摘要
目的研发一种能预防气管插管机械通气引发的呼吸机相关性肺炎的气管插管导管。
方法以医用聚乙烯气管插管导管为基材、载银二氧化钛为抗菌剂、TEOS为硅源、KH570和MTES为有机相前驱体,通过溶胶-凝胶法制备TEOS/KH570/MTES/Ag-TiO2抗菌有机硅溶胶,将聚乙烯气管插管导管表面活化处理,通过浸渍涂布法制备TEOS/KH570/MTES/Ag-TiO2抗菌涂层气管插管导管。进而研究分析抗菌涂层的表征：通过溶胶稳定性测试、涂层硬度和附着力测试、涂层红外光谱分析、涂层表面形貌分析、涂层透光性检测和ICP-MS测试,以确定载银二氧化钛抗菌涂层的成分配比；选取标准铜绿假单胞菌、大肠埃希菌、金黄色葡萄球菌作为实验观察菌株,通过浸渍菌液培养法检测涂层导管抗菌性能；通过口腔黏膜刺激试验、热原检查、溶血试验、急性全身毒性试验和体外细胞毒性试验,以明确其是否存在生物不良反应,确定抗菌涂层导管的生物相容性和生物安全性。
结果TEOS/KH570/MTES/Ag-TiO2=15/6/1/≤1.0抗菌溶胶在聚乙烯气管插管导管表面附着力(0级)、表面硬度(5H)、溶胶稳定不沉淀,说明抗菌溶胶涂层与聚乙烯气管插管导管表面紧密附着,既保证了导管的柔韧性,又保证涂层在压折后不易断裂,而且溶胶涂层均匀稳定；涂层红外光谱分析显示TEOS/KH570/MTES/Ag-TiO2(15/6/1/1.0)抗菌溶胶交联结合稳定,保证涂层成分形成一体,不易掉落；涂层表面形貌分析显示涂层表面非常均匀平整,无小颗粒和相分离现象,涂层表面网络结构致密,稳定无分离,保证了涂层导管的光滑；涂层透光性检测显示平均透过率>90%,且具有增透效果；ICP-MS测试,银离子析出几乎可以忽略不计,说明抗菌涂层管具有良好的抗菌性能和稳定性。抗菌试验显示载银二氧化钛抗菌涂层气管插管导管具有明确的抗菌作用,能杀灭铜绿假单胞菌、金黄色葡萄球菌、大肠埃希菌,在不同的抗菌剂浓度时杀菌强度不同。抗菌涂层气管插管导管涂层载银二氧化钛含量越高,则抗菌性能越强,达到1%浓度后,则处于饱和杀菌状态,可几乎完全杀灭所有细菌,说明1%载银二氧化钛抗菌涂层气管插管导管是有效抗菌的最低浓度。口腔黏膜刺激试验显示1%载银二氧化钛抗菌涂层气管插管导管浸提液对金黄地鼠口腔粘膜未出现刺激反应；热原检查显示涂层管浸提液3h内的最高升温分别为0℃,0℃,0.03℃,总升温为0.03℃；溶血试验显示涂层管的吸光度分别为：0.016、0.014、0.021,平均值为0.0170,计算得溶血率为0.7512%；急性全身毒性试验显示涂层管浸提液在整个试验过程均无动物死亡,且未见异常反应,体外细胞毒性试验细胞形态正常,贴壁生长良好,胞浆内有离散颗粒,无细胞溶解,评为无毒,判定分级为0级,相对细胞增殖率均大于100%。
结论以TEOS/KH570/MTES/Ag-Ti02=15/6/1≤1.0比例和1%浓度载银二氧化钛抗菌剂制备的抗菌涂层气管插管导管表征优良,抗菌性能优越,满意的生物相容性和安全性,可以作为预防VAP的临床前试验候选导管。
Object In order to prevent endotracheal intubation catheter-induced respiratory infection ventilator-associated pneumonia (VAP), we prepared the antibacterial coating endotracheal tube (ETT) with silver loaded titanium dioxide, analysed the characterization and the antibacterial property, and studied on adverse bioreaction.
Methods Useing the medical polyethylene ETT as the fundamental catheter, titanium dioxide with silver as the antibacterial agent, TEOS as the silicon source and KH570、MTES as the organic phase precursor, we prepared TEOS/KH570/MTES/Ag-TiO2antibacterial coating ETT with silver loaded titanium dioxide by the sol-gel method. Then we analysed the characterization of the antibacterial coating by sol stability test, coating hardness and adhesion test IR analysis of the coating, the coating surface morphology analysis, translucent coating test and ICP-MS test, and determined the composition proportion of the antibacterial coating. We selected standard Pseudomonas aeruginosa liquids, standard Escherichia coli liquids and standard Staphylococcus aureus liquids to carry out antibacterial property test of the antibacterial coating ETT with silver loaded titanium dioxide by impregnated bacterial liquid incubation method. In order to ensure adverse bioreactions of the antibacterial coating ETT with silver loaded titanium dioxide,we carried out oral mucous irritation test, pyrogen test, hemolysis test and toxicity test to determine biocompatibility and biological safet.
Results TEOS/KH570/MTES/Ag-TiO2=15/6/1/≤1.0antibacterial sol coated on the polyethylene ETT had an excellent adhesion (level0), suitable surface hardness (5H) and the sol stability, which showed that antibacterial sol coating adhered closely with polyethylene ETT surface, ensured that antibacterial ETT was flexible, stable and unbreakable, and that antibacterial sol coating was uniform and stable. IR analysis showed that TEOS/KH570/MTES/Ag-TiO2=15/6/1/1.0antibacterial coating had sufficient crosslinking reaction, and that the coating compositions had formed a whole, not easy to fall off. The antibacterial sol coating surface morphology under scanning electron microscopy showed smooth, no small particles and no any phase separation phenomenon, the network structure was compact, stable without separation, which explained the coating ETT surface was very smooth. UV-Vis spectrophotometer test showed that the average transmittance of the translucent was>90%and the antibacterial coating could improve anti-reflection of ETT. ICP-MS test of silver ion release showed that the silver ion release was almost negligible, which explained the antibacterial coating ETT had excellent antibacterial property and stability. The antibacterial property test showed that antibacterial coating ETT with silver loaded titanium dioxide could kill bacterias such as Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus. Its antibacterial property was excellent and relative to the antibacterial concentration. The higher of the antibacterial concentration of silver loaded titanium dioxide was used, the stronger the antibacterial property were shown. And above1%antibacterial concentration, tubes had shown the strong antibacterial effects, almost completely sterilized bacterias in the immersing liquid. The oral mucous irritation test showed that the extracts of the coating ETT was no irritation reactions to golden hamsters oral mucous. The pyrogen test showed that the maximum elevated temperature of the rabbits within3.0h time point after injected the extracts of the coating_ETT were respectively0℃,0℃and0.03℃, the total elevated temperature was0.3℃. The hemolysis test showed that the absorbances of the coating ETT were:0.016,0.014,0.021, average of0.0170, and the calculated hemolysis rate was0.7512%. The acute systemic toxicity testshowed that the coating ETT extracts were no animal died in the whole process of the experiment, and no abnormal reaction. The vitro cytotoxicity test showed that adherent growth of morphology normal cell was good, discrete particles in the cytoplasm of no cell lysis, determinated non-toxic and toxicity grade0, while the relative cell proliferation rate was more than100%.
Conclusion we determine the proportion of TEOS/KH570/MTES/Ag-TiO2=15/6/1/<1.0and the concentration of1%silver loaded titanium and dioxide to prepare the antibacterial coating ETT with silver loaded titanium dioxide which had good characterization, excellent antibacterial property and satisfy biocompatibility and biological safet. The antibacterial coating ETT could be used to Preclinical study.
引文
1.严蕊娜,黄相增.呼吸机相关性肺炎预防策略[J].中华实用诊断与治疗杂志,2011,25(2):105-107.
2.蒋旭宏,黄小民,曹俊敏.急诊科呼吸机相关性肺炎300株革兰阴性菌耐药性分析[J].浙江省中西医结合学会急救医学专业委员会第二次学术年会,2005,6：71-73.
3.周晴,胡必杰,高晓东等.2009-2010年上海市65所医院ICU导管相关性感染目标性监测分析[J].中华医院感染学杂志,2011,21(12)：2408-2410.
4.陈德昌.全身感染：观察、假设和验证[J].中华危重病急救医学,2013,25(1):1.
5.张祎博,倪语星,孙景勇等.2010年中国CHINET铜绿假单胞菌耐药性检测[J].中国感染与化疗杂志,2012,12(3)：161-166.
6.秦智英.关注困难脱机的研究现状[J].中国危重病急救医学,2012,24(2):65-67.
7.冷玉鑫,宋崖含,姚智渊,等.45。半卧位对机械通气患者呼吸机相关性肺炎影响的Meta分析[J].中国危重病急救医学,2012,24(10)：587-591.
8.莫敏,刘松桥,杨毅.热湿交换器和加温湿化器对呼吸机相关性肺炎发生率影响的荟萃分析[J].中国危重病急救医学,2011,23(9)：513-517.
9. American Thoracic Society, Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia [J]. Am J Respir Crit Care Med,2005,171(4):388-416.
10.张铂,秦英智.经验性抗生素治疗呼吸机相关性肺炎的监床意义[J].中国危重病急救医学,2008,20(2)：119-120.
11. Hong H, Landauer M R, Foriska M A, et al. Antibacterial activity of the soy isoflavone genistein [J]. Basic Microbiol,2006,46(4):329-335.
12. Ament P W, Jamshed N, Home J P. Linezo-lid:its role in the treatment of Gram-positive, drug-resistant bacterial infections [J]. Am Fam Physician,2002,65(4):663-671.
13.蒋旭宏,王原,华军益,等.急诊科C、D类COPD急性发作患者细菌分布及耐药性分析[J].中华急诊医学杂志,2013,22(6)：393-395.
14.张岩鹏,吕书勤.中西医结合治疗呼吸机相关性肺炎的临床观察[J].医学信息,2011,24(4)：1954-1955.
15.林梵,肖军.中西医结合治疗呼吸机相关性肺炎的临床观察[J].中国中医基础医学杂志,2013,19(2)：214-215.
16. Jae-Gyu,Jeon, Santosh, et al. Influences of trans-trans farnesol, a membrane-targeting sesquiterpenoid, on Streptococcus mutans physiology and survival within mixed-species oral biofilms[J]. International Journal of Oral Science,2011(2):98-106.
17. Politano Amani D, Campbell Kristin T, Rosenberger Laura H, et al. Use of silver in the prevention and treatment of infections:silver review[J]. Surgical Infections,2013,14(1):8-20.
18.张慧书,刘守新.Ti02光催化杀菌机理及应用研究进展[J].科学技术与工程,2009,9(17)：5049-5056.
19. Chen F N, Yang X D, Wu Q. Antifungal capability of TiO2 coated film on moist wood[J]. Building and Environment,2009,44(5):1088-1093.
20.李红彩.药用有机硅化合物的研究进展[J].中国现代应用药学,2010,27(8)：689-693.
21.韩秀秀,何文,田修营,等.银系无机抗菌材料抗菌机理及应用[J].山东轻工业学院学报(自然科学版),2010,24(1)：
22.夏金兰,王春,刘新星.抗菌剂及其抗菌机理[J].中南大学学报(自然科学版),2004,35(1)：32-36.
23.杨丽娜,周光强,高建峰等.纳米二氧化钛的制备及应用的研究进展[J].化工中间体,2011,3：17-21.
24.张莹,彭兵,柴立元等.载银纳米二氧化钛的分散及对PVC清漆的改性[J].涂料工业,2011,41(1)：24-28.
25.魏泓.医学实验动物学[M].成都：四川科学技术出版社,1999:149-163,170-179.
26.张慧书,刘守新.二氧化钛光催化杀菌机理及应用研究进展[J].科学技术与工程,2009,17(9):5049-5056.
27.夏振民,刘大英.发展中的热原检查法[J].中国药事,2003,17(1):48-49.
28.赵铠,章以洁,李河民,等.医学生物制品学[M].北京：人民卫生出版社.2007,424.
29.钱秋娟,席亮,赵小洁,等.影响家兔热原检查结果的因素分析[J].微生物学免疫学进展,2012,40(2):23-25.
30.李广州,蒋电明,谭祖键,等.载银二氧化钛纳米羟基磷灰石/聚酰胺66复合材料的生物相容性及其安全性[J].中国组织工程研究与临床康复,2009,13(47):9231-9235.
31.山广志,任连杰,李群,等.采用改进的溶血试验法考察低渗静脉注射液的安全性[J].中国药房,2013,24(29):2776-2778.
32. Hench L L, Polak J M. Third-generation biomedicalmatexial[J]. Science. 2002,295(5557):1014-1017.
33.医疗器械生物学评价.第5部分：体外细胞毒性试验.GB/T16886.5-2003.
34.李佳,金晶,黄芝瑛.上下法在急性毒性试验中的应用进展[J].中国比较医学杂志,2008,18(6)：70-72.
35.吕庆兵,于治,肖贵喜,等.浸浴结合银离子敷料治疗大面积烧伤患者残余创面的疗效[J].中华烧伤杂志,2013,29(2):203-204.
36.张静.急诊EICU病房呼吸机相关性肺炎98例流行病学分析[J].中国病案,2011,12(9)：69-71.
37. Rosenthal V D. Nosocomial infections in medical-surgical intensive care units in Argentina:attributable mortality and length of stay[J]. Am J Infect Control,2003,31(5):291-295.
38. Tejerina E. Incidence, risk factors, and outcome of ventilator associated pneumonia[J]. J Crit Care,2006,21 (1):56-65.
39. Chastre J. Ventilator associated pneumonia[J]. Am J Respir Crit Care Med,2002,165(7): 867-903.
40.张媛媛,孙皎.纳米银作为抗菌材料的生物安全性研究进展[J].中国医疗器械杂志,2007,31(I):36-38.
41.孙倩,李春明,马守栋.纳米银抗菌活性及生物安全性研究进展[J].中国药事,2013,27(8):842-863.
42.二氧化钛纳米管的理论研究及临床实践[J].中国组织工程研究,2013(47):8255-8262.
43.杨慧萍,陈昭斌,许欣.纳米Ag/TiO2复合材料部分特性与制备方法的研究现状[J].现代预防医学,2011,38(3):568-570.
44.孙皎.生物材料和医疗器械的生物学评价[J]中国医疗器械杂志,2003,27(1):1-3.
1.严蕊娜,黄相增.呼吸机相关性肺炎预防策略[J].中华实用诊断与治疗杂志,2011,25(2)：105-107.
2.蒋旭宏,黄小民,曹俊敏.急诊科呼吸机相关性肺炎300株革兰阴性菌耐药性分析[J].浙江省中西医结合学会急救医学专业委员会第二次学术年会,2005,6：71-73.
3.周晴,胡必杰,高晓东等.2009-2010年上海市65所医院ICU导管相关性感染目标性监测分析[J].中华医院感染学杂志,2011,21(12)：2408-2410.
4.陈德昌.全身感染：观察、假设和验证[J].中华危重病急救医学,2013,25(1)：1.
5.张祎博,倪语星,孙景勇等.2010年中国CHINET铜绿假单胞菌耐药性检测[J].中国感染与化疗杂志,2012,12(3)：161-166.
6.秦智英.关注困难脱机的研究现状[J].中国危重病急救医学,2012,24(2):65-67.
7.冷玉鑫,宋崖含,姚智渊,等.45°半卧位对机械通气患者呼吸机相关性肺炎影响的 Meta分析[J].中国危重病急救医学,2012,24(10)：587-591.
8.莫敏,刘松桥,杨毅.热湿交换器和加温湿化器对呼吸机相关性肺炎发生率影响的荟萃分析[J].中国危重病急救医学,2011,23(9)：513-517.
9. American Thoracic Society, Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia [J]. Am J Respir Crit Care Med,2005,171(4):388-416.
10.张铂,秦英智.经验性抗生素治疗呼吸机相关性肺炎的临床意义[J].中国危重病急救医学,2008,20(2)：119-120.
11. Hong H, Landauer M R, Foriska M A, et al. Antibacterial activity of the soy isoflavone genistein [J]. Basic Microbiol,2006,46(4):329-335.
12. Ament P W, Jamshed N, Horne J P. Linezo-lid:its role in the treatment of Gram-positive, drug-resistant bacterial infections [J]. Am Fam Physician,2002,65(4):663-671.
13.蒋旭宏,王原,华军益,等.急诊科C、D类COPD急性发作患者细菌分布及耐药性分析[J].中华急诊医学杂志,2013,22(6)：393-395.
14刘大为.重症医学.2010[M].北京：人民卫生出版社,2010:517.
15. Mariani J, Macchia A, Belziti C, et al. Noninvasive ventilation in acute cardiogenic pulmonary edema:a meta-analysis of randomized controlled trials[J]. J Card Fail,2011, 17(10):850-859.
16. Schmidbauer W, Ahlers O, Spies C, et al. Early prehospital use of non-invasive ventilation improves acute repiratory failure in acute exacerbation of chronic obstructive pulmonary disease[J]. Emerg Med J,2011,28(7):626-627.
17.倪宇洁.无创通气患者并发症的原因分析及护理对策[J].当代医学,2012,18(8)：133.
18. Pacheco-Fowler V;Gaonkar T;Wyer PC, et al. Antiseptic impregnated endotracheal tubes for the prevention of bacterial colonization[J]. J Hosp Infect.2004 Jun; 57(2):170-174.
19. Raad II, Mohamed JA, Reitzel RA, et al. The prevention of biofilm colonization by multidrug-resistant pathogens that cause ventilator-associated pneumonia with antimicrobial-coated endotracheal tubes[J]. Biomaterials.2011,32(11):2689-2694.
20.马荣华,左泽兰,刘卫娟,等.纳米银水凝胶涂膜干预气管导管表面铜绿假单胞菌黏附及生物膜形成的实验研究[J].中国微生态学杂志,2009,21(3)：217-222.
21. Berra L, Kolobow T, Laquerriere P, etal. Internally coated endotracheal tubes with silver sulfadiazine in polyurethane to prevent bacterial colonization:a clinical trial [J]. Intensive Care Med,2008,34(6):1030-1037.
22. Michael Klompas. Silver-coated endotracheal tubes and patient outcomes in ventilator-associated pneumonia[J]. JAMA,2008,300(22):2605-2606.
23. Kollef MH, Afessa B, Anzueto A, et al. Silver-coated endotracheal tubes and incidence of ventilator-associated pneumonia the NASCENT randomized trial[J]. JAMA,2008,300(7):805-813.
24. Lorente L, Lecuona M, Jimeneza A, et al. Influence of an endotracheal tube with polyurethane cuff and subglottic secretion drainage on pneumonia[J]. Am J Respir Crit Care Med,2007,176(11):1079-1083.
25. Andrea C, Lorenzo B, Luca M. B. Modifying endotracheal tubes to prevent ventilator-associated pneumonia[J]. Current Opinion in Infectious Diseases, 2011,24:157-162.
26.张丽,尹健,邵丽萍,等.有创呼吸机管路系统不同更换周期与呼吸机相关性肺炎发生的关系[J].新疆医科大学学报,2013,36(11)：1628-1630.
27. Joffe A R, Muscededere J, Marshall J C, et al. The safety of targeted antibiotic therapy for ventilator-associated pneumonia:a multicenter observational study [J. J Crit Care,2008,23(1): 82-90.
28. Sandiumenge A, Diaze, Bodim, et al. Therapy of ventilator-associated pneumonia:A patient-based approach based on the ten roles of The Tarragona Strategy [J]. Intensive Care Med,2003,29(6):876-883.
29. Ost DE, Hall CS, Joseph G,et al. Decision analysis of antibiotic and diagnostic strategies in ventilator-associated pneumonia[J]. Am Respir Criti Care Me,2003,168(9):1060-106.
30.张庆玲,刘明华,王仙园,等.呼吸机相关性肺炎的预防和治疗.中华医院感染学杂志,2004,14(8)：958-960.
31.范燕,王睿,安毛毛,等.磷霉素与氨基糖苷类药物联用对体外铜绿假单胞菌生物被膜形态学的影响[J].中国药物应用与检测,2007,4(5)：18-20.
32. Starner T D, Shrout J D, Parsek M R, et al. Subinhibitory concentrations of azithromycin decrease nontypeable Haemophilus influenzae biofilm formation and diminish established biofilms[J]. Antimicrob Agents Chemoth,2008,52(1):137-145.
33. Luyt CE, Clavel M, Guntupalli K, et al. Pharmacokinetics and lung delivery of PDDS-aerosolized amikacin (NKTR-061) in intubated and mechanically ventilated patients with nosocomial pneumonia[J]. Crit Care,2009,13:R200.
34. Ioannidou E, Siempos Ⅱ, Falagas ME. Administration of antimicrobials via the respiratory tract for the treatment ofpatients with nosocomial pneumonia:a meta-analysis[J]. J Antimicrob Chemo-ther,2007,60:1216-1226.
35. Chastre J, Wolff M, Fagon J Y, et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults:a randomized trial [J]. JAMA,2003,290(19): 2588-2598.
36. Kollff M H, Kollff K E. Antibiotic utilization and outcomes for patients with clinically suspected ventilator-associated pneumonia and negative quantitative BAL culture results [J]. Chest,2005,128(4):2706-2713.
37.覃英容,黄业清,黄向华.危重患者不同肠内营养置管支持的对比研究中医治疗[J].中华全科医学,2013,11(10)：1557-1558.
38.谢剑锋,黄力维,郭凤梅,等.经小肠营养对呼吸机相关性肺炎影响的荟萃分析[J].中华医学杂志,2013,93(35)：2786-2789.
39.张岩鹏,吕书勤.中西医结合治疗呼吸机相关性肺炎的临床观察[J].医学信息,2011,24(4)：1954-1955.
40.孙腾,杨建江.中西医结合治疗呼吸机相关性肺炎临床分析[J].辽宁中医杂志,2009,36(2)：247-248.
41.林梵,肖军.中西医结合治疗呼吸机相关性肺炎的临床观察[J].中国中医基础医学杂志,2013,19(2)：214-215.
42.蒋联章.半夏泻心汤预防呼吸机相关性肺炎临床观察[J].新中医,2012,44(9)：22-24.
43.于倩.呼吸机相关性肺炎中医辨证分型等的临床研究[D].哈尔滨：黑龙江中医药大学,2011.
44.蒋旭宏,黄小民,何煜舟.痰热清注射液对急性肺损伤大鼠肺内炎症因子的影响[J].中华急诊医学杂志,2011,20(8)：835-838.
45.章昕,蔡玲.痰热清注射液对呼吸机相关性肺炎患者感染参数和临床预后的影响[J].中国中医急症,2012,21(8)：1223,1241.
46.张娟.血必净在呼吸机相关性肺炎治疗中的疗效观察[J].浙江临床医学,2012,14(10)：1220-1221.
47.金超阳.BiBAP无创机械通气联合纳洛酮醒脑静治疗肺性脑病32例[J].中国实用神经疾病杂志,2013,16(18)：97-98.
48.付贵峰.机械通气发生呼吸机相关性肺炎危险因素的研究[J].临床肺科杂志,2007,12(7)：716-717.
49. Smulders K, van der Hoeven H, Weers-Pothoff I, et al. A randomized clinical trial of intermittent subglottic secretion drainage in patients receiving mechanical ventilation[J]. Chest,2002,121(3):858-862.
50.王雪娟,杨树栋,翁惠.拔除气管插管前清理气囊上液对预防吸入性肺炎的效果观察[J].广西中医药大学学报,2013,16(2):52-53.
51.傅自萍,向春,陈静,雷敏.纤维支气管镜吸痰处理对呼吸机相关肺炎患者的效果分析[J].国际检验医学杂志,2013,34(15)：1967-1968.
52.桑艳艳.标准序贯吸痰法在预防呼吸机相关性肺炎中的应用[J].中华现代护理杂志,2012,18(36)：4441-4443.
53. Chen YC, Wu LF, Mu PF, et al. Using chest vibration nursing intervention to improve expectoration of airway secretion and prevent lung collapse in ventilated ICU patients:a randomized controlled trial [J]. Chin Med Assoc,2009.72(6):316-322.
54.林洁芬.湿热交换器应用于机械通气患者的护理体会[J].当代护士,2012,(5)：107-108.
55.李玉珍.呼吸机相关性肺炎的常见原因与护理[J].齐齐哈尔医学院学报,2011,9(02)：42.
56.张庆玲,刘明华,刘玉馥,等.呼吸机相关肺炎-胃肺感染途径的前瞻性研究[J].中华烧伤杂志,2004,20(1)：20-22.
57.刘增霞,任蔚虹,潘海燕.半卧位对呼吸机相关肺炎影响的Meta分析[J].中华急诊医学杂志,2011,20(2)：147-150.
58.田春梅,李德保,孟明哲,等.3种不同护理干预措施对预防呼吸机相关性肺炎的作用[J].中国感染控制杂志,2012,11(1)：43-46.