Clinical trial NCT00561678: Perioperative Cognitive Function - Dexmedetomidine and Cognitive Reserve
Official title: Perioperative Cognitive Function - Dexmedetomidine and Cognitive Reserve
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Postoperative Delirium
PD
Postoperative Cognitive Dysfunction
POCD
Keywords: Postoperative Confusion
Postoperative Delirium
PD
Postoperative Cognitive Dysfunction
POCD
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2007-11-21
Enrollment: 404
Sex: ALL
Minimum age (years): 68
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Elderly patients who undergo anesthesia and non-cardiac surgery are subject to deterioration of brain function including the development of postoperative delirium (PD) and postoperative cognitive dysfunction (POCD). These disorders cause disability, distress for both patients and their families, are associated with other medical complications and account for significant additional health care costs. We currently use relatively primitive approaches to preventing and treating PD and POCD.

Dexmedetomidine is a drug used for sedation in critically ill patients that provides some pain relief and controls the bodies response to stress. The sedation produced by dexmedetomidine appears more similar to natural sleep than any other drug used for anesthesia and postoperative sedation. Data suggesting that dexmedetomidine can prevent delirium following cardiac surgery and the developing understanding of the causes of PD and POCD suggest that dexmedetomidine will be particularly effective.

Detailed description: Postoperative Delirium or PD and Postoperative Cognitive Dysfunction or POCD are syndromes of central nervous system dysfunction that significantly complicate the recovery of a proportion of elderly patients following surgery.

Delirium is typically a transient syndrome characterized by a de-novo appearance of several pathognomonic behaviors, including disorientation, decreased attention span, sensory misperceptions, a waxing-and-waning type of confusion, and disorganized thinking. PD typically occurs on postoperative days 1 to 3 and is associated with prolonged hospital stays, increased risks for morbidity and mortality and significant health care expenditures.

The neuroendocrine stress response to surgery, including the immediate postoperative period, remains an important potential etiologic factor. In particular, our data suggests that stress in the immediate postoperative period is poorly controlled by all anesthetic techniques and the normal diurnal variation in cortisol is suppressed in subjects who develop POCD.

Dexmedetomidine is a highly selective alpha 2A agonist currently approved for sedation in the ICU. Dexmedetomidine produces analgesia, sympatholysis, and a light sedation characterized by easy arousal. Its action converges on the endogenous substrates for natural sleep to produce their sedative action, an effect that could prove beneficial to elderly postoperative patients.

We hypothesize that treatment with dexmedetomidine will diminish both PD and POCD. The essential proposition is that modulation of perioperative stress can ameliorate perioperative delirium and cognitive dysfunction.

Based on both the concept of cognitive reserve as well as clinical experience, there is concern that patients with preoperative cognitive impairment are particularly vulnerable to POCD. In general, such patients have been excluded from previous studies. This study is unique in that we will assess all participants for mild cognitive impairment prior to surgery. Assessment of the impact of preexisting cognitive impairment is a secondary aim. A broad goal of this interdisciplinary project is to evaluate POCD, which is primarily an anesthesia concept, in the more general context of dementing illness as explored by geriatric psychiatry.

Eligibility criteria: Inclusion Criteria:

* 68 and older
* elective major surgery under general anesthesia(major surgery is defined by a planned 2 day hospitalization)
* ASA physical status I-III
* capable and willing to consent
* MMSE \> 20 (to exclude dementia)

Exclusion Criteria:

* Cardiac surgery
* Intracranial Surgery
* Emergency Surgery
* Patients with severe visual or auditory disorder/handicaps
* Illiteracy
* Patients with clinically significant Parkinson's Disease
* Patients not expected to be able to complete the 3 and 6 month postoperative tests
* Sick sinus syndrome without pacemaker
* Hypersensitivity to drug or class
* Current 2nd or 3rd degree AV block
* History of clinically significant bradycardia
* Contraindication to the use of an 2A-agonist
* Presence of a major psychiatric condition such as bipolar disorder, major depression, schizophrenia, or dementia
* ASA physical status IV or V

Primary outcomes:
measure: Delirium Battery
timeFrame: Day 1
Secondary outcomes:
measure: Neuropsychological Testing
timeFrame: at 3 months postoperatively
measure: Intraoperative Bradycardia
timeFrame: day 1
measure: Intraoperative Hypotension
timeFrame: day 1
measure: Intraoperative Hypertension
timeFrame: day 1
measure: Length of Stay
timeFrame: average 4 days
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami Medical Center
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Medical Center
state: Maryland
city: College Park
country: United States
facility: University of Maryland
state: Maryland
city: Rochester
country: United States
facility: The Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: St. Louis University
state: Missouri
city: Englewood
country: United States
facility: Englewood Hospital & Medical Center
state: New Jersey
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Jeff Silverstein, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Deiner S, Luo X, Lin HM, Sessler DI, Saager L, Sieber FE, Lee HB, Sano M; and the Dexlirium Writing Group; Jankowski C, Bergese SD, Candiotti K, Flaherty JH, Arora H, Shander A, Rock P. Intraoperative Infusion of Dexmedetomidine for Prevention of Postoperative Delirium and Cognitive Dysfunction in Elderly Patients Undergoing Major Elective Noncardiac Surgery: A Randomized Clinical Trial. JAMA Surg. 2017 Aug 16;152(8):e171505. doi: 10.1001/jamasurg.2017.1505. Epub 2017 Aug 16.