The ultimate objective of this work is to understand the major determinants of postoperative outcomes and to develop therapeutic modalities and practice parameters that maximize the rate, magnitude and quality of postoperative functional recovery in elderly surgical patients. The immediate objective is to evaluate the impact of anesthetic-coupled intra-operative beta-blockade on long term functional recovery in elders undergoing elective major abdominal surgery. The proposed research is a five-year randomized partial open-label trial of approximately 1100 patients 65 years of age or older having elective major abdominal surgery. Eligible patients will be divided into two groups: those currently receiving chronic beta-blockade or possessing risk factors for myocardial ischemia will be assigned to receive beta-blockers before and after surgery, those without risk factors will not. Within each group, eligible patients will be randomized to receive either a control anesthetic or anesthetic-coupled intra-operative beta-blockade. Patients will be evaluated preoperatively and postoperatively using a broad battery of functional and performance measures. Postoperative evaluations will take place over three stages: Stage 1 - end of surgery to discharge from the Post-Anesthesia Care Unit; Stage 2 - end of PACU stay through postoperative day three; and Stage 3 - postoperatively at one, three, and six weeks and three and six months. The impact of the intra-operative intervention will be assessed by pursuing the following specific aims: 1) comparison of the time course and extent of long-term (stage 3) functional recovery in elderly surgical patients receiving either a control or an anesthetic-coupled beta-blockade regimen; 2) comparison of the course of early (stage 1 and 2) recovery with particular reference to postoperative pain and analgesic medications in elderly surgical patients receiving either a control or an anesthetic-coupled beta-blockade regimen, and; 3) evaluation of the correlation between cardiac troponin release and cardiovascular outcome for six months following operation in elderly surgical patients receiving either a control or an anesthetic-coupled beta-blockade regimen. Primary outcomes measures will include: 1) Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) (Stage 3 recovery); 2) time to discharge from the Post Anesthesia Care Unit; 3) analgesic requirements self-reported pain by visual analogue scale; 4) incidence of delirium (confusion Assessment Method) (Stage 2 recovery); and 5) troponin I levels (Stage 1 and 2 recovery). The proposed trial leverages recent new data on the natural history of postoperative functional recovery in elders after abdominal surgery with pilot data suggesting that beta-blockade have beneficial effects on functional recovery to support the conduct of a randomized trial of an anesthetic intervention designed to improve short and long-term functional recovery in elders.
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