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BackgroundDexmedetomidine (DEX) is a centrally acting alpha-2-adrenoceptor agonist that has potential in the management of alcohol withdrawal syndrome (AWS) owing to its ability to produce arousable sedation and to inhibit the adrenergic system without respiratory depression. The objective of this randomized controlled study was to evaluate whether addition of DEX to benzodiazepine (BZD) therapy is effective and safe for AWS patients in the intensive care unit (ICU).MethodsEligible participants were randomly assigned to intervention (Group D; n = 36) or control (Group C; n = 36). In Group D, DEX infusion was started at a dose of 0.2–1.4 μg/kg/h and titrated to achieve the target sedation level (–2 to 0 on the Richmond Agitation Sedation Scale (RASS)) with symptom-triggered BZD (10 mg diazepam bolus) was used as needed. Patients in Group C received only symptom-triggered 10 mg boluses of diazepam. The primary efficacy outcomes were 24-h diazepam consumption and cumulative diazepam dose required over the course of the ICU stay; secondary outcomes included length of ICU stay, sedation and communication quality and haloperidol requirements.ResultsMedian 24-h diazepam consumption during the study was significantly lower in Group D (20 vs. 40 mg, p < 0.001), as well as median cumulative diazepam dose during the ICU stay (60 vs. 90 mg, p < 0.001). The median percentage of time in the target sedation range was higher in Group D (median 90 % (90–95) vs. 64.5 % (60–72.5; p < 0.001). DEX infusion was also associated with better nurse-assessed patient communication (<0.001) and fewer patients requiring haloperidol treatment (2 vs. 10 p = 0.02). One patient in Group D and four in Group C were excluded owing to insufficient control of AWS symptoms and use of additional sedatives (p = 0.36). There were no severe adverse events in either group. Spontaneous breathing remained normal in all patients. Bradycardia was a common adverse event in Group D (10 vs. 2; p = 0.03).ConclusionsDEX significantly reduced diazepam requirements in ICU patients with AWS and decreased the number of patients who required haloperidol for severe agitation and hallucinations. DEX use was also associated with improvement in diverse aspects of sedation quality and the quality of patient communication.Trial registration: ClinicalTrials.gov: NCT02496650

Three additional sub-states: without exacerbation, mild and severe exacerbation were considered. The effectiveness of treatment options and utilities for each health state were taken from the literature. Only direct health care costs were considered. Disease management and exacerbation costs were obtained from the literature. Drug costs were calculated based on ex-factory prices with mandatory 7.5% rebate. All costs were updated to € 2012. A 3% annual discount rate on costs and health outcomes was applied. Incremental ratios in terms of cost per life-year gained (LYG) and cost per quality-adjusted life-year gained (QALY) of the most effective therapy versus the comparator were calculated. One-way sensitivity analyses were performed modifying the following parameters: time horizon (10 years, lifetime), discount rate (0%, 5%), drug costs (±10%, ±20%) and utilities (±10%). Probabilistic sensitivity analysis (PSA) was also performed. Results: At 5 years, glycopyrronium bromide accounted a total cost of € 2,225.18 compared to € 2,374.81 accounted for tiotropium bromide. Glycopyrronium bromide yielded higher health benefits (4,321 LYG and 3,388 QALY) than tiotropium bromide (4,315 LYG and 3,377 QALY). In all oneway sensitivity analyses performed and in 100% of PSA simulations (1,000 iterations), glycopyrronium bromide compared to tiotropium bromide remained as a dominant strategy. ConClusions: Glycopyrronium bromide therapy in COPD patients is associated to less costs and higher health benefits than tiotropium in Spain.

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