Perioperative Cognitive Function - Dexmedetomidine and Cognitive Reserve

NCT ID: NCT00561678

Last Updated: 2018-04-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 404 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-02-29
• Study Completion Date: 2014-05-31

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.

Conditions

Postoperative Delirium; PD; Postoperative Cognitive Dysfunction; POCD

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Precedex

Precedex (Dexmedetomidine)

Group Type: EXPERIMENTAL

Precedex (Dexmedetomidine)

Intervention Type: DRUG

0.5/ug/kg/hr Dexmedetomidine infusions will begin prior to the surgery (no loading dose), and will be maintained at 0.5 mcg/kg/hour throughout surgery and titrated postoperatively for 2 hours postoperatively.

Placebo

Placebo - normal saline

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

0.5/ug/kg/hr Placebo infusions will begin prior to the surgery (no loading dose), and will be maintained at 0.5 mcg/kg/hour throughout surgery and titrated postoperatively for 2 hours postoperatively.

Interventions

Precedex (Dexmedetomidine)

0.5/ug/kg/hr Dexmedetomidine infusions will begin prior to the surgery (no loading dose), and will be maintained at 0.5 mcg/kg/hour throughout surgery and titrated postoperatively for 2 hours postoperatively.

Intervention Type: DRUG

Placebo

0.5/ug/kg/hr Placebo infusions will begin prior to the surgery (no loading dose), and will be maintained at 0.5 mcg/kg/hour throughout surgery and titrated postoperatively for 2 hours postoperatively.

Intervention Type: DRUG

Other Intervention Names

Dexmedetomidine; Normal Saline

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

• Minimum Eligible Age: 68 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: lead

Responsible Party

Stacie Deiner

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jeff Silverstein, MD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

University of Miami Medical Center

Miami, Florida, United States

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, United States

University of Maryland

College Park, Maryland, United States

The Mayo Clinic

Rochester, Minnesota, United States

St. Louis University

St Louis, Missouri, United States

Englewood Hospital & Medical Center

Englewood, New Jersey, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

Ohio State University

Columbus, Ohio, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 28593326 (View on PubMed)

Other Identifiers

1R01AG029656-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

GCO 06-0217

Identifier Type: -

Identifier Source: org_study_id