Neurocognitive Outcomes Are Not Improved by 17β-Estradiol in Postmenopausal Women Undergoing Cardiac Surgery

Abstract

Background and Purpose-Neurocognitive dysfunction is an important source of patient morbidity and mortality after cardiac surgery that may disproportionately affect postmenopausal women. 17␤-Estradiol limits the extent of ischemic neuronal injury in a variety of experimental models. The purpose of this study was to evaluate whether perioperative administration of 17␤-estradiol to postmenopausal women reduces the frequency of neurocognitive dysfunction after cardiac surgery. Methods-One hundred seventy-four postmenopausal women not on estrogen replacement therapy who were undergoing primary coronary artery bypass graft surgery and/or valve surgery with cardiopulmonary bypass were prospectively randomized to receive in a double-blinded manner either 17␤-estradiol or placebo beginning the day before surgery and continuing for 5 days postoperatively. The patients were evaluated before and after surgery with the National Institutes of Health Stroke Scale and a psychometric test battery. Results-There were no differences in the frequency of neurocognitive dysfunction (primary outcome) between patients randomized to perioperative 17␤-estradiol (nϭ86) and those randomized to placebo (nϭ88) 4 to 6 weeks after surgery 22.4% versus placebo, 21.4%, Pϭ0.45). The mean scores on tests of psychomotor speed were worse in women in the 17␤-estradiol group than in the placebo group at the 4-to 6-week (Pϭ0.005) postoperative testing sessions. Conclusions-Perioperative treatment with 17␤-estradiol did not result in improved neurocognitive outcomes in postmenopausal women undergoing cardiac surgery.

Advances in Vascular Cognitive Impairment 2007

“…28 Perioperative treatment of women with 17 betaestradiol in a small clinical trial has not shown to improve cognitive outcomes, however, in postmenopausal cardiac surgery patients. 29 Treatment 788 patients with probable vascular dementia were randomized to receive galantamine or placebo and were evaluated on the primary efficacy measures of the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-cog11) and the Alzheimer's Disease Cooperative Studies-Activities of Daily Living Inventory (ADCS-ADL) total score. 30 After 26 weeks, there was improvement in cognition, including executive function, favoring the galantamine treatment group, good safety and tolerability, but no major difference in activities of daily living between treatment groups.…”

The Role of Postoperative Neurocognitive Dysfunction on Quality of Life for Postmenopausal Women 6 Months After Cardiac Surgery

“…The protocol of the study has been described in detail. 18,21 The patients were prospectively randomized to receive either identical 25 cm 2 transdermal patches containing 17 β -estradiol (Climara, Berlex Laboratories, Wayne, NJ) or placebo (blank patches) in a double-blind manner beginning the day before surgery until the fifth postoperative day. Supplemental IV 17 β -estradiol or placebo was given during cardiopulmonary bypass.…”

“…18,21 The patients received midazolam, opioids, and volatile anesthetics and underwent nonpulsatile cardiopulmonary bypass with a membrane oxygenator and a 40 μ m in-line arterial filter at a body temperature between 32°C and 34°C. Epiaortic ultrasound scanning of the ascending aorta was used in all patients and the images recorded for off-line assessment of atherosclerosis of the ascending aorta.…”

“…2–4 Based on extensive experimental findings that estrogens limit the extent of ischemic neuronal injury, we conducted a prospectively randomized, double-blind, placebocontrolled trial to evaluate whether the perioperative use of 17 β -estradiol would provide neuroprotection in postmenopausal women undergoing cardiac surgery. 17,18 The study was stopped by the independent data and safety monitoring board after the second interim data analysis. Our findings were that treatment perioperatively with 17 β -estradiol did not improve neurocognitive end-points 4 to 6 wk after surgery for elderly women compared with placebo (primary end-point).…”

Neurocognitive outcomes after extracorporeal membrane oxygenation

“…Neuroprotection has been attempted with 17 beta-estradiol [49], magnesium [50], lidocaine [51], piracetam [52], steroids [53], ischemic preconditioning [54], and off-pump cardiopulmonary bypass [55,56]. Unfortunately, none of these approaches has provided any tangible improvements in relevant clinical outcomes.…”