Pretreatment with adalimumab reduces ventilator-induced lung injury in an experimental model

ABSTRACT Objective: To determine whether adalimumab administration before mechanical ventilation reduces ventilator-induced lung injury (VILI). Methods: Eighteen rats randomized into 3 groups underwent mechanical ventilation for 3 hours with a fraction of inspired oxygen = 0.40% including a low tidal volume group (n = 6), where tidal volume = 8mL/kg and positive end-expiratory pressure = 5cmH2O; a high tidal volume group (n = 6), where tidal volume = 35mL/kg and positive end-expiratory pressure = 0; and a pretreated + high tidal volume group (n = 6) where adalimumab (100ug/kg) was administered intraperitoneally 24 hours before mechanical ventilation + tidal volume = 35mL/kg and positive end-expiratory pressure = 0. ANOVA was used to compare histological damage (ATS 2010 Lung Injury Scoring System), pulmonary edema, lung compliance, arterial partial pressure of oxygen, and mean arterial pressure among the groups. Results: After 3 hours of ventilation, the mean histological lung injury score was higher in the high tidal volume group than in the low tidal volume group (0.030 versus 0.0051, respectively, p = 0.003). The high tidal volume group showed diminished lung compliance at 3 hours (p = 0.04) and hypoxemia (p = 0,018 versus control). Pretreated HVt group had an improved histological score, mainly due to a significant reduction in leukocyte infiltration (p = 0.003). Conclusion: Histological examination after 3 hours of injurious ventilation revealed ventilator-induced lung injury in the absence of measurable changes in lung mechanics or oxygenation; administering adalimumab before mechanical ventilation reduced lung edema and histological damage.

摘要
研究目的：明确机械通气前给予阿达木单抗（adalimumab）是否可减轻呼吸机相关性肺损伤（ventilator-induced lung injury, VILI）。
方法：将18只大鼠随机分为3组，所有大鼠均接受时长3小时的机械通气，吸入氧分数设定为0.40%。具体分组如下：低潮气量组（n=6），潮气量设置为8mL/kg，呼气末正压为5cmH₂O；高潮气量组（n=6），潮气量设置为35mL/kg，呼气末正压为0；预处理+高潮气量组（n=6），于机械通气前24小时腹腔注射阿达木单抗（100μg/kg），潮气量设置为35mL/kg，呼气末正压为0。采用方差分析（Analysis of Variance, ANOVA）比较各组间的组织损伤情况（采用2010年美国胸科学会（American Thoracic Society, ATS）肺损伤评分系统）、肺水肿程度、肺顺应性、动脉血氧分压及平均动脉压。
结果：通气3小时后，高潮气量组的平均肺组织损伤评分高于低潮气量组（分别为0.030与0.0051，p=0.003）。高潮气量组在通气3小时时出现肺顺应性下降（p=0.04）及低氧血症（与对照组相比p=0.018）。预处理+高潮气量组的肺组织损伤评分得到改善，主要表现为白细胞浸润程度显著降低（p=0.003）。
结论：损伤性通气3小时后的组织学检查结果显示，即使肺力学指标与氧合状态未出现可测量的变化，仍可发生呼吸机相关性肺损伤；机械通气前给予阿达木单抗可减轻肺水肿及肺组织损伤。