Lung injury is induced by abrupt increase in respiratory rate but prevented by recruitment maneuver in mild acute respiratory distress syndrome in rats

Background Gradually changing respiratory rate (RR) over time to reduce ventilation-induced lung injury (VILI) has not been investigated. We hypothesized that gradual, compared to abrupt, increments in RR would mitigate VILI and that recruitment maneuver (RM) prior to abrupt increasing RR may prevent injurious biological impact. Methods Twenty-four hours after intratracheal administration of Escherichia coli lipopolysaccharide, 49 male Wistar rats were anesthetized and mechanically ventilated (VT=6ml/kg, PEEP=3cmH2O) with RR increase patterns as follows (n=7/group): (1)control-1, RR=70bpm for 2h; (2) and (3)abrupt increases of RR for 1h and 2h, respectively, both for 2h; (4)shorter RR adaptation, gradually increasing RR (from 70 to 130bpm over 30min); (5)longer RR adaptation, more gradual increase in RR (from 70 to 130bpm over 60min), both for 2h; (6)control-2, abrupt increase of RR maintained for 1h; and (7)control-3, RM [CPAP=30cmH2O for 30s] followed by control-2 protocol. Results At the end of 1h of mechanical ventilation, cumulative diffuse alveolar damage scores were lower in shorter (11.0 [8.0–12.0]) and longer (13.0 [11.0–14.0]) RR adaptation groups than in animals with abrupt increase of RR for 1 h (25.0 [22.0–26.0] p=0.035, and p=0.048, respectively) and 2 h (35.0 [32.0–39.0], p=0.003, and p=0.040, respectively); mechanical power and lung heterogeneity were lower, and alveolar integrity was higher, in the longer RR adaptation group compared with abruptly adjusted groups; markers of lung inflammation (IL-6), epithelial (CC-16) and endothelial cell damage (VCAM-1) were higher in both abrupt groups, but not in either RR adaptation group, compared with controls. RM prevented the increase in VCAM-1 and CC-16 gene expressions in the abruptly increased RR groups. Conclusion In mild experimental ARDS in rats, gradually increasing RR, compared with abruptly doing so, can mitigate the development of VILI. In addition, recruitment maneuver prevented the injurious biological impact of abrupt increases in RR.