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Airway pressure release ventilation during ex vivo lung perfusion attenuates injury.

ABSTRACT: OBJECTIVE:Critical organ shortages have resulted in ex vivo lung perfusion gaining clinical acceptance for lung evaluation and rehabilitation to expand the use of donation after circulatory death organs for lung transplantation. We hypothesized that an innovative use of airway pressure release ventilation during ex vivo lung perfusion improves lung function after transplantation. METHODS:Two groups (n = 4 animals/group) of porcine donation after circulatory death donor lungs were procured after hypoxic cardiac arrest and a 2-hour period of warm ischemia, followed by a 4-hour period of ex vivo lung perfusion rehabilitation with standard conventional volume-based ventilation or pressure-based airway pressure release ventilation. Left lungs were subsequently transplanted into recipient animals and reperfused for 4 hours. Blood gases for partial pressure of oxygen/inspired oxygen fraction ratios, airway pressures for calculation of compliance, and percent wet weight gain during ex vivo lung perfusion and reperfusion were measured. RESULTS:Airway pressure release ventilation during ex vivo lung perfusion significantly improved left lung oxygenation at 2 hours (561.5 ± 83.9 mm Hg vs 341.1 ± 136.1 mm Hg) and 4 hours (569.1 ± 18.3 mm Hg vs 463.5 ± 78.4 mm Hg). Likewise, compliance was significantly higher at 2 hours (26.0 ± 5.2 mL/cm H2O vs 15.0 ± 4.6 mL/cm H2O) and 4 hours (30.6 ± 1.3 mL/cm H2O vs 17.7 ± 5.9 mL/cm H2O) after transplantation. Finally, airway pressure release ventilation significantly reduced lung edema development on ex vivo lung perfusion on the basis of percentage of weight gain (36.9% ± 14.6% vs 73.9% ± 4.9%). There was no difference in additional edema accumulation 4 hours after reperfusion. CONCLUSIONS:Pressure-directed airway pressure release ventilation strategy during ex vivo lung perfusion improves the rehabilitation of severely injured donation after circulatory death lungs. After transplant, these lungs demonstrate superior lung-specific oxygenation and dynamic compliance compared with lungs ventilated with standard conventional ventilation. This strategy, if implemented into clinical ex vivo lung perfusion protocols, could advance the field of donation after circulatory death lung rehabilitation to expand the lung donor pool.

SUBMITTER: Mehaffey JH

PROVIDER: S-EPMC5164862 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Airway pressure release ventilation during ex vivo lung perfusion attenuates injury.

Mehaffey J Hunter JH Charles Eric J EJ Sharma Ashish K AK Money Dustin T DT Zhao Yunge Y Stoler Mark H MH Lau Christine L CL Tribble Curtis G CG Laubach Victor E VE Roeser Mark E ME Kron Irving L IL

The Journal of thoracic and cardiovascular surgery 20160922 1

<h4>Objective</h4>Critical organ shortages have resulted in ex vivo lung perfusion gaining clinical acceptance for lung evaluation and rehabilitation to expand the use of donation after circulatory death organs for lung transplantation. We hypothesized that an innovative use of airway pressure release ventilation during ex vivo lung perfusion improves lung function after transplantation.<h4>Methods</h4>Two groups (n = 4 animals/group) of porcine donation after circulatory death donor lungs were ...[more]

PMID: 27742245

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Project description:Mortality in acute respiratory distress syndrome (ARDS) remains unacceptably high at approximately 39%. One of the only treatments is supportive: mechanical ventilation. However, improperly set mechanical ventilation can further increase the risk of death in patients with ARDS. Recent studies suggest that ventilation-induced lung injury (VILI) is caused by exaggerated regional lung strain, particularly in areas of alveolar instability subject to tidal recruitment/derecruitment and stress-multiplication. Thus, it is reasonable to expect that if a ventilation strategy can maintain stable lung inflation and homogeneity, regional dynamic strain would be reduced and VILI attenuated. A time-controlled adaptive ventilation (TCAV) method was developed to minimize dynamic alveolar strain by adjusting the delivered breath according to the mechanical characteristics of the lung. The goal of this review is to describe how the TCAV method impacts pathophysiology and protects lungs with, or at high risk of, acute lung injury. We present work from our group and others that identifies novel mechanisms of VILI in the alveolar microenvironment and demonstrates that the TCAV method can reduce VILI in translational animal ARDS models and mortality in surgical/trauma patients. Our TCAV method utilizes the airway pressure release ventilation (APRV) mode and is based on opening and collapsing time constants, which reflect the viscoelastic properties of the terminal airspaces. Time-controlled adaptive ventilation uses inspiratory and expiratory time to (1) gradually "nudge" alveoli and alveolar ducts open with an extended inspiratory duration and (2) prevent alveolar collapse using a brief (sub-second) expiratory duration that does not allow time for alveolar collapse. The new paradigm in TCAV is configuring each breath guided by the previous one, which achieves real-time titration of ventilator settings and minimizes instability induced tissue damage. This novel methodology changes the current approach to mechanical ventilation, from arbitrary to personalized and adaptive. The outcome of this approach is an open and stable lung with reduced regional strain and greater lung protection.

Project description:IntroductionThere is an increasing interest in biphasic positive airway pressure with spontaneous breathing (BIPAP+SBmean), which is a combination of time-cycled controlled breaths at two levels of continuous positive airway pressure (BIPAP+SBcontrolled) and non-assisted spontaneous breathing (BIPAP+SBspont), in the early phase of acute lung injury (ALI). However, pressure support ventilation (PSV) remains the most commonly used mode of assisted ventilation. To date, the effects of BIPAP+SBmean and PSV on regional lung aeration and ventilation during ALI are only poorly defined.MethodsIn 10 anesthetized juvenile pigs, ALI was induced by surfactant depletion. BIPAP+SBmean and PSV were performed in a random sequence (1 h each) at comparable mean airway pressures and minute volumes. Gas exchange, hemodynamics, and inspiratory effort were determined and dynamic computed tomography scans obtained. Aeration and ventilation were calculated in four zones along the ventral-dorsal axis at lung apex, hilum and base.ResultsCompared to PSV, BIPAP+SBmean resulted in: 1) lower mean tidal volume, comparable oxygenation and hemodynamics, and increased PaCO2 and inspiratory effort; 2) less nonaerated areas at end-expiration; 3) decreased tidal hyperaeration and re-aeration; 4) similar distributions of ventilation. During BIPAP+SBmean: i) BIPAP+SBspont had lower tidal volumes and higher rates than BIPAP+SBcontrolled; ii) BIPAP+SBspont and BIPAP+SBcontrolled had similar distributions of ventilation and aeration; iii) BIPAP+SBcontrolled resulted in increased tidal re-aeration and hyperareation, compared to PSV. BIPAP+SBspont showed an opposite pattern.ConclusionsIn this model of ALI, the reduction of tidal re-aeration and hyperaeration during BIPAP+SBmean compared to PSV is not due to decreased nonaerated areas at end-expiration or different distribution of ventilation, but to lower tidal volumes during BIPAP+SBspont. The ratio between spontaneous to controlled breaths seems to play a pivotal role in reducing tidal re-aeration and hyperaeration during BIPAP+SBmean.

Project description:ObjectivesLow tidal volume (= tidal volume ≤ 6 mL/kg, predicted body weight) ventilation using volume control benefits patients with acute respiratory distress syndrome. Airway pressure release ventilation is an alternative to low tidal volume-volume control ventilation, but the release breaths generated are variable and can exceed tidal volume breaths of low tidal volume-volume control. We evaluate the application of a low tidal volume-compatible airway pressure release ventilation protocol that manages release volumes on both clinical and feasibility endpoints.DesignWe designed a prospective randomized trial in patients with acute hypoxemic respiratory failure. We randomized patients to low tidal volume-volume control, low tidal volume-airway pressure release ventilation, and traditional airway pressure release ventilation with a planned enrollment of 246 patients. The study was stopped early because of low enrollment and inability to consistently achieve tidal volumes less than 6.5 mL/kg in the low tidal volume-airway pressure release ventilation arm. Although the primary clinical study endpoint was PaO2/FIO2 on study day 3, we highlight the feasibility outcomes related to tidal volumes in both arms.SettingFour Intermountain Healthcare tertiary ICUs.PatientsAdult ICU patients with hypoxemic respiratory failure anticipated to require prolonged mechanical ventilation.InterventionsLow tidal volume-volume control, airway pressure release ventilation, and low tidal volume-airway pressure release ventilation.Measurements and main resultsWe observed wide variability and higher tidal (release for airway pressure release ventilation) volumes in both airway pressure release ventilation (8.6 mL/kg; 95% CI, 7.8-9.6) and low tidal volume-airway pressure release ventilation (8.0; 95% CI, 7.3-8.9) than volume control (6.8; 95% CI, 6.2-7.5; p = 0.005) with no difference between airway pressure release ventilation and low tidal volume-airway pressure release ventilation (p = 0.58). Recognizing the limitations of small sample size, we observed no difference in 52 patients in day 3 PaO2/ FIO2 (p = 0.92). We also observed no significant difference between arms in sedation, vasoactive medications, or occurrence of pneumothorax.ConclusionsAirway pressure release ventilation resulted in release volumes often exceeding 12 mL/kg despite a protocol designed to target low tidal volume ventilation. Current airway pressure release ventilation protocols are unable to achieve consistent and reproducible delivery of low tidal volume ventilation goals. A large-scale efficacy trial of low tidal volume-airway pressure release ventilation is not feasible at this time in the absence of an explicit, generalizable, and reproducible low tidal volume-airway pressure release ventilation protocol.

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Airway pressure release ventilation during ex vivo lung perfusion attenuates injury.

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Airway pressure release ventilation during ex vivo lung perfusion attenuates injury.

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