Vanderbilt University Medical Center investigators have received a $2.8 million grant from the National Heart, Lung, and Blood Institute (NHLBI) to continue studying ways to improve sedation management for intensive care unit patients who are on mechanical ventilators.
Under the leadership of Wes Ely, M.D., MPH, professor of Medicine, and Pratik Pandharipande, M.D., MSCI, associate professor of Anesthesiology, the physicians, nurses, neuropsychologists and biostatisticians who make up the ICU Cognitive Impairment Study Group are taking their delirium and sedation research a step further with the new grant.
The MENDS II study (Maximizing the Efficacy of Sedation and Reducing Neurological Dysfunction and Mortality in Septic Patients with Acute Respiratory Failure) is funded by the National Institutes of Health (1R01 HL111111-01A1) and will compare the effects of sedation with propofol versus dexmedetomidine in patients with severe sepsis, with a goal of also studying the effect of these sedative regimens on inflammation, acute brain dysfunction and mortality.
This randomized, controlled study will involve an estimated 530 patients at VUMC, University of California at San Francisco Medical Center, Bay State University, Henry Ford Hospital, University of Wisconsin Hospitals and Clinics, and University of Texas Health Science Center at San Antonio, with plans to begin enrolling patients in March 2013.
Just a few years ago, ICU patients on ventilators while being treated for sepsis or acute respiratory failure would most likely have been in medically induced comas with a state of acute brain dysfunction known as delirium. As a result of previous research by a team led by Pandharipande and Ely, there has been a dramatic change in the way these patients are cared for, potentially improving their short- and long-term outcomes.
Delirium is an acute brain dysfunction that can be caused by factors associated with critical illness or as a complication of some of its treatments. Delirium increases the length of hospital stays and the cost of care, and is associated with an increased probability of death. Delirium also is believed to contribute to significant functional and cognitive decline for many years after a patient recovers from their initial critical illness.
In 2006, Pandharipande published data that for the first time showed an association between the commonly prescribed benzodiazepine sedatives and delirium in ICU patients. At that time, these sedative medications were almost universally prescribed to reduce anxiety and to keep patients sedated while on mechanical ventilation. In 2007, Ely and Pandharipande published a study in The Journal of the American Medical Association (JAMA) that resulted in changes to the standard of care for these patients.
“Our MENDS randomized controlled study compared sedation in the ICU with benzodiazepines (GABA receptor agonists) versus dexmedetomidine (an alpha2 agonist) because they target different receptors in the brain and may have differing effects on delirium,” Pandharipande said.
What the Vanderbilt investigators found after observing 106 adult mechanically ventilated ICU patients at two hospitals over a two-year period was that sedation with dexmedetomidine led to more days alive without brain dysfunction (delirium or coma) compared to sedation with benzodiazepines. Other investigators have since corroborated these findings and have also demonstrated that sedation with propofol (a different GABA receptor agonist) is also superior to sedation with benzodiazepines for a number of patient outcomes.
“Dexmedetomidine and propofol are now the standard of care for sedation of mechanically ventilated patients, versus eight-10 years ago when benzodiazepines were much more commonly used, but we still do not know which of these two drugs is safer and superior with regards to patient outcomes,” Pandharipande said.
“These sedatives work on different receptors in the brain, differentially affect inflammation and bacterial clearance, and one may be better than the other with regards to promoting sleep in the ICU. In addition, these medicines have different side effects, which may also be clinically important.”
More information can be found on the group’s Vanderbilt and Veterans Affairs Geriatric Research, Education, Clinical Center-affiliated website (www.icudelirium.org).
