Perioperative Cognitive Function - Dexmedetomidine and Cognitive Reserve

Postoperative Delirium Clinical Trial

Official title:

Perioperative Cognitive Function - Dexmedetomidine and Cognitive Reserve

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00561678
• Other study ID #: GCO 06-0217
• Secondary ID: 1R01AG029656-01A
• Status: Completed
• Phase: Phase 4
• First received: November 19, 2007
• Last updated: March 22, 2018
• Start date: February 2008
• Est. completion date: May 2014

Study information

• Verified date: March 2018
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 404
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 68 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Delirium
• PD
• POCD
• Postoperative Cognitive Dysfunction
• Postoperative Delirium

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
United States	Johns Hopkins Bayview Medical Center	Baltimore	Maryland
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Cleveland Clinic	Cleveland	Ohio
United States	University of Maryland	College Park	Maryland
United States	Ohio State University	Columbus	Ohio
United States	Englewood Hospital & Medical Center	Englewood	New Jersey
United States	University of Miami Medical Center	Miami	Florida
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	The Mayo Clinic	Rochester	Minnesota
United States	St. Louis University	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 Postoper — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Delirium Battery	Number of Participants with occurrence of Post-Operative Delirium in Post-Anesthesia Care Unit (PACU)	Day 1
Secondary	Neuropsychological Testing	Rate of change of cognitive function - data not collected because secondary analysis which was not performed	at 3 months postoperatively
Secondary	Intraoperative Bradycardia	Number of participants with intraoperative bradycardia	day 1
Secondary	Intraoperative Hypotension	Number of participants with intraoperative hypotension	day 1
Secondary	Intraoperative Hypertension	Number of participants with intraoperative hypertension	day 1
Secondary	Length of Stay	Length of Stay (LOS) in the hospital	average 4 days