The MENDSII Study, Maximizing the Efficacy of Sedation and Reducing Neurological Dysfunction and Mortality in Septic Patients With Acute Respiratory Failure
Ventilated ICU patients frequently have sepsis and the majority have delirium, a form of brain dysfunction that is an independent predictor of increased risk of dying, length of stay, costs, and prolonged cognitive impairment in survivors. Universally prescribed sedative medications—the GABA-ergic benzodiazepines—worsen this brain organ dysfunction. The available alternative sedation regimens, the shorter acting GABA-ergic propofol, and the alpha2 agonist, dexmedetomidine, have both been shown to be superior to benzodiazepines, and yet are different with regard to their effects on innate immunity, bacterial clearance, apoptosis, cognition and delirium. The MENDS II study will compare propofol and dexmedetomidine, and determine the best sedative medication to reduce delirium and improve survival and long-term brain function in our most vulnerable patients— the ventilated septic patient.
Study Start Date
Estimated Completion Date
- Drug: Propofol
- Drug: Dexmedetomidine
- Neurology: Critical Care,Neuro/Psych pharmacology
- Anesthesiology: Airway,Critical Care,Pharmacology/kinetics
- Pharmacy: Drug Trials,Neuro/Psych pharmacology
- Emergency Medicine: Airway/Respiratory,Clinical Pharmacology,Infectious Disease,Neurology/Neurosurgery
- Urgent Care:
Vanderbilt University -- R01HL111111
Consecutive patients will be eligible for inclusion in the MENDS II study if they are: 
adult patients (?18 years old)  in a medical and/or surgical ICU and  on MV and
requiring sedation and  have severe sepsis (defined as at least 3 systemic inflammatory
response (SIRS) criteria as used in the PROWESS study), suspected or known infection
(origin and organism data will be collected, when available), and signs of organ
dysfunction (since MV is an inclusion criteria, all patients will have at least
respiratory failure, but will be assessed for additional renal and cardiovascular organ
Patients will be excluded (i.e., not consented) for any of the following reasons:
1. Rapidly resolving organ failure, indicated by planned immediate discontinuation of
MV, at time of screening for study enrollment
2. Pregnant or breastfeeding
3. Severe dementia or neurodegenerative disease, defined as either impairment that
prevents the patient from living independently at baseline or IQCODE >4.5, measured
using a patient's qualified surrogate. This exclusion also pertains to mental
illnesses requiring long-term institutionalization, acquired or congenital mental
retardation, severe neuromuscular disorders, Parkinson's disease, and Huntington's
disease. It also excludes patients in coma or with severe deficits due to structural
brain diseases such as stroke, intracranial hemorrhage, cranial trauma, malignancy,
anoxic brain injury, or cerebral edema.
4. History of 2nd or 3rd degree heart block, bradycardia < 50 beats/minute, pacemaker
for bradyarrythmias or uncompensated shock.
5. Benzodiazepine dependency or history of alcohol dependency based on prehospital
6. Active seizures.
7. Expected death within 24 hours of enrollment or lack of commitment to aggressive
treatment by family/medical team (e.g., likely to withdraw life support measures
within 24 hrs of screening)
8. Inability to understand English or deafness or vision loss that will preclude
9. Inability to obtain informed consent from an authorized representative within 48
hours of meeting all inclusion criteria, i.e., developing sepsis and qualifying organ
dysfunction criteria for the following reasons:
1. Attending physician refusal.
2. Patient and/or surrogate refusal.
3. Patient unable to consent and no surrogate available.
4. 48-hour period of eligibility was exceeded before the patient was screened.
11. Medical team following patient unwilling to use the sedation regimens.
12. Documented allergy to propofol or dexmedetomidine.
13. Current enrollment in a study that does not allow co-enrollment or that uses delirium
as a primary outcome.
14. Patients who are on muscle relaxant infusions at time of screening with plans to
maintain paralysis >24 hours.
18 Years and older
Accepts Healthy Volunteers
Study Locations and Contact Information (5)
|Baystate Medical Center - Springfield, Massachusetts||78.8 miles||Patrick T Mailloux MDfirstname.lastname@example.org|
|Henry Ford Health System - Detroit, Michigan||612.3 miles||None||None||None|
|Baton Rouge General Medical Center - Baton Rouge, Louisiana||1,382.7 miles||Hollis R ONeal Jr MDemail@example.com|
|University of Texas Health Science Center at San Antonio - San Antonio, Texas||1,768.2 miles||Antonio R Anzueto MD||210-617-5256||None|
|University of California San Francisco - San Francisco, California||2,699.8 miles||Michael A Gropper MD PhDfirstname.lastname@example.org|