Schmalstieg Frank C, Keeney Susan E, Rudloff Helen E, Palkowetz Kimberly H, Cevallos Manuel, Zhou Xiaoquin, Cox Robert A, Hawkins Hal K, Traber Daniel L, Zwischenberger Joseph B
Department of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555, USA.
Ann Surg. 2007 Sep;246(3):512-21; discussion 521-3. doi: 10.1097/SLA.0b013e318148c6e6.
OBJECTIVES AND SUMMARY BACKGROUND: Low tidal volume ventilation (LTV) has improved survival with acute respiratory distress syndrome (ARDS) by reducing lung stretch associated with volutrauma and barotrauma. Additional strategies to reduce lung stretch include arteriovenous carbon dioxide removal (AVCO2R), and high frequency percussive ventilation (HFPV). We performed a prospective, randomized study comparing these techniques in our clinically relevant LD100 sheep model of ARDS to compare survival, pathology, and inflammation between the 3 ventilator methods.
Adult sheep (n = 61) received smoke inhalation (48 breaths) and a 40% third-degree burn. After ARDS developed (Pao2/FiO2 <200), animals were randomized. In experiment 1, animals were killed at 48 hours after randomization. Hemodynamics, pulmonary function, injury scores, myeloperoxidase (MPO) in lung tissues and neutrophils, IL-8 in lung tissues, and apoptosis were evaluated. In experiment 2, the end point was survival to 72 hours after onset of ARDS or end-of-life criteria with extension of the same studies performed in experiment 1.
There were no differences in hemodynamics, but minute ventilation was lower in the AVCO2R group and Paco2 for the HFPV and AVCO2R animals remained lower than LTV. Airway obstruction and injury scores were not different among the 3 ventilation strategies. In experiment 1, lung tissue MPO and IL-8 were not different among the ventilation strategies. However, in experiment 2, lung tissue MPO was significantly lower for AVCO2R-treated animals (AVCO2R < HFPV < LTV). TUNEL staining showed little DNA breakage in neutrophils from experiment 1, but significantly increased breakage in all 3 ventilator strategies in experiment 2. In contrast, AVCO2R tissue neutrophils showed significant apoptosis at 72 hours post-ARDS criteria as measured by nuclear condensation (P < 0.001). Survival 72 hours post-ARDS criteria was highest for AVCO2R (71%) compared with HFPV (55%) and LTV (33%) (AVCO2R vs. LTV, P = 0.05).
Significantly more animals survived AVCO2R than LTV. In experiment 2, Lung MPO was significantly lower for AVCO2R, compared with LTV (P < 0.05). This finding taken together with the TUNEL and neutrophil apoptosis results, suggested that disposition of neutrophils 72 hours post-ARDS criteria was different among the ventilatory strategies with neutrophils from AVCO2R-treated animals removed chiefly through apoptosis, but in the cases of HFPV and LTV, dying by necrosis in lung tissue.
目的与背景概述：低潮气量通气（LTV）通过减少与容积伤和气压伤相关的肺牵张，提高了急性呼吸窘迫综合征（ARDS）患者的生存率。减少肺牵张的其他策略包括动静脉二氧化碳清除（AVCO2R）和高频振荡通气（HFPV）。我们进行了一项前瞻性随机研究，在我们临床相关的ARDS LD100绵羊模型中比较这些技术，以比较三种通气方法之间的生存率、病理学和炎症情况。
成年绵羊（n = 61）吸入烟雾（48次呼吸）并遭受40%的三度烧伤。在ARDS发生后（动脉血氧分压/吸入氧分数值<200），将动物随机分组。在实验1中，动物在随机分组后48小时处死。评估血流动力学、肺功能、损伤评分、肺组织中的髓过氧化物酶（MPO）和中性粒细胞、肺组织中的白细胞介素-8以及细胞凋亡情况。在实验2中，终点是ARDS发作后72小时存活或达到生命终末期标准，并进行与实验1相同的扩展研究。
血流动力学无差异，但AVCO2R组的分钟通气量较低，HFPV和AVCO2R动物的动脉血二氧化碳分压仍低于LTV组。三种通气策略之间的气道阻塞和损伤评分无差异。在实验1中，三种通气策略之间肺组织MPO和IL-8无差异。然而，在实验2中，AVCO2R治疗的动物肺组织MPO显著较低（AVCO2R < HFPV < LTV）。TUNEL染色显示实验1中性粒细胞中DNA断裂很少，但在实验2中所有三种通气策略中均显著增加。相比之下，通过核浓缩测量，AVCO₂R组织中性粒细胞在ARDS标准后72小时显示出显著凋亡（P < 0.001）。ARDS标准后72小时的生存率，AVCO2R组最高（71%），而HFPV组为（55%），LTV组为（33%）（AVCO2R与LTV相比，P = 0.05）。
AVCO2R治疗存活的动物明显多于LTV组。在实验2中，与LTV组相比，AVCO2R组肺组织MPO显著较低（P < 0.05）。这一发现与TUNEL和中性粒细胞凋亡结果一起表明，ARDS标准后72小时中性粒细胞的处置在通气策略之间有所不同，AVCO2R治疗动物的中性粒细胞主要通过凋亡清除，但在HFPV和LTV组中，在肺组织中因坏死而死亡。
