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: 30.39). 02/2009; 301(5):489-99. DOI: 10.1001/jama.2009.56
Source: PubMed

ABSTRACT 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).

1 Follower
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Randomized controlled trials suggest clinical outcomes may be improved with dexmedetomidine as compared to benzodiazepines, however further study and validation is needed. The objective of this study was to determine the clinical effectiveness of a sedation protocol minimizing benzodiazepine use in favor of early dexmedetomidine. This was a before-after study including adult surgical and medical ICU patients requiring mechanical ventilation and continuous sedation for at least 24 hours. The before phase included consecutive patients admitted between April 1 and August 31, 2011. Subsequently, the protocol was modified to minimize use of benzodiazepines in favor of early dexmedetomidine through a multidisciplinary approach and staff education was provided. The after phase included consecutive eligible patients between May 1 and October 31, 2012. 199 patients were included, with 97 patients in the before and 102 in the after phase. Baseline characteristics were well balanced between groups. Use of midazolam as initial sedation (58% vs. 27%, p < 0.0001) or at any point during the ICU stay (76% vs. 48%, p < 0.0001) was significantly reduced in the after phase. Dexmedetomidine use as initial sedation (2% vs. 39%, p < 0.0001) or at any point during the ICU stay (39% vs. 82%, p < 0.0001) significantly increased. Both the prevalence (81% vs. 93%, p =0.013) and median percent of days with delirium (55% (IQR 18-83) vs. 71% (IQR 45-100), p = 0.001) were increased in the after phase. The median duration of mechanical ventilation was significantly reduced in the after phase (110 (IQR 59-192) vs. 74.5 (IQR 42-148) hrs, p = 0.029) and significantly fewer patients required tracheostomy (20% vs. 9%, p = 0.040). The median ICU length of stay was 8 (IQR 4-12) days in the before phase and 6 (IQR 3-11) days in the after phase (p = 0.252). Implementing a sedation protocol that targeted light sedation and reduced benzodiazepine use led to significant improvements in the duration of mechanical ventilation and requirement for tracheostomy despite increases in the prevalence and duration of ICU delirium.
    Critical care (London, England) 04/2015; 19(1):136. DOI:10.1186/s13054-015-0874-0
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hospitalists and others acute-care providers are limited by gaps in evidence addressing the needs of the acutely ill older adult population. The Society of Hospital Medicine sponsored the Acute Care of Older Patients Priority Setting Partnership to develop a research agenda focused on bridging this gap. Informed by the Patient-Centered Outcomes Research Institute framework for identification and prioritization of research areas, we adapted a methodology developed by the James Lind Alliance to engage diverse stakeholders in the research agenda setting process. The work of the Partnership proceeded through 4 steps: convening, consulting, collating, and prioritizing. First, the steering committee convened a partnership of 18 stakeholder organizations in May 2013. Next, stakeholder organizations surveyed members to identify important unanswered questions in the acute care of older persons, receiving 1299 responses from 580 individuals. Finally, an extensive and structured process of collation and prioritization resulted in a final list of 10 research questions in the following areas: advanced-care planning, care transitions, delirium, dementia, depression, medications, models of care, physical function, surgery, and training. With the changing demographics of the hospitalized population, a workforce with limited geriatrics training, and gaps in evidence to inform clinical decision making for acutely ill older patients, the identified research questions deserve the highest priority in directing future research efforts to improve care for the older hospitalized patient and enrich training. Journal of Hospital Medicine 2015. © 2015 Society of Hospital Medicine. © 2015 Society of Hospital Medicine.
    Journal of Hospital Medicine 04/2015; 10(5). DOI:10.1002/jhm.2356 · 2.08 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Ketamine/propofol admixture (ketofol) at induction in the critically ill against etomidate (KEEP PACE trial): study protocol for a randomized controlled trial Abstract Background: Endotracheal intubation (ETI) is commonly performed as a life-saving procedure in the intensive care unit (ICU). It is often associated with significant hemodynamic perturbations and can severely impact the outcome of ICU patients. Etomidate is often chosen by many critical care providers for the patients who are hypotensive because of its superior hemodynamic profile compared to other induction medications. However, recent evidence has raised concerns about the increased incidence of adrenal insufficiency and mortality associated with etomidate use. A combination of ketamine and propofol (known as ketofol) has been studied in various settings as an alternative induction agent. In recent years, studies have shown that this combination may provide adequate sedation while maintaining hemodynamic stability, based on the balancing of the hemodynamic effects of these two individual agents. We hypothesized that ketofol may offer a valuable alternative to etomidate in critically ill patients with or without hemodynamic instability. Methods/design: A randomized controlled parallel-group clinical trial of adult critically ill patients admitted to either a medical or surgical ICU at Mayo Clinic in Rochester, MN will be conducted. As part of planned emergency research, informed consent will be waived after appropriate community consultation and notification. Patients undergoing urgent or emergent ETI will receive either etomidate or a 1:1 admixture of ketamine and propofol (ketofol). The primary outcome will be hemodynamic instability during the first 15 minutes following drug administration. Secondary outcomes will include ICU length of stay, mortality, adrenal function, ventilator-free days and vasoactive medication use, among others. The planned sample size is 160 total patients. Discussion: The overall goal of this trial is to assess the hemodynamic consequences of a ketamine-propofol combination used in critically ill patients undergoing urgent or emergent ETI compared to etomidate, a medication with an established hemodynamic profile. The trial will address a crucial gap in the literature regarding the optimal induction agent for ETI in patients that may have potential or established hemodynamic instability. Greater experience with planned emergency research will, hopefully, pave the way for future prospective randomized clinical trials in the critically ill population.
    Trials 04/2015; 16(1):177. DOI:10.1186/s13063-015-0687-0 · 2.12 Impact Factor

Full-text (2 Sources)

Available from
May 28, 2014