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Benzodiazepine Sedatives Linked to Higher Mortality Rates Compared With Propofol

Propofol use lowers costs, authors say

Sedation is often required for mechanically ventilated patients in intensive care units (ICUs) to reduce anxiety, to provide comfort, and to assist in providing optimal respiratory support. It is estimated that nearly 1 million U.S. patients are treated with a continuous, intravenous sedative in an ICU setting each year.

A new study from the University of Utah has shown that continuous-infusion benzodiazepines — a class of sedatives that includes lorazepam and midazolam, once considered the standard of care in the ICU — are linked to an increased likelihood of death in patients who receive mechanical ventilation compared with the sedative propofol.

The research was published in the American Journal of Respiratory Critical Care Medicine.

“We found there are better, safer ways than benzodiazepines to sedate people that can still deliver all the sedation you need while minimizing some of the complications associated with mechanical ventilation,” said senior author Richard Barton, MD.

The authors analyzed data from 13,692 mechanically ventilated patients at 104 U.S. hospitals during the years 2003 to 2009. They found that overall ICU mortality was 19.7% in propofol-treated patients compared with 28.8% in midazolam-treated patients, and 19.3% in propofol-treated patients compared with 25.2% in lorazepam-treated patients. Those treated with benzodiazepines also spent significantly more time on mechanical ventilation and a longer period in the ICU.

“Patients with renal failure and liver dysfunction have trouble clearing benzodiazepines and are more likely to be over-sedated,” explained principal author Nick Lonardo, PharmD. “By staying on a ventilator longer, this puts patients at higher risk for developing ventilator-associated pneumonia and many of the other complications, including delirium, that come from being sedated for long periods in an ICU.”

Although this is the first study to associate benzodiazepines with increased mortality, several smaller studies have suggested that this class of drugs is associated with other adverse outcomes, especially delirium. Separate investigations have linked delirium occurring in the ICU to an increased risk of death. These smaller reports triggered a drop in the use of benzodiazepines during the last 10 years. In the new study, data from the 104 ICUs analyzed showed that nearly three times as many patients were treated with propofol compared with benzodiazepines.

Nevertheless, benzodiazepines are still the sedatives of choice in some U.S. hospitals and may be extensively used internationally, the authors say. This is largely because these drugs are generic and are less expensive than other sedatives. The authors indicate that while there are patient-specific uses for benzodiazepines in the ICU and in the hospital, they should not be the routine agents of choice for sedation.

The authors hope their work will help convince critical care clinicians around the world that the use of propofol can save lives as well as lower the rates of associated complications, resulting in decreased health care costs.

Source: Medical Xpress; September 30, 2014.

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