Dexmedetomidine versus propofol/midazolam for long-term sedation during mechanical ventilation
Department of Anesthesiology and Intensive Care Medicine, Kuopio University Hospital, P.O. Box 1777, 70211, Kuopio, Finland. Intensive Care Medicine
(Impact Factor: 7.21).
10/2008; 35(2):282-90. DOI: 10.1007/s00134-008-1296-0
To compare dexmedetomidine (DEX) with standard care (SC, either propofol or midazolam) for long-term sedation in terms of maintaining target sedation and length of intensive care unit (ICU) stay.
A pilot, phase III, double-blind multicenter study in randomized medical and surgical patients (n = 85) within the first 72 h of ICU stay with an expected ICU stay of >or=48 h and sedation need for >or=24 h after randomization. Patients were assigned to either DEX (<or=1.4 microg kg(-1) h(-1); n = 41) or SC (n = 44), with daily sedation stops.
Non-inferiority of DEX versus SC was not confirmed. Target Richmond agitation-sedation score (RASS) was reached a median of 64% (DEX) and 63% (SC) of the sedation time (ns). The length of ICU stay was similar in DEX and SC. Patients with RASS target 0-3 (DEX 78%, SC 80%) were at target sedation 74% (DEX) and 64% (SC) of the time (ns), whereas those with RASS target -4 or less reached the target 42% (DEX) and 62% (SC) of the time (P = .006). Post hoc analyses suggested shorter duration of mechanical ventilation for DEX (P = 0.025).
This pilot study suggests that in long-term sedation, DEX is comparable to SC in maintaining sedation targets of RASS 0 to -3 but not suitable for deep sedation (RASS -4 or less). DEX had no effect on length of ICU stay. Its effects on other relevant clinical outcomes, such as duration of mechanical ventilation, should be tested further.
Available from: Sébastien Perbet
- "Many treatments associated with dexmedetomidine in ICUs can worsen bradycardia, including treatments with anti-arrhythmic agents and opioids. Bradycardias in these studies were rarely severe, with reductions in infusions allowing heart rates to return to normal range[17,18]. Most of the studies included in our meta-analyses excluded patients with a low heart rate at admission and those with atrioventricular blockades without pacing. "
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Dexmedetomidine may help physicians target a low level of sedation. Unfortunately, the impact of dexmedetomidine on major endpoints remains unclear in intensive care unit (ICU).
Material and methods:
To evaluate the association between dexmedetomidine use with efficacy and safety outcomes, two reviewers independently identified randomized controlled trials comparing dexmedetomidine with other sedative agents in non-post-cardiac surgery critically ill patients in the PubMed and Cochrane databases. Random effects models were considered if heterogeneity was detected using the DerSimonian and Laird estimation method. Statistical heterogeneity between results was assessed by examining forest plots, confidence intervals (CI) and by using the I(2) statistic. The risk of bias was assessed using the risk of bias tool.
This meta-analysis included 1994 patients from 16 randomized controlled trials. Comparators were lorazepam, midazolam and propofol. Dexmedetomidine was associated with a reduction in ICU length of stays (WMD=-0.304; 95% CI [-0.477, -0.132]; P=0.001), mechanical ventilation duration (WMD=-0.313, 95% CI [-0.523, -0.104]; P=0.003) and delirium incidence (RR=0.812, 95% CI [0.680, 0.968]; P=0.020). Dexmedetomidine is also associated with an increase in the incidence of bradycardia (RR=1.947, 95% CI [1.387, 2.733]; P=0.001) and hypotension (RR=1.264; 95% CI [1.013, 1.576]; P=0.038).
Conclusions and relevance:
In this first meta-analysis including only randomized controlled trials related to ICU patients, dexmedetomidine was associated with a 48h reduction in ICU length of stay, mechanical ventilation duration and delirium occurrence despite a significant heterogeneity among studies. Dexmedetomidine was also associated with an increase in bradycardia and hypotension.
Available from: Luc Quintin
- "Ventilation : l'absence de dépression respiratoire   a des conséquences positives. Sous dexmédétomidine, la durée de ventilation est plus courte . Circulation : une amélioration de la fonction ventriculaire droite et gauche    a été observée mais l'incidence d'hypotensions et de bradycardies est plus élevée comme mentionné précédemment. "
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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.
Available from: Sandra L Kane-Gill
- "Other studies support the finding that dexmedetomidine should be used in patients requiring lighter sedation [3, 6]. Less information, however, is available about the interaction between home antidepressant use and alpha-2 agonists. "
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ABSTRACT: Fifty-five thousand patients are cared for in the intensive care unit (ICU) daily with sedation utilized to reduce anxiety and agitation while optimizing comfort. The Society of Critical Care Medicine (SCCM) released updated guidelines for management of pain, agitation, and delirium in the ICU and recommended nonbenzodiazepines, such as dexmedetomidine and propofol, as first line sedation agents. Dexmedetomidine, an alpha-2 agonist, offers many benefits yet its use is mired by the inability to consistently achieve sedation goals. Three hypotheses including patient traits/characteristics, pharmacokinetics in critically ill patients, and clinically relevant genetic polymorphisms that could affect dexmedetomidine response are presented. Studies in patient traits have yielded conflicting results regarding the role of race yet suggest that dexmedetomidine may produce more consistent results in less critically ill patients and with home antidepressant use. Pharmacokinetics of critically ill patients are reported as similar to healthy individuals yet wide, unexplained interpatient variability in dexmedetomidine serum levels exist. Genetic polymorphisms in both metabolism and receptor response have been evaluated in few studies, and the results remain inconclusive. To fully understand the role of dexmedetomidine, it is vital to further evaluate what prompts such marked interpatient variability in critically ill patients.
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