Michaela Kollisch-Singule1, Sumeet Jain1, Penny Andrews2, Bradford J Smith3, Katharine L Hamlington-Smith3, Shreyas Roy1, David DiStefano1, Emily Nuss1, Josh Satalin1, Qinghe Meng1, William Marx4, Jason H T Bates3, Louis A Gatto5, Gary F Nieman1, Nader M Habashi2. 1. Department of Surgery, State University of New York Upstate Medical University, Syracuse. 2. Department of Trauma Critical Care Medicine, R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore. 3. Department of Medicine, University of Vermont, Burlington. 4. Department of Surgery, State University of New York Upstate Medical University, Syracuse4Syracuse Veterans Affairs Medical Center, Syracuse, New York. 5. Department of Surgery, State University of New York Upstate Medical University, Syracuse5Department of Biological Sciences, State University of New York at Cortland, Cortland.
Abstract
IMPORTANCE: Ventilator-induced lung injury may arise from heterogeneous lung microanatomy, whereby some alveoli remain collapsed throughout the breath cycle while their more compliant or surfactant-replete neighbors become overdistended, and this is called dynamic alveolar heterogeneity. OBJECTIVE: To determine how dynamic alveolar heterogeneity is influenced by 2 modes of mechanical ventilation: low tidal-volume ventilation (LTVV) and airway pressure release ventilation (APRV), using in vivo microscopy to directly measure alveolar size distributions. DESIGN, SETTING, AND PARTICIPANTS: In a randomized, nonblinded laboratory animal study conducted between January 2013 and December 2014, 14 rats (450-500 g in size) were randomized to a control group with uninjured lungs (n = 4) and 2 experimental groups with surfactant deactivation induced by polysorbate lavage: the LTVV group (n = 5) and the APRV group (n = 5). For all groups, a thoracotomy and in vivo microscopy were performed. Following lung injury induced by polysorbate lavage, the LTVV group was ventilated with a tidal volume of 6 mL/kg and progressively higher positive end-expiratory pressure (PEEP) (5, 10, 16, 20, and 24 cm H2O). Following lung injury induced by polysorbate lavage, the APRV group was ventilated with a progressively shorter time at low pressure, which increased the ratio of the end-expiratory flow rate (EEFR) to the peak expiratory flow rate (PEFR; from 10% to 25% to 50% to 75%). MAIN OUTCOMES AND MEASURES: Alveolar areas were quantified (using PEEP and EEFR to PEFR ratio) to determine dynamic heterogeneity. RESULTS: Following lung injury induced by polysorbate lavage, a higher PEEP (20-24 cm H2O) with LTVV resulted in alveolar occupancy (reported as percentage of total frame area) at inspiration (39.9%-42.2%) and expiration (35.9%-38.7%) similar to that in the control group (inspiration 53.3%; expiration 50.3%; P > .01). Likewise, APRV with an increased EEFR to PEFR ratio (50%-75%) resulted in alveolar occupancy at inspiration (46.7%-47.9%) and expiration (40.2%-46.6%) similar to that in the control group (P > .01). At inspiration, the distribution of the alveolar area of the control group was similar to that of the APRV group (P > .01) (but not to that of the LTVV group [P < .01]). A lower PEEP (5-10 cm H2O) and a decreased EEFR to PEFR ratio (≤50%) demonstrated dynamic heterogeneity between inspiration and expiration (P < .01 for both) with a greater percentage of large alveoli at expiration. Dynamic alveolar homogeneity between inspiration and expiration occurred with higher PEEP (16-24 cm H2O) (P > .01) and an increased EEFR to PEFR ratio (75%) (P > .01). CONCLUSIONS AND RELEVANCE: Increasing PEEP during LTVV increased alveolar recruitment and dynamic homogeneity but had a significantly different alveolar size distribution compared with the control group. By comparison, reducing the time at low pressure (EEFR to PEFR ratio of 75%) in the APRV group provided dynamic homogeneity and a closer approximation of the dynamics observed in the control group.
RCT Entities:
IMPORTANCE: Ventilator-induced lung injury may arise from heterogeneous lung microanatomy, whereby some alveoli remain collapsed throughout the breath cycle while their more compliant or surfactant-replete neighbors become overdistended, and this is called dynamic alveolar heterogeneity. OBJECTIVE: To determine how dynamic alveolar heterogeneity is influenced by 2 modes of mechanical ventilation: low tidal-volume ventilation (LTVV) and airway pressure release ventilation (APRV), using in vivo microscopy to directly measure alveolar size distributions. DESIGN, SETTING, AND PARTICIPANTS: In a randomized, nonblinded laboratory animal study conducted between January 2013 and December 2014, 14 rats (450-500 g in size) were randomized to a control group with uninjured lungs (n = 4) and 2 experimental groups with surfactant deactivation induced by polysorbate lavage: the LTVV group (n = 5) and the APRV group (n = 5). For all groups, a thoracotomy and in vivo microscopy were performed. Following lung injury induced by polysorbate lavage, the LTVV group was ventilated with a tidal volume of 6 mL/kg and progressively higher positive end-expiratory pressure (PEEP) (5, 10, 16, 20, and 24 cm H2O). Following lung injury induced by polysorbate lavage, the APRV group was ventilated with a progressively shorter time at low pressure, which increased the ratio of the end-expiratory flow rate (EEFR) to the peak expiratory flow rate (PEFR; from 10% to 25% to 50% to 75%). MAIN OUTCOMES AND MEASURES: Alveolar areas were quantified (using PEEP and EEFR to PEFR ratio) to determine dynamic heterogeneity. RESULTS: Following lung injury induced by polysorbate lavage, a higher PEEP (20-24 cm H2O) with LTVV resulted in alveolar occupancy (reported as percentage of total frame area) at inspiration (39.9%-42.2%) and expiration (35.9%-38.7%) similar to that in the control group (inspiration 53.3%; expiration 50.3%; P > .01). Likewise, APRV with an increased EEFR to PEFR ratio (50%-75%) resulted in alveolar occupancy at inspiration (46.7%-47.9%) and expiration (40.2%-46.6%) similar to that in the control group (P > .01). At inspiration, the distribution of the alveolar area of the control group was similar to that of the APRV group (P > .01) (but not to that of the LTVV group [P < .01]). A lower PEEP (5-10 cm H2O) and a decreased EEFR to PEFR ratio (≤50%) demonstrated dynamic heterogeneity between inspiration and expiration (P < .01 for both) with a greater percentage of large alveoli at expiration. Dynamic alveolar homogeneity between inspiration and expiration occurred with higher PEEP (16-24 cm H2O) (P > .01) and an increased EEFR to PEFR ratio (75%) (P > .01). CONCLUSIONS AND RELEVANCE: Increasing PEEP during LTVV increased alveolar recruitment and dynamic homogeneity but had a significantly different alveolar size distribution compared with the control group. By comparison, reducing the time at low pressure (EEFR to PEFR ratio of 75%) in the APRV group provided dynamic homogeneity and a closer approximation of the dynamics observed in the control group.
Authors: Maurizio Cereda; Yi Xin; Hooman Hamedani; Giacomo Bellani; Stephen Kadlecek; Justin Clapp; Luca Guerra; Natalie Meeder; Jennia Rajaei; Nicholas J Tustison; James C Gee; Brian P Kavanagh; Rahim R Rizi Journal: Thorax Date: 2017-06-20 Impact factor: 9.139
Authors: J Hunter Mehaffey; Eric J Charles; Ashish K Sharma; Dustin T Money; Yunge Zhao; Mark H Stoler; Christine L Lau; Curtis G Tribble; Victor E Laubach; Mark E Roeser; Irving L Kron Journal: J Thorac Cardiovasc Surg Date: 2016-09-22 Impact factor: 5.209
Authors: Mao Wang; Alex Gauthier; LeeAnne Daley; Katelyn Dial; Jiaqi Wu; Joanna Woo; Mosi Lin; Charles Ashby; Lin L Mantell Journal: Antioxid Redox Signal Date: 2019-07-11 Impact factor: 8.401
Authors: Pierre Esnault; Bertrand Prunet; Cédric Nguyen; Jean Marie Forel; Christophe Guervilly; Yongfang Zhou; Yan Kang Journal: Intensive Care Med Date: 2017-11-09 Impact factor: 17.440
Authors: Michaela C Kollisch-Singule; Sumeet V Jain; Penny L Andrews; Joshua Satalin; Louis A Gatto; Jesús Villar; Daniel De Backer; Luciano Gattinoni; Gary F Nieman; Nader M Habashi Journal: J Appl Physiol (1985) Date: 2017-11-16
Authors: Katharine L Hamlington; Bradford J Smith; Celia M Dunn; Chantel M Charlebois; Gregory S Roy; Jason H T Bates Journal: Respir Physiol Neurobiol Date: 2018-05-06 Impact factor: 1.931