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中华重症医学电子杂志

中华重症医学电子杂志 ›› 2016, Vol. 02 ›› Issue (01) : 50 -58. doi: 10.3877/cma.j.jssn.2096-1537.2016.01.012

所属专题： 文献；

基础研究

跨肺压法设置呼气末正压通气对急性呼吸窘迫综合征模型猪肺保护作用的研究
张敏1, 颜培夏2, 吴晓燕2, 郑瑞强2,*,*()   
  1. 1. 225001　扬州，苏北人民医院重症医学科；215600　张家港市第一人民医院重症医学科
    2. 225001　扬州，苏北人民医院重症医学科
  • 收稿日期:2015-12-27 出版日期:2016-02-28
  • 通信作者: 郑瑞强
  • 基金资助:
    江苏省"333高层次人才培养工程"基金(2011-15); 扬州市科技攻关-社会发展科技攻关(2012133)

Positive end expiratory pressure guided by transpulmonary pressure on lung protection in pig model with acute respiratory distress syndrome

Min Zhang1, Peixia Yan2, Xiaoyan Wu2, Ruiqiang Zhang2()   

  1. 1. Intensive Care Unit, Intensive Care Unit, Northern Jian gsu People's Hospital, Yangzhou 225001, China; Zhangjiagang First People's Hospital, Zhangjiagang 215600, China
    2. Intensive Care Unit, Intensive Care Unit, Northern Jiangsu People's Hospital, Yangzhou 225001, China
  • Received:2015-12-27 Published:2016-02-28
  • Corresponding author: Ruiqiang Zhang
  • About author:
    Corresponding author: Zhang Ruiqiang, Email:
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引用本文：

张敏, 颜培夏, 吴晓燕, 郑瑞强. 跨肺压法设置呼气末正压通气对急性呼吸窘迫综合征模型猪肺保护作用的研究[J]. 中华重症医学电子杂志, 2016, 02(01): 50-58.

Min Zhang, Peixia Yan, Xiaoyan Wu, Ruiqiang Zhang. Positive end expiratory pressure guided by transpulmonary pressure on lung protection in pig model with acute respiratory distress syndrome[J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2016, 02(01): 50-58.

目的

比较跨肺压法与最佳氧合法选择最佳呼气末正压通气（PEEP），对急性呼吸窘迫综合征（ARDS）模型猪肺损伤作用的影响。

方法

12只普通家猪随机分为跨肺压组和最佳氧合组，均给予有创通气、留置股动脉导管接PiCCO仪监测血流动力学及留置右颈内静脉导管测中心静脉压（CVP），稳定30 min后，行0.9%氯化钠溶液肺泡灌洗复制猪ARDS模型。模型成功后，在充分肺复张的基础上，两组分别使用跨肺压法和最佳氧合法设置最佳PEEP，并以此维持通气4 h。观察并记录基础状态（PEEP 5 cmH2O）（Tbase）、ARDS模型稳定（PEEP 5 cmH2O）（T0）和最佳PEEP维持机械通气4 h期间（T1-T4）的肺毛细血管通透性指数（PVPI）、血管外肺水指数（EVLWI）及呼吸力学变化，并在Tbase、T0、T4 3个时间点采集血标本，酶联免疫吸附剂测定法（ELISA）测定血白介素1β（IL-1β）、白介素6（IL-6）炎症因子表达水平。实验结束处死动物，留取猪右上肺、右下肺背侧、右下肺腹侧，行免疫组化测肺组织核转录因子kappa B（NF-κB）、IL-1β、IL-6水平，比色法测肺组织抗髓过氧化物酶（MPO）活性，同时观察病理改变及测湿干比反应肺水含量。

结果

呼吸力学方面：跨肺压组最佳PEEP、Pm、Paw-exp、Ptrans-exp明显低于最佳氧合组（P<0.05），而跨肺压组Ptrans-ins在最佳PEEP通气第3小时、第4小时明显低于最佳氧合组（P<0.05）。炎症反应方面：右肺上叶肺组织NF-κB、右全肺肺组织IL-6、右肺下叶背侧及右全肺MPO表达跨肺压组均明显低于最佳氧合组（P<0.05）。肺水肿指标方面：两组最佳PEEP通气4h后PVPI、EVLWI以及各部位湿干比（W/D）差异无统计学意义（P>0.05）。病理方面：跨肺压组右肺上叶、下叶背侧及右全肺损伤病理评分低于最佳氧合组（P>0.05）。

结论

通过跨肺压法设置最佳PEEP能够在维持肺泡开放状态的同时，减少肺炎症反应发生，预防肺损伤，达到肺保护作用。

关键词: 急性呼吸窘迫综合征, 机械通气, 肺损伤
Objective

To investigate the effect of positive end expiratory pressure (PEEP) guided by transpulmonary pressure compared with the optimal oxygenation-directed PEEP on lung injury in a pig model with acute respiratory distress syndrome(ARDS) .

Methods

Twelve ordinary pigs were randomly divided into a transpulmonary pressure group (n=6) and an optimal oxygenation group (n=6) . Both groups were given invasive mechanical ventilation. Their hemodynamics was monitored, and catheterization of the right internal jugular vein was done to test CVP. The hemodynamics was stable 30 minutes after the operation. The pigs were given lung lavage with normal saline to induce ARDS. The optimal PEEP was set by transpulmonary pressure titration or optimal oxygenation after lung recruitment. Thereafter, ventilation continued for 4 hours. PVPI, EVLWI and respiratory mechanics changes were recorded before lung lavage with saline (PEEP 5 cmH2O) (Tbase), after stabilization of ARDS (PEEP 5 cmH2O) (T0) and after using optimal PEEP for 0, l, 2, 3 and 4 hours (T1-T4) . At the time of Tbase, T0 and T4, blood was collected to detect interleukin-1β and -6. At the end the experiment, the right upper, right lower ventral, right lower dorsal lung tissues were taken for immunohistochemical test of NF-ΚB, IL-1β and IL-6. Lung homogenates were prepared to detect myeloperoxidase (MPO) . At the same time, lung tissue was taken to observe pathological changes and record the lung wet/dry weight ratio (W/D) .

Results

The levels of PEEP, Pm, Paw-exp, and Ptrans-exp in the transpulmonary pressure group were significantly lower than those in the optimal oxygenation group (P<0. 05), and the levels of Ptrans-ins at T3 and T4 were also significantly lower than those in the optimal oxygenation group (P<0. 05) . The levels of NF-κB in the right upper lung tissue, IL-6 in the right lung tissue and MPO in the right lower dorsal lung tissue were significantly lower in the transpulmonary pressure group than those in the optimal oxygenation group (P<0. 05) . After mechanical ventilation set by optimal PEEP in the two groups, the levels of PVPI, EVLWI and W/D were not significantly different between the two groups (P>0. 05) . The pathological scores of the right upper, right lower dorsal, and right lung tissues were all significantly lower in the transpulmonary pressure group than those in the optimal oxygenation group (P>0. 05) .

Conclusion

PEEP guided by transpulmonary pressure can open the alveoli, reduce the inflammatory response, prevent the ventilator-associated lung injury, and then reach the effect of lung protection.

Key words: Acute respiratory distress syndrom, Mechanical ventilation, Lung injury
表1 各组ARDS模型猪呼吸力学各指标的变化（±s）
组别 猪数 PEEP（cmH2O）
T base T0 T1 T2 T3 T4
跨肺压组 6 5.00±0.00 5.00±0.00 6.00±0.89 c 6.17±0.98abc 6.50±0.55abc 6.00±0.89c
最佳氧合组 6 5.00±0.00 5.00±0.00 11.33±2.07ab 11.33±2.07ab 11.33±2.07ab 11.33±2.07ab
组别 猪数 Pm（cmH2O）
T base T0 T1 T2 T3 T4
跨肺压组 6 7.92±1.32 9.87±2.38 11.06±2.01c 10.63±1.55c 11.10±1.99c 10.83±1.43c
最佳氧合组 6 8.13±0.27 11.33±2.07a 13.50±0.55ab 13.67±1.51ab 13.33±1.03ab 13.50±0.55ab
组别 猪数 Paw-ins（cmH2O）
T base T0 T1 T2 T3 T4
跨肺压组 6 14.00±4.00 20.33±8.02 23.17±5.78 23.17±3.92 22.67±4.5 21.00±6.20
最佳氧合组 6 17.00±4.58 25.16±4.58a 24.67±4.03a 24.67±4.59a 22.67±6.09a 23.67±2.88a
组别 猪数 Paw-exp（cmH2O）
T base T0 T1 T2 T3 T4
跨肺压组 6 5.23±0.81 4.98±0.44 6.06±0.72bc 6.42±0.82abc 6.50±0.60abc 6.12±0.58bc
最佳氧合组 6 5.38±0.62 4.61±0.56 12.01±2.12ab 11.95±1.85ab 11.68±3.09ab 12.25±2.96ab
组别 猪数 PES-ins（cmH2O）
T base T0 T1 T2 T3 T4
跨肺压组 6 6.37±1.37 7.00±1.03 6.97±1.29 7.58±0.46 6.12±0.58 7.45±0.90
最佳氧合组 6 7.33±1.39 5.97±1.40 7.27±2.51 7.10±1.70 6.93±1.52 6.97±1.89
组别 猪数 PES-exp（cmH2O）
T base T0 T1 T2 T3 T4
跨肺压组 6 4.93±1.54 5.10±0.99 5.12±1.13 5.78±0.60 5.20±0.54 5.42±0.56
最佳氧合组 6 5.10±1.47 5.16±0.74 5.50±2.13 5.03±1.75 4.60±1.40 4.27±1.77
组别 猪数 Ptrans-ins（cmH2O）
T base T0 T1 T2 T3 T4
跨肺压组 6 6.58±0.96 11.48±3.12a 12.77±2.07a 12.68±2.58a 12.30±0.84ac 11.10±2.35ac
最佳氧合组 6 6.13±4.40 15.40±6.30a 15.33±6.23a 15.36±3.58a 15.88±3.79a 16.40±3.70a
组别 猪数 Ptrans-exp（cmH2O）
T base T0 T1 T2 T3 T4
跨肺压组 6 0.30±1.01 -0.12±0.83 0.95±0.64c 0.63±0.38c 1.30±0.43bc 0.70±0.79c
最佳氧合组 6 0.28±1.78 -0.55±0.97a 6.52±4.02ab 6.91±3.18ab 7.08±4.18ab 7.98±4.40ab
组别 猪数 Crs（ml/cmH2O）
T base T0 T1 T2 T3 T4
跨肺压组 6 36.33±12.64 15.09±3.17a 15.44±2.71a 17.47±5.53a 18.81±3.04a 17.31±5.56a
最佳氧合组 6 26.53±9.22 10.25±4.30a 16.95±6.48a 14.56±5.07a 14.29±5.85a 15.36±4.41a
组别 猪数 CCW（ml/cmH2O）
T base T0 T1 T2 T3 T4
跨肺压组 6 109.45±19.28 74.60±30.92 72.27±19.8 72.26±47.72 95.71±34.03 93.52±23.03
最佳氧合组 6 92.69±24.34 70.25±6.45 103.59±55.34 80.46±45.47 77.78±56.34 72.68±47.87
组别 猪数 CL（ml/cmH2O）
T base T0 T1 T2 T3 T4
跨肺压组 6 52.42±25.75 19.36±5.04a 18.58±2.45a 21.23±7.17a 21.63±4.29a 23.10±8.74a
最佳氧合组 6 42.16±24.53 12.47±6.19a 20.42±7.27a 18.30±5.25a 18.25±6.08a 20.77±4.38a
表2 各组ARDS模型猪肺组织炎症指标测量（HIS评分）（±s）
组别 猪数 NF-KB
右上肺 右肺下叶腹侧 右肺下叶背侧 右肺
跨肺压组 6 3.67±1.51a 4.33±1.51 4.67±1.03 4.33±1.10
最佳氧合组 6 5.33±1.03 5.33±1.03 5.67±0.82 5.33±0.60
组别 猪数 IL-1β
右上肺 右肺下叶腹侧 右肺下叶背侧 右肺
跨肺压组 6 3.67±1.51 4.33±0.639 5.00±1.10 4.33±0.82
最佳氧合组 6 4.67±1.03 5.33±1.03 5.33±1.03 5.11±0.34
组别 猪数 IL-6
右上肺 右肺下叶腹侧 右肺下叶背侧 右肺
跨肺压组 6 3.67±1.51 5.00±1.10 5.33±1.03 4.67±0.73a
最佳氧合组 6 5.00±1.10 5.33±1.03 6.00±0.00 5.44±0.27
组别 猪数 MPO
右上肺 右肺下叶腹侧 右肺下叶背侧 右肺
跨肺压组 6 2.23±0.16 2.40±0.64 2.67±0.46a 2.43±0.27a
最佳氧合组 6 2.25±0.26 2.45±0.55 2.73±0.23 2.48±0.23
表3 各组ARDS模型猪血清炎症指标测量（ng/L， ±s）
组别 猪数 IL-1β
基础 成模 通气4h
跨肺压组 6 297.76±3.28 333.79±11.66a 374.77±7.94ab
最佳氧合组 6 292.74±14.58 339.95±14.58a 387.80±14.77ab
组别 猪数 IL-6
基础 成模 通气4h
跨肺压组 6 34.22±1.13 39.66±1.34a 46.21±0.99ab
最佳氧合组 6 33.29±0.90 38.84±1.96a 46.42±2.78ab
表4 各组ARDS模型猪肺水肿指标变化（±s）
组别 猪数 PVPI（ml/kg）
T base T0 T1 T2 T3 T4
跨肺压组 6 2.48±0.33 5.17±1.43a 4.77±1.77a 4.88±1.53a 4.65±1.07a 4.52±0.91a
最佳氧合组 6 2.35±0.38 4.65±0.73a 5.12±0.96a 4.95±1.09a 5.22±0.96a 4.52±0.53a
组别 猪数 EVLWI（ml/kg）
T base T0 T1 T2 T3 T4
跨肺压组 6 15.83±1.33 27.5±5.05a 28.00±3.16a 30.67±5.50a 29.17±4.26a 28.67±4.46a
最佳氧合组 6 15.83±1.72 30.33±2.87a 27.33±3.67a 27.33±3.67a 29.00±2.61a 25.17±3.49a
表5 各组ARDS模型猪肺组织W/D测量（±s）
组别 猪数 右上肺 右肺下叶腹侧 右肺下叶背侧 右全肺
跨肺压组 6 5.98±0.40 6.99±0.73 8.15±0.27 7.04±0.36
最佳氧合组 6 6.18±0.34 7.49±0.65 8.07±0.74 7.25±0.58
t值 0.910 1.25 0.265 0.734
P值 0.384 0.240 0.800 0.483
表6 各组ARDS模型猪肺组织各部位病理评分（±s）
组别 猪数 右上肺 右肺下叶腹侧 右肺下叶背侧 右肺
跨肺压组 6 2.750±0.562a 4.625±0.354 5.923±1.297 a 4.433±0.630 a
最佳氧合组 6 3.507±0.259 5.323±0.836 7.423±0.157 5.418±0.245
t值 2.994 1.883 2.813 3.569
P值 0.013 0.089 0.036 0.005
图6 最佳氧合组猪急性呼吸窘迫综合征模型右下叶背侧肺组织光镜病理图（HE×200）
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