Appraisal of systemic inflammation and diagnostic markers in a porcine model of VAP: secondary analysis from a study on novel preventive strategies.
Appraisal of systemic inflammation and diagnostic markers in a porcine model of VAP: secondary analysis from a study on novel preventive strategies.
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DOI：
10.1186/s40635-018-0206-1
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发表时间：
2018-10-20
影响因子：
3.5
通讯作者：
Torres A
中科院分区：
文献类型：
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作者：
Li Bassi G;Prats RG;Artigas A;Xiol EA;Marti JD;Ranzani OT;Rigol M;Fernandez L;Meli A;Battaglini D;Luque N;Ferrer M;Martin-Loeches I;Póvoa P;Chiumello D;Pelosi P;Torres A
我们先前评估了一种预防策略的有效性，以实现呼气流量偏差和呼气末正压（EFB + PEEP）或Trendelenburg位置（TP），以预防呼吸机相关性肺炎（VAP）。这些预防措施旨在改善粘液清除和减少肺部吸入含细菌的口咽分泌物。二次分析旨在评价上述干预措施对全身炎症的影响，并证实临床参数和细胞因子在VAP诊断中的价值。将20头雌性猪随机分配至半卧位/俯卧位，以占空比0.33通气，不使用PEEP（对照组）;与对照组相同定位，PEEP 5 cmH 2 O，占空比达到呼气流量偏差（EFB+PEEP）;与对照组相同通气，但采用头低脚高位（头低脚高位）。随机分组后，将铜绿假单胞菌滴入口咽部。每24小时定量全身细胞因子和气管分泌物铜绿假单胞菌浓度。收集肺活检用于VAP的微生物学确认。在对照组、EFB + PEEP组和Trendelenburg组中，肺组织铜绿假单胞菌浓度分别为2.4 ± 1.5、1.9 ± 2.1和0.3 ± 0.6 log cfu/mL（p = 0.020）。而VAP组和非VAP组分别为2.4 ± 1.9和0.6 ± 0.9logcfu/mL（p < 0.001）。在特伦德伦堡动物中发现白细胞介素（IL）-1β（p = 0.021）、IL-1 RA（p < 0.001）、IL-4（p = 0.005）、IL-8（p = 0.008）和IL-18（p = 0.050）水平较低。VAP增加了IL-10（p = 0.035）、肿瘤坏死因子-α（p = 0.041）和气管内抽吸物（ETA）铜绿假单胞菌浓度（p = 0.024）。包含ETA细菌负荷、IL-10和TNF-α的模型对VAP的诊断产生了中等区分度（受试者工作曲线面积0.82，95%CI 0.61-1.00）。我们的研究结果证明了与特伦德伦伯卧位相关的抗炎作用。在这种可靠的VAP模型中，ETA培养显示出良好的诊断准确性，而全身IL-10和TNF-α略微提高了准确性。进一步的临床研究将是必要的，以确认Trendelenburg位作为机械通气期间阻碍炎症的措施的临床价值以及全身IL-10和TNF-α在VAP诊断中的意义。
We previously evaluated the efficacy of a ventilatory strategy to achieve expiratory flow bias and positive end-expiratory pressure (EFB + PEEP) or the Trendelenburg position (TP) for the prevention of ventilator-associated pneumonia (VAP). These preventive measures were aimed at improving mucus clearance and reducing pulmonary aspiration of bacteria-laden oropharyngeal secretions. This secondary analysis is aimed at evaluating the effects of aforementioned interventions on systemic inflammation and to substantiate the value of clinical parameters and cytokines in the diagnosis of VAP. Twenty female pigs were randomized to be positioned in the semirecumbent/prone position, and ventilated with duty cycle 0.33 and without PEEP (control); positioned as in the control group, PEEP 5 cmH2O, and duty cycle to achieve expiratory flow bias (EFB+PEEP); ventilated as in the control group, but in the Trendelenburg position (Trendelenburg). Following randomization, P. aeruginosa was instilled into the oropharynx. Systemic cytokines and tracheal secretions P. aeruginosa concentration were quantified every 24h. Lung biopsies were collected for microbiological confirmation of VAP. In the control, EFB + PEEP, and Trendelenburg groups, lung tissue Pseudomonas aeruginosa concentration was 2.4 ± 1.5, 1.9 ± 2.1, and 0.3 ± 0.6 log cfu/mL, respectively (p = 0.020). Whereas, it was 2.4 ± 1.9 and 0.6 ± 0.9 log cfu/mL in animals with or without VAP (p < 0.001). Lower levels of interleukin (IL)-1β (p = 0.021), IL-1RA (p < 0.001), IL-4 (p = 0.005), IL-8 (p = 0.008), and IL-18 (p = 0.050) were found in Trendelenburg animals. VAP increased IL-10 (p = 0.035), tumor necrosis factor-α (p = 0.041), and endotracheal aspirate (ETA) P. aeruginosa concentration (p = 0.024). A model comprising ETA bacterial burden, IL-10, and TNF-α yielded moderate discrimination for the diagnosis of VAP (area of the receiver operating curve 0.82, 95% CI 0.61–1.00). Our findings demonstrate anti-inflammatory effects associated with the Trendelenburg position. In this reliable model of VAP, ETA culture showed good diagnostic accuracy, whereas systemic IL-10 and TNF-α marginally improved accuracy. Further clinical studies will be necessary to confirm clinical value of the Trendelenburg position as a measure to hinder inflammation during mechanical ventilation and significance of systemic IL-10 and TNF-α in the diagnosis of VAP.