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

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          Abstract

          To evaluate the clinical effectiveness, safety, and cost of dexmedetomidine for the treatment of agitated delirium refractory to haloperidol in nonintubated critically ill patients.

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          Most cited references24

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          Prospective evaluation of the Sedation-Agitation Scale for adult critically ill patients.

          Subjective scales to assess agitation and sedation in adult intensive care unit (ICU) patients have rarely been tested for validity or reliability. We revised and prospectively tested the Sedation-Agitation Scale (SAS) for interrater reliability and compared it with the Ramsay scale and the Harris scale to test construct validity. A convenience sample of ICU patients was simultaneously and independently examined by pairs of trained evaluators by using the revised SAS, Ramsay, and Harris Scales. Multidisciplinary 34-bed ICU in a nonuniversity, academic medical center. Forty-five ICU patients (surgical and medical) were examined a total of 69 times by evaluator pairs. The mean patient age was 63.2 yrs, 36% were female, and 71% were intubated. When classified by using SAS, 45% were anxious or agitated (SAS 5 to 7), 26% were calm (SAS 4), and 29% were sedated (SAS 1 to 3). Interrater correlation was high for SAS (r2 = .83; p < .001) and the weighted kappa score for interrater agreement was 0.92 (p < .001). Of 41 assessments scored as Ramsay 1, 49% scored SAS 6, 41% were SAS 5, 5% were SAS 4, and 2% each were SAS 3 or 7. SAS was highly correlated with the Ramsay (r2 = .83; p < .001) and Harris (r2 = .86; p < .001) scales. SAS is both reliable (high interrater agreement) and valid (high correlation with the Harris and Ramsay scales) in assessing agitation and sedation in adult ICU patients. SAS provides additional information by stratifying agitation into three categories (compared with one for the Ramsay scale) without sacrificing validity or reliability.
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            Efficacy and safety of quetiapine in critically ill patients with delirium: a prospective, multicenter, randomized, double-blind, placebo-controlled pilot study.

            To compare the efficacy and safety of scheduled quetiapine to placebo for the treatment of delirium in critically ill patients requiring as-needed haloperidol. Prospective, randomized, double-blind, placebo-controlled study. Three academic medical centers. Thirty-six adult intensive care unit patients with delirium (Intensive Care Delirium Screening Checklist score > or = 4), tolerating enteral nutrition, and without a complicating neurologic condition. Patients were randomized to receive quetiapine 50 mg every 12 hrs or placebo. Quetiapine was increased every 24 hrs (50 to 100 to 150 to 200 mg every 12 hrs) if more than one dose of haloperidol was given in the previous 24 hrs. Study drug was continued until the intensive care unit team discontinued it because of delirium resolution, therapy > or = 10 days, or intensive care unit discharge. Baseline characteristics were similar between the quetiapine (n = 18) and placebo (n = 18) groups. Quetiapine was associated with a shorter time to first resolution of delirium [1.0 (interquartile range [IQR], 0.5-3.0) vs. 4.5 days (IQR, 2.0-7.0; p =.001)], a reduced duration of delirium [36 (IQR, 12-87) vs. 120 hrs (IQR, 60-195; p =.006)], and less agitation (Sedation-Agitation Scale score > or = 5) [6 (IQR, 0-38) vs. 36 hrs (IQR, 11-66; p =.02)]. Whereas mortality (11% quetiapine vs. 17%) and intensive care unit length of stay (16 quetiapine vs. 16 days) were similar, subjects treated with quetiapine were more likely to be discharged home or to rehabilitation (89% quetiapine vs. 56%; p =.06). Subjects treated with quetiapine required fewer days of as-needed haloperidol [3 [(IQR, 2-4)] vs. 4 days (IQR, 3-8; p = .05)]. Whereas the incidence of QTc prolongation and extrapyramidal symptoms was similar between groups, more somnolence was observed with quetiapine (22% vs. 11%; p = .66). Quetiapine added to as-needed haloperidol results in faster delirium resolution, less agitation, and a greater rate of transfer to home or rehabilitation. Future studies should evaluate the effect of quetiapine on mortality, resource utilization, post-intensive care unit cognition, and dependency after discharge in a broader group of patients.
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              Dexmedetomidine and the reduction of postoperative delirium after cardiac surgery.

              Delirium is a neurobehavioral syndrome caused by the transient disruption of normal neuronal activity secondary to systemic disturbances. The authors investigated the effects of postoperative sedation on the development of delirium in patients undergoing cardiac-valve procedures. Patients underwent elective cardiac surgery with a standardized intraoperative anesthesia protocol, followed by random assignment to one of three postoperative sedation protocols: dexmedetomidine, propofol, or midazolam. The incidence of delirium for patients receiving dexmedetomidine was 3%, for those receiving propofol was 50%, and for patients receiving midazolam, 50%. Patients who developed postoperative delirium experienced significantly longer intensive-care stays and longer total hospitalization. The findings of this open-label, randomized clinical investigation suggest that postoperative sedation with dexmedetomidine was associated with significantly lower rates of postoperative delirium and lower care costs.
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                Author and article information

                Journal
                Critical Care Medicine
                Critical Care Medicine
                Ovid Technologies (Wolters Kluwer Health)
                0090-3493
                2016
                July 2016
                : 44
                : 7
                : 1295-1306
                Article
                10.1097/CCM.0000000000001622
                26925523
                0e929186-3b47-43c6-b95c-1e9c9b6b9f90
                © 2016
                History

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