胃内定植菌与慢性阻塞性肺病患者呼吸机相关肺炎的关系及其部分影响因素的研究
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摘要
目的:①探讨胃内细菌定植在慢性阻塞性肺病(COPD)机械通气患者呼吸机相关性肺炎(VAP)发病机制中的作用;②探讨COPD机械通气患者胃液pH值、SIgA和TBA水平对其胃内细菌定植的影响;③探讨抑酸剂或黏膜保护剂的使用,营养支持类型对COPD机械通气患者胃液pH值、SIgA和TBA水平的影响。为预防COPD机械通气患者VAP的发生提供依据。
方法:对35例COPD行机械通气患者,采用半定量培养法对下呼吸道、胃液、咽拭子标本进行细菌学检测;采用双抗体夹心放免法测定胃液SIgA水平;采用循环酶法测定胃液TBA水平;采用精密pH试纸测定胃液pH值;记录抑酸剂或黏膜保护剂的使用,营养支持类型,评价VAP发生情况。数据以SPSS13.0统计软件进行处理。
结果:①35例患者121份胃液标本中有21例(60%)40份(33.06%)发生胃腔细菌定植,共分离菌株45株,主要为鲍曼不动杆菌、肺炎克雷白杆菌、铜绿假单胞、大肠埃希菌和嗜麦芽窄食单胞菌等。其中16例发生VAP(16/21),高于未定植组(5/14),差别均有统计学意义(p＜0.05)。其中6例(17.14%)6株病原菌出现胃腔→口咽部→下呼吸道的定植次序,且对比其药敏谱完全相同,表明其可能具有同源性。②胃腔细菌定植组胃液pH(5.65±1.03)和TBA(57.06±54.75μmol/L)均高于无定植组(4.56±1.51、25.36±16.62μmol/L)(p＜0.01),胃液细菌定植组奥美拉唑使用(22/40)多于无定植组(28/81)(p=0.032),胃液细菌定植组SIgA(12.67±20.1μg/L)高于无定植组(12.18±14.22μg/L),但差别无统计学意义(p＞0.05)。③使用奥美拉唑的两组胃液pH(A组5.50±0.69、B组6.32±0.57)显著高于使用磷酸铝的两组(C组3.30±0.67,D组4.23±1.41),差别有统计学意义(p＜0.01),而在使用奥美拉唑的两组和使用磷酸铝的两组内(即A组与B组间,C组与D组间)胃液pH值差别无统计学意义(p＞0.05);各组胃液TBA(A组43.42±58.94μmol/L,B组31.78±23.18μmol/L,C组20.14±12.86μmol/L,D组36.39±30.25μmol/L)差别均无统计学意义;应用TPN两组胃液SIgA(A组3.50±5.13μg/L、C组1.97±0.896μg/L)显著低于应用EN的两组(B组24.27±22.30μg/L,D组13.81±15.45μg/L),差别有统计学意义(p＜0.01),而在应用TPN的两组和EN的两组内(即A组与C组间,B组与D组间)胃液SIgA水平差别无统计学意义(p＞0.05)。④胃液pH与TBA(r=0.175,P=0.055)、pH与SIgA(r=0.169,P=0.064)、TBA与SIgA(r=0.094,P=0.307)均不存在相关性。
结论:①COPD机械通气发生VAP患者中部分胃液、咽拭子和下呼吸道标本的培养结果出现致病菌的胃腔→口咽部→下呼吸道的逆向定植次序,验证了COPD机械通气患者胃肠道定植菌逆行与吸入是VAP的感染途径之一。②COPD机械通气患者胃液pH增高是胃内细菌定植的危险因素,使用奥美拉唑较磷酸铝因升高胃液pH而增加了胃内细菌定植的危险性,因此提示使用磷酸铝对VAP的发生有保护作用。③COPD机械通气患者胃液pH普遍偏高,可能与其疾病状态、鼻饲、年龄和胃十二指肠返流等因素有关。④COPD机械通气患者接受TPN可导致胃液SIgA水平降低,但SIgA水平既受营养类型的影响,同时也受感染等多方面因素影响,胃内细菌定植组与未定植组胃液SIgA水平未显示出差异。⑤胆汁返流是COPD机械通气患者胃内细菌定植的危险因素,胃液TBA与pH无直接相关性。
Objective:In order to provide some clues to keep the chronic obstructive pulmonary disease(COPD)patients undergoing mechanical ventilation away from ventilator associated pneumonia(VAP),we set out to investigate:①the part the intragastric bacteria plays in the pathogenesis of VAP in COPD patients,②the influences of the physiochemical features of the gastric fluid,including pH value,SIgA and TBA level on the colonization of the intragastric bacteria and③the effects of acid inhibitors, mucosal protective agents and the type of nutrition support on the above mentioned features of the gastric fluid of the mechanical ventilated COPD patients.
Methods:35 COPD patients undergoing mechanical ventilation were enrolled in our study.Bacteriological examination was made for the samples of lower respiratory tract,gastric fluid and pharyngeal swab by means of semi-quantitative cultivation. SIgA and TBA level in the gastric fluid was measured by means of double antibody sandwich radiation immunological test and enzymatic cycling assay,respectively.The pH value of the gastric fluid was determined by precision pH test paper.The administration of acidic inhibitor,mucosal protective agents and the type of nutritious support was recorded,and the occurrence of VAP was assessed.All the experimental data were processed and analyzed by SPSS13.0 statistic software package.
Results:①Of all the 121 gastric fluid samples obtained from the 35 patients, intragastric bacteria colonization was spotted in 40 samples belonging to 21 cases. Totally,45 bacterial strains were isolated,which were mainly Acinetobacter baumannii,Klebsiella pneumoniae,Pseudomonas aeruginosa,Escherichia coli and Stenotrophomonas maltophilia.Among all these colonized cases,16(16/21) developed VAP,which was significantly higher than the non-colonized group(5/14, p＜0.05).In 6 cases,6 strains manifested a colonization order of gastric cavity, oropharynx and lower respiratory tract.All the colonies obtained from various positions share the same antibiotic sensitive spectrum,indicating the homogeneity among them.②The pH value and TBA level of the gastric fluid from the colonized group(5.65±1.03 and 57.06±54.75μmol/L,respectively)was significantly higher than that of the non-colonized group(4.56±1.51 and 25.36±16.62μmol/L,respectively) (p＜0.01).The frequency of omeprazole administration in the colonized group(22/40) was higher than that of the non-colonized group(28/81,p=0.032).The SIgA level in the gastric fluid of the colonized group(12.67±20.1μg/L)was higher than that of the non-colonized group(12.18±14.22μg/L),although the difference was statistically insignificant(p＞0.05).③Significant difference was spotted between the pH value of the gastric fluid from the 2 omeprazole treatment groups(group A,5.50±0.69;group B,6.32±0.57)and the 2 non-omeprazole treatment groups(group C,3.30±0.67;group D,4.23±1.41)(p＜0.01).No significant difference was found within the 2 omeprazole treatment groups and the 2 non-omeprazole treatment groups(p＞0.05).There was no significant difference among the four groups in TBA level,which was 43.42±58.94, 31.78±23.18,20.14±12.86,and 36.39±30.25μmol/L for group A,B,C and D, respectively.The SIgA levels in the gastric fluid of the 2 TPN groups(group A, 3.50±5.13μg/L and group C,1.97±0.896μg/L)were significantly lower than those of the 2 EN groups(group B,24.27±22.30μg/L and group D,13.81±15.45μg/L) (p＜0.01),while no significant difference existed within the 2 TPN groups and the 2 EN groups(p＞0.05).④No correlations had been spotted between pH and TBA (r=0.175,P=0.055),pH and SIgA(r=0.169,P=0.064)and TBA and SIgA(r=0.094, P=0.307)in the gastric fluid samples.
Conclusions:①The positive cultivation results of pathogenic bacteria in the gastric fluid,pharyngeal swabs and the lower respiratory tract samples revealed a colonization order of gastric cavity,oropharynx and lower respiratory tract and further demonstrated that retrogradation and aspiration was one of the infection routes of VAP in mechanical ventilated COPD patients.②Higher pH value of gastric fluid was a risk factor of intragastric bacteria colonization and omeprazole could increase the risk of the colonization by elevating this index,which indicated that compared with omeprazole,mucosal protective agent aluminum phosphate could provide more protective effects against VAP.③The gastric fluid pH value of the mechanical ventilated COPD patients trended to be much higher,which could be attributed to the influential factors such as morbid state,nasogastric feeding,age and gastroduodenal reflux.④TPN could decrease the SIgA level in the gastric fluid of mechanical ventilated COPD patients.However,since the SIgA level was affected by not only the type of nutrition support but also other factors such as infection,no difference had been spotted between the colonized and the non-colonized groups.⑤Bile reflux was a risk factor of intragastric bacteria colonization.No correlation existed between TBA level and pH value in gastric fluid.
方法:对35例COPD行机械通气患者,采用半定量培养法对下呼吸道、胃液、咽拭子标本进行细菌学检测;采用双抗体夹心放免法测定胃液SIgA水平;采用循环酶法测定胃液TBA水平;采用精密pH试纸测定胃液pH值;记录抑酸剂或黏膜保护剂的使用,营养支持类型,评价VAP发生情况。数据以SPSS13.0统计软件进行处理。
结果:①35例患者121份胃液标本中有21例(60%)40份(33.06%)发生胃腔细菌定植,共分离菌株45株,主要为鲍曼不动杆菌、肺炎克雷白杆菌、铜绿假单胞、大肠埃希菌和嗜麦芽窄食单胞菌等。其中16例发生VAP(16/21),高于未定植组(5/14),差别均有统计学意义(p＜0.05)。其中6例(17.14%)6株病原菌出现胃腔→口咽部→下呼吸道的定植次序,且对比其药敏谱完全相同,表明其可能具有同源性。②胃腔细菌定植组胃液pH(5.65±1.03)和TBA(57.06±54.75μmol/L)均高于无定植组(4.56±1.51、25.36±16.62μmol/L)(p＜0.01),胃液细菌定植组奥美拉唑使用(22/40)多于无定植组(28/81)(p=0.032),胃液细菌定植组SIgA(12.67±20.1μg/L)高于无定植组(12.18±14.22μg/L),但差别无统计学意义(p＞0.05)。③使用奥美拉唑的两组胃液pH(A组5.50±0.69、B组6.32±0.57)显著高于使用磷酸铝的两组(C组3.30±0.67,D组4.23±1.41),差别有统计学意义(p＜0.01),而在使用奥美拉唑的两组和使用磷酸铝的两组内(即A组与B组间,C组与D组间)胃液pH值差别无统计学意义(p＞0.05);各组胃液TBA(A组43.42±58.94μmol/L,B组31.78±23.18μmol/L,C组20.14±12.86μmol/L,D组36.39±30.25μmol/L)差别均无统计学意义;应用TPN两组胃液SIgA(A组3.50±5.13μg/L、C组1.97±0.896μg/L)显著低于应用EN的两组(B组24.27±22.30μg/L,D组13.81±15.45μg/L),差别有统计学意义(p＜0.01),而在应用TPN的两组和EN的两组内(即A组与C组间,B组与D组间)胃液SIgA水平差别无统计学意义(p＞0.05)。④胃液pH与TBA(r=0.175,P=0.055)、pH与SIgA(r=0.169,P=0.064)、TBA与SIgA(r=0.094,P=0.307)均不存在相关性。
结论:①COPD机械通气发生VAP患者中部分胃液、咽拭子和下呼吸道标本的培养结果出现致病菌的胃腔→口咽部→下呼吸道的逆向定植次序,验证了COPD机械通气患者胃肠道定植菌逆行与吸入是VAP的感染途径之一。②COPD机械通气患者胃液pH增高是胃内细菌定植的危险因素,使用奥美拉唑较磷酸铝因升高胃液pH而增加了胃内细菌定植的危险性,因此提示使用磷酸铝对VAP的发生有保护作用。③COPD机械通气患者胃液pH普遍偏高,可能与其疾病状态、鼻饲、年龄和胃十二指肠返流等因素有关。④COPD机械通气患者接受TPN可导致胃液SIgA水平降低,但SIgA水平既受营养类型的影响,同时也受感染等多方面因素影响,胃内细菌定植组与未定植组胃液SIgA水平未显示出差异。⑤胆汁返流是COPD机械通气患者胃内细菌定植的危险因素,胃液TBA与pH无直接相关性。
Objective:In order to provide some clues to keep the chronic obstructive pulmonary disease(COPD)patients undergoing mechanical ventilation away from ventilator associated pneumonia(VAP),we set out to investigate:①the part the intragastric bacteria plays in the pathogenesis of VAP in COPD patients,②the influences of the physiochemical features of the gastric fluid,including pH value,SIgA and TBA level on the colonization of the intragastric bacteria and③the effects of acid inhibitors, mucosal protective agents and the type of nutrition support on the above mentioned features of the gastric fluid of the mechanical ventilated COPD patients.
Methods:35 COPD patients undergoing mechanical ventilation were enrolled in our study.Bacteriological examination was made for the samples of lower respiratory tract,gastric fluid and pharyngeal swab by means of semi-quantitative cultivation. SIgA and TBA level in the gastric fluid was measured by means of double antibody sandwich radiation immunological test and enzymatic cycling assay,respectively.The pH value of the gastric fluid was determined by precision pH test paper.The administration of acidic inhibitor,mucosal protective agents and the type of nutritious support was recorded,and the occurrence of VAP was assessed.All the experimental data were processed and analyzed by SPSS13.0 statistic software package.
Results:①Of all the 121 gastric fluid samples obtained from the 35 patients, intragastric bacteria colonization was spotted in 40 samples belonging to 21 cases. Totally,45 bacterial strains were isolated,which were mainly Acinetobacter baumannii,Klebsiella pneumoniae,Pseudomonas aeruginosa,Escherichia coli and Stenotrophomonas maltophilia.Among all these colonized cases,16(16/21) developed VAP,which was significantly higher than the non-colonized group(5/14, p＜0.05).In 6 cases,6 strains manifested a colonization order of gastric cavity, oropharynx and lower respiratory tract.All the colonies obtained from various positions share the same antibiotic sensitive spectrum,indicating the homogeneity among them.②The pH value and TBA level of the gastric fluid from the colonized group(5.65±1.03 and 57.06±54.75μmol/L,respectively)was significantly higher than that of the non-colonized group(4.56±1.51 and 25.36±16.62μmol/L,respectively) (p＜0.01).The frequency of omeprazole administration in the colonized group(22/40) was higher than that of the non-colonized group(28/81,p=0.032).The SIgA level in the gastric fluid of the colonized group(12.67±20.1μg/L)was higher than that of the non-colonized group(12.18±14.22μg/L),although the difference was statistically insignificant(p＞0.05).③Significant difference was spotted between the pH value of the gastric fluid from the 2 omeprazole treatment groups(group A,5.50±0.69;group B,6.32±0.57)and the 2 non-omeprazole treatment groups(group C,3.30±0.67;group D,4.23±1.41)(p＜0.01).No significant difference was found within the 2 omeprazole treatment groups and the 2 non-omeprazole treatment groups(p＞0.05).There was no significant difference among the four groups in TBA level,which was 43.42±58.94, 31.78±23.18,20.14±12.86,and 36.39±30.25μmol/L for group A,B,C and D, respectively.The SIgA levels in the gastric fluid of the 2 TPN groups(group A, 3.50±5.13μg/L and group C,1.97±0.896μg/L)were significantly lower than those of the 2 EN groups(group B,24.27±22.30μg/L and group D,13.81±15.45μg/L) (p＜0.01),while no significant difference existed within the 2 TPN groups and the 2 EN groups(p＞0.05).④No correlations had been spotted between pH and TBA (r=0.175,P=0.055),pH and SIgA(r=0.169,P=0.064)and TBA and SIgA(r=0.094, P=0.307)in the gastric fluid samples.
Conclusions:①The positive cultivation results of pathogenic bacteria in the gastric fluid,pharyngeal swabs and the lower respiratory tract samples revealed a colonization order of gastric cavity,oropharynx and lower respiratory tract and further demonstrated that retrogradation and aspiration was one of the infection routes of VAP in mechanical ventilated COPD patients.②Higher pH value of gastric fluid was a risk factor of intragastric bacteria colonization and omeprazole could increase the risk of the colonization by elevating this index,which indicated that compared with omeprazole,mucosal protective agent aluminum phosphate could provide more protective effects against VAP.③The gastric fluid pH value of the mechanical ventilated COPD patients trended to be much higher,which could be attributed to the influential factors such as morbid state,nasogastric feeding,age and gastroduodenal reflux.④TPN could decrease the SIgA level in the gastric fluid of mechanical ventilated COPD patients.However,since the SIgA level was affected by not only the type of nutrition support but also other factors such as infection,no difference had been spotted between the colonized and the non-colonized groups.⑤Bile reflux was a risk factor of intragastric bacteria colonization.No correlation existed between TBA level and pH value in gastric fluid.
引文
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[31] Valles J. Severe pneumonia: sources of infection and implications for treatment [J]. Sepsis, 1998,12(1): 199-209.
[32] DeWitt RC, Wu Y, Renegar KB, et al. Bombesin recovers gut-associated lymphoid tissue and preserves immunity to bacterial pneumonia in mice receiving total parenteral nutrition[J]. Annals of surgery, 2000, 231(1): 1-8.
[33] Fukatsu K, Moriya T, Maeshima Y, Exogenous interleukin 7 affects gut-associated lymphoid tissue in mice receiving total parenteral nutrition.[J]. Shock, .2005 , 24(6): 541-546.
[34] Cebra CK, Tornquist SJ, Bildfell RJ, et al. Bile acids in gastric fluids from llamas and alpacas with and without ulcers[J]. ret Intern Med 2003, 17(4): 567-567.
[35] Tae Young Oh, Chang Yell Shin, Yong Sung Sohn, et al. Therapeutic effect of DA-9601 on chronic reflux gastritis induced by sodium taurocholate in rats [J]. World J Gastroenterol, 2005, 11(47): 7430-7435.
[36] Takeuchi K, Ogawa Y, Kagawa S, et al. Gastric ulcerogenic responses following barrier disruption in knockout mice lackin g prostaglandin EP1 receptors [J]. Aliment PharmacofTher, 2002, 16(2) : 74-82.
[37] Vere CC, Cazacu S, Comanescu V, et al. Endoscopical and histological features in bile reflux gastritis[J]. Rom J Morphol Embryol., 2005, 46(4): 269-274.
[38] Kauer WK, Stein HJ. Bile reflux in the constellation of gastroesophageal reflux disease_[J]. Thorac Surg Clin., 2005, 15(3): 335-340.
[39]朱宜人,陈维顺,李舜午,等.危重病人24h动态胃内pH和胆汁反流监测的研究[J].中国医学工程,2006,14(5):487-496.
[40]Zhang C,Liu ZK,Yu PW.Effects of bile reflux and intragastric microflora changes on lesions of remnant gastric mucosa after gastric operation[J].World J Gastroenterol,2004,10(10):1537-1539.
[41]Fuchs KH,Maroske J,Fein M,et al.Variability in the composition of physiologic duodenogastric reflux[J].J Gastrointest Surg,1999,3(4):389-395.
[1]Young PJ,Ridley SA.Ventilator- associated pneumonia.Diagnosis pathogenesis and prevention[J].Anaesthesia,1999,54(12):1183-1197.
[2]方智野,王健,袁本通.呼吸机相关肺炎病原菌来源分析[J].临床医药实践杂志,2002,11(11):808-810.
[3]杨敬芳,王鑫,时东彦,李继红.呼吸机相关性肺炎患者下呼吸道和胃液分离菌的分布特点及耐药性分析[J].医师进修杂志(内科版),2004,27(8):32-34.
[4]代芊,周涌,宁涛,等.院内肺炎逆行感染途径的Southern印迹杂交分析[J].中华医院感染学杂志,2003,13(4):301-304.
[5]闫春良,赵呈恩.慢性阻塞性肺病患者机械通气期间营养支持的方法与时机[J]..中国航天医药杂志,2003,5(3):28-30.
[6]刘又宁主编.机械通气与临床(第二版)[M].北京:科学出版社,1998:172.
[7]刘明华,张庆玲,文亮,等.机械通气患者胃液sIgA含量、pH值与胃内细菌定植的关系[J].中国感染控制杂志,2004,3(4):305-307.
[8]Kantorova I,Svoboda P,Scheer P,et al.Stress ulcer prophylaxis in critically ill patients:a randomized controlled trial[J].Hepatogastroenterology,2004,51(57):757-761.
[9]蔡少华.呼吸机相关肺炎的预防新策略[J].国外医学内科学分册,2000,27(6):242-245.
[10]Valles J.Severe pneumonia:sources of infection and implications for treatment [J].Sepsis,1998,1:199-209.
[11]R.Chance DeWitt,Yong Wu,Kathryn B,et al.Bombesin recovers gut-associated lymphoid tissue and preserves immunity to bacterial pneumonia in mice receiving total parenteral nutrition[J].Annals of surgery,2000,231(1):1-8.
[12]周宏,任玲,郑雯,等.ICU呼吸机相关肺炎发病危险因素研究[J].中国感染控制杂志,2005,4(4):308-311.
[13]张庆玲,刘明华,刘玉馥,等.呼吸机相关性肺炎胃肺感染路径的前瞻性研究[J].中华烧伤杂志,2004,20(1):20-22.
[14]Nind G,Chen WH,Protheroe R,et al.Mechanisms of gastroesophageal reflux in critically ill mechanically ventilated patients[J].Gastroenterology,2005,128(3):600-606.
[15]胡奕.22例危重病症胃液胆汁酸水平测定分析[J].浙江临床医学,2003,5(3):211.
[16]Montejo JC,Enteral nutrition,related gastrointestinal complications in critically iI patients:a multicenter study:The Nutritional and Meta.belie Working Group of the Spanish Society of Intensive Care Medicine and Coronary Units[J].Crit Care Med,1999,27(8):1447-1453.
[17]Neora P,Anne M,Nancy B,et al.PuimonaryAspiration In Aliong-Term Care Setting:ClincialAnd Laboratory Observations And An Analysis Of Risk Factors[J].The American Geriatrics Society,1996,44:763-768.
[18]Wilmer A,Tack J,Frans E,et.Duodenogastroesophageal reflux and esophageal mucosal in ury in mechanically ventilated patients[J].Gastrentemlogy,1999,116(6):1293-1299.
[19]Loeb M,McGreer A,McArthur M,et al.Risk factors for pneumonia and other lower respiratory tract infections in elderly residents of long-term care facilities [J].Arch Intern Med,1999,159(3):2058-2064.
[20]Vergis EN,Brennen C,Wagener M,et al.Pneumonia in long-term care:a prospective case-control study of risk factors and impact on survival.[J].Arch Intern Med,2001,161(5):2378-2381.
[21]Akinci IO,Cakar N,Mutlu GM,et al.Gastric intramucosal pH is stable during titration of positive end-expiratory pressure to improve oxygenation in acute respiratory distress syndrome[J].Crit Care.2003,7(3):17-23.
[22]Tulaimat A,Laghi F,Mikrut K,et al.Potassium sorbate reduces gastric colonization in patients receiving mechanical ventilation.[J].J Crit Care,2006,20(3):212-230.
[23]Hevlan DK,Cook D,Scamenfeldl,et al.The effect of acidified enteral feeds on gastric colonization in critically ill patients:Results of a muticenter randomizedl trial[J].Crit Care Med,1999,27(11):2395-2406.
[24]Kappstein I。Schulgen G,Friedrich T,et al.Incidence of pneumonia in mechanically patients treated with ventilated patients treated with suralfate or cimetidine as prophylaxis for stress bleeding,bacterial colonization of the stomach[J].Am J Med.1998.151:1255-1315.
[25]Hulst VD,Prof VM,T iebo sch A,et al.Glutam ine and intestinal immune cells in humans.JPEN,1997,21(6):310-315
[26]谢江霞,吴升,邝志诚.机械通气患者早期肠内外营养支持的比较研究[J].广州医药,2003,34(1):36-38.
[27]Kmeger WA,HeiningerA,Unertl KE.Selectivedigestive digestive tract decontamination in intensive care medicine.Fundamentals and current evalution [J].Anathesist,2003,52(2):142-152.
[28]Parra M M,Arias R S,la caIL M,et al.Effect of selective digestive decontamination on the nosomial infection and mutiresistant microorganisms incidence in critically ill patients[J].Ther Apher,2002,23(6):361-364.
[29]Veelo DP,Bulut T,Dongelmans DA,et al.The incidence and microbial spectrum of ventilator-associated pneumonia after tracheotomy in a selective decontamination of the digestive tract-setting.[J]J Infect,2008,56(1):20-26.
[30]Sanchez G M,Cambronero GJ,Lopez DJ,et al.effectiveness and cost of selective decntamination of the digestive tract in critically ill intubate patients.A randomized,double—blind,placebo—controlled,multicenter trial[J].Am J Respir Crit Care Med,1998,158(3):908-916.
[31]Tulamait A,Laghi F,Mikrut K,et al.Potassium sorbate reduces gastric colonization in patients receiving mechanical ventilation.[J].Crit Care.2005,20(3):281-287.
[32]Gowardman J,Sleigh J,Barnes N,et al.Intermittent enteral nutrition a comparative study examining the effect on gastric pH and microbial colonization rates[J].Anaesth Intensive Care,2003,1(1):28-33.
[33]Pneumatikos J,Koulouras B,Frangides C,et al.Cisapride decreases gastrieontenl aspiration in mechanically ventilated patients[J].Crit Care,1999,21(3):39-43.
[2]Craven DE.Preventing Ventilator-Associated Pneumonia in Adults.[J].Chest,2006,130(1):251-260.
[3]Suka M,Yoshida K,Uno H,et al..Incidence and outcomes of ventilator-associated pneumonia in Japanese intensive care units:the Japanese nosocomial infection surveillance system[J].Infect Control Hosp Epidemiol,2007,28(3):307-313.
[4]Koeman M,van der Ven AJ,et al.Oral decontamination with chlorhexidine reduces the incidence of ventilator-associated pneumonia.[J].Am J Respir Crit Care Med.,2006,173(12):1348-1355.
[5]Safdar N,Cmich CJ,Maki DG,et al.The pathogenesis of ventilator-associated pneumonia:its relevance to developing effective strategies for prevention[J].Respir Care,2006,51(1):67-69.
[6]Kanafani ZA,Kara L,Hayek S,et al.Ventilator-Associated Pneumonia at a Tertiary-Care Center in a Developing Country:Incidence,Microbiology,and Susceptibility Patterns of Isolated Microorganisms[J].Infect Control Hosp Epidemiol,2003,24(11):864-869.
[7]中华医学会呼吸病学分会慢性阻塞性肺疾病学组.慢性阻塞性肺疾病诊治指南[J].中华结核和呼吸杂志,2002,25(8):453-460.
[8]Tulaimat A,Laghi F,Mikrut K,et al.Potassium sorbate reduces gastric colonization in patients receiving mechanical ventilation.[J].J Crit Care,2006,20(3):212-230.
[9]van Saene HK,Zandstra DF.Selective decontamination of the digestive tract: rationale behind evidence-based use in liver transplantation.[J].Liver Transpl,2004,10(7):828-833.
[10]Mobbs KJ,van Saene HK,Sunderland D,et al.Oropharyngeal Gram-negative bacillary carriage in chronic obstructive pulmonary disease:relation to severity of disease[J].RespirMed,1999,93(8):540-545.
[11]Kallet RH,Quinn TE.The Gastrointestinal Tract and Ventilator-Associated Pneumonia[J].RespirCare,2005,50(7):910-921.
[12]Veelo DP,Bulut T,Dongelmans DA,et al.The incidence and microbial spectrum of ventilator-associated pneumonia after tracheotomy in a selective decontamination of the digestive tract-setting.[J]J Infect,2008,56(1):20-26.
[13]Feldman C,Kassel M,Cantrell J,et al.The presence and sequence of endotracheal tube colonization in patients undergoing mechanical ventilation[J].Eur Respir J,1999,13(3):546-551.
[14]方智野,王健,袁本通.呼吸机相关肺炎病原菌来源分析[J].临床医药实践杂志,2002,11(11):808-810..
[15]杨敬芳,王鑫,时东彦,李继红.呼吸机相关性肺炎患者下呼吸道和胃液分离菌的分布特点及耐药性分析[J].医师进修杂志(内科版),2004,27(8):32-34.
[16]代芊,周涌,宁涛,等.院内肺炎逆行感染途径的Southern印迹杂交分析[J].中华医院感染学杂志,2003,13(4):301-303.
[17]李华茵,何礼贤,胡必杰,等.呼吸机相关肺炎内源性感染途径的分子流行病学研究[J].中华医院感染杂志,2004,14(2):121-125.
[18]Na A,Smith G.Gastroesophageal reflux and aspiration of gastric contents in anesthetic practice[J].Anesth Analg,2001,93(2):494-513.
[19]Nind G,Chen WH,Protheroe R,et al.Mechanisms of gastroesophageal reflux in critically ill mechanically ventilated patients.[J].Gastroenterology,2005,128(3): 600-606.
[20]张庆玲,刘明华,刘玉馥,等.呼吸机相关性肺炎胃肺感染路径的前瞻性研究.[J].中华烧伤杂志,2004,20(1):20-22.
[21]代芊,邓宏,黄汉朝,等.院内感染性肺炎逆行感染途径的基因多态性研究[J].第三军医大学学报,2000,22(6):565-567.
[22]Montejo JC,Enteral nutrition,related gastrointestinal complications in critically iI patients:a multicenter study:The Nutritional and Meta.belie Working Group of the Spanish Society of Intensive Care Medicine and Coronary Units[J].Crit Care Med,1999,27(8):1447-1453.
[23]Neora P,Anne M,Nancy B,et al.PuimonaryAspiration In a long-Term Care Setting:ClincialAnd Laboratory Observations and an analysis of Risk Factors[J].The American Geriatrics Society,1996,44(7):763-768.
[24]Kantorova I,Svoboda P,Scheer P,et al.Stress ulcer prophylaxis in critically ill patients:a randomized controlled trial.[J].Hepatogastroenterology,2004,51(57):757-761.
[25]刘明华,张庆玲,文亮,等.机械通气患者胃液SIgA含量、pH值与胃内细菌定植的关系[J].中国感染控制杂志,2004,3(4):305-307.
[26]Hevlan DK,Cook D,Scamenfeldl,et al.The effect of acidified enteral feeds on gastric colonization in critically ill patients:Results of a muticenter randomizedl trial[J].Crit Care Med,1999,27(11):2395-2406.
[27]Talon D,Mulin B,Rouget C,et al.Risks and mutes for Ventilator—associated pneumonia with pseudomonas aeruginosa[J].Am J Respir Crit Care,1998,16(2):157-163.
[28]Cocanour CS,Dial ED,Lichtenberger LM,et al.Gastric alkalinization after major trauma.[J].Trauma.,2008,64(3):681-687.
[29]Dial E,Lopez-Storey M,Adams S,et al.A report on associations among gastric pH, bleeding, duodenogastric reflux, and outcomes after trauma.[J]. Trauma, 2008 , 64(1): 105-110.
[30] Godding V, SibilleY, MassionPP, et al. Secretory component production by human bronchial epithelial cells is upregulated by interferon gamma. Eur Respir J, 1998, 11(5): 1043-1052.
[31] Valles J. Severe pneumonia: sources of infection and implications for treatment [J]. Sepsis, 1998,12(1): 199-209.
[32] DeWitt RC, Wu Y, Renegar KB, et al. Bombesin recovers gut-associated lymphoid tissue and preserves immunity to bacterial pneumonia in mice receiving total parenteral nutrition[J]. Annals of surgery, 2000, 231(1): 1-8.
[33] Fukatsu K, Moriya T, Maeshima Y, Exogenous interleukin 7 affects gut-associated lymphoid tissue in mice receiving total parenteral nutrition.[J]. Shock, .2005 , 24(6): 541-546.
[34] Cebra CK, Tornquist SJ, Bildfell RJ, et al. Bile acids in gastric fluids from llamas and alpacas with and without ulcers[J]. ret Intern Med 2003, 17(4): 567-567.
[35] Tae Young Oh, Chang Yell Shin, Yong Sung Sohn, et al. Therapeutic effect of DA-9601 on chronic reflux gastritis induced by sodium taurocholate in rats [J]. World J Gastroenterol, 2005, 11(47): 7430-7435.
[36] Takeuchi K, Ogawa Y, Kagawa S, et al. Gastric ulcerogenic responses following barrier disruption in knockout mice lackin g prostaglandin EP1 receptors [J]. Aliment PharmacofTher, 2002, 16(2) : 74-82.
[37] Vere CC, Cazacu S, Comanescu V, et al. Endoscopical and histological features in bile reflux gastritis[J]. Rom J Morphol Embryol., 2005, 46(4): 269-274.
[38] Kauer WK, Stein HJ. Bile reflux in the constellation of gastroesophageal reflux disease_[J]. Thorac Surg Clin., 2005, 15(3): 335-340.
[39]朱宜人,陈维顺,李舜午,等.危重病人24h动态胃内pH和胆汁反流监测的研究[J].中国医学工程,2006,14(5):487-496.
[40]Zhang C,Liu ZK,Yu PW.Effects of bile reflux and intragastric microflora changes on lesions of remnant gastric mucosa after gastric operation[J].World J Gastroenterol,2004,10(10):1537-1539.
[41]Fuchs KH,Maroske J,Fein M,et al.Variability in the composition of physiologic duodenogastric reflux[J].J Gastrointest Surg,1999,3(4):389-395.
[1]Young PJ,Ridley SA.Ventilator- associated pneumonia.Diagnosis pathogenesis and prevention[J].Anaesthesia,1999,54(12):1183-1197.
[2]方智野,王健,袁本通.呼吸机相关肺炎病原菌来源分析[J].临床医药实践杂志,2002,11(11):808-810.
[3]杨敬芳,王鑫,时东彦,李继红.呼吸机相关性肺炎患者下呼吸道和胃液分离菌的分布特点及耐药性分析[J].医师进修杂志(内科版),2004,27(8):32-34.
[4]代芊,周涌,宁涛,等.院内肺炎逆行感染途径的Southern印迹杂交分析[J].中华医院感染学杂志,2003,13(4):301-304.
[5]闫春良,赵呈恩.慢性阻塞性肺病患者机械通气期间营养支持的方法与时机[J]..中国航天医药杂志,2003,5(3):28-30.
[6]刘又宁主编.机械通气与临床(第二版)[M].北京:科学出版社,1998:172.
[7]刘明华,张庆玲,文亮,等.机械通气患者胃液sIgA含量、pH值与胃内细菌定植的关系[J].中国感染控制杂志,2004,3(4):305-307.
[8]Kantorova I,Svoboda P,Scheer P,et al.Stress ulcer prophylaxis in critically ill patients:a randomized controlled trial[J].Hepatogastroenterology,2004,51(57):757-761.
[9]蔡少华.呼吸机相关肺炎的预防新策略[J].国外医学内科学分册,2000,27(6):242-245.
[10]Valles J.Severe pneumonia:sources of infection and implications for treatment [J].Sepsis,1998,1:199-209.
[11]R.Chance DeWitt,Yong Wu,Kathryn B,et al.Bombesin recovers gut-associated lymphoid tissue and preserves immunity to bacterial pneumonia in mice receiving total parenteral nutrition[J].Annals of surgery,2000,231(1):1-8.
[12]周宏,任玲,郑雯,等.ICU呼吸机相关肺炎发病危险因素研究[J].中国感染控制杂志,2005,4(4):308-311.
[13]张庆玲,刘明华,刘玉馥,等.呼吸机相关性肺炎胃肺感染路径的前瞻性研究[J].中华烧伤杂志,2004,20(1):20-22.
[14]Nind G,Chen WH,Protheroe R,et al.Mechanisms of gastroesophageal reflux in critically ill mechanically ventilated patients[J].Gastroenterology,2005,128(3):600-606.
[15]胡奕.22例危重病症胃液胆汁酸水平测定分析[J].浙江临床医学,2003,5(3):211.
[16]Montejo JC,Enteral nutrition,related gastrointestinal complications in critically iI patients:a multicenter study:The Nutritional and Meta.belie Working Group of the Spanish Society of Intensive Care Medicine and Coronary Units[J].Crit Care Med,1999,27(8):1447-1453.
[17]Neora P,Anne M,Nancy B,et al.PuimonaryAspiration In Aliong-Term Care Setting:ClincialAnd Laboratory Observations And An Analysis Of Risk Factors[J].The American Geriatrics Society,1996,44:763-768.
[18]Wilmer A,Tack J,Frans E,et.Duodenogastroesophageal reflux and esophageal mucosal in ury in mechanically ventilated patients[J].Gastrentemlogy,1999,116(6):1293-1299.
[19]Loeb M,McGreer A,McArthur M,et al.Risk factors for pneumonia and other lower respiratory tract infections in elderly residents of long-term care facilities [J].Arch Intern Med,1999,159(3):2058-2064.
[20]Vergis EN,Brennen C,Wagener M,et al.Pneumonia in long-term care:a prospective case-control study of risk factors and impact on survival.[J].Arch Intern Med,2001,161(5):2378-2381.
[21]Akinci IO,Cakar N,Mutlu GM,et al.Gastric intramucosal pH is stable during titration of positive end-expiratory pressure to improve oxygenation in acute respiratory distress syndrome[J].Crit Care.2003,7(3):17-23.
[22]Tulaimat A,Laghi F,Mikrut K,et al.Potassium sorbate reduces gastric colonization in patients receiving mechanical ventilation.[J].J Crit Care,2006,20(3):212-230.
[23]Hevlan DK,Cook D,Scamenfeldl,et al.The effect of acidified enteral feeds on gastric colonization in critically ill patients:Results of a muticenter randomizedl trial[J].Crit Care Med,1999,27(11):2395-2406.
[24]Kappstein I。Schulgen G,Friedrich T,et al.Incidence of pneumonia in mechanically patients treated with ventilated patients treated with suralfate or cimetidine as prophylaxis for stress bleeding,bacterial colonization of the stomach[J].Am J Med.1998.151:1255-1315.
[25]Hulst VD,Prof VM,T iebo sch A,et al.Glutam ine and intestinal immune cells in humans.JPEN,1997,21(6):310-315
[26]谢江霞,吴升,邝志诚.机械通气患者早期肠内外营养支持的比较研究[J].广州医药,2003,34(1):36-38.
[27]Kmeger WA,HeiningerA,Unertl KE.Selectivedigestive digestive tract decontamination in intensive care medicine.Fundamentals and current evalution [J].Anathesist,2003,52(2):142-152.
[28]Parra M M,Arias R S,la caIL M,et al.Effect of selective digestive decontamination on the nosomial infection and mutiresistant microorganisms incidence in critically ill patients[J].Ther Apher,2002,23(6):361-364.
[29]Veelo DP,Bulut T,Dongelmans DA,et al.The incidence and microbial spectrum of ventilator-associated pneumonia after tracheotomy in a selective decontamination of the digestive tract-setting.[J]J Infect,2008,56(1):20-26.
[30]Sanchez G M,Cambronero GJ,Lopez DJ,et al.effectiveness and cost of selective decntamination of the digestive tract in critically ill intubate patients.A randomized,double—blind,placebo—controlled,multicenter trial[J].Am J Respir Crit Care Med,1998,158(3):908-916.
[31]Tulamait A,Laghi F,Mikrut K,et al.Potassium sorbate reduces gastric colonization in patients receiving mechanical ventilation.[J].Crit Care.2005,20(3):281-287.
[32]Gowardman J,Sleigh J,Barnes N,et al.Intermittent enteral nutrition a comparative study examining the effect on gastric pH and microbial colonization rates[J].Anaesth Intensive Care,2003,1(1):28-33.
[33]Pneumatikos J,Koulouras B,Frangides C,et al.Cisapride decreases gastrieontenl aspiration in mechanically ventilated patients[J].Crit Care,1999,21(3):39-43.