Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome historically characterized by the presence of severe hypoxemia, high-permeability pulmonary edema manifesting as diffuse alveolar infiltrate on chest radiograph, and reduced compliance of the integrated respiratory system as a result of widespread compressive atelectasis and fluid-filled alveoli. Coronavirus disease 19 (COVID-19)-associated ARDS (C-ARDS) is a novel etiology caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that may present with distinct clinical features as a result of the viral pathobiology unique to SARS-CoV-2. In particular, severe injury to the pulmonary vascular endothelium, accompanied by the presence of diffuse microthrombi in the pulmonary microcirculation, can lead to a clinical presentation in which the severity of impaired gas exchange becomes uncoupled from lung capacity and respiratory mechanics. The purpose of this review is to highlight the key mechanistic features of C-ARDS and to discuss the implications these features have on its treatment. In some patients with C-ARDS, rigid adherence to guidelines derived from clinical trials in the pre-COVID era may not be appropriate.

Clinicians monitor mechanical ventilatory support using airway pressures—primarily the plateau and driving pressure, which are considered by many to determine the safety of the applied tidal volume. These airway pressures are influenced not only by the ventilator prescription, but also by the mechanical properties of the respiratory system, which consists of the series-coupled lung and chest wall. Actively limiting chest wall expansion through external compression of the rib cage or abdomen is seldom performed in the ICU. Recent literature describing the respiratory mechanics of patients with late-stage, unresolving, ARDS, however, has raised awareness of the potential diagnostic (and perhaps therapeutic) value of this unfamiliar and somewhat counterintuitive practice. In these patients, interventions that reduce resting lung volume, such as loading the chest wall through application of external weights or manual pressure, or placing the torso in a more horizontal position, have unexpectedly improved tidal compliance of the lung and integrated respiratory system by reducing previously undetected end-tidal hyperinflation. In this interpretive review, we first describe underappreciated lung and chest wall interactions that are clinically relevant to both normal individuals and to the acutely ill who receive ventilatory support. We then apply these physiologic principles, in addition to published clinical observation, to illustrate the utility of chest wall modification for the purposes of detecting end-tidal hyperinflation in everyday practice.

OBJECTIVES: Head-elevated body positioning, a default clinical practice, predictably increases end-expiratory transpulmonary pressure and aerated lung volume. In acute respiratory distress syndrome (ARDS), however, the net effect of such vertical inclination on tidal mechanics depends upon whether lung recruitment or overdistension predominates. We hypothesized that in moderate to severe ARDS, bed inclination toward vertical unloads the chest wall but adversely affects overall respiratory system compliance (Crs). DESIGN: Prospective physiologic study. SETTING: Two medical ICUs in the United States. PATIENTS: Seventeen patients with ARDS, predominantly moderate to severe. INTERVENTION: Patients were ventilated passively by volume control. We measured airway pressures at baseline (noninclined) and following bed inclination toward vertical by an additional 15°. At baseline and following inclination, we manually loaded the chest wall to determine if Crs increased or paradoxically declined, suggestive of end-tidal overdistension. MEASUREMENTS AND MAIN RESULTS: Inclination resulted in a higher plateau pressure (supineΔ: 2.8 ± 3.3 cm H₂O [p = 0.01]; proneΔ: 3.3 ± 2.5 cm H₂O [p = 0.004]), higher driving pressure (supineΔ: 2.9 ± 3.3 cm H₂O [p = 0.01]; proneΔ: 3.3 ± 2.8 cm H₂O [p = 0.007]), and lower Crs (supine Δ: 3.4 ± 3.7 mL/cm H₂O [p = 0.01]; proneΔ: 3.1 ± 3.2 mL/cm H₂O [p = 0.02]). Following inclination, manual loading of the chest wall restored Crs and driving pressure to baseline (preinclination) values. CONCLUSIONS: In advanced ARDS, bed inclination toward vertical adversely affects Crs and therefore affects the numerical values for plateau and driving tidal pressures commonly targeted in lung protective strategies. These changes are fully reversed with manual loading of the chest wall, suggestive of end-tidal overdistension in the upright position. Body inclination should be considered a modifiable determinant of transpulmonary pressure and lung protection, directionally similar to tidal volume and positive end-expiratory pressure.

Background: Chest wall loading has been shown to paradoxically improve respiratory system compliance (C_RS) in patients with moderate to severe acute respiratory distress syndrome (ARDS). The most likely, albeit unconfirmed, mechanism is relief of end-tidal overdistension in ‘baby lungs’ of low-capacity. The purpose of this study was to define how small changes of tidal volume (V_T) and positive end-expiratory pressure (PEEP) affect C_RS(and its associated airway pressures) in patients with ARDS who demonstrate a paradoxical response to chest wall loading. We hypothesized that small reductions of V_Tor PEEP would alleviate overdistension and favorably affect C_RSand conversely, that small increases of V_Tor PEEP would worsen C_RS.Methods: Prospective, multi-center physiologic study of seventeen patients with moderate to severe ARDS who demonstrated paradoxical responses to chest wall loading. All patients received mechanical ventilation in volume control mode and were passively ventilated. Airway pressures were measured before and after decreasing/increasing V_Tby 1 ml/kg predicted body weight and decreasing/increasing PEEP by 2.5 cmH₂O.Results: Decreasing either V_Tor PEEP improved C_RSin all patients. Driving pressure (DP) decreased by a mean of 4.9 cmH₂O (supine) and by 4.3 cmH₂O (prone) after decreasing V_T, and by a mean of 2.9 cmH₂O (supine) and 2.2 cmH₂O (prone) after decreasing PEEP. C_RSincreased by a mean of 3.1 ml/cmH₂O (supine) and by 2.5 ml/cmH₂O (prone) after decreasing V_T.C_RSincreased by a mean of 5.2 ml/cmH₂O (supine) and 3.6 ml/cmH₂O (prone) after decreasing PEEP (P < 0.01 for all). Small increments of either V_Tor PEEP worsened C_RSin the majority of patients.Conclusion: Patients with a paradoxical response to chest wall loading demonstrate uniform improvement in both DP and C_RSfollowing a reduction in either V_Tor PEEP, findings in keeping with prior evidence suggesting its presence is a sign of end-tidal overdistension. The presence of ‘paradox’ should prompt re-evaluation of modifiable determinants of end-tidal overdistension, including V_T, PEEP, and body position.

Diffuse alveolar hemorrhage (DAH) is a life-threatening condition requiring prompt recognition. Conventional therapy, even when initiated early, may not have an immediate effect, and in severe cases, bleeding can persist despite treatment. We report the case of a previously healthy 33-year-old male who developed DAH secondary to granulomatosis with polyangiitis, resulting in respiratory failure and the need for mechanical ventilation. High-dose corticosteroids, plasma exchange, and remission induction with cyclophosphamide failed to control bleeding, leading to severely impaired gas exchange. 20 mcg/kg of systemic recombinant activated Factor VII (rFVIIa), a dose lower than previously reported for management of DAH, resulted in hemostasis and improved oxygenation after only three doses. No complications were observed, and our patient was liberated from ventilatory support eight days later. In the setting of DAH with refractory bleeding, hemostasis may be achievable with a lower dose of rFVIIa than commonly used, potentially mitigating the risk of dose-dependent side effects.