Effects of positive end-expiratory pressure and recruitment maneuvers in a ventilator-induced injury mouse model

• Published in: PloS one Vol. 12; no. 11; p. e0187419
• Main Authors: Cagle, Laura A, Franzi, Lisa M, Linderholm, Angela L, Last, Jerold A, Adams, Jason Y, Harper, Richart W, Kenyon, Nicholas J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07-11-2017; Public Library of Science (PLoS)
• Subjects: Adult respiratory distress syndrome; Alveoli; Analysis; Animal models; Animals; Biology; Biology and Life Sciences; Bronchoalveolar lavage; Bronchoalveolar Lavage Fluid; Bronchus; Capillary pressure; Critical care; Cytokines; Development and progression; Disease Models, Animal; Female; Histology; Inflammation; Injury prevention; Intensive care; Leukocytes (neutrophilic); Lungs; Maneuvers; Mechanical ventilation; Mechanics; Medicine; Medicine and Health Sciences; Mice; Mice, Inbred BALB C; Neutrophils; Positive-Pressure Respiration - methods; Pressure; Prevention; Recruitment; Research and Analysis Methods; Respiration, Artificial - adverse effects; Respiratory distress syndrome; Respiratory therapy; Short term; Sleep; Studies; Ventilation; Ventilators
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0187419

Positive-pressure mechanical ventilation is an essential therapeutic intervention, yet it causes the clinical syndrome known as ventilator-induced lung injury. Various lung protective mechanical ventilation strategies have attempted to reduce or prevent ventilator-induced lung injury but few modalities have proven effective. A model that isolates the contribution of mechanical ventilation on the development of acute lung injury is needed to better understand biologic mechanisms that lead to ventilator-induced lung injury.
To evaluate the effects of positive end-expiratory pressure and recruitment maneuvers in reducing lung injury in a ventilator-induced lung injury murine model in short- and longer-term ventilation.
5-12 week-old female BALB/c mice (n = 85) were anesthetized, placed on mechanical ventilation for either 2 hrs or 4 hrs with either low tidal volume (8 ml/kg) or high tidal volume (15 ml/kg) with or without positive end-expiratory pressure and recruitment maneuvers.
Alteration of the alveolar-capillary barrier was noted at 2 hrs of high tidal volume ventilation. Standardized histology scores, influx of bronchoalveolar lavage albumin, proinflammatory cytokines, and absolute neutrophils were significantly higher in the high-tidal volume ventilation group at 4 hours of ventilation. Application of positive end-expiratory pressure resulted in significantly decreased standardized histology scores and bronchoalveolar absolute neutrophil counts at low- and high-tidal volume ventilation, respectively. Recruitment maneuvers were essential to maintain pulmonary compliance at both 2 and 4 hrs of ventilation.
Signs of ventilator-induced lung injury are evident soon after high tidal volume ventilation (as early as 2 hours) and lung injury worsens with longer-term ventilation (4 hrs). Application of positive end-expiratory pressure and recruitment maneuvers are protective against worsening VILI across all time points. Dynamic compliance can be used guide the frequency of recruitment maneuvers to help ameloriate ventilator-induced lung injury.