Early pathophysiology-driven airway pressure release ventilation versus low tidal volume ventilation strategy for patients with moderate-severe ARDS: study protocol for a randomized, multicenter, controlled trial.

BACKGROUND: Conventional Mechanical ventilation modes used for individuals suffering from acute respiratory distress syndrome have the potential to exacerbate lung injury through regional alveolar overinflation and/or repetitive alveolar collapse with shearing, known as atelectrauma. Animal studies have demonstrated that airway pressure release ventilation (APRV) offers distinct advantages over conventional mechanical ventilation modes. However, the methodologies for implementing APRV vary widely, and the findings from clinical studies remain controversial. This study (APRVplus trial), aims to assess the impact of an early pathophysiology-driven APRV ventilation approach compared to a low tidal volume ventilation (LTV) strategy on the prognosis of patients with moderate to severe ARDS. METHODS: The APRVplus trial is a prospective, multicenter, randomized clinical trial, building upon our prior single-center study, to enroll 840 patients from at least 35 hospitals in China. This investigation plans to compare the early pathophysiology-driven APRV ventilation approach with the control intervention of LTV lung-protective ventilation. The primary outcome measure will be all-cause mortality at 28 days after randomization in the intensive care units (ICU). Secondary outcome measures will include assessments of oxygenation, and physiology parameters at baseline, as well as on days 1, 2, and 3. Additionally, clinical outcomes such as ventilator-free days at 28 days, duration of ICU and hospital stay, ICU and hospital mortality, and the occurrence of adverse events will be evaluated. TRIAL ETHICS AND DISSEMINATION: The research project has obtained approval from the Ethics Committee of West China Hospital of Sichuan University (2019-337). Informed consent is required. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences. TRIAL REGISTRATION: The study was registered at Clinical Trials.gov (NCT03549910) on June 8, 2018.

Airway pressure release ventilation (APRV) versus pressure support ventilation (PSV)-A prospective intervention trial comparing haemodynamic parameters in intensive care patients.

BACKGROUND AND AIM: Assisted mechanical ventilation may alter the pressure profile in the thorax compared to normal breathing, which can affect the blood flow to and from the heart. Studies suggest that in patients with severe lung disease, airway pressure release ventilation (APRV) may be haemodynamically beneficial compared to other ventilator settings. The primary aim of this study was to investigate if APRV affects cardiac index in intubated intensive care patients without severe lung disease when compared to pressure support ventilation (PSV). The secondary aim comprised potential changes in other haemodynamic and ventilatory parameters. METHODS: Twenty patients were enrolled in the intensive care unit (ICU) at Sahlgrenska University Hospital. Eligible patients met the inclusion criteria; 18 years of age or above, intubated and mechanically ventilated, triggering and stable on PSV mode, with indwelling haemodynamic monitoring via a pulse-induced continuous cardiac output (PiCCO) catheter. The study protocol started with a 30-min interval on PSV mode, followed by a 30-min interval on APRV mode, and finally a 30-min interval back on PSV mode. At the end of each interval, PiCCO outputs, ventilator outputs, arterial and venous blood gas analyses, heart rate and central venous pressure were recorded and compared between modes. RESULTS: There was no significant difference in cardiac index (3.42 vs. 3.39 L/min/m2) between PSV and APRV, but a significant increase in central venous pressure (+1.0 mmHg, p = .027). Furthermore, we found a significant reduction in peak airway pressure (-3.16 cmH2O, p < .01) and an increase in mean airway pressure (+2.1 cmH2O, p < .01). No statistically significant change was found in oxygenation index (partial pressure of O2 [pO2]/fraction of inspired oxygen) nor in other secondary outcomes when comparing PSV and APRV. There was no significant association between global end-diastolic volume index and cardiac index (R2 = 0.0089) or central venous pressure (R2 = 0.278). All parameters returned to baseline after switching the ventilator mode back to PSV. CONCLUSION: We could not detect any changes in cardiac index in ICU patients without severe lung disease during APRV compared to PSV mode, despite lower peak airway pressure and increased mean airway pressure.

Effects of Lung Injury and Abdominal Insufflation on Respiratory Mechanics and Lung Volume During Time-Controlled Adaptive Ventilation.

BACKGROUND: Lung volume measurements are important for monitoring functional aeration and recruitment, and may help guide adjustments in ventilator settings. The expiratory phase of APRV may provide physiologic information about lung volume based on the expiratory flow-time slope, angle, and time to approach a no-flow state (TExp). We hypothesized that expiratory flow rate would correlate with estimated lung volume (ELV), as measured using a modified nitrogen washout/washin technique in a large animal lung injury model. METHODS: Eight pigs (35.2±1.0kg) were mechanically ventilated using an Engström Carescape R860 on the APRV mode. All settings were held constant except the expiratory duration (TLow), which was adjusted based on the expiratory flow curve. Abdominal pressure was increased to 15mmHg in normal and Tween-injured lungs to replicate a combination of pulmonary and extrapulmonary lung injury. ELV was estimated using the Carescape FRC InView Tool. The expiratory flow-time slope and TExp were measured from the expiratory flow profile. RESULTS: Lung elastance increased with Tween-induced lung injury from 29.3±7.3cmH2O/L to 39.9±15.1cmH2O/L and chest wall elastance increased with increasing intra-abdominal pressures from 15.3±4.1cmH2O/L to 25.7±10.0cmH2O/L in the normal lung and 15.8±6.0cmH2O/L to 33.0±6.2cmH2O/L in the Tween-injured lung (p=0.39). ELV decreased from 1.90±0.83L in the Tween-Injured lung to 0.67±0.1L by increasing intra-abdominal pressures to 15mmHg. This had a significant correlation with a TExp decrease from 2.3±0.8s to 1.0±0.1s in the Tween-injured group with increasing insufflation pressures (ρ = 0.95) and with the expiratory flow-time slope, which increased from 0.29±0.06L/s2 to 0.63±0.05L/s2 (ρ = 0.78). CONCLUSIONS: Changes in ELV over time, and the TExp and flow-time slope, can be used to demonstrate evolving lung injury during APRV. Using the slope to infer changes in functional lung volume represents a unique, reproducible, real-time, bedside technique that does not interrupt ventilation and may be used for clinical interpretation.

Successful application of airway pressure release ventilation in a child with severe acute respiratory distress syndrome induced by trauma: a case report.

BACKGROUND: Trauma has been identified as one of the risk factors for acute respiratory distress syndrome. Respiratory support can be further complicated by comorbidities of trauma such as primary or secondary lung injury. Conventional ventilation strategies may not be suitable for all trauma-related acute respiratory distress syndrome. Airway pressure release ventilation has emerged as a potential rescue method for patients with acute respiratory distress syndrome and hypoxemia refractory to conventional mechanical ventilation. However, there is a lack of research on the use of airway pressure release ventilation in children with trauma-related acute respiratory distress syndrome. We report a case of airway pressure release ventilation applied to a child with falling injury, severe acute respiratory distress syndrome, hemorrhagic shock, and bilateral hemopneumothorax. We hope this case report presents a potential option for trauma-related acute respiratory distress syndrome and serves as a basis for future research. CASE PRESENTATION: A 15-year-old female with falling injury who developed severe acute respiratory distress syndrome, hemorrhagic shock, and bilateral hemopneumothorax was admitted to the surgical intensive care unit. She presented refractory hypoxemia despite the treatment of conventional ventilation with deep analgesia, sedation, and muscular relaxation. Lung recruitment was ineffective and prone positioning was contraindicated. Her oxygenation significantly improved after the use of airway pressure release ventilation. She was eventually extubated after 12 days of admission and discharged after 42 days of hospitalization. CONCLUSION: Airway pressure release ventilation may be considered early in the management of trauma patients with severe acute respiratory distress syndrome when prone position ventilation cannot be performed and refractory hypoxemia persists despite conventional ventilation and lung recruitment maneuvers.

The use of protective mechanical ventilation during extracorporeal membrane oxygenation for the treatment of acute respiratory failure.

Acute respiratory failure (ARF) strikes an estimated two million people in the United States each year, with care exceeding US$50 billion. The hallmark of ARF is a heterogeneous injury, with normal tissue intermingled with a large volume of low compliance and collapsed tissue. Mechanical ventilation is necessary to oxygenate and ventilate patients with ARF, but if set inappropriately, it can cause an unintended ventilator-induced lung injury (VILI). The mechanism of VILI is believed to be overdistension of the remaining normal tissue known as the 'baby' lung, causing volutrauma, repetitive collapse and reopening of lung tissue with each breath, causing atelectrauma, and inflammation secondary to this mechanical damage, causing biotrauma. To avoid VILI, extracorporeal membrane oxygenation (ECMO) can temporally replace the pulmonary function of gas exchange without requiring high tidal volumes (VT) or airway pressures. In theory, the lower VT and airway pressure will minimize all three VILI mechanisms, allowing the lung to 'rest' and heal in the collapsed state. The optimal method of mechanical ventilation for the patient on ECMO is unknown. The ARDSNetwork Acute Respiratory Management Approach (ARMA) is a Rest Lung Approach (RLA) that attempts to reduce the excessive stress and strain on the remaining normal lung tissue and buys time for the lung to heal in the collapsed state. Theoretically, excessive tissue stress and strain can also be avoided if the lung is fully open, as long as the alveolar re-collapse is prevented during expiration, an approach known as the Open Lung Approach (OLA). A third lung-protective strategy is the Stabilize Lung Approach (SLA), in which the lung is initially stabilized and gradually reopened over time. This review will analyze the physiologic efficacy and pathophysiologic potential of the above lung-protective approaches.

Ratchet recruitment in the acute respiratory distress syndrome: lessons from the newborn cry.

Patients with acute respiratory distress syndrome (ARDS) have few treatment options other than supportive mechanical ventilation. The mortality associated with ARDS remains unacceptably high, and mechanical ventilation itself has the potential to increase mortality further by unintended ventilator-induced lung injury (VILI). Thus, there is motivation to improve management of ventilation in patients with ARDS. The immediate goal of mechanical ventilation in ARDS should be to prevent atelectrauma resulting from repetitive alveolar collapse and reopening. However, a long-term goal should be to re-open collapsed and edematous regions of the lung and reduce regions of high mechanical stress that lead to regional volutrauma. In this paper, we consider the proposed strategy used by the full-term newborn to open the fluid-filled lung during the initial breaths of life, by ratcheting tissues opened over a series of initial breaths with brief expirations. The newborn's cry after birth shares key similarities with the Airway Pressure Release Ventilation (APRV) modality, in which the expiratory duration is sufficiently short to minimize end-expiratory derecruitment. Using a simple computational model of the injured lung, we demonstrate that APRV can slowly open even the most recalcitrant alveoli with extended periods of high inspiratory pressure, while reducing alveolar re-collapse with brief expirations. These processes together comprise a ratchet mechanism by which the lung is progressively recruited, similar to the manner in which the newborn lung is aerated during a series of cries, albeit over longer time scales.

First Stabilize and then Gradually Recruit: A Paradigm Shift in Protective Mechanical Ventilation for Acute Lung Injury.

Acute respiratory distress syndrome (ARDS) is associated with a heterogeneous pattern of injury throughout the lung parenchyma that alters regional alveolar opening and collapse time constants. Such heterogeneity leads to atelectasis and repetitive alveolar collapse and expansion (RACE). The net effect is a progressive loss of lung volume with secondary ventilator-induced lung injury (VILI). Previous concepts of ARDS pathophysiology envisioned a two-compartment system: a small amount of normally aerated lung tissue in the non-dependent regions (termed "baby lung"); and a collapsed and edematous tissue in dependent regions. Based on such compartmentalization, two protective ventilation strategies have been developed: (1) a "protective lung approach" (PLA), designed to reduce overdistension in the remaining aerated compartment using a low tidal volume; and (2) an "open lung approach" (OLA), which first attempts to open the collapsed lung tissue over a short time frame (seconds or minutes) with an initial recruitment maneuver, and then stabilize newly recruited tissue using titrated positive end-expiratory pressure (PEEP). A more recent understanding of ARDS pathophysiology identifies regional alveolar instability and collapse (i.e., hidden micro-atelectasis) in both lung compartments as a primary VILI mechanism. Based on this understanding, we propose an alternative strategy to ventilating the injured lung, which we term a "stabilize lung approach" (SLA). The SLA is designed to immediately stabilize the lung and reduce RACE while gradually reopening collapsed tissue over hours or days. At the core of SLA is time-controlled adaptive ventilation (TCAV), a method to adjust the parameters of the airway pressure release ventilation (APRV) modality. Since the acutely injured lung at any given airway pressure requires more time for alveolar recruitment and less time for alveolar collapse, SLA adjusts inspiratory and expiratory durations and inflation pressure levels. The TCAV method SLA reverses the open first and stabilize second OLA method by: (i) immediately stabilizing lung tissue using a very brief exhalation time (≤0.5 s), so that alveoli simply do not have sufficient time to collapse. The exhalation duration is personalized and adaptive to individual respiratory mechanical properties (i.e., elastic recoil); and (ii) gradually recruiting collapsed lung tissue using an inflate and brake ratchet combined with an extended inspiratory duration (4-6 s) method. Translational animal studies, clinical statistical analysis, and case reports support the use of TCAV as an efficacious lung protective strategy.

Combined Effects of Prone Positioning and Airway Pressure Release Ventilation on Oxygenation in Patients with COVID-19 ARDS.

Objective: Coronavirus disease 2019 (COVID-19) can cause acute respiratory distress syndrome (ARDS). Invasive mechanical ventilation (IMV) support and prone positioning are essential treatments for severe COVID-19 ARDS. We aimed to determine the combined effect of prone position and airway pressure release ventilation (APRV) modes on oxygen improvement in mechanically-ventilated patients with COVID-19. Methods: This prospective observational study included 40 eligible patients (13 female, 27 male). Of 40 patients, 23 (57.5%) were ventilated with APRV and 17 (42.5%) were ventilated with controlled modes. A prone position was applied when the PaO2/FiO2 ratio <150 mmHg despite IMV in COVID-19 ARDS. The numbers of patients who completed the first, second, and third prone were 40, 25, and 15, respectively. Incident barotrauma events were diagnosed by both clinical findings and radiological images. Results: After the second prone, the PaO2/FiO2 ratio of the APRV group was higher compared to the PaO2/FiO2 ratio of the control group [189 (150-237)] vs. 127 (100-146) mmHg, respectively, (P=0.025). Similarly, after the third prone, the PaO2/FiO2 ratio of the APRV group was higher compared to the PaO2/FiO2 ratio of the control group [194 (132-263)] vs. 83 (71-136) mmHg, respectively, (P=0.021). Barotrauma events were detected in 13.0% of the patients in the APRV group and 11.8% of the patients in the control group (P=1000). The 28-day mortality was not different in the APRV group than in the control group (73.9% vs. 70.6%, respectively, P=1000). Conclusion: Using the APRV mode during prone positioning improves oxygenation, especially in the second and third prone positions, without increasing the risk of barotrauma. However, no benefit on mortality was detected.

Effects of airway pressure release ventilation on lung physiology assessed by electrical impedance tomography in patients with early moderate-to-severe ARDS.

OBJECTIVE: The aim of this study was to investigate the physiological impact of airway pressure release ventilation (APRV) on patients with early moderate-to-severe acute respiratory distress syndrome (ARDS) by electrical impedance tomography (EIT). METHODS: In this single-center prospective physiological study, adult patients with early moderate-to-severe ARDS mechanically ventilated with APRV were assessed by EIT shortly after APRV (T0), and 6 h (T1), 12 h (T2), and 24 h (T3) after APRV initiation. Regional ventilation and perfusion distribution, dead space (%), shunt (%), and ventilation/perfusion matching (%) based on EIT measurement at different time points were compared. Additionally, clinical variables related to respiratory and hemodynamic condition were analyzed. RESULTS: Twelve patients were included in the study. After APRV, lung ventilation and perfusion were significantly redistributed to dorsal region. One indicator of ventilation distribution heterogeneity is the global inhomogeneity index, which decreased gradually [0.61 (0.55-0.62) to 0.50 (0.42-0.53), p < 0.001]. The other is the center of ventilation, which gradually shifted towards the dorsal region (43.31 ± 5.07 to 46.84 ± 4.96%, p = 0.048). The dorsal ventilation/perfusion matching increased significantly from T0 to T3 (25.72 ± 9.01 to 29.80 ± 7.19%, p = 0.007). Better dorsal ventilation (%) was significantly correlated with higher PaO2/FiO2 (r = 0.624, p = 0.001) and lower PaCO2 (r = -0.408, p = 0.048). CONCLUSIONS: APRV optimizes the distribution of ventilation and perfusion, reducing lung heterogeneity, which potentially reduces the risk of ventilator-induced lung injury.

Management of refractory hypoxemia using recruitment maneuvers and rescue therapies: A comprehensive review.

Refractory hypoxemia in patients with acute respiratory distress syndrome treated with mechanical ventilation is one of the most challenging conditions in human and veterinary intensive care units. When a conventional lung protective approach fails to restore adequate oxygenation to the patient, the use of recruitment maneuvers and positive end-expiratory pressure to maximize alveolar recruitment, improve gas exchange and respiratory mechanics, while reducing the risk of ventilator-induced lung injury has been suggested in people as the open lung approach. Although the proposed physiological rationale of opening and keeping open previously collapsed or obstructed airways is sound, the technique for doing so, as well as the potential benefits regarding patient outcome are highly controversial in light of recent randomized controlled trials. Moreover, a variety of alternative therapies that provide even less robust evidence have been investigated, including prone positioning, neuromuscular blockade, inhaled pulmonary vasodilators, extracorporeal membrane oxygenation, and unconventional ventilatory modes such as airway pressure release ventilation. With the exception of prone positioning, these modalities are limited by their own balance of risks and benefits, which can be significantly influenced by the practitioner's experience. This review explores the rationale, evidence, advantages and disadvantages of each of these therapies as well as available methods to identify suitable candidates for recruitment maneuvers, with a summary on their application in veterinary medicine. Undoubtedly, the heterogeneous and evolving nature of acute respiratory distress syndrome and individual lung phenotypes call for a personalized approach using new non-invasive bedside assessment tools, such as electrical impedance tomography, lung ultrasound, and the recruitment-to-inflation ratio to assess lung recruitability. Data available in human medicine provide valuable insights that could, and should, be used to improve the management of veterinary patients with severe respiratory failure with respect to their intrinsic anatomy and physiology.

Airway Pressure Release Ventilation for Acute Respiratory Failure Due to Coronavirus Disease 2019: A Systematic Review and Meta-Analysis.

Objective: To explore the evidence surrounding the use of Airway Pressure Release Ventilation (APRV) in patients with coronavirus disease 2019 (COVID-19). Methods: A Systematic electronic search of PUBMED, EMBASE, and the WHO COVID-19 database. We also searched the grey literature via Google and preprint servers (medRxive and research square). Eligible studies included randomised controlled trials and observational studies comparing APRV to conventional mechanical ventilation (CMV) in adults with acute hypoxemic respiratory failure due to COVID-19 and reporting at least one of the following outcomes; in-hospital mortality, ventilator free days (VFDs), ICU length of stay (LOS), changes in gas exchange parameters, and barotrauma. Two authors independently screened and selected articles for inclusion and extracted data in a pre-specified form. Results: Of 181 articles screened, seven studies (one randomised controlled trial, two cohort studies, and four before-after studies) were included comprising 354 patients. APRV was initiated at a mean of 1.2-13 days after intubation. APRV wasn't associated with improved mortality compared to CMV (relative risk [RR], 1.20; 95% CI 0.70-2.05; I2, 61%) neither better VFDs (ratio of means [RoM], 0.80; 95% CI, 0.52-1.24; I2, 0%) nor ICU LOS (RoM, 1.10; 95% CI, 0.79-1.51; I2, 57%). Compared to CMV, APRV was associated with a 33% increase in PaO2/FiO2 ratio (RoM, 1.33; 95% CI, 1.21-1.48; I2, 29%) and a 9% decrease in PaCO2 (RoM, 1.09; 95% CI, 1.02-1.15; I2, 0%). There was no significant increased risk of barotrauma compared to CMV (RR, 1.55; 95% CI, 0.60-4.00; I2, 0%). Conclusions: In adult patients with COVID-19 requiring mechanical ventilation, APRV is associated with improved gas exchange but not mortality nor VFDs when compared with CMV. The results were limited by high uncertainty given the low quality of the available studies and limited number of patients. Adequately powered and well-designed clinical trials to define the role of APRV in COVID-19 patients are still needed. Registration: PROSPERO; CRD42021291234.

Effects of airway pressure release ventilation on multi-organ injuries in severe acute respiratory distress syndrome pig models.

BACKGROUND: Extra-pulmonary multi-organ failure in patients with severe acute respiratory distress syndrome (ARDS) is a major cause of high mortality. Our purpose is to assess whether airway pressure release ventilation (APRV) causes more multi-organ damage than low tidal volume ventilation (LTV). METHODS: Twenty one pigs were randomized into control group (n = 3), ARDS group (n = 3), LTV group (n = 8) and APRV group (n = 7). Severe ARDS model was induced by repeated bronchial saline lavages. Pigs were ventilated and monitored continuously for 48 h. Respiratory data, hemodynamic data, serum inflammatory cytokines were collected throughout the study. Histological injury and apoptosis were assessed by two pathologists. RESULTS: After severe ARDS modeling, pigs in ARDS, LTV and APRV groups experienced significant hypoxemia and reduced lung static compliance (Cstat). Oxygenation recovered progressively after 16 h mechanical ventilation (MV) in LTV and APRV group. The results of the repeated measures ANOVA showed no statistical difference in the PaO2/FiO2 ratio between the APRV and LTV groups (p = 0.54). The Cstat showed a considerable improvement in APRV group with statistical significance (p < 0.01), which was significantly higher than in the LTV group since 16 h (p = 0.04). Histological injury scores showed a significantly lower injury score in the middle and lower lobes of the right lung in the APRV group compared to LTV (pmiddle = 0.04, plower = 0.01), and no significant increase in injury scores for extra-pulmonary organs, including kidney (p = 0.10), small intestine (p = 1.0), liver (p = 0.14, p = 0.13) and heart (p = 0.20). There were no significant differences in serum inflammatory cytokines between the two groups. CONCLUSION: In conclusion, in the experimental pig models of severe ARDS induced by repetitive saline lavage, APRV improved lung compliance with reduced lung injury of middle and lower lobes, and did not demonstrate more extra-pulmonary organ injuries as compared with LTV.

Early use of airway pressure release ventilation in acute respiratory distress syndrome induced by coronavirus disease 2019: a case report.

BACKGROUND: Coronavirus disease 2019 is a highly transmissible and pathogenic viral infection caused by severe acute respiratory syndrome coronavirus 2, a novel coronavirus that was identified in early January 2020 in Wuhan, China, and has become a pandemic disease worldwide. The symptoms of coronavirus disease 2019 range from asymptomatic to severe respiratory failure. In moderate and severe cases, oxygen therapy is needed. In severe cases, high-flow nasal cannula, noninvasive ventilation, and invasive mechanical ventilation are needed. Many ventilation methods in mechanical ventilation can be used, but not all are suitable for coronavirus disease 2019 patients. Airway pressure release ventilation, which is one of the mechanical ventilation methods, can be considered for patients with moderate-to-severe acute respiratory distress syndrome. It was found that oxygenation in the airway pressure release ventilation method was better than in the conventional method. How about airway pressure release ventilation in coronavirus disease 2019 patients? We report a case of confirmed coronavirus disease 2019 in which airway pressure release ventilation mode was used. CASE PRESENTATION: In this case study, we report a 74-year-old Chinese with a history of hypertension and uncontrolled diabetes mellitus type 2. He came to our hospital with the chief complaint of difficulty in breathing. He was fully awake with an oxygen saturation of 82% on room air. The patient was admitted and diagnosed with severe coronavirus disease 2019, and he was given a nonrebreathing mask at 15 L per minute, and oxygen saturation went back to 95%. After a few hours with a nonrebreathing mask, his condition worsened. On the third day after admission, saturation went down despite using noninvasive ventilation. We decided to intubate the patient and used airway pressure release ventilation mode. Finally, after 14 days of being intubated, the patient could be extubated and discharged after 45 days of hospitalization. CONCLUSION: Early use of airway pressure release ventilation may be considered as one of the ventilation strategies to treat severe coronavirus disease 2019 acute respiratory distress syndrome. Although reports on airway pressure release ventilation and protocols on its initiation and titration methods are limited, it may be worthwhile to consider, given its known ability to maximize alveolar recruitment, preserve alveolar epithelial integrity, and surfactant, all of which are crucial for handling the "fragile" lungs of coronavirus disease 2019 patients.

The Effects of Airway Pressure Release Ventilation on Pulmonary Permeability in Severe Acute Respiratory Distress Syndrome Pig Models.

Objective: The aim of the study was to compare the effects of APRV and LTV ventilation on pulmonary permeability in severe ARDS. Methods: Mini Bama adult pigs were randomized into the APRV group (n = 5) and LTV group (n = 5). A severe ARDS animal model was induced by the whole lung saline lavage. Pigs were ventilated and monitored continuously for 48 h. Results: Compared with the LTV group, CStat was significantly better (p < 0.05), and the PaO2/FiO2 ratio showed a trend to be higher throughout the period of the experiment in the APRV group. The extravascular lung water index and pulmonary vascular permeability index showed a trend to be lower in the APRV group. APRV also significantly mitigates lung histopathologic injury determined by the lung histopathological injury score (p < 0.05) and gross pathological changes of lung tissues. The protein contents of occludin (p < 0.05), claudin-5 (p < 0.05), E-cadherin (p < 0.05), and VE-cadherin (p < 0.05) in the middle lobe of the right lung were higher in the APRV group than in the LTV group; among them, the contents of occludin (p < 0.05) and E-cadherin (p < 0.05) of the whole lung were higher in the APRV group. Transmission electron microscopy showed that alveolar-capillary barrier damage was more severe in the middle lobe of lungs in the LTV group. Conclusion: In comparison with LTV, APRV could preserve the alveolar-capillary barrier architecture, mitigate lung histopathologic injury, increase the expression of cell junction protein, improve respiratory system compliance, and showed a trend to reduce extravascular lung water and improve oxygenation. These findings indicated that APRV might lead to more profound beneficial effects on the integrity of the alveolar-capillary barrier architecture and on the expression of biomarkers related to pulmonary permeability.

Myths and Misconceptions of Airway Pressure Release Ventilation: Getting Past the Noise and on to the Signal.

In the pursuit of science, competitive ideas and debate are necessary means to attain knowledge and expose our ignorance. To quote Murray Gell-Mann (1969 Nobel Prize laureate in Physics): "Scientific orthodoxy kills truth". In mechanical ventilation, the goal is to provide the best approach to support patients with respiratory failure until the underlying disease resolves, while minimizing iatrogenic damage. This compromise characterizes the philosophy behind the concept of "lung protective" ventilation. Unfortunately, inadequacies of the current conceptual model-that focuses exclusively on a nominal value of low tidal volume and promotes shrinking of the "baby lung" - is reflected in the high mortality rate of patients with moderate and severe acute respiratory distress syndrome. These data call for exploration and investigation of competitive models evaluated thoroughly through a scientific process. Airway Pressure Release Ventilation (APRV) is one of the most studied yet controversial modes of mechanical ventilation that shows promise in experimental and clinical data. Over the last 3 decades APRV has evolved from a rescue strategy to a preemptive lung injury prevention approach with potential to stabilize the lung and restore alveolar homogeneity. However, several obstacles have so far impeded the evaluation of APRV's clinical efficacy in large, randomized trials. For instance, there is no universally accepted standardized method of setting APRV and thus, it is not established whether its effects on clinical outcomes are due to the ventilator mode per se or the method applied. In addition, one distinctive issue that hinders proper scientific evaluation of APRV is the ubiquitous presence of myths and misconceptions repeatedly presented in the literature. In this review we discuss some of these misleading notions and present data to advance scientific discourse around the uses and misuses of APRV in the current literature.

Validation of at-the-bedside formulae for estimating ventilator driving pressure during airway pressure release ventilation using computer simulation.

BACKGROUND: Airway pressure release ventilation (APRV) is widely available on mechanical ventilators and has been proposed as an early intervention to prevent lung injury or as a rescue therapy in the management of refractory hypoxemia. Driving pressure ([Formula: see text]) has been identified in numerous studies as a key indicator of ventilator-induced-lung-injury that needs to be carefully controlled. [Formula: see text] delivered by the ventilator in APRV is not directly measurable in dynamic conditions, and there is no "gold standard" method for its estimation. METHODS: We used a computational simulator matched to data from 90 patients with acute respiratory distress syndrome (ARDS) to evaluate the accuracy of three "at-the-bedside" methods for estimating ventilator [Formula: see text] during APRV. RESULTS: Levels of [Formula: see text] delivered by the ventilator in APRV were generally within safe limits, but in some cases exceeded levels specified by protective ventilation strategies. A formula based on estimating the intrinsic positive end expiratory pressure present at the end of the APRV release provided the most accurate estimates of [Formula: see text]. A second formula based on assuming that expiratory flow, volume and pressure decay mono-exponentially, and a third method that requires temporarily switching to volume-controlled ventilation, also provided accurate estimates of true [Formula: see text]. CONCLUSIONS: Levels of [Formula: see text] delivered by the ventilator during APRV can potentially exceed levels specified by standard protective ventilation strategies, highlighting the need for careful monitoring. Our results show that [Formula: see text] delivered by the ventilator during APRV can be accurately estimated at the bedside using simple formulae that are based on readily available measurements.

Expanding unilateral lung collapse using airway pressure release ventilation applied independently to the collapsed lung through the double-lumen endotracheal tube.

Unilateral lung collapse (ULC) is a clinical challenge in the intensive care unit and requires sophisticated treatment approaches, especially if the collapse continued over several hours. If not responded to ordinary measures such as postural drainage and bronchoscopy, it may require insertion of a double-lumen endotracheal tube and independent lung ventilation or high-pressure manual re-expansion of the collapsed lung which may result in lung injury. In this article, a safe and gradual re-expansion method using airway pressure release ventilation is presented for the treatment of a ULC.

Does airway pressure release ventilation offer new hope for treating acute respiratory distress syndrome?

Mechanical ventilation (MV) is an essential life support method for patients with acute respiratory distress syndrome (ARDS), which is one of the most common critical illnesses with high mortality in the intensive care unit (ICU). A lung-protective ventilation strategy based on low tidal volume (LTV) has been recommended since a few years; however, as this did not result in a significant decrease of ARDS-related mortality, a more optimal ventilation mode was required. Airway pressure release ventilation (APRV) is an old method defined as a continuous positive airway pressure (CPAP) with a brief intermittent release phase based on the open lung concept; it also perfectly fits the ARDS treatment principle. Despite this, APRV has not been widely used in the past, rather only as a rescue measure for ARDS patients who are difficult to oxygenate. Over recent years, with an increased understanding of the pathophysiology of ARDS, APRV has been reproposed to improve patient prognosis. Nevertheless, this mode is still not routinely used in ARDS patients given its vague definition and complexity. Consequently, in this paper, we summarize the studies that used APRV in ARDS, including adults, children, and animals, to illustrate the settings of parameters, effectiveness in the population, safety (especially in children), incidence, and mechanism of ventilator-induced lung injury (VILI) and effects on extrapulmonary organs. Finally, we found that APRV is likely associated with improvement in ARDS outcomes, and does not increase injury to the lungs and other organs, thereby indicating that personalized APRV settings may be the new hope for ARDS treatment.

A narrative review of advanced ventilator modes in the pediatric intensive care unit.

Respiratory failure is a common reason for pediatric intensive care unit admission. The vast majority of children requiring mechanical ventilation can be supported with conventional mechanical ventilation (CMV) but certain cases with refractory hypoxemia or hypercapnia may require more advanced modes of ventilation. This paper discusses what we have learned about the use of advanced ventilator modes [e.g., high-frequency oscillatory ventilation (HFOV), high-frequency percussive ventilation (HFPV), high-frequency jet ventilation (HFJV) airway pressure release ventilation (APRV), and neurally adjusted ventilatory assist (NAVA)] from clinical, animal, and bench studies. The evidence supporting advanced ventilator modes is weak and consists of largely of single center case series, although a few RCTs have been performed. Animal and bench models illustrate the complexities of different modes and the challenges of applying these clinically. Some modes are proprietary to certain ventilators, are expensive, or may only be available at well-resourced centers. Future efforts should include large, multicenter observational, interventional, or adaptive design trials of different rescue modes (e.g., PROSpect trial), evaluate their use during ECMO, and should incorporate assessments through volumetric capnography, electric impedance tomography, and transpulmonary pressure measurements, along with precise reporting of ventilator parameters and physiologic variables.