Cognitive Effects of Inhalational Versus Intravenous General Anesthesia in the Elderly

• Sponsor: Duke University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00788008
• Collaborator: US Department of Veterans Affairs (U.S. Fed)
• Enrollment: 200
• Locations: 2
• Arms: 2
• Duration (Months): 61
• Patients Per Site: 100
• Patients Per Site Per Month: 1.6

Study Details

Study Description

Brief Summary

The purpose of this research is to determine if post-operative cognition will be better if the general anesthesia for surgery is done with an inhaled (gas through a breathing tube) or intravenous (medicine injected in the IV) general anesthetic technique.

Condition or Disease	Intervention/Treatment	Phase
Lumbar Spondylosis; Cervical Spondylosis; Hip Osteoarthritis; Knee Osteoarthritis	Drug: inhalation anesthesia with isoflurane vs. TIVA with propofol	N/A

Detailed Description

A prospective randomized pre-test post-test design will be used. After obtaining informed consent, patients will be randomized to either: 1) Inhalational anesthesia with isoflurane or 2) Total intravenous anesthesia(TIVA) with propofol. Randomization will be stratified by surgical type so that this variable is equally distributed between the treatment groups. All patients will be maintained at a standard depth of anesthesia (40-60) using a Bispectral Index (BIS®) monitor. Normocarbia will be maintained in the operating room using capnography monitoring. Normothermia will be maintained throughout the procedure.

The anesthesia team providing care for these patients will be able to choose the premedication and muscle relaxant for the anesthetic technique. Patient controlled anesthesia or regional anesthetic techniques may be used for post-operative analgesia at the discretion of the anesthesia team providing care for these patients. Anesthesia will be induced with intravenous propofol and fentanyl in all patients, unless contraindicated. Patients will be mechanically ventilated with air/oxygen. Temperature will be maintained > 35º C and ventilation will be adjusted to maintain end-tidal carbon dioxide (CO2) at 35 ± 5 mmHg. Mean arterial pressure will be maintained ≥ 75% of baseline or ≥ 60 mmHg, whichever is greater, in both groups. After induction of anesthesia, the maintenance anesthesia will consist of either:

1. Inhalational anesthesia group - isoflurane will be used for maintenance of anesthesia. Intravenous fentanyl and/or remifentanil will be used for supplementary analgesia. These agents will be administered to maintain a normal depth of anesthesia using the BIS® monitor and traditional signs of anesthetic depth.

2. TIVA group - propofol and opioid infusions (fentanyl or remifentanil) will be used for the maintenance of anesthesia. The infusions will be adjusted to maintain a normal depth of anesthesia using the BIS® monitor along with traditional signs of anesthetic depth.

All subjects will undergo pre-operative neurocognitive testing within two weeks of their surgery, and at 3 months post-surgery. The persistence versus resolution of cognitive deficits over time will be determined with a 1 year post-surgical follow-up assessment. Pre- to post-test change scores will be compared across groups on primary and secondary outcome variables (see below) while controlling for relevant demographic variables (age, education, sex).

Study Design

• Study Type: Interventional
• Actual Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Does Inhalational Anesthesia Accelerate Postoperative Cognitive Decline?
• Study Start Date: Nov 1, 2008
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 Inhalational anesthesia with isoflurane	Drug: inhalation anesthesia with isoflurane vs. TIVA with propofol; variable depending upon patient; Other Names: Diprivan
Active Comparator: 2 total intravenous anesthesia with propofol	Drug: inhalation anesthesia with isoflurane vs. TIVA with propofol; variable depending upon patient; Other Names: Diprivan

Outcome Measures

Primary Outcome Measures

1. Change in Neurocognitive Performance (Z-score) [3 months post operatively]

   Mean change on composite scores (z-score) for memory and executive function measures. Memory measures: Hopkins Verbal Learning Test-Revised and the Brief Visuospatial Memory Test-Revised. Executive function measures: the Trail Making Test (Army, 1944), Digit-symbol substitution and Symbol Search subtests of the Processing Speed Index of the Wechsler Adult Intelligence Scale-III (WAIS-III; Wechsler, 1997) and the Controlled Oral Word Association subtest of the Multilingual Aphasia Examination. The outcomes were constructed as summed z-score composites. They are scaled as standard deviations. Thus, a score of 0 was central on each composite, and 95% of the scores would fall within -2.0 and +2.0. While there is no minimum or maximum value is rare for any score (<1%) to fall outside the -3.0 to +3.0 range. Higher scores (and thus positive change value) indicate an improvement of function.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• patients (aged 65 years or older) scheduled for elective spine or major joint replacement (total hip or total knee arthroplasty) at Duke University Medical Center or the Durham VA Medical Center

Exclusion Criteria:

• not fluent in English and able to comprehend the English language

• have severe visual or auditory handicaps

• Carry a diagnosis of dementia or score < 18 on the Mini-Mental State Examination (MMSE) as calculated from the Modified Mini-Mental State (3MS) (see D4 below)

• have allergies to eggs, propofol, isoflurane, fentanyl, remifentanil, or pregabalin

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duke University Medical Center	Durham	North Carolina	United States	27710
2	VAMC	Durham	North Carolina	United States	27710

Sponsors and Collaborators

• Duke University
• US Department of Veterans Affairs

Investigators

• Principal Investigator: Terri G Monk, MD, Duke University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT00788008
• Other Study ID Numbers: Pro00010070
• First Posted: Nov 10, 2008
• Last Update Posted: Mar 26, 2015
• Last Verified: Mar 1, 2015

• Keywords provided by Duke University: spinal, joint
• Additional relevant MeSH terms: Osteoarthritis; Osteoarthritis, Knee; Osteoarthritis, Hip; Spondylosis; Propofol; Isoflurane

Study Results

Participant Flow

Pre-assignment Detail	200 patients were consented. One person dropped out prior to baseline testing.

Arm/Group Title	Isoflurane	Propofol
Arm/Group Description	Inhalational anesthesia with isoflurane	Total intravenous anesthesia with propofol
Period Title: Overall Study
STARTED	98	101
COMPLETED	98	101
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Isoflurane	Propofol	Total
Arm/Group Description	Inhalational anesthesia with isoflurane	Total intravenous anesthesia with propofol	Total of all reporting groups
Overall Participants	98	101	199
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	73.38	73.13	73.25
Sex: Female, Male (Count of Participants)
Female	32 32.7%	39 38.6%	71 35.7%
Male	66 67.3%	62 61.4%	128 64.3%
Region of Enrollment (participants) [Number]
United States	98 100%	101 100%	199 100%

Outcome Measures

1. Primary Outcome

Title	Change in Neurocognitive Performance (Z-score)
Description	Mean change on composite scores (z-score) for memory and executive function measures. Memory measures: Hopkins Verbal Learning Test-Revised and the Brief Visuospatial Memory Test-Revised. Executive function measures: the Trail Making Test (Army, 1944), Digit-symbol substitution and Symbol Search subtests of the Processing Speed Index of the Wechsler Adult Intelligence Scale-III (WAIS-III; Wechsler, 1997) and the Controlled Oral Word Association subtest of the Multilingual Aphasia Examination. The outcomes were constructed as summed z-score composites. They are scaled as standard deviations. Thus, a score of 0 was central on each composite, and 95% of the scores would fall within -2.0 and +2.0. While there is no minimum or maximum value is rare for any score (<1%) to fall outside the -3.0 to +3.0 range. Higher scores (and thus positive change value) indicate an improvement of function.
Time Frame	3 months post operatively

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Isoflurane	Propofol
Arm/Group Description	Inhalational anesthesia with isoflurane	Total intravenous anesthesia with propofol
Measure Participants	98	101
Memory measures	.09	-.20
Executive Function measures	-.42	.01

Adverse Events

Adverse Event Reporting Description	Only unexpected adverse events that were related to the study were collected.
Arm/Group Title	Isoflurane		Propofol
Arm/Group Description	Inhalational anesthesia with isoflurane		Total intravenous anesthesia with propofol
All Cause Mortality
	Isoflurane		Propofol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Isoflurane		Propofol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/98 (0%)		0/101 (0%)
Other (Not Including Serious) Adverse Events
	Isoflurane		Propofol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/98 (0%)		0/101 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.