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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    • "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.
    Le Praticien en Anesthésie Réanimation 06/2015; 19(3). DOI:10.1016/j.pratan.2015.04.005
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    • "After 40 min, when a suitable sedation level was achieved and the hemodynamic variables were stabilized , a second PLR test (PLR2) was then performed. Treatment methods for hypotension were followed; that is, when a systolic blood pressure of <80 mm Hg or a 30% decrease from the baseline [7] was observed, a bolus of intravenous fluid was administered, the sedative drug infusion was interrupted, and vasoactive agents were administered if needed. "
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    ABSTRACT: Background Predicting fluid responsiveness is crucial for fluid administration in septic shock patients. Midazolam and propofol decrease vascular tone and venous return, which may influence preload dependency. However, little is known about the effects of these two sedatives on preload dependency in septic shock patients. We evaluated the effects of sedation with propofol or midazolam on preload dependency in septic shock patients who have been fluid resuscitated. Methods Forty-three septic shock patients who were undergoing EGDT (Early Goal-Directed Therapy) resuscitated within 24 hours were enrolled. The patients were randomly divided into the midazolam group and the propofol group. An initial passive leg raising test (PLR1) was performed to evaluate PLR responsiveness. Then, the patients were infused with midazolam or propofol. After increasing the doses of the sedatives to titrate to a Ramsay 4 score, a second passive leg raising test (PLR2) was conducted to evaluate PLR responsiveness. The primary end-point was the preload dependency before and after sedation with midazolam or propofol. Results In the Midazolam-PLR1-negative patients, there was no difference between the changes in the cardiac index induced by PLR1 (PLR1-ΔCI) and the changes in the cardiac index induced by PLR2 (PLR2-ΔCI) (+1.4%±7.4% vs. +1.7%±6.4%, p>0.05). However, in the Propofol-PLR1-negative patients, there was a significant increase in the PLR-ΔCI after sedation to a Ramsay 4 score compared with a Ramsay 3 score (+7.3%±4.8% vs. +3.2%±4.7%, p=0.008). There were no differences between PLR1-ΔCI and PLR2-ΔCI within the Midazolam-PLR1-positive patients or within the Propofol-PLR1-positive patients. Conclusions In titrating the sedation level from a Ramsay 3 score to a Ramsay 4 score, propofol but not midazolam increased preload dependency in septic shock patients with fluid nonresponsiveness.
    Journal of Surgical Research 09/2014; 193(2). DOI:10.1016/j.jss.2014.08.050 · 1.94 Impact Factor
    • "Our finding of dexmedetomidine treated patients is in concurrence with previous studies.[911] However, our findings are in contrast with those of Riker et al.[12] who suggested that dexmedetomidine attained target sedation less frequently. They recruited only medical patients, while our most patients were postsurgical. "
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    ABSTRACT: Background and Objectives:Patients on mechanical ventilation in intensive care unit (ICU) are often uncomfortable because of anxiety, pain, and endotracheal intubation; therefore, require sedation. Alpha-2 agonists are known to produce sedation. We compared clonidine and dexmedetomidine as sole agents for sedation.Study Design:Prospective, randomized, controlled open-label study.Materials and Methods:A total of 70 patients requiring a minimum of 12 h of mechanical ventilation with concomitant sedation, were randomly allocated into two groups. Group C (n = 35) received intravenous (IV) clonidine (1 μg/kg/h titrated up to 2 μg/kg/h to attain target sedation), and Group D (n = 35) received IV dexmedetomidine for sedation (loading 0.7 μg/kg and maintenance 0.2 μg/kg/h titrated up to 0.7 μg/kg/h to achieve target sedation). A Ramsay Sedation Score of 3-4 was considered as target sedation. Additional sedation with diazepam was given when required to achieve target sedation. The quality of sedation, hemodynamic changes and adverse effects were noted and compared between the two groups.Results:Target sedation was achieved in 86% observations in Group D and 62% in Group C (P = 0.04). Additional sedation was needed by more patients in Group C compared with Group D (14 and 8 in Groups C and D, respectively, P = 0.034), mainly due to concomitant hypotension on increasing the dose of clonidine. Hypotension was the most common side-effect in Group C, occurring in 11/35 patients of Group C and 3/35 patients of Group D (P = 0.02). Rebound hypertension was seen in four patients receiving clonidine, but none in receiving dexmedetomidine.Conclusion:Both clonidine and dexmedetomidine produced effective sedation; however, the hemodynamic stability provided by dexmedetomidine gives it an edge over clonidine for short-term sedation of ICU patients.
    Indian Journal of Critical Care Medicine 07/2014; 18(7):431-6. DOI:10.4103/0972-5229.136071
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