Comprehensive Intervention And Pathogenesis Of Ventilator-associated Pneumonia In Elderly Patients: Clinical Trial And Experiment Study

Background: Ventilator-associated pneumonia (VAP) is one of the most common noscomial pneumonia (NP) and had serious influence on the outcome. Incidence and mortality of VAP are considerably high, especially in the elderly patients. Prevention becomes very critical. There are relative short of multi-center, prospective, randomized design, including large population participated clinical research of VAP as well as prevention measures in the elderly patients. The animal experiments are also not mature.Objective: To assess the value of comprehensive prevention measure to VAP of patients more than 60ys and investigate the pathogenesis of VAP.Methods: Patients more than 60ys with expected mechanical ventilation >48h were randomly assigned to control group receiving a standard endotracheal tube or comprehensive intervention group being given semi-recumbent, mosapride citrate, and endotracheal tube for continuous subglottic secretions drainage. The characteristics of cases were record when they enrolled the clinical trial and bacterial culture of gastric juice, material from subglottic drainage and lower respiratory tract (LRT) were taken. Compare the duration of mechanical ventilation, length of ICU/ hospital stay, the incidence, mortality, contributable mortality, relative risk as well as the bacterial concordance in gastric juice or LRT between two groups. Some cases were given methylene blue through the gastric tube and the time, rates of methylene blue found in LRT under microscope were observed to illustrate the aspiration. Pulsed-field gel electrophoresis of DNA macro-restriction fragments was used to identify the relatedness of the pathogen from different part and analyzed the incidence rates of homology in two groups. In the animal 1 experiment, the VAP model established first. The bacterium of gastric fluid and blood gas were monitored during ventilation. Wet weight of the lung, blood stream and lung homogenized were both cultured after the rabbits sacrificed. Some animals were given computerized tomography (CT) of thechest before death. Then mosapride citrate or loperamide were administered and the flora in oropharynx and airway were monitored in different time.Results: (1) Eighty-six cases enrolled the clinical trial, including 41 in I group and 45 in C group. The duration of mechanical ventilation, length of ICU/hospital stay in I group were all less than C group. The incidence of VAP among whole cases was 51. 2%,34.1% in I group and 66. 7 % inC(p<0. 05). Two (4. 9%)cases ingroup I get EOP while 9 cases (20. 0 %) in group C(p<0. 05). The mortality, attributable mortality in group C was higher (p>0. 05). The RR was 0. 51 (95% CI 0.164—0. 634). The same bacterium type (28. 9%) predominantly are G- rod, commonly happened in LOP. Methylene blue in LRT or oropharynx under microscope being detected later in group I than C. (2) Fifteen cases including 35 strains (G—29 strains, G+ 6 strains) enrolled in PFGE. Twenty-nine identical strains mainly G-rod, were found in 12 cases including 4 of cross-infection. The ratio of same strains among LRT, gastric juice or the drain from subglottic were 11.9%, and 19.4 in group C, 3.2% in group I (p<0. 05). (3) In VAP model established experiment, different degree of inflammation were found in both MV and BMV group and much more serious in BMV group. Ratio of positive lung culture (bacterium concentration more than 10'cfu/g) was 40.09^ 81.8% separately in MV and BMV, and lung infection caused by inoculated bacterium was 9. 1%. The WW/BW and score of the lung were different (p<0. 05). CT shows density in multi-lobe of two lungs patchy increased, mainly distributed in lower and middle lobe. Positive blood stream was 45.5% in MV. In 37 animals 94.4% have bacterial colonization in oropharynx and 83.3% in airway, predominately Bord. bronchi sept ica. Ratio of lung infection caused by inoculate bacteria was 10.8%. Four negative colonization in upper airway also negative culture of lung. No significant variance about colonization was seen between I and P group, while the semi-quantitative concentration of inoculated bacterium in I was higher than in P. Although no significance difference of the VAP whole incidence found, VAP caused by inoculated bacterium in I was much higher than in P (15. 8% vs. 5.5%, p<0. 05). About 45. 9% in 37 cases, 63. 2% in inoculated...