Santos Cíntia Lourenco, Moraes Lillian, Santos Raquel Souza, dos Santos Samary Cynthia, Silva Johnatas Dutra, Morales Marcelo Marcos, Capelozzi Vera Lucia, de Abreu Marcelo Gama, Schanaider Alberto, Silva Pedro Leme, Garcia Cristiane Sousa Nascimento Baez, Pelosi Paolo, Rocco Patricia Rieken Macedo
Crit Care. 2014 Jun 13;18(3):R121. doi: 10.1186/cc13920.
Mechanical ventilation with high positive end-expiratory pressure (PEEP) has been used in patients with acute respiratory distress syndrome (ARDS) and intra-abdominal hypertension (IAH), but the role of PEEP in minimizing lung injury remains controversial. We hypothesized that in the presence of acute lung injury (ALI) with IAH: 1) higher PEEP levels improve pulmonary morphofunction and minimize lung injury; and 2) the biological effects of higher PEEP are more effective in extrapulmonary (exp) than pulmonary (p) ALI.
In 48 adult male Wistar rats, ALIp and ALIexp were induced by Escherichia coli lipopolysaccharide intratracheally and intraperitoneally, respectively. After 24 hours, animals were anesthetized and mechanically ventilated (tidal volume of 6 mL/kg). IAH (15 mmHg) was induced and rats randomly assigned to PEEP of 5 (PEEP5), 7 (PEEP7) or 10 (PEEP10) cmH2O for 1 hour.
In both ALIp and ALIexp, higher PEEP levels improved oxygenation. PEEP10 increased alveolar hyperinflation and epithelial cell damage compared to PEEP5, independent of ALI etiology. In ALIp, PEEP7 and PEEP10 increased lung elastance compared to PEEP5 (4.3 ± 0.7 and 4.3 ± 0.9 versus 3.1 ± 0.3 cmH2O/mL, respectively, P <0.01), without changes in alveolar collapse, interleukin-6, caspase-3, type III procollagen, receptor for advanced glycation end-products, and vascular cell adhesion molecule-1 expressions. Moreover, PEEP10 increased diaphragmatic injury compared to PEEP5. In ALIexp, PEEP7 decreased lung elastance and alveolar collapse compared to PEEP5 (2.3 ± 0.5 versus 3.6 ± 0.7 cmH2O/mL, P <0.02, and 27.2 (24.7 to 36.8) versus 44.2 (39.7 to 56.9)%, P <0.05, respectively), while PEEP7 and PEEP10 increased interleukin-6 and type III procollagen expressions, as well as type II epithelial cell damage compared to PEEP5.
In the current models of ALI with IAH, in contrast to our primary hypothesis, higher PEEP is more effective in ALIp than ALIexp as demonstrated by the activation of biological markers. Therefore, higher PEEP should be used cautiously in the presence of IAH and ALI, mainly in ALIexp.
高呼气末正压（PEEP）机械通气已应用于急性呼吸窘迫综合征（ARDS）和腹腔内高压（IAH）患者，但PEEP在减轻肺损伤方面的作用仍存在争议。我们假设在伴有IAH的急性肺损伤（ALI）中：1）较高的PEEP水平可改善肺形态功能并使肺损伤最小化；2）较高PEEP的生物学效应在肺外（exp）ALI中比肺内（p）ALI更有效。
在48只成年雄性Wistar大鼠中，分别通过气管内和腹腔内注射大肠杆菌脂多糖诱导肺内ALI（ALIp）和肺外ALI（ALIexp）。24小时后，动物麻醉并进行机械通气（潮气量6 mL/kg）。诱导IAH（15 mmHg），大鼠随机分为5（PEEP5）、7（PEEP7）或10（PEEP10）cmH₂O的PEEP组，持续1小时。
在ALIp和ALIexp中，较高的PEEP水平均改善了氧合。与PEEP5相比，PEEP10增加了肺泡过度充气和上皮细胞损伤，与ALI病因无关。在ALIp中，与PEEP5相比，PEEP7和PEEP10增加了肺弹性（分别为4.3±0.7和4.3±0.9 vs 3.1±0.3 cmH₂O/mL，P<0.01），肺泡萎陷、白细胞介素-6、半胱天冬酶-3、III型前胶原、晚期糖基化终产物受体和血管细胞黏附分子-1表达无变化。此外，与PEEP5相比，PEEP10增加了膈肌损伤。在ALIexp中，与PEEP5相比，PEEP7降低了肺弹性和肺泡萎陷（分别为2.3±0.5 vs 3.6±0.7 cmH₂O/mL，P<0.02，以及27.2（24.7至36.8）% vs 44.2（39.7至56.9）%，P<0.05），而与PEEP5相比，PEEP7和PEEP10增加了白细胞介素-6和III型前胶原表达，以及II型上皮细胞损伤。
在当前伴有IAH的ALI模型中，与我们的主要假设相反，如生物学标志物的激活所示，较高的PEEP在ALIp中比ALIexp更有效。因此，在存在IAH和ALI时，应谨慎使用较高的PEEP，主要是在ALIexp中。
