goal. RESULTS: Sedation with dexmedetomidine resulted in more days alive without delirium or coma (median days, 7.0 vs 3.0; P = .01) and a lower prevalence of coma (63% vs 92%; P < .001) than sedation with lorazepam. Patients sedated with dexmedetomidine spent more time within 1 RASS point of their sedation goal compared with patients sedated with lorazepam (median percentage of days, 80% vs 67%; P = .04). The 28-day mortality in the dexmedetomidine group was 17% vs 27% in the lorazepam group (P = .18) and cost of care was similar between groups. More patients in the dexmedetomidine group (42% vs 31%; P = .61) were able to complete post-ICU neuropsychological testing, with similar scores in the tests evaluating global cognitive, motor speed, and attention functions. The 12-month time to death was 363 days in the dexmedetomidine group vs 188 days in the lorazepam group (P = .48). CONCLUSION: In mechanically ventilated ICU patients managed with individualized targeted sedation, use of a dexmedetomidine infusion resulted in more days alive without delirium or coma and more time at the targeted level of sedation than with a lorazepam infusion. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00095251.

Addition of dexmedetomidine to standard sedation regimens after cardiac surgery: an outcomes analysis.

STUDY OBJECTIVE: To characterize inpatient use of intravenous sedatives in the real-world setting, and to evaluate clinical and economic outcomes when dexmedetomidine was used with midazolam and propofol for select cardiovascular procedures. DESIGN: 12-month retrospective analysis. DATA SOURCE: An administrative claims database of operational data from a nationally representative sample of 250 medical and surgical hospitals. PATIENTS: Patients who received midazolam plus propofol (9996 patients) or dexmedetomidine, midazolam, plus propofol (356 patients) after cardiac valve or vessel surgery. MEASUREMENTS AND MAIN RESULTS: The source of patient demographics (e.g., age, sex, Charlson Comorbidity Index) and outcomes (e.g., charges, length of stay, mortality rate) was the hospital billing claim form. Patients in the dexmedetomidine-midazolam-propofol cohort tended to be younger and male and to have fewer comorbidities than those midazolam-propofol cohort. The primary outcomes for the three-drug cohort showed significant reductions in total charges/patient (approximately $18,000, p<0.05), total hospital length of stay (0.6 days, p<0.0001), days in the intensive care unit or cardiac care unit (3.87 days, p<0.0001), and mortality (2%, p=0.0142). Although pharmacy charges were higher (approximately $4000/patient), lower charges for the intensive care or cardiac care unit, operating room, room and board, and respiratory services were observed in the dexmedetomidinemidazolam-propofol cohort compared with the two-drug cohort. Also, mechanical ventilation was shorter by approximately 0.5 day in the three-drug cohort (p<0.01). CONCLUSION: These initial findings of a real-world assessment of dexmedetomidine use with other agents suggest favorable clinical and economic outcomes. Further research through randomized clinical trials of dexmedetomidine is warranted to better understand its optimum patient population, dosage, and the causality of the results, and to confirm the potential clinical and economic benefits observed in our patients.