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. © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article' s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article'

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 ventilatorinduced 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.

Background Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in intensive care units. Distal airway mucus clearance has been shown to reduce VAP incidence. Studies suggest that mucus clearance is enhanced when the rate of expiratory flow is greater than inspiratory flow. The time-controlled adaptive ventilation (TCAV) protocol using the airway pressure release ventilation (APRV) mode has a significantly increased expiratory relative to inspiratory flow rate, as compared with the Acute Respiratory Distress Syndrome Network (ARDSnet) protocol using the conventional ventilation mode of volume assist control (VAC). We hypothesized the TCAV protocol would be superior to the ARDSnet protocol at clearing mucus by a mechanism of net flow in the expiratory direction. Methods Preserved pig lungs fitted with an endotracheal tube (ETT) were used as a model to study the effect of multiple combinations of peak inspiratory (I PF ) and peak expiratory flow rate (E PF ) on simulated mucus movement within the ETT. Mechanical ventilation was randomized into 6 groups ( n = 10 runs/group): group 1—TCAV protocol settings with an end-expiratory pressure (P Low ) of 0 cmH 2 O and P High 25 cmH 2 O, group 2—modified TCAV protocol with increased P Low 5 cmH 2 O and P High 25 cmH 2 O, group 3—modified TCAV with P Low 10 cmH 2 O and P High 25 cmH 2 O, group 4—ARDSnet protocol using low tidal volume (LTV) and PEEP 0 cmH 2 O, group 5—ARDSnet protocol using LTV and PEEP 10 cmH 2 O, and group 6—ARDSnet protocol using LTV and PEEP 20 cmH 2 O. PEEP of ARDSnet is analogous to P Low of TCAV. Proximal (towards the ventilator) mucus movement distance was recorded after 1 min of ventilation in each group. Results The TCAV protocol groups 1, 2, and 3 generated significantly greater peak expiratory flow (E PF 51.3 L/min, 46.8 L/min, 36.8 L/min, respectively) as compared to the ARDSnet protocol groups 4, 5, and 6 (32.9 L/min, 23.5 L/min, and 23.2 L/min, respectively) ( p < 0.001). The TCAV groups also demonstrated the greatest proximal mucus movement (7.95 cm/min, 5.8 cm/min, 1.9 cm/min) ( p < 0.01). All ARDSnet protocol groups (4–6) had zero proximal mucus movement (0 cm/min). Conclusions The TCAV protocol groups promoted the greatest proximal movement of simulated mucus as compared to the ARDSnet protocol groups in this excised lung model....

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BackgroundSepsis is one of the leading causes of death in the United States and the most common cause of death among critically ill patients in non-coronary intensive care units. Previous studies have showed pulse pressure (PP) to be a predictor of fluid responsiveness in patients with sepsis. Additionally, previous studies have correlated PP to cardiovascular risk factors and increase in mortality in end-stage renal disease patients.ObjectivesTo determine the correlation between PP and mortality in patients with sepsis.MethodsA retrospective review was conducted on 5,003 patients admitted with the diagnosis of sepsis using ICD-9 codes during the time period from January 2010 to December 2014 at two community-based hospitals in central Pennsylvania.ResultsOur study findings showed significant decrease in the mortality when the PP was greater than 70 mmHg of patients with sepsis (p-value: 0.0003, odds ratio: 0.67, 95% confidence limit: 0.54–0.83).ConclusionBased on our findings, we suggest that PP could be a valuable clinical tool in the early assessment of patients admitted with sepsis and could be used as a prognostic factor to assess and implement management therapy for the patients with sepsis.