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Benzodiazepine Versus Nonbenzodiazepine-Based Sedation for Mechanically Ventilated, Critically Ill Adults: A Systematic Review and Meta-Analysis of Randomized Trials

Fraser, Gilles L. PharmD, FCCM1; Devlin, John W. PharmD, FCCM2; Worby, Craig P. PharmD3; Alhazzani, Waleed MD4; Barr, Juliana MD, FCCM5,6; Dasta, Joseph F. MSc, FCCM, FCCP7,8; Kress, John P. MD9; Davidson, Judy E. DNP, RN10; Spencer, Frederick A. MD11,12

doi: 10.1097/CCM.0b013e3182a16898
Creating and Implementing the 2013 ICU Pain, Agitation, and Delirium Guidelines for Adult Icu Patients

Background: Use of dexmedetomidine or propofol rather than a benzodiazepine sedation strategy may improve ICU outcomes. We reviewed randomized trials comparing a benzodiazepine and nonbenzodiazepine regimen in mechanically ventilated adult ICU patients to determine if differences exist between these sedation strategies with respect to ICU length of stay, time on the ventilator, delirium prevalence, and short-term mortality.

Methods: We searched CINAHL, MEDLINE, the Cochrane databases, and the American College of Critical Care Medicine’s Pain, Agitation, Delirium Management Guidelines’ literature database from 1996 to 2013. Citations were screened for randomized trials that enrolled critically ill, mechanically ventilated adults comparing an IV benzodiazepine-based to a nonbenzodiazepine-based sedative regimen and reported duration of ICU length of stay, duration of mechanical ventilation, delirium prevalence, and/or short-term mortality. Trial characteristics and results were abstracted in duplicate and independently, and the Cochrane risk of bias tool was used for quality assessment. We performed random effects model meta-analyses where possible.

Results: We included six trials enrolling 1,235 patients: midazolam versus dexmedetomidine (n = 3), lorazepam versus dexmedetomidine (n = 1), midazolam versus propofol (n = 1), and lorazepam versus propofol (n = 1). Compared to a benzodiazepine sedative strategy, a nonbenzodiazepine sedative strategy was associated with a shorter ICU length of stay (n = 6 studies; difference = 1.62 d; 95% CI, 0.68–2.55; I2 = 0%; p = 0.0007) and duration of mechanical ventilation (n = 4 studies; difference = 1.9 d; 95% CI, 1.70–2.09; I2 = 0%; p < 0.00001) but a similar prevalence of delirium (n = 2; risk ratio = 0.83; 95% CI, 0.61–1.11; I2 = 84%; p = 0.19) and short-term mortality rate (n = 4; risk ratio = 0.98; 95% CI, 0.76–1.27; I2 = 30%; p = 0.88).

Conclusions: Current controlled data suggest that use of a dexmedetomidine- or propofol-based sedation regimen rather than a benzodiazepine-based sedation regimen in critically ill adults may reduce ICU length of stay and duration of mechanical ventilation. Larger controlled studies are needed to further define the impact of nonbenzodiazepine sedative regimens on delirium and short-term mortality.

1Department of Pharmacy, Tufts University School of Medicine and Department of Critical Care Medicine, Maine Medical Center, Portland, ME.

2Department of Pharmacy Practice, Northeastern University and the Division of Pulmonary, Critical Care, and Sleep Medicine, Tufts Medical Center, Boston, MA.

3Department of Pharmacy, Maine Medical Center, Portland, ME.

4Department of Medicine, McMaster University, Hamilton, ON, Canada.

5VA Palo Alto Health Care System, Palo Alto, CA.

6Stanford University School of Medicine, Stanford, CA.

7College of Pharmacy, The Ohio State University, Columbus, OH.

8College of Pharmacy, The University of Texas, Austin, TX.

9Department of Medicine, Section of Pulmonary and Critical Care, University of Chicago, Chicago, IL.

10Evidence-based Practice and Research Liaison, UCSD Medical Center, San Diego, CA.

11Division of Cardiology, McMaster University, Hamilton, ON, Canada.

12Division of Hematology/Thrombosis, McMaster University, Hamilton, ON, Canada.

Dr. Devlin has received grants, honoraria, and payment for the development of educational presentations from Hospira. Dr. Barr has received an honorarium and travel expenses from SCCM and payment for lectures from Cynosure Health. Mr. Dasta has disclosed consultancies with Hospira, Cadence Pharmaceuticals, and Pacira Pharmaceuticals; he is also a member of the France Foundation Speaker Program, sponsored by Hospira. Dr. Kress has received honoraria from Hospira. Dr. Davidson has received honoraria from Hospira and the France Foundation. Dr. Spencer has disclosed that his institution has received grants from the National Institutes of Health and Ontario Heart and Stroke. The remaining authors have disclosed that they do not have any potential conflicts of interest.

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© 2013 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins