It has been shown that mechanical ventilation in patients with, or at high-risk for, the development of acute respiratory distress syndrome (ARDS) can be a double-edged sword. If the mechanical breath is improperly set, it can amplify the lung injury associated with ARDS, causing a secondary ventilator-induced lung injury (VILI). Conversely, the mechanical breath can be adjusted to minimize VILI, which can reduce ARDS mortality. The current standard of care ventilation strategy to minimize VILI attempts to reduce alveolar over-distension and recruitment-derecruitment (R/D) by lowering tidal volume (Vt) to 6 cc/kg combined with adjusting positive-end expiratory pressure (PEEP) based on a sliding scale directed by changes in oxygenation. Thus, Vt is often but not always set as a “one-size-fits-all” approach and although PEEP is often set arbitrarily at 5 cmH2O, it may be personalized according to changes in a physiologic parameter, most often to oxygenation. However, there is evidence that oxygenation as a method to optimize PEEP is not congruent with the PEEP levels necessary to maintain an open and stable lung. Thus, optimal PEEP might not be personalized to the lung pathology of an individual patient using oxygenation as the physiologic feedback system. Multiple methods of personalizing PEEP have been tested and include dead space, lung compliance, lung stress and strain, ventilation patterns using computed tomography (CT) or electrical impedance tomography (EIT), inflection points on the pressure/volume curve (P/V), and the slope of the expiratory flow curve using airway pressure release ventilation (APRV). Although many studies have shown that personalizing PEEP is possible, there is no consensus as to the optimal technique. This review will assess various methods used to personalize PEEP, directed by physiologic parameters, necessary to adaptively adjust ventilator settings with progressive changes in lung pathophysiology.

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.

Acute respiratory distress syndrome causes a heterogeneous lung injury with normal and acutely injured lung tissue in the same lung. Improperly adjusted mechanical ventilation can exacerbate ARDS causing a secondary ventilator-induced lung injury (VILI). We hypothesized that a peak airway pressure of 40 cmH2O (static strain) alone would not cause additional injury in either the normal or acutely injured lung tissue unless combined with high tidal volume (dynamic strain). Pigs were anesthetized, and heterogeneous acute lung injury (ALI) was created by Tween instillation via a bronchoscope to both diaphragmatic lung lobes. Tissue in all other lobes was normal. Airway pressure release ventilation was used to precisely regulate time and pressure at both inspiration and expiration. Animals were separated into two groups: (1) over-distension + high dynamic strain (OD + HDS, n = 6) and (2) over-distension + low dynamic strain (OD + LDS, n = 6). OD was caused by setting the inspiratory pressure at 40 cmH2O and dynamic strain was modified by changing the expiratory duration, which varied the tidal volume. Animals were ventilated for 6 h recording hemodynamics, lung function, and inflammatory mediators followed by an extensive necropsy. In normal tissue (NT), OD + LDS caused minimal histologic damage and a significant reduction in BALF total protein (p < 0.05) and MMP-9 activity (p < 0.05), as compared with OD + HDS. In acutely injured tissue (ALIT), OD + LDS resulted in reduced histologic injury and pulmonary edema (p < 0.05), as compared with OD + HDS. Both NT and ALIT are resistant to VILI caused by OD alone, but when combined with a HDS, significant tissue injury develops.

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.

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.

It was recently shown that acute respiratory distress syndrome (ARDS) mortality has not been reduced in over 15 years and remains ~40 %, even with protective low tidal volume (LVt) ventilation. Thus, there is a critical need to develop novel ventilation strategies that will protect the lung and reduce ARDS mortality. Protti et al. have begun to analyze the impact of mechanical ventilation on lung tissue using engineering methods in normal pigs ventilated for 54 h. They used these methods to assess the impact of a mechanical breath on dynamic and static global lung strain and energy load. Strain is the change in lung volume in response to an applied stress (i.e., Tidal Volume-Vt). This study has yielded a number of exciting new concepts including the following: (1) Individual mechanical breath parameters (e.g., Vt or Plateau Pressure) are not directly correlated with VILI but rather any combination of parameters that subject the lung to excessive dynamic strain and energy/power load will cause VILI; (2) all strain is not equal; dynamic strain resulting in a dynamic energy load (i.e., kinetic energy) is more damaging to lung tissue than static strain and energy load (i.e., potential energy); and (3) a critical consideration is not just the size of the Vt but the size of the lung that is being ventilated by this Vt. This key concept merits attention since our current protective ventilation strategies are fixated on the priority of keeping the Vt low. If the lung is fully inflated, a large Vt is not necessarily injurious. In conclusion, using engineering concepts to analyze the impact of the mechanical breath on the lung is a novel new approach to investigate VILI mechanisms and to help design the optimally protective breath. Data generated using these methods have challenged some of the current dogma surrounding the mechanisms of VILI and of the components in the mechanical breath necessary for lung protection.