大型研究確認手術前後使用乙型阻斷劑的好處

e48585 發表於 2009-11-9 08:04:34 [顯示全部樓層] 回覆獎勵 閱讀模式 1 2068
本帖最後由 lsc0019 於 2009-11-11 23:19 編輯

作者:Caroline Helwick  
出處:WebMD醫學新聞

  October 23, 2009(紐澳良)-美國麻醉醫學會2009年年會發表的研究結果,確認了有心血管疾病危險因子病患,術前使用乙型阻斷劑有存活上的好處;這項研究是根據舊金山退伍軍人管理(VA)醫院的大資料庫。
  
  十幾年前,術前使用乙型阻斷劑即已在臨床研究中被證實可以降低死亡率,因而被心臟科醫學會採用作為標準照護。接下來,不只一項大型研究,例如術前缺血評估(POISE)研究,質疑使用這些藥物的好處,事實上,發現病患的死亡是上升的,且使用這些藥物與中風有關(Devereaux PJ等人,發表於美國心臟醫學會2007年科學座談會,摘要編號LBCT20825)。
  
  這項分析的主要作者、舊金山大學醫學院麻醉與術前醫學教授Atrhur Wallace醫師發現POISE研究的缺失,他指出,這可能已經影響研究結果,特別是使用高出標準8倍劑量的metoprolol。
  
  他表示,他與他的同事們進行的研究,被廣泛散佈的術前心臟風險降低療法(PCRRT)方案,使用標準劑量且結合許多「基本準則」,已被證實可以改善預後,因而被許多醫療系統採用。
  
  【PCRRT方案基本內容】
  乙型阻斷劑
  * 一開始口服atenolol 25 mg每天一次。如果心跳速率高於每分鐘60下,且收縮壓高於120 mmHg,就調整劑量,直到發生藥效。
  * 在手術的那一天使用atenolol或是靜脈注射metoprolol。術後繼續使用atenolol或靜脈metoprolol,直到開始口服藥物。
  * 術後每天口服atenolol 100 mg,持續一個星期以上。
  * 如果已知有冠狀動脈血管疾病或是周邊血管疾病,繼續無限期地使用乙型阻斷劑。
  
  如果無法使用乙型阻斷劑
  * 手術前一天晚上口服clonidine 0.2 mg錠劑
  * 手術前一天晚上使用clonidine TTS 2片(0.2 mg/24小時)
  * 手術當天早上使用口服clonidine 0.2 mg錠劑
  
  Wallace博士表示,研究檢驗使用我們於舊金山VA醫學中心發展的策略,於術前投予乙型阻斷劑降可以降低30天與1年的死亡率。
  
  從VA電子資料庫取得1996年至2008年之間所有手術術式的資料。根據是否有已知冠狀動脈血管疾病或是周邊血管疾病、或有兩種標準危險因子,來確認病患的心血管疾病風險。以未使用、持續使用(術前與術後投予)、加上(住院前未使用,但是在手術當天加上乙型阻斷劑)、或是停用(住院前使用,但是住院或出院時未使用)來分析乙型阻斷劑使用情形。
  
  研究者們分析20,937位病患(平均年齡63歲)接受的38,779次手術。住院病患手術中,最常使用的是metoprolol(75%);門診病患手術中,最常使用的是atenolol(54%)。
  
  Wallace博士報告,當與沒有使用乙型阻斷劑比較,預防性加上乙型阻斷劑顯著地降低30天時與1年時的死亡率將近50%。
  
  30天死亡率偏向使用乙型阻斷劑(勝算比為0.52;95%信賴區間[CI]為0.33-0.83;P=0.0055),而1年時死亡率勝算比為0.64(勝算比為0.51-0.79;P=0.0001)。持續使用於30天死亡的勝算比為0.68(95% CI為0.47-0.98;P=0.037)、於1年時死亡的勝算比0.82(95% CI為0.67-1.0;P=0.05)。
  
  已經在使用這些藥物的病患,停用後使得30天時死亡率將近上升4倍(P<0.0001),且1年時死亡率將近加倍(P>0.0001)。
  
  Wallace博士附帶表示,臨床醫師應該積極地確認出適合使用乙型阻斷劑的病患,並且立即對他們開始治療。他表示,預計接受手術的病患,當我們確認他們正處於風險時,應該儘快開始接受乙型阻斷劑治療。
  
  壁報討論會主持人、伯明罕阿拉巴馬大學醫學院的麻醉科教授Gwendolyn Boyd醫師表示,自從POISE研究發表後,乙型阻斷劑的使用再度變成一個懸而未決的議題。
  
  她指出,當病患住院時,目前的趨勢是傾向停用乙型阻斷劑。我已經聽聞高達50%病患會停止服用這些藥物。這可能是因為POISE與其他研究矛盾的結果。這裡,VA研究給了我們使用這些好處令人感到有信心的數據。
  
  Wallance博士與Boyd博士表示已無相關資金上的往來。

Benefit of Perioperative Beta Blockers Confirmed in Large Study

By Caroline Helwick
Medscape Medical News

October 23, 2009 (New Orleans, Louisiana) — Findings from a huge database at the San Francisco Veterans Administration (VA) Hospital, presented here at the American Society of Anesthesiologists 2009 Annual Meeting, confirmed the survival benefits of perioperative beta blockers for patients with cardiovascular risk.

More than 10 years ago, perioperative beta blockers were shown to reduce mortality in clinical trials and were therefore adopted as the standard of care by cardiology societies. Subsequently, at least 1 large study — the Perioperative Ischemic Evaluation (POISE) trial — called into question their benefit and, in fact, found an increased rate of mortality and stroke associated with their use (Devereaux PJ et al. American Heart Association 2007 Scientific Sessions. Abstract LBCT 20825).

Lead author of the current analysis, Arthur Wallace, MD, professor of anesthesiology and perioperative medicine at the University of California at San Francisco School of Medicine, finds flaws in the POISE trial, which he said could have affected the results, especially the use of metoprolol in a dose that is 8 times higher than the standard.

The study he and his colleagues developed and have disseminated widely is the Perioperative Cardiac Risk Reduction Therapy (PCRRT) protocol, which uses standard doses and incorporates several "basic rules" that have been shown to improve outcomes and that can be applied across hospital systems, he said.

Basics of PCCRT Protocol

Beta Blockers

Oral atenolol 25 mg once daily to start. If heart rate is higher than 60 beats per minute and systolic blood pressure is higher than 120 mm Hg, titrate dose to effect.
Atenolol or intravenous (IV) metoprolol on the day of surgery. Atenolol or IV metoprolol postop until taking orally.
Oral atenolol 100 mg once daily for 1 week or more postop.
If known coronary artery or peripheral vascular disease, continue beta blocker indefinitely.
If Unable to Take Beta Blockers

Oral clonidine 0.2 mg tablet the night before surgery.
Clonidine TTS 2 patch (0.2 mg/24 hours) the night before surgery.
Oral clonidine 0.2 mg tablet the morning of surgery.


"Our study tested the hypothesis that the administration of perioperative beta blockade using the protocol we developed at the San Francisco VA Medical Center would reduce the incidence of 30-day and 1-year mortality," Dr. Wallace said.

Data from all surgical procedures between 1996 and 2008 were extracted from the VA computerized database. Patients were identified for cardiovascular risk on the basis of the presence of known coronary artery or peripheral vascular disease, or the presence of 2 standard risk factors. Beta blocker use was analyzed as none, continuous (preoperative and postoperative administration), addition (no prehospital administration but beta blocker added on the day of surgery), or withdrawal (prehospital administration but none in hospital or after discharge).

Investigators analyzed 38,779 surgical procedures in 20,937 patients (average age, 63 years). For in-patient procedures, metoprolol was most common (75%); for out-patient procedures, atenolol was most common (54%).

When compared with no use of beta blockers, the prophylactic addition of beta blockers significantly reduced 30-day and 1-year mortality by approximately 50%, Dr. Wallace reported.

The odds ratios favoring beta blockers were 0.52 (95% confidence interval [CI], 0.33 - 0.83; P =.0055) for 30-day mortality and 0.64 (95% CI, 0.51 - 0.79; P =.0001) for 1-year mortality. Continuous use carried an odds ratio of 0.68 (95% CI, 0.47 - 0.98; P =.037) for mortality at 30 days and 0.82 (95% CI, 0.67 - 1.0; P =.05) at 1 year.

Withdrawal of beta blockers in patients already taking the drugs raised the risk for 30-day mortality almost 4-fold (P < .0001) and nearly doubled 1-year mortality (P > .0001).

Dr. Wallace added that clinicians should be aggressive in identifying candidates for beta blockers and starting them on therapy right away. "Patients scheduled for surgery start receiving a beta blocker as soon as we identify them as at-risk," he said.

Poster discussion moderator Gwendolyn Boyd, MD, professor of anesthesiology at the University of Alabama School of Medicine, Birmingham, noted that since the POISE results were announced, the use of beta blockers has become controversial again.

"There is a big tendency now to discontinue beta blockers when the patient is admitted," she said. "I've heard as many as 50% may be taken off these drugs. That is probably because of the conflicting data from POISE. Here, the VA study gives us convincing data of their benefit."

Dr. Wallace and Dr. Boyd have disclosed no relevant financial relationships.

American Society of Anesthesiologists (ASA) 2009 Annual Meeting: Abstract A705. Presented October 19, 2009.

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