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      Early Sedation with Dexmedetomidine in Critically Ill Patients

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          Abstract

          Dexmedetomidine produces sedation while maintaining a degree of arousability and may reduce the duration of mechanical ventilation and delirium among patients in the intensive care unit (ICU). The use of dexmedetomidine as the sole or primary sedative agent in patients undergoing mechanical ventilation has not been extensively studied.

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          Caring for Critically Ill Patients with the ABCDEF Bundle

          Brenda Pun, Michele Balas, Mary Barnes-Daly … (2018)
          Decades-old, common ICU practices including deep sedation, immobilization, and limited family access are being challenged. We endeavoured to evaluate the relationship between ABCDEF bundle performance and patient-centered outcomes in critical care.
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            Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials.

            Stephan Jakob, Esko Ruokonen, R Michael Grounds … (2012)
            Long-term sedation with midazolam or propofol in intensive care units (ICUs) has serious adverse effects. Dexmedetomidine, an α(2)-agonist available for ICU sedation, may reduce the duration of mechanical ventilation and enhance patient comfort. To determine the efficacy of dexmedetomidine vs midazolam or propofol (preferred usual care) in maintaining sedation; reducing duration of mechanical ventilation; and improving patients' interaction with nursing care. Two phase 3 multicenter, randomized, double-blind trials carried out from 2007 to 2010. The MIDEX trial compared midazolam with dexmedetomidine in ICUs of 44 centers in 9 European countries; the PRODEX trial compared propofol with dexmedetomidine in 31 centers in 6 European countries and 2 centers in Russia. Included were adult ICU patients receiving mechanical ventilation who needed light to moderate sedation for more than 24 hours (midazolam, n = 251, vs dexmedetomidine, n = 249; propofol, n = 247, vs dexmedetomidine, n = 251). Sedation with dexmedetomidine, midazolam, or propofol; daily sedation stops; and spontaneous breathing trials. For each trial, we tested whether dexmedetomidine was noninferior to control with respect to proportion of time at target sedation level (measured by Richmond Agitation-Sedation Scale) and superior to control with respect to duration of mechanical ventilation. Secondary end points were patients' ability to communicate pain (measured using a visual analogue scale [VAS]) and length of ICU stay. Time at target sedation was analyzed in per-protocol population (midazolam, n = 233, vs dexmedetomidine, n = 227; propofol, n = 214, vs dexmedetomidine, n = 223). Dexmedetomidine/midazolam ratio in time at target sedation was 1.07 (95% CI, 0.97-1.18) and dexmedetomidine/propofol, 1.00 (95% CI, 0.92-1.08). Median duration of mechanical ventilation appeared shorter with dexmedetomidine (123 hours [IQR, 67-337]) vs midazolam (164 hours [IQR, 92-380]; P = .03) but not with dexmedetomidine (97 hours [IQR, 45-257]) vs propofol (118 hours [IQR, 48-327]; P = .24). Patients' interaction (measured using VAS) was improved with dexmedetomidine (estimated score difference vs midazolam, 19.7 [95% CI, 15.2-24.2]; P < .001; and vs propofol, 11.2 [95% CI, 6.4-15.9]; P < .001). Length of ICU and hospital stay and mortality were similar. Dexmedetomidine vs midazolam patients had more hypotension (51/247 [20.6%] vs 29/250 [11.6%]; P = .007) and bradycardia (35/247 [14.2%] vs 13/250 [5.2%]; P < .001). Among ICU patients receiving prolonged mechanical ventilation, dexmedetomidine was not inferior to midazolam and propofol in maintaining light to moderate sedation. Dexmedetomidine reduced duration of mechanical ventilation compared with midazolam and improved patients' ability to communicate pain compared with midazolam and propofol. More adverse effects were associated with dexmedetomidine. clinicaltrials.gov Identifiers: NCT00481312, NCT00479661.
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              Delirium duration and mortality in lightly sedated, mechanically ventilated intensive care patients.

              , Wayne Wisemandle, Richard R Riker … (2010)
              To determine the relationship between the number of delirium days experienced by intensive care patients and mortality, ventilation time, and intensive care unit stay. Prospective cohort analysis. Patients from 68 intensive care units in five countries. Three hundred fifty-four medical and surgical intensive care patients enrolled in the SEDCOM (Safety and Efficacy of Dexmedetomidine Compared with Midazolam) trial received a sedative study drug and completed at least one delirium assessment. Sedative drug interruption and/or titration to maintain light sedation with daily arousal and delirium assessments up to 30 days of mechanical ventilation. The primary outcome was all-cause 30-day mortality. Multivariable analysis using Cox regression incorporating delirium duration as a time-dependent variable and adjusting for eight relevant baseline covariates was conducted to quantify the relationship between number of delirium days and the three main outcomes. Overall, delirium was diagnosed in 228 of 354 patients (64.4%). Mortality was significantly lower in patients without delirium compared to those with delirium (15 of 126 [11.9%] vs. 69 of 228 [30.3%]; p<.001). Similarly, the median time to extubation and intensive care unit discharge were significantly shorter among nondelirious patients (3.6 vs. 10.7 days [p<.001] and 4 vs. 16 days [p<.001], respectively). In multivariable analysis, the duration of delirium exhibited a nonlinear relationship with mortality (p=.02), with the strongest association observed in the early days of delirium. In comparison to 0 days of delirium, an independent dose-response increase in mortality was observed, which increased from 1 day of delirium (hazard ratio, 1.70; 95% confidence interval, 1.27-2.29; p<.001), 2 days of delirium (hazard ratio, 2.69; confidence interval, 1.58-4.57; p<.001), and ≥3 days of delirium (hazard ratio, 3.37; confidence interval, 1.92-7.23; p<.001). Similar independent relationships were observed between delirium duration and ventilation time and intensive care length of stay. In ventilated and lightly sedated intensive care unit patients, the duration of delirium was the strongest independent predictor of death, ventilation time, and intensive care unit stay after adjusting for relevant covariates.
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                Author and article information

                Journal
                Title: New England Journal of Medicine
                Abbreviated Title: N Engl J Med
                Publisher: Massachusetts Medical Society
                ISSN (Print): 0028-4793
                ISSN (Electronic): 1533-4406
                Publication date Created: May 19 2019
                Publication date (Electronic): May 19 2019
                Affiliations
                [1 ]From the School of Clinical Sciences (Y.S.) and the Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine (B.D.H., R.B., M.B., L.M., S.A.W.), Monash University, Monash Health (Y.S.), the Faculty of Medicine, University of Melbourne (R.B., M.B.), Melbourne, VIC, and Austin Hospital, Heidelberg, VIC (R.B.), the Prince of Wales Clinical School of Medicine, University of New South Wales (Y.S.), Royal North Shore Hospital, the George Institute for Global...
                Article
                DOI: 10.1056/NEJMoa1904710
                PubMed ID: 31112380
                SO-VID: 767c370e-1193-4278-9045-10712bd12310
                Copyright © © 2019
                License:

                http://www.nejmgroup.org/legal/terms-of-use.htm

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