Increased dead-space fraction is a feature of the early phase of the acute respiratory distress syndrome. Elevated values are associated with an increased risk of death.

Prolonged breathing of very high FIO2 (FIO2 ≥ 0.9) uniformly causes severe hyperoxic acute lung injury (HALI) and, without a reduction of FIO2, is usually fatal. The severity of HALI is directly proportional to PO2 (particularly above 450 mm Hg, or an FIO2 of 0.6) and exposure duration. Hyperoxia produces extraordinary amounts of reactive O2 species that overwhelms natural antioxidant defenses and destroys cellular structures through several pathways. Genetic predisposition has been shown to play an important role in HALI among animals, and some genetics-based epidemiologic research suggests that this may be true for humans as well. Clinically, the risk of HALI likely occurs when FIO2exceeds 0.7, and may become problematic when FIO2 exceeds 0.8 for an extended period of time. Both high-stretch mechanical ventilation and hyperoxia potentiate lung injury and may promote pulmonary infection. During the 1960s, confusion regarding the incidence and relevance of HALI largely reflected such issues as the primitive control of FIO2, the absence of PEEP, and the fact that at the time both ALI and ventilator-induced lung injury were unknown. The advent of PEEP and precise control over FIO2, as well as lung-protective ventilation, and other adjunctive therapies for severe hypoxemia, has greatly reduced the risk of HALI for the vast majority of patients requiring mechanical ventilation in the 21st century. However, a subset of patients with very severe ARDS requiring hyperoxic therapy is at substantial risk for developing HALI, therefore justifying the use of such adjunctive therapies.

Ventilatory Ratio correlates well with in ARDS and higher values at baseline are associated with increased risk of adverse outcomes. These results are promising for the use of Ventilatory Ratio as a simple bedside index of impaired ventilation in ARDS.

Prone position (PP) has been used since the 1970s to treat severe hypoxemia in patients with ARDS because of its effectiveness at improving gas exchange. Compared with the supine position (SP), placing patients in PP effects a more even tidal volume distribution, in part, by reversing the vertical pleural pressure gradient, which becomes more negative in the dorsal regions. PP also improves resting lung volume in the dorsocaudal regions by reducing the superimposed pressure of both the heart and the abdomen. In contrast, pulmonary perfusion remains preferentially distributed to the dorsal lung regions, thus improving overall alveolar ventilation/perfusion relationships. 1660RESPIRATORY CARE • NOVEMBER 2015 VOL 60 NO 11Moreover, the larger tissue mass suspended from a wider dorsal chest wall effects a more homogeneous distribution of pleural pressures throughout the lung that reduces abnormal strain and stress development. This is believed to ameliorate the severity or development of ventilator-induced lung injury and may partly explain why PP reduces mortality in severe ARDS. Over 40 years of clinical trials have consistently reported improved oxygenation in approximately 70% of subjects with ARDS. Early initiation of PP is more likely to improve oxygenation than initiation during the subacute phase. Maximal oxygenation improvement occurs over a wide time frame ranging from several hours to several days. Meta-analyses of randomized controlled trials suggest that PP provides a survival advantage only in patients with relatively severe ARDS (P aO 2 /F IO 2 <150 mm Hg). Moreover, survival is enhanced when patients are managed with a smaller tidal volume (<8 mL/kg), higher PEEP (10 -13 cm H 2 O), and longer duration of PP sessions (>10 -12 h/session). Combining adjunctive therapies (high PEEP, recruitment maneuvers, and inhaled vasodilators) with PP has an additive effect in improving oxygenation and may be particularly helpful in stabilizing gas exchange in very severe ARDS.

No abstract

Rationale: Microvascular injury, inflammation, and coagulation play critical roles in the pathogenesis of acute lung injury (ALI). Plasma protein C levels are decreased in patients with acute lung injury and are associated with higher mortality and fewer ventilator-free days. Objectives: To test the efficacy of activated protein C (APC) as a therapy for patients with ALI. Methods: Eligible subjects were critically ill patients who met the American/European consensus criteria for ALI. Patients with severe sepsis and an APACHE II score of 25 or more were excluded. Participants were randomized to receive APC (24 mg/kg/h for 96 h) or placebo in a double-blind fashion within 72 hours of the onset of ALI. The primary endpoint was ventilator-free days. Measurements and Main Results: APC increased plasma protein C levels (P 5 0.002) and decreased pulmonary dead space fraction (P 5 0.02). However, there was no statistically significant difference between patients receiving placebo (n 5 38) or APC (n 5 37) in the number of ventilator-free days (median [25-75% interquartile range]: 19 [0-24] vs. 19 [14-22], respectively; P 5 0.78) or in 60-day mortality (5/38 vs. 5/37 patients, respectively; P 5 1.0). There were no differences in the number of bleeding events between the two groups. Conclusions: APC did not improve outcomes from ALI. The results of this trial do not support a large clinical trial of APC for ALI in the absence of severe sepsis and high disease severity. Clinical trial registered with www.clinicaltrials.gov (NCT 00112164).

Coronavirus disease (COVID-19) is a rapidly expanding global pandemic. In March 2020, models forecasted imminent exhaustion of regional ventilator supply in New York (1). In response, we developed a novel ventilator sharing strategy to support two patients simultaneously with one ventilator. This report details our initial ventilator sharing experience among patients with COVID-19-associated acute respiratory distress syndrome (ARDS). Methods This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.

Background: Lung protective ventilation has been widely adopted for the management of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Consequently, ventilator associated lung injury and mortality have decreased. It is not known if this ventilation strategy changes the prognostic value of previously identified demographic and pulmonary predictors of mortality, such as respiratory compliance and the arterial oxygen tension to inspired oxygen fraction ratio (PaO 2 /FiO 2 ). Methods: Demographic, clinical, laboratory and pulmonary variables were recorded in 149 patients with ALI/ ARDS. Significant predictors of mortality were identified in bivariate analysis and these were entered into multivariate analysis to identify independent predictors of mortality. Results: Hospital mortality was 41%. In the bivariate analysis, 17 variables were significantly correlated with mortality, including age, APACHE II score and the presence of cirrhosis. Pulmonary parameters associated with death included PaO 2 /FiO 2 and oxygenation index ((mean airway pressure6FiO 2 6100)4PaO 2 ). In unadjusted analysis, the odds ratio (OR) of death for PaO 2 /FiO 2 was 1.57 (CI 1.12 to 3.04) per standard deviation decrease. However, in adjusted analysis, PaO 2 /FiO 2 was not a statistically significant predictor of death, with an OR of 1.29 (CI 0.82 to 2.02). In contrast, oxygenation index (OI) was a statistically significant predictor of death in both unadjusted analysis (OR 1.89 (CI 1.28 to 2.78)) and in adjusted analysis (OR 1.84 (CI 1.13 to 2.99)). Conclusions: In this cohort of patients with ALI/ARDS, OI was an independent predictor of mortality, whereas PaO 2 / FiO 2 was not. OI may be a superior predictor because it integrates both airway pressure and oxygenation into a single variable.Despite advances in our understanding of the pathophysiology and treatment of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), mortality remains high; approximately 30-60% of patients die before hospital discharge.1-3 Lung protective ventilation, a strategy that targets lower tidal volumes (Vt) and limits plateau pressure (P plat ) to less than 30 cm H 2 O is the only clinical intervention that has shown a mortality benefit in large randomised trials. Observational studies performed before widespread application of lung protective ventilation identified demographic, pulmonary specific and clinical variables that predict mortality in ALI/ ARDS.2 3 6-9These included age, Severe Acute Physiology Score (SAPS II), Acute Physiology and Chronic Health Evaluation (APACHE II) score, cirrhosis, immunosuppression and pulmonary specific variables, including the arterial oxygen tension to fraction of inspired oxygen (PaO 2 /FiO 2 ) ratio, 9 respiratory system compliance (Crs) 3 and oxygenation index (OI).7 To our knowledge, no large study of mortality predictors has been conducted in North America since the implementation of the lung protective ventilation. Thus we conducted a retrospective study of these variables t...