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Original Investigation | Association of VA Surgeons

Airway Pressure Release Ventilation Prevents Ventilator-Induced Lung Injury in Normal Lungs

Bryanna Emr, MD1; Louis A. Gatto, PhD2; Shreyas Roy, MD1; Joshua Satalin, BS1; Auyon Ghosh, BS1; Kathy Snyder, BS1; Penny Andrews, RN3; Nader Habashi, MD3; William Marx, DO1,4; Lin Ge, PhD1; Guirong Wang, PhD1; David A. Dean, PhD5; Yoram Vodovotz, PhD6; Gary Nieman, BA1
[+] Author Affiliations
1State University of New York Upstate Medical University, Syracuse, New York
2State University of New York, Cortland, New York
3University of Maryland Shock Trauma Center, Baltimore
4Syracuse VA Medical Center, Syracuse, New York
5University of Rochester, Rochester, New York
6University of Pittsburgh, Pittsburgh, Pennsylvania
JAMA Surg. 2013;148(11):1005-1012. doi:10.1001/jamasurg.2013.3746.
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Importance  Up to 25% of patients with normal lungs develop acute lung injury (ALI) secondary to mechanical ventilation, with 60% to 80% progressing to acute respiratory distress syndrome (ARDS). Once established, ARDS is treated with mechanical ventilation that can paradoxically elevate mortality. A ventilation strategy that reduces the incidence of ARDS could change the clinical paradigm from treatment to prevention.

Objectives  To demonstrate that (1) mechanical ventilation with tidal volume (Vt) and positive end-expiratory pressure (PEEP) settings used routinely on surgery patients causes ALI/ARDS in normal rats and (2) preemptive application of airway pressure release ventilation (APRV) blocks drivers of lung injury (ie, surfactant deactivation and alveolar edema) and prevents ARDS.

Design, Setting, and Subjects  Rats were anesthetized and tracheostomy was performed at State University of New York Upstate Medical University. Arterial and venous lines, a peritoneal catheter, and a rectal temperature probe were inserted. Animals were randomized into 3 groups and followed up for 6 hours: spontaneous breathing ventilation (SBV, n = 5), continuous mandatory ventilation (CMV, n = 6), and APRV (n = 5). Rats in the CMV group were ventilated with Vt of 10 cc/kg and PEEP of 0.5 cm H2O. Airway pressure release ventilation was set with a PHigh of 15 to 20 cm H2O; PLow was set at 0 cm H2O. Time at PHigh (THigh) was 1.3 to 1.5 seconds and a TLow was set to terminate at 75% of the peak expiratory flow rate (0.11-0.14 seconds), creating a minimum 90% cycle time spent at PHigh. Bronchoalveolar lavage fluid and lungs were harvested for histopathologic analysis at necropsy.

Results  Acute lung injury/ARDS developed in the CMV group (mean [SE] Pao2/FiO2 ratio, 242.96 [24.82]) and was prevented with preemptive APRV (mean [SE] Pao2/FIO2 ratio, 478.00 [41.38]; P < .05). Airway pressure release ventilation also significantly reduced histopathologic changes and bronchoalveolar lavage fluid total protein (endothelial permeability) and preserved surfactant proteins A and B concentrations as compared with the CMV group.

Conclusions and Relevance  Continuous mandatory ventilation in normal rats for 6 hours with Vt and PEEP settings similar to those of surgery patients caused ALI. Preemptive application of APRV blocked early drivers of lung injury, preventing ARDS. Our data suggest that APRV applied early could reduce the incidence of ARDS in patients at risk.

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Figure 1.
Lung Histology

Continuous mandatory ventilation (CMV) histopathology typical of acute respiratory distress syndrome includes atelectasis and thickened alveolar walls (circle), alveolar edema and fibrin (arrow), and cellular infiltration (arrowhead). Airway pressure release ventilation (APRV) histology was very similar to spontaneous breathing ventilation (SBV). Histology was conducted by L. A. Gatto.

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Figure 2.
Histologic Alveolar Airspace

Quantitative airspace percentage in alveoli was highest in the spontaneous breathing ventilation (SBV) lung, reduced slightly with airway pressure release ventilation (APRV) and markedly reduced in the continuous mandatory ventilation (CMV) group (Table). The green areas indicate air and the red areas indicate tissue/edema. P < .05 vs all groups. Histology was conducted by L. A. Gatto.

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Figure 3.
Bronchoalveolar Lavage Data

Bronchoalveolar lavage fluid (BALF) data including total protein (A), interleukin-6 (IL-6) (B), surfactant protein-A (SP-A) (C), and surfactant protein-B (SP-B) (D). APRV indicates airway pressure release ventilation; CMV, continuous mandatory ventilation; h, human; r, relative; SBV, spontaneous breathing ventilation.aP < .05.

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Figure 4.
Classic (A) and Alternative (B) Hypotheses for Acute Respiratory Distress Syndrome (ARDS) Pathogenesis

In the classic hypothesis, systemic inflammatory response syndrome (SIRS) initiates pathology, whereas in the alternative, ventilation-induced surfactant alteration (VISA) initiates pathology. RACE indicates repetitive alveolar collapse and expansion; VILI, ventilator-induced lung injury.

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