Perioperative Cognitive Function - Dexmedetomidine and Cognitive Reserve

Phase 4

Completed

• Conditions: PD; POCD; Postoperative Cognitive Dysfunction; Postoperative Delirium
• Interventions: Drug: Precedex (Dexmedetomidine); Drug: Placebo

• Registration Number: NCT00561678
• Lead Sponsor: Icahn School of Medicine at Mount Sinai

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.

Study Timeline

• Study First Submitted: 2007-11-19
• Study First Submitted QC: 2007-11-20
• Study First Posted: 2007-11-21
• Study Start: 2008-02
• Primary Completion: 2014-05
• Study Completion: 2014-05
• Results First Submitted: 2017-02-10
• Results First Submitted QC: 2017-02-10
• Results First Posted: 2017-03-29
• Status Verified: 2018-03
• Last Update Submitted: 2018-03-22
• Last Update Posted: 2018-04-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 404

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)

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Precedex	Precedex (Dexmedetomidine)	Precedex (Dexmedetomidine)
Placebo	Placebo	Placebo - normal saline

Primary Outcome Measures

Name	Time	Method
Delirium Battery	Day 1	Number of Participants with occurrence of Post-Operative Delirium in Post-Anesthesia Care Unit (PACU)

Secondary Outcome Measures

Name	Time	Method
Length of Stay	average 4 days	Length of Stay (LOS) in the hospital
Neuropsychological Testing	at 3 months postoperatively	Rate of change of cognitive function - data not collected because secondary analysis which was not performed
Intraoperative Hypertension	day 1	Number of participants with intraoperative hypertension
Intraoperative Bradycardia	day 1	Number of participants with intraoperative bradycardia
Intraoperative Hypotension	day 1	Number of participants with intraoperative hypotension

Trial Locations

Locations (10)

Johns Hopkins Bayview Medical Center; 🇺🇸 Baltimore, Maryland, United States

University of Miami Medical Center; 🇺🇸 Miami, Florida, United States

University of Maryland; 🇺🇸 College Park, Maryland, United States

St. Louis University; 🇺🇸 Saint Louis, Missouri, United States

The Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Englewood Hospital & Medical Center; 🇺🇸 Englewood, New Jersey, United States

Icahn School of Medicine at Mount Sinai; 🇺🇸 New York, New York, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Ohio State University; 🇺🇸 Columbus, Ohio, United States

University of North Carolina at Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States