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

• Published in: Revista Brasileira de terapia intensiva Vol. 32; no. 1; pp. 58 - 65
• Main Authors: Correger, Enrique, Marcos, Josefina, Laguens, Graciela, Stringa, Pablo, Cardinal-Fernández, Pablo, Blanch, Lluis
• Format: Journal Article
• Language: English
• Published: Brazil Associação de Medicina Intensiva Brasileira - AMIB 01.03.2020
• Subjects: Adalimumab - therapeutic use; Animals; Disease Models, Animal; Humans; Original; Random Allocation; Rats; Rats, Wistar; Respiration, Artificial - methods; Ventilator-Induced Lung Injury - prevention & control; Young Adult
• ISSN: 0103-507X; 1982-4335
• DOI: 10.5935/0103-507X.20200010

To determine whether adalimumab administration before mechanical ventilation reduces ventilator-induced lung injury (VILI). 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. 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). 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.