Riker RR, Shehabi Y, Bokesch PM, et al: Dexmedetomidine vs midazolam for sedation of critically ill patients: A randomized trial

University of Vermont College of Medicine, USA.
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 02/2009; 301(5):489-99. DOI: 10.1001/jama.2009.56
Source: PubMed


Gamma-aminobutyric acid receptor agonist medications are the most commonly used sedatives for intensive care unit (ICU) patients, yet preliminary evidence indicates that the alpha(2) agonist dexmedetomidine may have distinct advantages.
To compare the efficacy and safety of prolonged sedation with dexmedetomidine vs midazolam for mechanically ventilated patients.
Prospective, double-blind, randomized trial conducted in 68 centers in 5 countries between March 2005 and August 2007 among 375 medical/surgical ICU patients with expected mechanical ventilation for more than 24 hours. Sedation level and delirium were assessed using the Richmond Agitation-Sedation Scale (RASS) and the Confusion Assessment Method for the ICU.
Dexmedetomidine (0.2-1.4 microg/kg per hour [n = 244]) or midazolam (0.02-0.1 mg/kg per hour [n = 122]) titrated to achieve light sedation (RASS scores between -2 and +1) from enrollment until extubation or 30 days.
Percentage of time within target RASS range. Secondary end points included prevalence and duration of delirium, use of fentanyl and open-label midazolam, and nursing assessments. Additional outcomes included duration of mechanical ventilation, ICU length of stay, and adverse events.
There was no difference in percentage of time within the target RASS range (77.3% for dexmedetomidine group vs 75.1% for midazolam group; difference, 2.2% [95% confidence interval {CI}, -3.2% to 7.5%]; P = .18). The prevalence of delirium during treatment was 54% (n = 132/244) in dexmedetomidine-treated patients vs 76.6% (n = 93/122) in midazolam-treated patients (difference, 22.6% [95% CI, 14% to 33%]; P < .001). Median time to extubation was 1.9 days shorter in dexmedetomidine-treated patients (3.7 days [95% CI, 3.1 to 4.0] vs 5.6 days [95% CI, 4.6 to 5.9]; P = .01), and ICU length of stay was similar (5.9 days [95% CI, 5.7 to 7.0] vs 7.6 days [95% CI, 6.7 to 8.6]; P = .24). Dexmedetomidine-treated patients were more likely to develop bradycardia (42.2% [103/244] vs 18.9% [23/122]; P < .001), with a nonsignificant increase in the proportion requiring treatment (4.9% [12/244] vs 0.8% [1/122]; P = .07), but had a lower likelihood of tachycardia (25.4% [62/244] vs 44.3% [54/122]; P < .001) or hypertension requiring treatment (18.9% [46/244] vs 29.5% [36/122]; P = .02).
There was no difference between dexmedetomidine and midazolam in time at targeted sedation level in mechanically ventilated ICU patients. At comparable sedation levels, dexmedetomidine-treated patients spent less time on the ventilator, experienced less delirium, and developed less tachycardia and hypertension. The most notable adverse effect of dexmedetomidine was bradycardia. Identifier: NCT00216190 Published online February 2, 2009 (doi:10.1001/jama.2009.56).

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Available from: Paula Bokesch
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    • "Traditionally, γ-aminobutyric acid (GABA) receptor agonists such as benzodiazepines and propofol are commonly administered sedative agents in the ICU [6] [9]. Recently, studies have highlighted sedative and analgesic properties of selective α 2 receptor agonists such as dexmedetomidine [10] [11]. After its binding "
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    ABSTRACT: Purpose: The aim of this systematic review was to evaluate the effectiveness and safety of dexmedetomidine used for sedation of patients with sepsis. Methods: We searched Medline, Scopus, TRIP and CENTRAL, DART, OpenGrey, and ProQuest without applying any language filter up to July 15, 2015. Two of the authors independently reviewed search results for irrelevant and duplicate studies and extracted data and assessed methodological quality of the studies. We used tabulation to synthesize the findings of the studies and transformed data into a common rubric and calculated a weighted treatment effect across studies using Review Manager. Results: We found 124 references in 7 databases, and after exclusion of irrelevant and duplicate studies, 6 studies with total number of 242 patients with sepsis were included. The risk ratio for 28-day mortality was 0.49 (95% confidence interval, 0.24-0.99; P = .05) for the dexmedetomidine group vs the control group. The weighted mean difference for the length of stay in the intensive care unit was 1.54 (95% confidence interval, -1.73 to 4.81; P = .36). No adverse effect including hypertensive, hypotensive, or bradycardia response was reported in any studies. Conclusion: In a small group of studies of patients with sepsis, dexmedetomidine improved short-term mortality compared with other sedatives without affecting the intensive care unit length of stay. Further studies are warranted to confirm whether using this particular agent improves sepsis outcomes in comparison to other commonly used sedating agents.
    Full-text · Article · Jan 2016 · Journal of Critical Care
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    • "La réduction de coûts est liée à la réduction de l'incidence du délirium de réanimation [21]. Une étude multicentrique américaine [19] montre également une réduction des coûts de −9679 US$ (coûts de ventilation mécanique : −2958 US$ ; durée de séjour en réanimation : −6584 US$) [95] : le retour précoce de la ventilation spontanée exploite la molécule au maximum pour réduire les coûts globaux [21] [95]. "
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    ABSTRACT: La dexmédétomidine a une autorisation de mise sur le marché pour la sédation en réanimation en France depuis 2013. Par rapport à la clonidine, les avantages de la dexmédétomidine sont les suivants : délai d’action plus court même en cas d’administration sans dose de charge, délai d’élimination plus court par voie hépatique. L’intérêt de la dexmédétomidine par rapport aux protocoles de sédations conventionnels appliqués en réanimation est lié à l’atténuation de certains effets délétères (facilitation de l’émergence de la sédation, moindre incidence de délirium), à l’absence d’effets dépresseurs respiratoires, à l’amélioration des conditions de pré-charge et post-charge des ventricules. Les médicaments coadministrés avec la dexmédétomidine en vue d’une sédation plus profonde sont les neuroleptiques et les analgésiques non-morphiniques. Le développement clinique de la dexmédétomidine doit être poursuivi pour utiliser pleinement ses propriétés pharmacodynamiques, afin d’amener la sédation au niveau des progrès réalisés en réanimation aux plans ventilatoire, circulatoire et rénal.
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    • "and general anesthesia in the setting of certain operations and invasive medical procedures, such as colonoscopy [3] [4] [5]. "
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    ABSTRACT: The aim of this study was to examine the role played by substance P and calcitonin gene-related peptide (CGRP) within the dorsal horn of the spinal cord in engagement of antinociception evoked by dexmedetomidine (DEX). Paw withdrawal threshold (PWT) to mechanical stimulation was determined after chronic intrathecal infusion of DEX and enzyme-linked immunosorbent assay (ELISA) was employed to examine the levels of spinal substance P and CGRP. Our results show that PWT was significantly increased by intrathecal administration of DEX in rats (P < 0.05 vs. vehicle control, n = 20 in each group). Also, intrathecal infusion of DEX significantly decreased the concentrations of substance P and CGRP as compared with vehicle control (P < 0.05 DEX vs. vehicle control, n = 20 in each group). Blocking α2-adrenoreceptors (α2-AR) blunted the decreases of substance P and CGRP levels and the enhancement of PWT evoked by DEX. Additionally, a linear relationship was observed between PWT and the levels of spinal substance P (r = 0.87; P < 0.005) and CGRP (r = 0.85; P < 0.005). Moreover, blocking individual substance P and CGRP receptors amplified PWT without altering substance P and CGRP levels. Thus, DEX plays a role in stimulating α2-AR receptors, which thereby decreases substance P and CGRP levels within the dorsal horn. This contributes to DEX-evoked antinociception.
    Full-text · Article · Jan 2015 · Translational Neuroscience
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