实验性脓毒症诱导的不同程度急性肺炎症下快速与缓慢复张手法的比较

Fast Versus Slow Recruitment Maneuver at Different Degrees of Acute Lung Inflammation Induced by Experimental Sepsis.

作者信息

Santos Raquel S, Moraes Lillian, Samary Cynthia S, Santos Cíntia L, Ramos Maíra B A, Vasconcellos Ana P, Horta Lucas F, Morales Marcelo M, Capelozzi Vera L, Garcia Cristiane S N B, Marini John J, Gama de Abreu Marcelo, Pelosi Paolo, Silva Pedro L, Rocco Patricia R M

机构信息

From the *Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, †Laboratory of Experimental Surgery, Faculty of Medicine, and ‡Laboratory of Cellular and Molecular Physiology, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; §Department of Pathology, School of Medicine, University of São Paulo, São Paulo, Brazil; ‖Rio de Janeiro Federal Institute of Education, Science and Technology, Rio de Janeiro, Brazil; ¶Department of Medicine, University of Minnesota, Minneapolis/Regions Hospital, Pulmonary and Critical Care Medicine, St Paul, Minnesota; #Pulmonary Engineering Group, Department of Anesthesiology and Intensive Care Therapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; and **IRCCS AOU San Martino-IST, Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy.

出版信息

Anesth Analg. 2016 Apr;122(4):1089-100. doi: 10.1213/ANE.0000000000001173.

DOI:10.1213/ANE.0000000000001173

PMID:26836136

Abstract

BACKGROUND

Large tidal volume (VT) breaths or "recruitment maneuvers" (RMs) are used commonly to open collapsed lungs, but their effectiveness may depend on how the RM is delivered. We hypothesized that a stepped approach to RM delivery ("slow" RM) compared with a nonstepped ("fast" RM), when followed by decremental positive end-expiratory pressure (PEEP) titration to lowest dynamic elastance, would (1) yield a more homogeneous inflation of the lungs, thus reducing the PEEP obtained during post-RM titration; (2) produce less lung morphofunctional injury, regardless of the severity of sepsis-induced acute lung inflammation; and (3) result in less biological damage in severe, but not in moderate, acute lung inflammation.

METHODS

Sepsis was induced by cecal ligation and puncture surgery in 51 Wistar rats. After 48 hours, animals were anesthetized, mechanically ventilated (VT = 6 mL/kg), and stratified by PO2/fraction of inspired oxygen ratio into moderate (≥300) and severe (<300) acute lung inflammation groups. Each group was then subdivided randomly into 3 subgroups: (1) nonrecruited; (2) RM with continuous positive airway pressure (30 cm H2O for 30 seconds; CPAPRM or fast RM); and (3) RM with stepwise airway pressure increase (5 cm H2O/step, 8.5 seconds/step, 6 steps, 51 seconds; STEPRM or slow RM), with a maximum pressure hold for 10 seconds. All animals underwent decremental PEEP titration to determine the level of PEEP required to optimize dynamic compliance after RM and were then ventilated for 60 minutes with VT = 6 mL/kg, respiratory rate = 80 bpm, fraction of inspired oxygen = 0.4, and the newly adjusted PEEP for each animal. Respiratory mechanics, hemodynamics, and arterial blood gases were measured before and at the end of 60-minute mechanical ventilation. Lung histology and biological markers of inflammation and damage inflicted to endothelial cells were evaluated at the end of the 60-minute mechanical ventilation.

RESULTS

Respiratory system mean airway pressure was lower in STEPRM than that in CPAPRM. The total RM time was greater, and the RM rise angle was lower in STEPRM than that in CPAPRM. In both moderate and severe acute lung inflammation groups, STEPRM reduced total diffuse alveolar damage score compared with the score in nonrecruited rats. In moderate acute lung inflammation, STEPRM rats compared with CPAPRM rats had less endothelial cell damage and angiopoietin (Ang)-2 expression. In severe acute lung inflammation, STEPRM compared with CPAPRM reduced hyperinflation, endothelial cell damage, Ang-2, and intercellular adhesion molecule-1 expressions. RM rise angle correlated with Ang-2 expression.

CONCLUSIONS

Compared with CPAPRM, STEPRM reduced biological markers associated with endothelial cell damage and ultrastructural endothelial cell injury in both moderate and severe sepsis-induced acute lung inflammation.

摘要

背景

大潮气量（VT）呼吸或“肺复张手法”（RM）常用于打开萎陷的肺，但它们的有效性可能取决于RM的实施方式。我们假设，与非阶梯式（“快速”RM）相比，采用阶梯式方法实施RM（“缓慢”RM），随后进行呼气末正压（PEEP）递减滴定至最低动态弹性，将（1）使肺膨胀更均匀，从而降低RM后滴定期间获得的PEEP；（2）无论脓毒症诱导的急性肺炎症的严重程度如何，产生的肺形态功能损伤更少；（3）在严重但非中度急性肺炎症中导致的生物损伤更少。

方法

通过盲肠结扎和穿刺手术在51只Wistar大鼠中诱导脓毒症。48小时后，将动物麻醉、机械通气（VT = 6 mL/kg），并根据动脉血氧分压/吸入氧分数比分为中度（≥300）和重度（<300）急性肺炎症组。然后将每组随机再分为三个亚组：（1）未复张组；（2）持续气道正压通气的RM（30 cm H2O持续30秒；CPAPRM或快速RM）；（3）气道压力逐步增加的RM（5 cm H2O/步，8.5秒/步，6步，51秒；STEPRM或缓慢RM），最大压力保持10秒。所有动物均进行PEEP递减滴定，以确定RM后优化动态顺应性所需的PEEP水平，然后以VT = 6 mL/kg、呼吸频率 = 80次/分钟、吸入氧分数 = 0.4以及为每只动物新调整的PEEP进行60分钟通气。在60分钟机械通气前后测量呼吸力学、血流动力学和动脉血气。在60分钟机械通气结束时评估肺组织学以及炎症和内皮细胞损伤的生物学标志物。

结果

STEPRM组的呼吸系统平均气道压力低于CPAPRM组。STEPRM组的总RM时间更长，RM上升角度低于CPAPRM组。在中度和重度急性肺炎症组中，与未复张大鼠相比，STEPRM均降低了总弥漫性肺泡损伤评分。在中度急性肺炎症中，与CPAPRM大鼠相比，STEPRM大鼠的内皮细胞损伤和血管生成素（Ang）-2表达更少。在重度急性肺炎症中，与CPAPRM相比，STEPRM减少了肺过度膨胀、内皮细胞损伤、Ang-2和细胞间黏附分子-1表达。RM上升角度与Ang-2表达相关。