膽鹼酯酶抑制劑不會惡化失智病患的術後併發症
作者：Pam Harrison
出處：WebMD醫學新聞
March 9, 2010 — 對於進行髖骨骨折手術而接受全身麻醉的年長失智患者，使用膽鹼酯酶抑制劑不會惡化術後併發症之風險，因此認為，目前在手術前停用該類藥物的標準實務並沒有必要。
加拿大安大略多倫多Baycrest中心的Dallas Seitz醫師發現，不論是一般社區住民或長照病患，進行緊急髖骨骨折手術時，全身麻醉使用的肌肉鬆弛劑和膽鹼酯酶抑制劑之間並無交互作用。
獲得訓練中會員研究獎的這篇研究結果，發表於美國老年精神科2010年會中，該研究主要的初級結果包括術後30天死亡率、加護病房住院率、以及需住院急救的需求。
研究者發現，當病患接受全身麻醉時，相較於未使用膽鹼酯酶抑制劑的配對對照組，社區住民患者使用膽鹼酯酶抑制劑的相對風險為0.89。
類似結果包括，相較於未使用膽鹼酯酶抑制劑者，長照病患進行全身麻醉時接受膽鹼酯酶抑制劑的相對風險為0.78，而且，不論社區住民或長照病患、不論有無使用膽鹼酯酶抑制劑，接受局部麻醉下進行髖骨骨折手術時，都沒有額外的術後副作用。
Seitz醫師表示，我們曾經看過病患停用膽鹼酯酶抑制劑之後出現行為症狀，所以我認為，持平而論，基於今日的標準麻醉實務，這些藥物並不會顯著增加術後併發症的風險，我將建議不需停用它們。
【預防依舊是上策】
這個以人口為基礎的世代研究與管理健康照護資料庫有關，該世代包括了於2002-2007年間接受髖骨骨折手術的66歲以上失智病患，區分為骨折前居住於社區者以及居住於長照機構者，再分為手術時接受全身麻醉或局部麻醉。
對於手術時有無使用膽鹼酯酶抑制劑進行仔細配對之後，研究團隊最後獲得624組接受全身麻醉的社區住民，以及719組接受全身麻醉的長照機構住民。
Seitz醫師表示，兩組的性別、平均年紀、共病症、手術時所用藥物數量、發生失智的期間等，都有仔細配對，所以我們可以持平地比較各組之間的主要共同變項。
不論病患是否使用膽鹼酯酶抑制劑，兩個配對組的髖骨手術預後都不好，甚至在相對上比較健康的社區住民中，術後30天死亡率為10%，另有5%在術後須住進加護病房，長照病患的術後預後更不好，術後30天死亡率為12%-15%。
Seitz醫師表示，我們依舊須對這類病患的藥物使用保持警惕，他們很不容易開始進行膽鹼酯酶抑制劑、也不容易在共病症之下獲得邊際效應，加上他們的髖骨骨折手術結果這麼糟，最需要的是預防這類病患的骨折與相關併發症。
【無需停止藥物】
Burlington、Vermont大學的Paul Newhouse醫師向Medscape Psychiatry表示，在1990s年代初期，服用膽鹼酯酶抑制劑的病患會在手術前被要求停用藥物，當時，有許多人會發生令人困擾的一些行為症狀 — 也因此讓醫師們首次確認這類製劑對於行為有正向效應。
關注的焦點在於膽鹼酯酶抑制劑在全身麻醉時可能會延長肌肉鬆弛劑、膽鹼類藥物的效果，減弱呼吸道肌肉與增加術後併發症風險。
Newhouse醫師表示，不過，因為停用藥物可能會發生相當嚴重的行為問題，我認為，在現代，我們已經具有讓病患繼續使用膽鹼酯酶抑制劑的智慧。
Seitz醫師與Newhouse醫師皆表示沒有相關財務關係。
美國老年精神科協會(American Association for Geriatric Psychiatry (AAGP)) 2010年會：會議小組214。發表於2010年3月6日。
Cholinesterase Inhibitors Do Not Exacerbate Postoperative Complications in Patients With Dementia
By Pam Harrison
Medscape Medical News
March 9, 2010 — The risk of postoperative complications is not exacerbated by cholinesterase inhibitor therapy in elderly adults with dementia who receive general anesthesia during hip fracture surgery, suggesting the once-standard practice of discontinuing medication use in patients before surgery is not necessary.
Dallas Seitz, MD, Baycrest Centre, Toronto, Ontario, Canada, found no interaction between the muscle relaxants used in general anesthesia and cholinesterase inhibitor use in either community-dwelling or long-term care patients undergoing emergency hip fracture surgery.
Results from the member-in-training research award were presented during the American Association for Geriatric Psychiatry 2010 Annual Meeting. The study's primary composite outcome consisted of 30-day postoperative mortality, intensive care unit admissions, and the need for in-hospital resuscitation.
The investigators found the relative risk of community-based patients who were taking a cholinesterase inhibitor when they received general anesthesia was 0.89 compared with matched controls who were not taking cholinesterase inhibitors.
Similarly, the relative risk of long-term care patients who were receiving a cholinesterase inhibitor while undergoing general anesthesia was 0.78 compared with those who were not taking such medications. There was also no excess of adverse postoperative outcomes among either community or long-term care patients taking or not taking cholinesterase inhibitors who received regional anesthesia during hip fracture surgery.
"We do see patients who develop behavioral symptoms after withdrawal from the [cholinesterase inhibitors], so I think it’s fair to say that given standard anesthetic practice today, these medications do not appear to confer significant increased risk of postoperative complications, and I would recommend not discontinuing them," Dr. Seitz said.
Prevention Still the Best Medicine
The population-based cohort study linked administrative healthcare databases. The cohort consisted of patients 66 years and older with dementia who underwent hip fracture surgery between 2002 and 2007. The cohort was stratified into those who lived in the community before their fracture vs those who lived in long-term care facilities, as well as patients who received general vs regional anesthetic during surgery.
After carefully matching patients taking and not taking a cholinesterase inhibitor at the time of surgery, the team ended up with 624 matched community-dwelling pairs who received general anesthesia and 719 long-term care pairs who again received general anesthesia.
Both groups of pairs were well matched for sex, mean age, comorbidities, number of medications at the time of surgery, and duration of dementia, “so we had fairly comparable groups in terms of all the major covariates,” Dr. Seitz said.
Regardless of whether patients were taking a cholinesterase inhibitor, the prognosis after hip surgery for both matched pairs was poor. Even in "relatively healthy" community-dwelling pairs, the 30-day postoperative mortality rate was 10%, with an additional 5% requiring intensive care unit postoperative care. The postoperative prognosis for long-term care patients was even poorer, with a 30-day postoperative mortality rate of 12% to 15%.
"We still need to be vigilant about medication use in this population, but their outcome is so bad that by the time they have their hip fracture and come in for surgery, they are a very frail group to begin with and the marginal effect of the cholinesterase inhibitors is washed out in the rest of their comorbidities," Dr. Seitz said. "There is a definite need to prevent hip fractures and their complications in this population."
No Need to Withdraw Medication
Paul Newhouse, MD, University of Vermont, Burlington, told Medscape Psychiatry that in the early 1990s, patients taking cholinesterase inhibitors would routinely discontinue use of the medication before surgery, at which point, many would develop quite disturbing behavioral symptoms — and this was when physicians first recognized that these agents had positive effects on behavior.
The concern was that cholinesterase inhibitors might prolong the effects of muscle relaxants, themselves cholinergic drugs, used during general anesthesia, weakening respiratory muscles and increasing the risk of postoperative complications.
"Today, however, I think it is accepted wisdom that patients should generally be left on cholinesterase inhibitors because they can develop quite serious behavioral issues when the drug is withdrawn," said Dr. Newhouse.
Dr. Seitz and Dr. Newhouse have disclosed no relevant financial relationships.
American Association for Geriatric Psychiatry (AAGP) 2010 Annual Meeting: Session 214. Presented March 6, 2010.
