Benzodiazepines May Adversely Affect ICU Patients On Ventilators

Nick Lonardo, PharmD Pharmacy, Clinical Coordinator Department of Pharmacy Services Salt Lake City, Utah Interview with:
Nick Lonardo, PharmD
Pharmacy, Clinical Coordinator
Department of Pharmacy Services
Salt Lake City, Utah 84132

Medical Research: What are the main findings of the study?

Dr. Lonardo: To our knowledge, this is the first, large, multicenter, retrospective cohort study to show that continuous infusion benzodiazepines are independently associated with increased mortality in mechanically ventilated ICU patients. In addition, benzodiazepines were associated with an increased time of mechanical ventilation and ICU length of stay.

Medical Research: What was most surprising about the results?

Dr. Lonardo: Prior studies had shown that propofol was associated with more rapid time to extubation and a shorter ICU length of stay, so these results were not unexpected. We were most surprised by the increased mortality even after matching the patients closely for important considerations such as the severity of illness and hemodynamic instability. In addition, the magnitude of the mortality differences is surprising. When propofol treated patients were matched to midazolam treated patients, the overall ICU mortality was 19.7% and 28.8%, respectively. When propofol treated patients were matched to the lorazepam treated patients, the overall ICU mortality was 19.3% and 25.2%, respectively.

Medical Research: What should clinicians and patients take away from your report?

Dr. Lonardo: Given the recommendation from the Society of Critical Care Medicine in 2013 for dropping benzodiazepines as the sedation agent of choice, and our study results that showed an association to increased mortality, increased time of mechanical ventilation, and longer ICU stays, as well as results from earlier studies that linked benzodiazepines to delirium; ICU clinicians should discontinue the use of benzodiazepines for prolonged sedation.

Clinicians should first attempt to make the patient comfortable with good pain management. If a sedative is still needed, clinicians should consider using propofol and/or dexmedetomidine as their first choice. Critical care clinicians must continue to change the culture of sedation management in the modern ICU. Adequate and proper sedation for patients is a multidisciplinary effort that involves the entire ICU team of nurses, physicians, and pharmacists. Proper sedation along with pain management can produce dramatic improvements in patient outcomes, by allowing earlier discontinuation from ventilator use, earlier ambulation, less delirium, and earlier discharge from the ICU and the hospital.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Lonardo: The following research questions are still unanswered.

Why exactly is propofol associated with a decreased mortality? Is it related to the pharmacokinetic advantages of this drug, since it is shorter acting with respect to the half-life and way it is metabolized by the body? Could it also be related to the fact that there is a lower associated risk for delirium with propofol when compared to those treated with a benzodiazepines? Is it somehow related to immune modulating properties of benzodiazepines?


Nick W. Lonardo, Mary C. Mone, Raminder Nirula, Edward J. Kimball, Kyle Ludwig, Xi Zhou, Brian C. Sauer, Kevin Nechodom, Chiachen Teng, and Richard G. Barton “Propofol Is Associated with Favorable Outcomes Compared with Benzodiazepines in Ventilated Intensive Care Unit Patients”, American Journal of Respiratory and Critical Care Medicine, Vol. 189, No. 11 (2014), pp. 1383-1394.

doi: 10.1164/rccm.201312-2291OC