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.

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).

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

Only unexpected adverse events that were related to the study were collected.