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Perioperative Cognitive Function - Dexmedetomidine and Cognitive Reserve

Perioperative Cognitive Function - Dexmedetomidine and Cognitive Reserve

Status
Completed
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00561678
Enrollment
404
Registered
2007-11-21
Start date
2008-02-29
Completion date
2014-05-31
Last updated
2018-04-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

PD, POCD, Postoperative Cognitive Dysfunction, Postoperative Delirium

Keywords

Postoperative Confusion, Postoperative Delirium, PD, Postoperative Cognitive Dysfunction, POCD

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.

Interventions

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.

DRUGPlacebo

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.

Sponsors

National Institute on Aging (NIA)
CollaboratorNIH
Icahn School of Medicine at Mount Sinai
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender
ALL
Age
68 Years to No maximum
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
Delirium BatteryDay 1Number of Participants with occurrence of Post-Operative Delirium in Post-Anesthesia Care Unit (PACU)

Secondary

MeasureTime frameDescription
Neuropsychological Testingat 3 months postoperativelyRate of change of cognitive function - data not collected because secondary analysis which was not performed
Intraoperative Bradycardiaday 1Number of participants with intraoperative bradycardia
Intraoperative Hypotensionday 1Number of participants with intraoperative hypotension
Intraoperative Hypertensionday 1Number of participants with intraoperative hypertension
Length of Stayaverage 4 daysLength of Stay (LOS) in the hospital

Countries

United States

Participant flow

Recruitment details

Trial was conducted at 10 sites from February 2008 to May 2014. The lead site was The Mount Sinai Hospital in New York City.

Participants by arm

ArmCount
Precedex
Precedex (Dexmedetomidine) 0.5/ug/kg/hr
189
Placebo
Placebo - normal saline 0.5/ug/kg/hr
201
Total390

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall Studyanesthesia provider refusal10
Overall Studysurgery cancelled11
Overall Studysurgery rescheduled to different site22
Overall StudyWithdrawal by Subject43

Baseline characteristics

CharacteristicPrecedexPlaceboTotal
Age, Continuous74.0 years74.0 years74.0 years
Anesthesia Time252.0 minutes254.0 minutes253.0 minutes
ASA Status
1 or 2
73 Participants63 Participants136 Participants
ASA Status
3
108 Participants133 Participants241 Participants
ASA Status
4
8 Participants5 Participants13 Participants
Body Mass Index (BMI)28.1 kg/m^227.7 kg/m^228.0 kg/m^2
Cancer (CA)81 Participants77 Participants158 Participants
Congestive Heart Failure (CHF)0 Participants1 Participants1 Participants
Coronary Artery Disease (CAD)14 Participants18 Participants32 Participants
Diabetes (DM)39 Participants40 Participants79 Participants
Dosage of Fentanyl used prior to this study250.0 µg/h250.0 µg/h250.0 µg/h
Education16.0 years15.0 years16.0 years
Hypertension (HTN)124 Participants116 Participants240 Participants
Mild Cognitive Impairment (MCI)124 Participants122 Participants246 Participants
Propofol170.0 mg/kg160.0 mg/kg165.0 mg/kg
Sex: Female, Male
Female
97 Participants103 Participants200 Participants
Sex: Female, Male
Male
92 Participants98 Participants190 Participants
Surgical Procedure
General
40 Participants53 Participants93 Participants
Surgical Procedure
Orthopedic
54 Participants36 Participants90 Participants
Surgical Procedure
Spine
70 Participants77 Participants147 Participants
Surgical Procedure
Thoracic
5 Participants6 Participants11 Participants
Surgical Procedure
Urologic
20 Participants29 Participants49 Participants
Surgical Time174.0 minutes180.0 minutes177.0 minutes

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
1 / 1893 / 201
other
Total, other adverse events
0 / 1890 / 201
serious
Total, serious adverse events
12 / 1899 / 201

Outcome results

Primary

Delirium Battery

Number of Participants with occurrence of Post-Operative Delirium in Post-Anesthesia Care Unit (PACU)

Time frame: Day 1

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
PrecedexDelirium BatteryPostoperative Delirium23 Participants
PrecedexDelirium BatteryPACU Delirium6 Participants
PrecedexDelirium BatteryBoth5 Participants
PrecedexDelirium BatteryNone155 Participants
PlaceboDelirium BatteryNone166 Participants
PlaceboDelirium BatteryPostoperative Delirium23 Participants
PlaceboDelirium BatteryBoth4 Participants
PlaceboDelirium BatteryPACU Delirium8 Participants
Secondary

Intraoperative Bradycardia

Number of participants with intraoperative bradycardia

Time frame: day 1

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
PrecedexIntraoperative BradycardiaRequiring treatment35 Participants
PrecedexIntraoperative BradycardiaRequiring interruption of the drug2 Participants
PrecedexIntraoperative BradycardiaResolved spontaneously45 Participants
PrecedexIntraoperative BradycardiaDid not occur107 Participants
PlaceboIntraoperative BradycardiaDid not occur137 Participants
PlaceboIntraoperative BradycardiaRequiring treatment20 Participants
PlaceboIntraoperative BradycardiaResolved spontaneously42 Participants
PlaceboIntraoperative BradycardiaRequiring interruption of the drug2 Participants
Secondary

Intraoperative Hypertension

Number of participants with intraoperative hypertension

Time frame: day 1

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
PrecedexIntraoperative HypertensionRequiring treatment26 Participants
PrecedexIntraoperative HypertensionRequiring interruption of the drug0 Participants
PrecedexIntraoperative HypertensionResolved spontaneoulsy17 Participants
PrecedexIntraoperative HypertensionDid not occur146 Participants
PlaceboIntraoperative HypertensionDid not occur134 Participants
PlaceboIntraoperative HypertensionRequiring treatment36 Participants
PlaceboIntraoperative HypertensionResolved spontaneoulsy30 Participants
PlaceboIntraoperative HypertensionRequiring interruption of the drug1 Participants
Secondary

Intraoperative Hypotension

Number of participants with intraoperative hypotension

Time frame: day 1

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
PrecedexIntraoperative HypotensionRequiring Treatment81 Participants
PrecedexIntraoperative HypotensionRequiring interruption of the drug3 Participants
PrecedexIntraoperative HypotensionResolved Spontaneously18 Participants
PrecedexIntraoperative HypotensionDid not occur87 Participants
PlaceboIntraoperative HypotensionDid not occur106 Participants
PlaceboIntraoperative HypotensionRequiring Treatment69 Participants
PlaceboIntraoperative HypotensionResolved Spontaneously21 Participants
PlaceboIntraoperative HypotensionRequiring interruption of the drug5 Participants
Secondary

Length of Stay

Length of Stay (LOS) in the hospital

Time frame: average 4 days

ArmMeasureValue (MEDIAN)
PrecedexLength of Stay4.0 days
PlaceboLength of Stay4.0 days
Secondary

Neuropsychological Testing

Rate of change of cognitive function - data not collected because secondary analysis which was not performed

Time frame: at 3 months postoperatively

Source: ClinicalTrials.gov · Data processed: Feb 26, 2026