Cognitive Effects of Inhalational Versus Intravenous General Anesthesia in the Elderly

Does Inhalational Anesthesia Accelerate Postoperative Cognitive Decline?

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.

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis; Hip Osteoarthritis; Cervical Spondylosis; Lumbar Spondylosis
• Intervention / Treatment: Drug: inhalation anesthesia with isoflurane vs. TIVA with propofol

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 Type: Interventional
• Enrollment (Actual): 200
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Durham, North Carolina, United States, 27710
      • VAMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Neurocognitive Performance (Z-score)	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.	3 months post operatively

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: US Department of Veterans Affairs
• Investigators: Principal Investigator: Terri G Monk, MD, Duke University

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: November 6, 2008
• First Submitted That Met QC Criteria: November 7, 2008
• First Posted (Estimate): November 10, 2008

Study Record Updates

• Last Update Posted (Estimate): March 26, 2015
• Last Update Submitted That Met QC Criteria: March 23, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: spinal, joint
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Spinal Diseases; Bone Diseases; Osteoarthritis; Osteoarthritis, Knee; Osteoarthritis, Hip; Spondylosis; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Hypnotics and Sedatives; Anesthetics, Inhalation; Propofol; Isoflurane
• Other Study ID Numbers: Pro00010070