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The American Society of Anesthesiologists is an educational, research and scientific association of physicians organized to raise and maintain the standards of the medical practice of anesthesiology and improve the care of the patient.


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N. Martin Giesecke, M.D., Chair



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June 1, 2013 Volume 77, Number 6
Subspecialty News: Anesthesia Care for Specific Aging-Associated Diseases: Have We Figured It Out? Zhongcong Xie, M.D., Ph.D. President, Society for the Advancement of Geriatric Anesthesia ASA Committee on Geriatric Anesthesia

On a hot summer night in Boston in 1999, I was a CA-2 resident on call in Massachusetts General Hospital. Around midnight, a case was booked in for an exploratory laparotomy. The patient was a 78-year-old female with coronary artery disease (CAD) and Alzheimer’s disease (AD). I was well trained in caring for a patient with CAD, e.g., avoiding the reduction in blood pressure and the increase in heart rate. However, I did not know how to provide good anesthesia care, even in principle, for a patient with AD.

I called my attending anesthesiologist to ask what I could do for this patient. In particular, I asked what drugs I should or should not use to avoid worsening the cognitive dysfunction symptoms in this AD patient. Hesitating on the other end of the phone, my attending, who was in the call room, finally told me: “Figure it out.”

Unfortunately, even 14 years later, we have not yet figured out the best way to provide anesthesia care for AD patients. As we all know, AD is one of the greatest public health problems in the U.S. and the world, and its impact will only increase with demographic changes anticipated in the coming decades. Each year, approximately 8.5 million AD patients need surgery under anesthesia around the world. Anesthesia and surgery can induce postoperative cognitive dysfunction (POCD), which AD and senior patients are susceptible to developing. In addition, a much greater number of senior patients will need surgery under anesthesia each year. These patients, who are vulnerable to AD, also (or even more so) should avoid any anesthetics that may worsen AD pathogenesis and/or impair cognitive function. Thus, it is important to avoid any anesthetics that could worsen AD pathophysiology (e.g., Abeta accumulation, Tau phosphorylation) and cognitive dysfunction in AD patients and senior patients when surgeries become necessary. Identifying such anesthetics and understanding the underlying mechanisms are urgently needed, which would ultimately optimize anesthesia care for AD and senior patients. This opinion has been emphasized in both AD and anesthesia research.1

Many studies have been performed to determine the effects of anesthetics on AD pathophysiology and cognitive function in cultured cells inside test tubes and rodents [reviewed in Vlisides and Xie2]. The efforts have identified some anesthetics that may promote AD pathophysiology and have suggested the potential underlying mechanisms.

It is also promising to see that several human studies have demonstrated the clinical relevance of these test tube and animal studies, and suggested that certain anesthetics may cause biochemical changes consistent with AD pathophysiology. Among them, Tang et al. from the University of Pennsylvania found that the idiopathic nasal cerebrospinal fluid (CSF) leak correction under anesthesia with propofol, remifentanil, or sevoflurane increased the human CSF levels of Tau and pro-inflammatory cytokines.3 Zhang et al. from Capital Medical University in Beijing, China suggested that isoflurane and desflurane may have different effects on human CSF Abeta levels4 and cognitive function.5 Tau, cytokines and Abeta are the proteins associated with AD pathophysiology. These studies are pioneer but still preliminary.

However, other studies have suggested that anesthesia and surgery may not be associated with cognitive dysfunction [reviewed by Avidan and Evers6]. Many more clinical studies are needed to rule in or rule out the role of anesthesia in AD pathophysiology and POCD, moreover, to determine whether some anesthetics are better than others in terms of providing safer anesthesia care for AD and senior patients.

Clinically, it has been recommended that a close family member or guardian of an AD patient accompany the patient to provide accurate medical and surgical history. The family member or guardian should remain with the AD patient the evening prior to surgery to ensure compliance with preoperative instructions, such as the “nothing by mouth” order. AD patients can easily become agitated; therefore anesthesiologists should be very patient in dealing with them. Preoperative sedative drugs may increase mental confusion, and thus should be given cautiously. AD patients may fall from the bed or operation table when being brought to the O.R. AD patients with middle- or later-stage dementia are not good candidates for regional anesthesia because they may not cooperate. In addition, the medicine to treat AD (e.g., donepezil, galantamine) may have interactions with anesthetics. Finally, AD patients may have a delayed recovery from anesthesia and surgery, which could require prolonged observation in the recovery room.7,8

Hopefully, all of these efforts will ultimately lead to an establishment of a guideline regarding how better to provide anesthesia care for AD patients. So, next time when residents ask, “what is the anesthesia plan for AD patients?”, the attending can say: “we have figured it out.”

AD is not the only aging-associated disease that needs guidelines for anesthesia care. Parkinson’s disease and Huntington’s disease are others, just to name a couple. The question is how can we create these guidelines?

It is obvious that the National Institute of Health, ASA, International Anesthesia Research Society, Association of University of Anesthesiologists, and other organizations, including the Society for the Advancement of Geriatric Anesthesia (SAGA), should HAVE joint efforts to perform basic science research, clinical investigation and education to ultimately lead to the establishment of guidelines and provisions for better anesthesia care for patients with specific aging-associated diseases.

SAGA ( is an organization dedicated to improving the anesthesia care for senior patients who need surgery. The members of SAGA include clinical anesthesiologists who are experts in providing anesthesia care for senior patients, basic science researchers who are interested in studying the effects of anesthetics in the aging brain, and teachers who can educate anesthesiologists and other clinical specialists about anesthesia care for older adults.

One of the missions of SAGA is to coordinate basic research scientists and clinical investigators to study neurotoxicity of anesthetics and other perioperative factors. The goal of such a mission is to identify any perioperative risk factors, including anesthetics, which may contribute to AD neuropathogenesis and worsen POCD.

At last year’s ASA annual meeting in Washington, D.C., SAGA organized an “International Night of Postoperative Cognitive Dysfunction (POCD).” The speakers for this event were internationally known experts of POCD and AD research. They were Alex Bekker, M.D., Ph.D. (Rutgers University), Deborah Culley, M.D. (Harvard University), Stacie Deiner, M.D. (Mount Sinai School of Medicine), Maryellen Eckenhoff, Ph.D. (University of Pennsylvania), Roderic Eckenhoff, M.D. (University of Pennsylvania, co-chair), Lars Eriksson, M.D., Ph.D., F.R.C.A. (Karolinska Institute, Sweden), Gregory Crosby, M.D. (Harvard University), Daqing Ma, M.D., Ph.D. (Imperial College London, United Kingdom), Mervyn Maze, M.B.,Ch.B. (University of California at San Francisco), Terri Monk, M.D. (Duke University), Wen Ouyang, M.D. (Xiangya Medical College, Zhongnan University, China), Lars Rasmussen, M.D. (Copenhagen University Hospital, Denmark), Frederick E. Sieber, M.D. (Johns Hopkins University), Jeffrey Silverstein, M.D. (Mount Sinai School of Medicine), Niccolo Terrando, Ph.D. (Karolinska Institute, Sweden), and Zhongcong Xie, M.D., Ph.D. (Harvard University, co-chair). The speakers at the SAGA meeting presented the progress and current state of research in anesthesia and surgery in AD pathophysiology, POCD and offered their insight about the mechanisms underlying POCD.

The speakers and other SAGA members also discussed the establishment of the “International Association of POCD” and have formed a committee for this purpose (Roderic Eckenhoff, Daqing Ma, Jeffrey Silverstein and Zhongcong Xie). Many SAGA members attended the meeting, including Frederick E. Sieber, M.D. (immediate past president, Johns Hopkins University) Michael Lewis, M.D. (president-elect, University of Miami), Shamsuddin Akhtar, M.D. (secretary, Yale University), Alec Rooke, M.D. (treasurer, University of Washington), Sheila Barnett, M.B.,B.S., B.Sc. (board member, Harvard University), Gwendolyn Boyd, M.D. (board member, University of Alabama), Martin H. Dauber, M.D. (board member, University of Chicago), John Mitchell, M.D. (board member, Harvard University) and Mary Ann Vann, M.D. (board member, Harvard University).

SAGA will continue to dedicate itself to anesthesia research and clinical care for older adults. As the president of SAGA, I sincerely welcome you to join us.

Zhongcong Xie, M.D., Ph.D. is Associate Professor of Anesthesia, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston.

1. Baranov D, Bickler PE, Crosby GJ, et al. Consensus statement: First International Workshop on Anesthetics and Alzheimer’s Disease. Anesth Analg. 2009;108(5):1627-1630.
2. Vlisides P, Xie Z. Neurotoxicity of general anesthetics: an update. Curr Pharm Des. 2012;18(38):6232-6240.
3. Tang JX, Baranov D, Hammond M, Shaw LM, Eckenhoff MF, Eckenhoff RG. Human Alzheimer and inflammation biomarkers after anesthesia and surgery. Anesthesiology. 2011;115(4):727-732.
4. Zhang B, Tian M, Zheng H, Zhen Y, Yue Y, Li T, Li S, Marcantonio ER, Xie Z. Effects of anesthetic isoflurane and desflurane on human cerebrospinal fluid Aβ and tau level [published online ahead of print February 22, 2013]. Anesthesiology. doi: 10.1097/ALN.0b013e31828ce55d.

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