使用吸入型支氣管擴張劑可能會增加呼吸器相關肺炎的風險

作者：Deborah Brauser  
出處：WebMD醫學新聞

　　January 13, 2010 (佛州邁阿密) — 根據發表於重症照護醫學會第39屆重症照護研討會中的觀察型研究結果，吸入型支氣管擴張劑與重症病患的呼吸器相關肺炎(ventilator-associated pneumonia，VAP)風險增加有獨立相關。
　　
　　第一作者、法國里爾Calmette醫院加護病房(ICU)的Saad Nseir醫師在口頭發表時報告指出，雖然支氣管擴張劑的使用在機械輔助呼吸病患中增加，以前有研究認為，吸入型治療可能會增加呼吸器管路的菌落以及後續的VAP。
　　
　　Nseir醫師表示，我們認為，這方面的問題以及其他使用吸入型治療的可能副作用相當值得探討。
　　
　　為了進行研究，這個研究團隊以1年期間納入Calmette醫院加護病房所有需要插管和機械輔助呼吸超過48小時的病患(n= 439人)，並指出任何初次發生的VAP。
　　
　　研究者使用單一變項和多變項分析來確認VAP的風險因素。
　　
　　【結果】
　　研究結束時，結果顯示，439名病患中有137人(31%)發生VAP，其中，13%是早發型VAP。
　　
　　最常發現的細菌是綠膿桿菌(42%)，其次依序為鮑氏不動桿菌(13%)以及腸桿菌(9%)。
　　
　　在有VAP和沒有VAP病患的單一變項分析中，發現有顯著差異(P< .05)的風險因素，包括簡化急性生理評分 II (SAPS II)) (有VAP者為54 ± 16分、沒有VAP者為48 ± 20分)、從其他病房轉入(分別是71% 和60%)、使用吸入型salbutamol(分別是49%和34%)、使用靜脈注射salbutamol (分別是24%和12%)、使用皮質類固醇(分別是78%和62%)、預防壓力性潰瘍(分別是94%和86%)、輸血(分別是62%和40%)、以及VAP前使用機械輔助呼吸的期間(分別是18 ±16和13±12 天)。
　　
　　多變項分析發現的VAP獨立風險因素，包括使用吸入型salbutamol (勝算比[OR]為1.7；95%信心區間[CI]為1.1- 2.6；P= .012)、SAPS II (OR，每1分增加1.01；P= .031)以及輸血(OR，2.05；95% CI，1.3- 3.1；P= .001)。
　　
　　Nseir醫師報告指出，VAP病患在ICU的住院天數也顯著較長，且死亡率也較高。
　　
　　他建議，最需記住的是，避免讓機械輔助呼吸病患例行性地使用吸入型治療，除非有更強烈的證據證明這類治療有幫助。
　　
　　Nseir醫師指出，值得進行隨機研究來比較吸入型和靜脈注射型支氣管擴張劑，看是否都有這個副作用。
　　
　　研究限制包括，它是觀察型研究設計，只有在1個中心進行，支氣管擴張劑處方並無規定。
　　
　　【需要更多資訊】
　　會議共同主持人、麻州大學肺部重症照護部教授Sean Townsend醫師表示，我認為，這個研究中最值得一提的部份是，其ICU的VAP比率這麼高；31%實在是相當高。
　　
　　未參與該研究的Townsend醫師表示，很多中心可能一整年都沒有任何VAP案例，也就是說，這或許是研究吸入型支氣管擴張劑與VAP關聯的好對象，或許這是異常。通常，歐洲收治於ICU的病患比美國重症，或許本研究發現的較高VAP比率是因為該中心的病症更嚴重。
　　
　　他表示，他另外擔心的是，該研究未探討支氣管擴張劑的需求，所有病患也只有使用一種藥物。需要使用支氣管擴張劑的時機，包括支氣管攣縮與對呼吸器順從性不佳的慢性阻塞性肺部疾病患者。因此，使用的必要性可能大過增加VAP的風險。
　　
　　當被問到他為何將這篇選為該會議中的前100名摘要時，Townsend醫師表示，這是一個新研究，以前只有另一篇研究區隔此風險因素，我們現在需要有更多樣本的前瞻性研究來做一些評估，看那些有共病症的病患是否可以適合使用支氣管擴張劑。
　　
　　Nseir醫師與Townsend醫師皆宣告沒有相關財務關係。
　　
　　重症照護醫學會(SCCM)第39屆重症照護研討會：摘要10。發表於2010年1月10日。


Aerosolized Bronchodilator Use May Increase Risk for Ventilator-Associated Pneumonia

By Deborah Brauser
Medscape Medical News

January 13, 2010 (Miami, Florida) — Aerosolized bronchodilators are independently associated with an increased risk for ventilator-associated pneumonia (VAP) in critically ill patients, according to results from an observational study presented here at the Society of Critical Care Medicine 39th Critical Care Congress.

Lead author Saad Nseir, MD, from the Medical Intensive Care Unit (ICU) at Calmette Hospital, CHRU, in Lille, France, reported during his oral presentation that although bronchodilator use has increased for mechanically ventilated patients, past studies "have suggested that aerosol therapy may promote bacterial colonization of ventilator circuit and subsequent VAP."

"We thought it would be interesting to look more at that aspect, along with other possible side effects of using inhaled therapy," said Dr. Nseir.

For this study, his investigative team enrolled all patients at the Calmette Hospital's ICU over a 1-year period who required intubation and mechanical ventilation for more than 48 hours (n?= 439) and noted any first episodes of VAP.

The investigators used both univariate and multivariate analysis to determine the risk factors for VAP.

Results

At the end of the study, results showed that 137 of 439 patients (31%) developed VAP. Of these, 13% developed early-onset VAP.

The most frequent bacteria found was Pseudomonas aeruginosa (42%), followed by Acinetobacter baumannii (13%) and Enterobacter species (9%).

Significant differences (P?< .05) were found on univariate analysis between patients with and without VAP. These risk factors included the Simplified Acute Physiologic Score (SAPS)?II (54?± 16 for those with VAP vs 48?± 20 for those without VAP), transfer from other wards (71% vs 60%, respectively), aerosolized salbutamol use (49% vs 34%, respectively), intravenous salbutamol use (24% vs 12%, respectively), corticosteroid use (78% vs 62%, respectively), stress ulcer prophylaxis (94% vs 86%, respectively), red blood cell transfusion (62% vs 40%, respectively), and duration of mechanical ventilation before VAP (18?± 16 vs 13?± 12 days, respectively).

Independent risk factors for VAP found by multivariate analysis included aerosolized salbutamol use (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.1?- 2.6; P?= .012), SAPS?II (OR, 1.01 per point; P?= .031), and red blood cell transfusion (OR, 2.05; 95% CI, 1.3?- 3.1; P?= .001).

"Patients with VAP also had a significantly longer ICU length of stay and significantly higher mortality," reported Dr. Nseir.

"I think the number?1 takeaway message is to avoid using inhaled therapy routinely in mechanically ventilated patients and to wait for stronger evidence of the benefit of these therapies," he advised.

"It would be interesting to now do a randomized study comparing inhaled therapy with bronchodilators against [intravenous] bronchodilators and to see the side effects of each," Dr. Nseir added.

Limitations of this study include its observational design, the fact that it was conducted at only 1 center, and the fact that the bronchodilator prescriptions were not protocolized.

More Information Needed

"I think one of the most notable parts about this study is the high rate of [VAP] in their ICU; 31% is extraordinarily large," said session comoderator Sean Townsend, MD, professor of medicine at the University of Massachusetts in the Department of Pulmonary Critical Care, in Worcester.

Dr. Townsend, who was not involved with this study, said that many centers often go a year at a time without any cases of VAP. "That said, perhaps this was a good population in which to study inhaled bronchodilators and their association with VAP. Or perhaps it's an anomaly. Often, the ICUs in Europe have patients who are more critically ill than in the United States and perhaps the higher VAP rate found in this study corresponds to the higher acuity of illness there."

He said that he was also concerned that the study did not look at the need for the bronchodilator and only used 1 type for all patients. "There are times when bronchodilator use is called for, such as with [chronic obstructive pulmonary disease] patients who are bronchospastic and [who have poor] compliance?.?.?. on the ventilator. So the necessity to use it may overwhelm the risk for increased VAP."

When asked why he thought this was selected as one of the Top?100 Abstracts at the event, Dr. Townsend said: "This is a novel study. Only one other study previously isolated this risk factor. We now need a prospective study with much larger numbers, and some assessment should be made as to whether a patient has a comorbidity that justifies the use of the bronchodilator."

Dr. Nseir and Dr. Townsend have disclosed no relevant financial relationships.

Society of Critical Care Medicine (SCCM) 39th Critical Care Congress: Abstract?10. Presented January?10, 2010.