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Original Investigation | Association of VA Surgeons

Effect of Airway Pressure Release Ventilation on Dynamic Alveolar Heterogeneity

Michaela Kollisch-Singule, MD1; Sumeet Jain, MD, MBA1; Penny Andrews, RN2; Bradford J. Smith, PhD3; Katharine L. Hamlington-Smith, PhD3; Shreyas Roy, MD1; David DiStefano, BS1; Emily Nuss, BS1; Josh Satalin, BS1; Qinghe Meng, MD1; William Marx, DO1,4; Jason H. T. Bates, PhD3; Louis A. Gatto, PhD1,5; Gary F. Nieman, BA1; Nader M. Habashi, MD2
[+] Author Affiliations
1Department of Surgery, State University of New York Upstate Medical University, Syracuse
2Department of Trauma Critical Care Medicine, R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore
3Department of Medicine, University of Vermont, Burlington
4Syracuse Veterans Affairs Medical Center, Syracuse, New York
5Department of Biological Sciences, State University of New York at Cortland, Cortland
JAMA Surg. 2016;151(1):64-72. doi:10.1001/jamasurg.2015.2683.
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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.

Figures in this Article

Figures

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Figure 1.
Mean Plateau Pressures in Low Tidal-Volume Ventilation (LTVV) Group With Increasing Positive End-Expiratory Pressure (PEEP) and in Airway Pressure Release Ventilation (APRV) Group

Error bars indicate standard error of the mean.

aP < .01 vs APRV.

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Figure 2.
Qualitative Comparison of Dynamic Alveolar Heterogeneity Between Inspiration and Expiration at Low Tidal-Volume Ventilation (LTVV) and at Airway Pressure Release Ventilation (APRV)

Alveoli from in vivo photomicrograph are ordered from largest to smallest area. EEFR indicates end-expiratory flow rate; PEEP, positive end-expiratory pressure; and PEFR, peak expiratory flow rate.

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Figure 3.
Comparison of Alveolar Distributions at Inspiration vs Expiration in Experimental Groups vs Control Group

A, All of the settings (ie, ratios of end-expiratory flow rate [EEFR] to peak expiratory flow rate [PEFR]) in the airway pressure release ventilation (APRV) group demonstrated an alveolar distribution similar to that observed in the control group at inspiration (P > .01). B, None of the settings (ie, progressively higher positive end-expiratory pressures [PEEPs]) in the low tidal-volume ventilation (LTVV) group at inspiration demonstrated distributions that were similar to the distribution observed in the control group (P < .01). C and D, None of the settings at inspiration (ie, progressively higher PEEPs or EEFR to PEFR ratios) in either experimental group demonstrated distributions that were similar to the distributions observed in the control group (P < .01).

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Figure 4.
Alveolar Distributions at Inspiration and Expiration

Comparison of alveolar distributions between inspiration and expiration in the control group (A), the airway pressure release ventilation group with increasing ratio of end-expiratory flow rate (EEFR) to peak expiratory flow rate (PEFR) (B-E), and the low tidal-volume ventilation group with increasing positive end-expiratory pressure (PEEP) (F-J). Alveolar distribution at inspiration (solid curve) is compared with alveolar distribution at expiration (dotted curve). Median values are represented by the 2 vertical lines (solid line = median at inspiration; dotted line = median at expiration). P < .01 indicates statistical significance for dynamic heterogeneity (dissimilar alveolar distributions between inspiration and expiration), and P > .01 indicates dynamic homogeneity.

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