This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Elderly patients undergoing total knee arthroplasty (TKA) surgery are at high risk of developing postoperative cognitive dysfunction (POCD) or memory impairment following surgery. Transcranial Doppler (TCD) monitoring of blood flow to the brain has detected cerebral emboli in 60% of patients following release of the thigh tourniquet during TKA surgery. These cerebral embolic events may represent one of the mechanisms responsible for postoperative cognitive decline. Research using transesophageal echocardiography (TEE) monitoring of blood flow into the heart during TKA has demonstrated that the amount of systemic and pulmonary embolic following tourniquet release is related to duration of the tourniquet inflation time. Current surgical practice uses a thigh tourniquet for the entire TKA procedure to decrease surgical bleeding. Minimal tourniquet techniques (in which the tourniquet is inflated only while the cement is drying) are used for patients at risk for developing postoperative deep vein thrombosis (DVT). This technique decreases the tourniquet time from an average of 2 hours to less than 20 minutes. The primary objective of this proposal is to determine if the tourniquet technique correlates with the number of cerebral emboli, postoperative MRI changes, and postoperative cognitive decline. Secondary objectives include the evaluation of other potential mechanisms for cognitive injury during TKA, including the relationship between biochemical markers of Alzheimer's disease, inflammatory mediators, and intra-operative cerebral oxygenation and postoperative cognitive decline.This prospective, randomized protocol will enroll 100 elderly patients undergoing TKA within Orthopedic Surgery and/or Anesthesiology Departments at the University of Florida Preoperative neuropsychological testing will establish baseline cognitive function. Magnetic resonance imaging (MRI) will be performed to identify cerebral abnormalities before and after surgery. At the start of surgery, patients will be randomized to either a minimal or standard tourniquet techniques. During surgery, patients will be monitored with TEE and TCD to quantify the number of cerebral and pulmonary emboli that occur. Automated measurements of physiologic deadspace volumes will be made to determine if pulmonary emboli change as a result of tourniquet type. Neuropsychological testing will be repeated at two weeks, three months, and one year after surgery to determine if cognitive decline has occurred. During the hospitalization, whole blood will be drawn to identify subject markers for Alzheimer's disease, namely the apolipoprotein E genotype and elevations in isoprostane 8 and homocysteine levels. Blood will also be drawn in the perioperative period to determine the relationship between the biochemical markers of the inflammatory response, intraoperative events and postoperative cognitive decline.
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