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压力支持通气对轻度急性呼吸窘迫综合征呼吸机相关性肺损伤的影响取决于呼气末正压水平:一项随机动物研究。

Effects of pressure support ventilation on ventilator-induced lung injury in mild acute respiratory distress syndrome depend on level of positive end-expiratory pressure: A randomised animal study.

机构信息

From the Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro (PAFM, GAP, LM, CLS, LAM, CLB, PRMR, PLS), Graduate Program in Maternal and Child Health, Professor Fernando Figueira Institute of Comprehensive Medicine, Recife, Pernambuco (PAFM, MCMBD, LBA), Faculty of Medicine, Laboratory of Experimental Surgery, Federal University of Rio de Janeiro, Rio de Janeiro (CLS, AS), Department of Pathology, School of Medicine, University of São Paulo, São Paulo, Brazil (VLC), Department of Anesthesiology and Intensive Care Therapy, Pulmonary Engineering Group, University Hospital Carl Gustav Carus (RH, MGA), Dresden University of Technology, Dresden, Germany (RH, MGA) and Department of Surgical Sciences and Integrated Diagnostics, IRCCS AOU San Martino-IST, University of Genoa, Genoa, Italy (PP).

出版信息

Eur J Anaesthesiol. 2018 Apr;35(4):298-306. doi: 10.1097/EJA.0000000000000763.

DOI:10.1097/EJA.0000000000000763
PMID:29324568
Abstract

BACKGROUND

Harmful effects of spontaneous breathing have been shown in experimental severe acute respiratory distress syndrome (ARDS). However, in the clinical setting, spontaneous respiration has been indicated only in mild ARDS. To date, no study has compared the effects of spontaneous assisted breathing with those of fully controlled mechanical ventilation at different levels of positive end-expiratory pressure (PEEP) on lung injury in ARDS.

OBJECTIVE

To compare the effects of assisted pressure support ventilation (PSV) with pressure-controlled ventilation (PCV) on lung function, histology and biological markers at two different PEEP levels in mild ARDS in rats.

DESIGN

Randomised controlled experimental study.

SETTING

Basic science laboratory.

PARTICIPANTS

Thirty-five Wistar rats (weight ± SD, 310 ± 19) g received Escherichia coli lipopolysaccharide (LPS) intratracheally. After 24 h, the animals were anaesthetised and randomly allocated to either PCV (n=14) or PSV (n=14) groups. Each group was further assigned to PEEP = 2 cmH2O or PEEP = 5 cmH2O. Tidal volume was kept constant (≈6 ml kg). Additional nonventilated animals (n=7) were used as a control for postmortem analysis.

MAIN OUTCOME MEASURES

Ventilatory and mechanical parameters, arterial blood gases, diffuse alveolar damage score, epithelial integrity measured by E-cadherin tissue expression, and biological markers associated with inflammation (IL-6 and cytokine-induced neutrophil chemoattractant, CINC-1) and type II epithelial cell damage (surfactant protein-B) were evaluated.

RESULTS

In both PCV and PSV, peak transpulmonary pressure was lower, whereas E-cadherin tissue expression, which is related to epithelial integrity, was higher at PEEP = 5 cmH2O than at PEEP = 2 cmH2O. In PSV, PEEP = 5 cmH2O compared with PEEP = 2 cmH2O was associated with significantly reduced diffuse alveolar damage score [median (interquartile range), 11 (8.5 to 13.5) vs. 23 (19 to 26), P = 0.005] and expressions of IL-6 and CINC-1 (P = 0.02 for both), whereas surfactant protein-B mRNA expression increased (P = 0.03). These changes suggested less type II epithelial cell damage at a PEEP of 5 cmH2O. Peak transpulmonary pressure correlated positively with IL-6 [Spearman's rho (ρ) = 0.62, P = 0.0007] and CINC-1 expressions (ρ = 0.50, P = 0.01) and negatively with E-cadherin expression (ρ = -0.67, P = 0.0002).

CONCLUSION

During PSV, PEEP of 5 cmH2O, but not a PEEP of 2 cmH2O, reduced lung damage and inflammatory markers while maintaining epithelial cell integrity.

摘要

背景

实验性严重急性呼吸窘迫综合征(ARDS)表明,自主呼吸会产生有害影响。然而,在临床环境中,仅在轻度 ARDS 中指示了自主呼吸。迄今为止,尚无研究比较不同水平呼气末正压(PEEP)下的自主辅助通气与完全控制机械通气对 ARDS 中肺损伤的影响。

目的

比较辅助压力支持通气(PSV)与压力控制通气(PCV)在轻度 ARDS 大鼠中在两种不同 PEEP 水平下对肺功能、组织学和生物标志物的影响。

设计

随机对照实验研究。

设置

基础科学实验室。

参与者

35 只 Wistar 大鼠(体重[±]SD,310[±]19)g 接受大肠杆菌脂多糖(LPS)气管内给药。24 小时后,动物麻醉并随机分配到 PCV 组(n=14)或 PSV 组(n=14)。每组进一步分为 PEEP=2 cmH2O 或 PEEP=5 cmH2O。潮气量保持恒定(≈6 ml/kg)。另外,还使用了 7 只未通气的动物(n=7)作为死后分析的对照。

主要观察指标

通气和机械参数、动脉血气、弥漫性肺泡损伤评分、上皮完整性用 E-钙黏蛋白组织表达测量、以及与炎症(白细胞介素-6 和细胞因子诱导的中性粒细胞趋化因子,CINC-1)和 II 型上皮细胞损伤(表面活性蛋白-B)相关的生物标志物。

结果

在 PCV 和 PSV 中,峰值跨肺压较低,而在 PEEP=5 cmH2O 时 E-钙黏蛋白组织表达(与上皮完整性相关)高于 PEEP=2 cmH2O。在 PSV 中,与 PEEP=2 cmH2O 相比,PEEP=5 cmH2O 与弥漫性肺泡损伤评分明显降低[中位数(四分位距),11(8.5 至 13.5)比 23(19 至 26),P=0.005]和白细胞介素-6 和 CINC-1 的表达(两者均为 P=0.02),而表面活性蛋白-B mRNA 表达增加(P=0.03)。这些变化表明在 PEEP 为 5 cmH2O 时 II 型上皮细胞损伤较少。峰值跨肺压与白细胞介素-6[Spearman's rho(ρ)=0.62,P=0.0007]和 CINC-1 表达呈正相关(ρ=0.50,P=0.01),与 E-钙黏蛋白表达呈负相关(ρ=-0.67,P=0.0002)。

结论

在 PSV 期间,与 PEEP 为 2 cmH2O 相比,PEEP 为 5 cmH2O 可降低肺损伤和炎症标志物,同时保持上皮细胞完整性。

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