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.

AARC Clinical Practice Guideline: Management of Adult Patients With Oxygen in the Acute Care Setting.

Providing supplemental oxygen to hospitalized adults is a frequent practice and can be administered via a variety of devices. Oxygen therapy has evolved over the years, and clinicians should follow evidence-based practices to provide maximum benefit and avoid harm. This systematic review and subsequent clinical practice guidelines were developed to answer questions about oxygenation targets, monitoring, early initiation of high-flow oxygen (HFO), benefits of HFO compared to conventional oxygen therapy, and humidification of supplemental oxygen. Using a modification of the RAND/UCLA Appropriateness Method, 7 recommendations were developed to guide the delivery of supplemental oxygen to hospitalized adults: (1) aim for [Formula: see text] range of 94-98% for most hospitalized patients (88-92% for those with COPD), (2) the same [Formula: see text] range of 94-98% for critically ill patients, (3) promote early initiation of HFO, (4) consider HFO to avoid escalation to noninvasive ventilation, (5) consider HFO immediately postextubation to avoid re-intubation, (6) either HFO or conventional oxygen therapy may be used with patients who are immunocompromised, and (7) consider humidification for supplemental oxygen when flows > 4 L/min are used.

A Physiologically Informed Strategy to Effectively Open, Stabilize, and Protect the Acutely Injured Lung.

Acute respiratory distress syndrome (ARDS) causes a heterogeneous lung injury and remains a serious medical problem, with one of the only treatments being supportive care in the form of mechanical ventilation. It is very difficult, however, to mechanically ventilate the heterogeneously damaged lung without causing secondary ventilator-induced lung injury (VILI). The acutely injured lung becomes time and pressure dependent, meaning that it takes more time and pressure to open the lung, and it recollapses more quickly and at higher pressure. Current protective ventilation strategies, ARDSnet low tidal volume (LVt) and the open lung approach (OLA), have been unsuccessful at further reducing ARDS mortality. We postulate that this is because the LVt strategy is constrained to ventilating a lung with a heterogeneous mix of normal and focalized injured tissue, and the OLA, although designed to fully open and stabilize the lung, is often unsuccessful at doing so. In this review we analyzed the pathophysiology of ARDS that renders the lung susceptible to VILI. We also analyzed the alterations in alveolar and alveolar duct mechanics that occur in the acutely injured lung and discussed how these alterations are a key mechanism driving VILI. Our analysis suggests that the time component of each mechanical breath, at both inspiration and expiration, is critical to normalize alveolar mechanics and protect the lung from VILI. Animal studies and a meta-analysis have suggested that the time-controlled adaptive ventilation (TCAV) method, using the airway pressure release ventilation mode, eliminates the constraints of ventilating a lung with heterogeneous injury, since it is highly effective at opening and stabilizing the time- and pressure-dependent lung. In animal studies it has been shown that by "casting open" the acutely injured lung with TCAV we can (1) reestablish normal expiratory lung volume as assessed by direct observation of subpleural alveoli; (2) return normal parenchymal microanatomical structural support, known as alveolar interdependence and parenchymal tethering, as assessed by morphometric analysis of lung histology; (3) facilitate regeneration of normal surfactant function measured as increases in surfactant proteins A and B; and (4) significantly increase lung compliance, which reduces the pathologic impact of driving pressure and mechanical power at any given tidal volume.

Prevention and treatment of acute lung injury with time-controlled adaptive ventilation: physiologically informed modification of airway pressure release ventilation.

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.

Carbogen for Apnea Testing During the Brain Death Declaration Process in Subjects on Extracorporeal Membrane Oxygenation.

BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) in adult patients continues to increase. Suspicion of brain death while on ECMO creates a conundrum. The American Academy of Neurology states that apnea testing is a critical component of the process to declare brain death. However, there is a paucity of literature on apnea testing for confirmation of brain death in patients on venoarterial ECMO and venovenous ECMO. Traditional apnea testing does not consider ECMO physiology or de-recruitment of the lungs in this subset of critically ill patients. Complications with traditional apnea testing include hemodynamic instability that may lead to cardiac arrest and death. METHODS: We conducted a retrospective review of apnea tests using the carbogen method performed for brain death determination on 5 subjects on ECMO. A positive apnea test was used in confirmation of brain death in all 5 subjects on either venovenous ECMO (n = 2) or venoarterial ECMO (n = 3) while remaining on mechanical ventilation. A formula was used to calculate the subject's target value for CO2 production and completion of the apnea test. RESULTS: In all 5 cases, the carbogen method resulted in 100% accuracy of the targeted CO2 goal, and apnea testing was confirmed with no adverse events. CONCLUSIONS: In 5 subjects on ECMO, the carbogen method for apnea testing as part of the process to declare brain death was accurate in predicting the end point of the apnea test. With the increased use of ECMO in adults and the ongoing need for organs, methods to confirm brain death with apnea testing while on ECMO should be further studied.

Preemptive Mechanical Ventilation Based on Dynamic Physiology in the Alveolar Microenvironment: Novel Considerations of Time-Dependent Properties of the Respiratory System.

The acute respiratory distress syndrome (ARDS) remains a serious clinical problem with the current treatment being supportive in the form of mechanical ventilation. However, mechanical ventilation can be a double-edged sword; if set properly, it can significantly reduce ARDS associated mortality but if set improperly it can have unintended consequences causing a secondary ventilator induced lung injury (VILI). The hallmark of ARDS pathology is a heterogeneous lung injury, which predisposes the lung to a secondary VILI. The current standard of care approach is to wait until ARDS is well established and then apply a low tidal volume (LVt) strategy to avoid over-distending the remaining normal lung. However, even with the use of LVt strategy, the mortality of ARDS remains unacceptably high at ~40%. In this review, we analyze the lung pathophysiology associated with ARDS that renders the lung highly vulnerable to a secondary VILI. The current standard of care LVt strategy is critiqued as well as new strategies used in combination with LVt to protect the lung. Using the current understanding of alveolar mechanics (i.e. the dynamic change in alveolar size and shape with tidal ventilation) we provide a rationale for why the current protective ventilation strategies have not further reduced ARDS mortality. New strategies of protective ventilation based on dynamic physiology in the micro-environment (i.e. alveoli and alveolar ducts) are discussed. Current evidence suggests that alveolar inflation and deflation is viscoelastic in nature, with a fast and slow phase in both alveolar recruitment and collapse. Using this knowledge, a ventilation strategy with a prolonged time at inspiration would recruit alveoli and a brief release time at expiration would prevent alveolar collapse, converting heterogeneous to homogeneous lung inflation significantly reducing ARDS incidence and mortality.

Acute lung injury: how to stabilize a broken lung.

The pathophysiology of acute respiratory distress syndrome (ARDS) results in heterogeneous lung collapse, edema-flooded airways and unstable alveoli. These pathologic alterations in alveolar mechanics (i.e. dynamic change in alveolar size and shape with each breath) predispose the lung to secondary ventilator-induced lung injury (VILI). It is our viewpoint that the acutely injured lung can be recruited and stabilized with a mechanical breath until it heals, much like casting a broken bone until it mends. If the lung can be "casted" with a mechanical breath, VILI could be prevented and ARDS incidence significantly reduced.