A New Global Definition of Acute Respiratory Distress Syndrome.

Background: Since publication of the 2012 Berlin definition of acute respiratory distress syndrome (ARDS), several developments have supported the need for an expansion of the definition, including the use of high-flow nasal oxygen, the expansion of the use of pulse oximetry in place of arterial blood gases, the use of ultrasound for chest imaging, and the need for applicability in resource-limited settings. Methods: A consensus conference of 32 critical care ARDS experts was convened, had six virtual meetings (June 2021 to March 2022), and subsequently obtained input from members of several critical care societies. The goal was to develop a definition that would 1) identify patients with the currently accepted conceptual framework for ARDS, 2) facilitate rapid ARDS diagnosis for clinical care and research, 3) be applicable in resource-limited settings, 4) be useful for testing specific therapies, and 5) be practical for communication to patients and caregivers. Results: The committee made four main recommendations: 1) include high-flow nasal oxygen with a minimum flow rate of ⩾30 L/min; 2) use PaO2:FiO2 ⩽ 300 mm Hg or oxygen saturation as measured by pulse oximetry SpO2:FiO2 ⩽ 315 (if oxygen saturation as measured by pulse oximetry is ⩽97%) to identify hypoxemia; 3) retain bilateral opacities for imaging criteria but add ultrasound as an imaging modality, especially in resource-limited areas; and 4) in resource-limited settings, do not require positive end-expiratory pressure, oxygen flow rate, or specific respiratory support devices. Conclusions: We propose a new global definition of ARDS that builds on the Berlin definition. The recommendations also identify areas for future research, including the need for prospective assessments of the feasibility, reliability, and prognostic validity of the proposed global definition.

Oxidation increases mucin polymer cross-links to stiffen airway mucus gels.

Airway mucus in cystic fibrosis (CF) is highly elastic, but the mechanism behind this pathology is unclear. We hypothesized that the biophysical properties of CF mucus are altered because of neutrophilic oxidative stress. Using confocal imaging, rheology, and biochemical measures of inflammation and oxidation, we found that CF airway mucus gels have a molecular architecture characterized by a core of mucin covered by a web of DNA and a rheological profile characterized by high elasticity that can be normalized by chemical reduction. We also found that high levels of reactive oxygen species in CF mucus correlated positively and significantly with high concentrations of the oxidized products of cysteine (disulfide cross-links). To directly determine whether oxidation can cross-link mucins to increase mucus elasticity, we exposed induced sputum from healthy subjects to oxidizing stimuli and found a marked and thiol-dependent increase in sputum elasticity. Targeting mucin disulfide cross-links using current thiol-amino structures such as N-acetylcysteine (NAC) requires high drug concentrations to have mucolytic effects. We therefore synthesized a thiol-carbohydrate structure (methyl 6-thio-6-deoxy-α-D-galactopyranoside) and found that it had stronger reducing activity than NAC and more potent and fast-acting mucolytic activity in CF sputum. Thus, oxidation arising from airway inflammation or environmental exposure contributes to pathologic mucus gel formation in the lung, which suggests that it can be targeted by thiol-modified carbohydrates.

Higher pulmonary dead space may predict prolonged mechanical ventilation after cardiac surgery.

Children undergoing congenital heart surgery are at risk for prolonged mechanical ventilation and length of hospital stay. We investigated the prognostic value of pulmonary dead space fraction as a non-invasive, physiologic marker in this population. In a prospective, cross-sectional study, we measured pulmonary dead space fraction in 52 intubated, pediatric patients within 24 hr postoperative from congenital heart surgery. Measurements were obtained with a bedside, non-invasive cardiac output (NICO) monitor (Respironics Novametrix, Inc., Wallingford, CT). Median pulmonary dead space fraction was 0.46 (25-75% IQR 0.34-0.55). Pulmonary dead space fraction significantly correlated with duration of mechanical ventilation and length of hospital stay in the entire cohort (r(s) = 0.51, P = 0.0002; r(s) = 0.51, P = 0.0002) and in the subset of patients without residual intracardiac shunting (r(s) = 0.45, P = 0.008; r(s) = 0.49, P = 0.004). In a multivariable logistic regression model, pulmonary dead space fraction remained an independent predictor for prolonged mechanical ventilation in the presence of cardiopulmonary bypass time and ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (OR 2.2; 95% CI 1.14-4.38; P = 0.02). The area under the receiver operator characteristic curve for this model was 0.91. Elevated pulmonary dead space fraction is associated with prolonged mechanical ventilation and hospital stay in pediatric patients who undergo surgery for congenital heart disease and has additive predictive value in identifying those at risk for longer duration of mechanical ventilation. Pulmonary dead space may be a useful prognostic tool for clinicians in patients who undergo congenital heart surgery.

Accuracy of physiologic dead space measurements in patients with acute respiratory distress syndrome using volumetric capnography: comparison with the metabolic monitor method.

BACKGROUND: Volumetric capnography is an alternative method of measuring expired carbon dioxide partial pressure (P(eCO2)) and physiologic dead-space-to-tidal-volume ratio (V(D)/V(T)) during mechanical ventilation. In this method, P(eCO2) is measured at the Y-adapter of the ventilator circuit, thus eliminating the effects of compression volume contamination and the need to apply a correction factor. We investigated the accuracy of volumetric capnography in measuring V(D)/V(T), compared to both uncorrected and corrected measurements, using a metabolic monitor in patients with acute respiratory distress syndrome (ARDS). METHODS: There were 90 measurements of V(D)/V(T) made in 23 patients with ARDS. The P(eCO2) was measured during a 5-min expired-gas collection period with a Delta-trac metabolic monitor, and was corrected for compression volume contamination using a standard formula. Simultaneous measurements of P(eCO2) and V(D)/V(T) were obtained using volumetric capnography. RESULTS: V(D)/V(T) measured by volumetric capnography was strongly correlated with both the uncorrected (r2 = 0.93, p < 0.0001) and corrected (r2 = 0.89, p < 0.0001) measurements of V(D)/V(T) made using the metabolic monitor technique. Measurements of V(D)/V(T) made with volumetric capnography had a bias of 0.02 and a precision of 0.05 when compared to the V(D)/V(T) corrected for estimated compression volume contamination. CONCLUSION: Volumetric capnography measurements of V(D)/V(T) in mechanically-ventilated patients with ARDS are as accurate as those obtained by metabolic monitor technique. .

Differential effects of sustained inflation recruitment maneuvers on alveolar epithelial and lung endothelial injury.

OBJECTIVE: The role of recruitment maneuvers in mechanical ventilation for patients with the acute respiratory distress syndrome and acute lung injury remains uncertain in part due to a lack of data on the effects of specific recruitment maneuvers on lung injury severity. The primary objective of this study was to determine the effect of one type of recruitment maneuver--sustained inflation--on alveolar epithelial and lung endothelial injury in experimental acute lung injury. DESIGN: Randomized experimental study. SETTING: Academic research laboratory. SUBJECTS: Forty-nine Sprague-Dawley rats. INTERVENTIONS: Lung injury was induced in anesthetized, ventilated rats by instillation of acid (pH 1.5) into the airspaces. Rats were ventilated with a tidal volume of 6 mL/kg and a positive end-expiratory pressure of 5 cm H(2)O with or without a sustained inflation recruitment maneuver repeated every 30 mins. Each recruitment maneuver consisted of two 30-sec inflations to total lung capacity (30 cm H(2)O) 1 min apart. MEASUREMENTS AND MAIN RESULTS: The use of recruitment maneuvers significantly improved oxygenation, compliance, end-expiratory lung volume, functional residual capacity, and deadspace fraction. Recruitment maneuvers reduced extravascular lung water and lung endothelial injury as measured by protein permeability (217 +/- 28 vs. 314 +/- 70 extravascular plasma equivalents [microL], p < .05). However, recruitment maneuvers did not prevent alveolar epithelial injury. Epithelial permeability and bronchoalveolar lavage RTI40 levels, a marker of type I cell injury, were similar with or without recruitment maneuvers. Recruitment maneuvers decreased epithelial fluid transport, a functional marker of epithelial injury. Recruitment maneuvers did not reduce markers of airspace inflammation. CONCLUSIONS: Sustained inflation recruitment maneuvers improve respiratory mechanics and oxygenation and may protect the lung endothelium but do not reduce alveolar epithelial injury. Because of the differential effects of recruitment maneuvers on the lung endothelium and alveolar epithelium, the net effect in clinical acute lung injury may not be beneficial. Additional clinical studies will be needed to assess the net impact of recruitment maneuvers in patients with acute lung injury.

Pulmonary dead-space fraction as a risk factor for death in the acute respiratory distress syndrome.

BACKGROUND: No single pulmonary-specific variable, including the severity of hypoxemia, has been found to predict the risk of death independently when measured early in the course of the acute respiratory distress syndrome. Because an increase in the pulmonary dead-space fraction has been described in observational studies of the syndrome, we systematically measured the dead-space fraction early in the course of the illness and evaluated its potential association with the risk of death. METHODS: The dead-space fraction was prospectively measured in 179 intubated patients, a mean (+/-SD) of 10.9+/-7.4 hours after the acute respiratory distress syndrome had developed. Additional clinical and physiological variables were analyzed with the use of multiple logistic regression. The study outcome was mortality before hospital discharge. RESULTS: The mean dead-space fraction was markedly elevated (0.58+/-0.09) early in the course of the acute respiratory distress syndrome and was higher among patients who died than among those who survived (0.63+/-0.10 vs. 0.54+/-0.09, P<0.001). The dead-space fraction was an independent risk factor for death: for every 0.05 increase, the odds of death increased by 45 percent (odds ratio, 1.45; 95 percent confidence interval, 1.15 to 1.83; P=0.002). The only other independent predictors of an increased risk of death were the Simplified Acute Physiology Score II, an indicator of the severity of illness (odds ratio, 1.06; 95 percent confidence interval, 1.03 to 1.08; P<0.001) and quasistatic respiratory compliance (odds ratio, 1.06; 95 percent confidence interval, 1.01 to 1.10; P=0.01). CONCLUSIONS: 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.