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Background: PEEP is a cornerstone treatment for children with pediatric ARDS. Unfortunately, its titration is often performed solely by evaluating oxygen saturation, which can lead to inadequate PEEP level settings and consequent adverse effects. This study aimed to assess the impact of increasing PEEP on hemodynamics, respiratory system mechanics, and oxygenation in children with ARDS., Methods: Children receiving mechanical ventilation and on pressure-controlled volume-guaranteed mode were prospectively assessed for inclusion. PEEP was sequentially changed to 5, 12, 10, 8 cm H 2 O, and again to 5 cm H 2 O. After 10 min at each PEEP level, hemodynamic, ventilatory, and oxygenation variables were collected., Results: A total of 31 subjects were included, with median age and weight of 6 months and 6.3 kg, respectively. The main reasons for pediatric ICU admission were respiratory failure caused by acute viral bronchiolitis (45%) and community-acquired pneumonia (32%). Most subjects had mild or moderate ARDS (45% and 42%, respectively), with a median (interquartile range) oxygenation index of 8.4 (5.8-12.7). Oxygen saturation improved significantly when PEEP was increased. However, although no significant changes in blood pressure were observed, the median cardiac index at PEEP of 12 cm H 2 O was significantly lower than that observed at any other PEEP level ( P = .001). Fourteen participants (45%) experienced a reduction in cardiac index of > 10% when PEEP was increased to 12 cm H 2 O. Also, the estimated oxygen delivery was significantly lower, at 12 cm H 2 O PEEP. Finally, respiratory system compliance significantly reduced when PEEP was increased. At a PEEP of 12 cm H 2 O, static compliance had a median reduction of 25% in relation to the initial assessment (PEEP of 5 cm H 2 O)., Conclusions: Although it may improve arterial oxygen saturation, inappropriately high PEEP levels may reduce cardiac output, oxygen delivery, and respiratory system compliance in pediatric subjects with ARDS with low potential for lung recruitability., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

Background: The use of prone position (PP) has been widespread during the COVID-19 pandemic. Whereas it has demonstrated benefits, including improved oxygenation and lung aeration, the factors influencing the response in terms of gas exchange to PP remain unclear. In particular, the association between baseline quantitative computed tomography (CT) scan results and gas exchange response to PP in invasively ventilated subjects with COVID-19 ARDS is unknown. The present study aimed to compare baseline quantitative CT results between subjects responding to PP in terms of oxygenation or CO 2 clearance and those who did not., Methods: This was a single-center, retrospective observational study including critically ill, invasively ventilated subjects with COVID-19-related ARDS admitted to the ICUs of Niguarda Hospital between March 2020-November 2021. Blood gas samples were collected before and after PP. Subjects in whom the P aO 2 /F IO 2 increase was ≥ 20 mm Hg after PP were defined as oxygen responders. CO 2 responders were defined when the ventilatory ratio (VR) decreased during PP. Automated quantitative CT analyses were performed to obtain tissue mass and density of the lungs., Results: One hundred twenty-five subjects were enrolled, of which 116 (93%) were O 2 responders and 51 (41%) CO 2 responders. No difference in quantitative CT characteristics and oxygen were observed between responders and non-responders (tissue mass 1,532 ± 396 g vs 1,654 ± 304 g, P = .28; density -544 ± 109 HU vs -562 ± 58 HU P = .42). Similar findings were observed when dividing the population according to CO 2 response (tissue mass 1,551 ± 412 g vs 1,534 ± 377 g, P = .89; density -545 ± 123 HU vs -546 ± 94 HU, P = .99)., Conclusions: Most subjects with COVID-19-related ARDS improved their oxygenation at the first pronation cycle. The study suggests that baseline quantitative CT scan data were not associated with the response to PP in oxygenation or CO 2 in mechanically ventilated subjects with COVID-19-related ARDS., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

Background: The first aim of this study was to evaluate the capacity of electrical impedance tomography (EIT) to identify the effect of PEEP on regional ventilation distribution and the regional risk of collapse, overdistention, hypoventilation, and pendelluft in mechanically ventilated patients. The second aim was to evaluate the feasibility of EIT for estimating airway opening pressure (AOP)., Methods: The EIT signal was recorded both during baseline cyclic ventilation and slow insufflation for one breath for 9 subjects with moderate-to-severe ARDS. From these data, the AOP and volumes insufflated to lung regions with or without the risk of either collapse, overdistention, hypoventilation, or pendelluft were assessed at 3 PEEP levels (5, 10, and 15 cm H 2 O). PEEP levels were compared by Friedman analysis of variance and the AOP measured by EIT evaluated using an F-test and the Bland and Altman method., Results: The volume for which there was no specific risk significantly decreased at the highest PEEP from 55 ± 31% tidal volume (V T ) at PEEP 5 or 82 ± 18% V T at PEEP 10 to 10 ± 30% V T at PEEP 15 ( P = .038 between PEEP 5 vs PEEP 15; P = .01 between PEEP 10 vs PEEP 15). The volume associated with overdistention significantly increased with increasing PEEP, whereas that associated with atelectrauma significantly decreased. Pendelluft significantly decreased with increasing PEEP: V T of 8.9 ± 18.6%, 3.6 ± 7.0%, and 3.2 ± 7.1% for PEEP 5, PEEP 10, and PEEP 15, respectively. The center of ventilation tended to increase in the dependent direction with higher PEEP. The AOPs assessed by EIT and from the pressure-volume curve were in good agreement (bias 0.48 cm H 2 O)., Conclusions: Our results suggest that EIT could aid clinicians in making personalized and reasoned choices in setting the PEEP for subjects with ARDS., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

Background: During invasive ventilation, external flow jet nebulization results in increases in displayed exhaled tidal volumes (V T ). We hypothesized that the magnitude of the increase is inaccurate. An ASL 5000 simulator measured ventilatory parameters over a wide range of adult settings: actual V T , peak inspiratory pressure (PIP), and time to minimum pressure., Methods: Ventilators with internal and external flow sensors were tested by using a variety of volume and pressure control modes (the target V T was 420 mL). Patient conditions (normal, COPD, ARDS) defined on the ASL 5000 were assessed at baseline and with 3.5 or 8 L/min of added external flow. Patient-triggering was assessed by reducing muscle effort to the level that resulted in backup ventilation and by changing ventilator sensitivity to the point of auto-triggering., Results: Results are reported as percentage change from baseline after addition of 3.5 or 8 L/min external flow. For ventilators with internal flow sensors, changes in displayed exhaled V T ranged from 10% to 118%, however, when using volume control, actual increases in actual V T and PIP were only 4%-21% ( P = .063, .031) and 6%-24% ( P = .25, .031), respectively. Changes in actual V T correlated closely with changes in PIP ( P < .001; R 2 = 0.68). For pressure control, actual V T decreased by 3%-5% ( P = .031) and 4%-9% ( P = .031) with 3.5 and 8 L/min respectively, PIP was unchanged. With external flow sensors at the distal Y-piece junction, volume and pressure changes were statistically insignificant. The time to minimum pressure increased at most by 8% ( P = .02) across all modes and ventilators. The effects on muscle pressure were minimal (∼1 cm H 2 O), and ventilator sensitivity effects were nearly undetectable., Conclusions: External flow jet nebulization resulted in much smaller changes in volume than indicated by the ventilator display. Statistically significant effects were confined primarily to machines with internal flow sensors. Differences approached the manufacturer-reported variation in ventilator baseline performance. During nebulizer therapy, effects on V T can be estimated at the bedside by monitoring PIP., (Copyright © 2024 by Daedalus Enterprises.)

Background: The ratio of end-tidal CO 2 pressure to arterial partial pressure of CO 2 ([Formula: see text]) was recently suggested for monitoring pulmonary gas exchange in patients with ARDS associated with COVID-19, yet no evidence was offered supporting that claim. Therefore, we evaluated whether [Formula: see text] might be relevant in assessing ARDS not associated with COVID-19., Methods: We evaluated the correspondence between [Formula: see text] and the ratio of dead space to tidal volume (V D /V T ) measured in 561 subjects with ARDS from a previous study in whom [Formula: see text] data were also available. Subjects also were analyzed according to 4 ranges of [Formula: see text] representing increasing illness severity (≥ 0.80, 0.6-0.79, 0.50-0.59, and < 0.50). Correlation was assessed by either Pearson or Spearman tests, grouped comparisons were assessed using either ANOVA or Kruskal-Wallis tests and dichotomous variables assessed by Fisher Exact tests. Normally distributed data are presented as mean and standard deviation(SD) and non-normal data are presented as median and inter-quartile range (IQR). Overall mortality risk was assessed with multivariate logistic regression. Alpha was set at 0.05., Results: [Formula: see text] correlated strongly with V D /V T (r = -0.87 [95% CI -0.89 to -0.85], P < .001). Decreasing [Formula: see text] was associated with increased V D /V T and hospital mortality between all groups. In the univariate analysis, for every 0.01 decrease in [Formula: see text], mortality risk increased by ∼1% (odds ratio 0.009, 95% CI 0.003-0.029, P < .001) and maintained a strong independent association with mortality risk when adjusted for other variables (odds ratio 0.19, 95% CI 0.04-0.91, P = .039). [Formula: see text] < 0.50 was characterized by very high mean ± SD value for V D /V T (0.82 ± 0.05, P < .001) and high hospital mortality (70%)., Conclusions: Using [Formula: see text] as a surrogate for V D /V T may be a useful and practical measurement for both management and ongoing research into the nature of ARDS., Competing Interests: Mr Kallet has disclosed a relationship with Nihon Kohden. Dr Lipnick has disclosed no conflicts of interest., (Copyright © 2021 by Daedalus Enterprises.)

Background: New-generation ventilators display dynamic measures of respiratory mechanics, such as compliance, resistance, and auto-PEEP. Knowledge of the respiratory mechanics is paramount to clinicians at the bedside. These calculations are obtained automatically by using the least squares fitting method of the equation of motion. The accuracy of these calculations in static and dynamic conditions have not been fully validated or examined in different clinical conditions or various ventilator modes., Methods: A bench study was performed by using a lung simulator to compare the ventilator automated calculations during passive and active conditions. Three clinical scenarios (normal, COPD, and ARDS) were simulated with known compliances and resistance set per respective condition: normal (compliance 50 mL/cm H 2 O, resistance 10 cm H 2 O/L/s), COPD (compliance 60 mL/cm H 2 O, resistance 22 cm H 2 O/L/s), and ARDS (compliance 30 mL/cm H 2 O, and resistance 13 cm H 2 O/L/s). Each scenario was subjected to 4 different muscle pressures (P mus ): 0, -5, -10, and -15 cm H 2 O. All the experiments were done using adaptive support ventilation. The resulting automated dynamic calculations of compliance and resistance were then compared based on the clinical scenarios., Results: There was a small bias (average error) and level of agreement in the passive conditions in all the experiments; however, these errors and levels of agreement got progressively higher proportional to the increased P mus . There was a strong positive correlation between P mus and compliance measured as well as a strong negative correlation between P mus and resistance measured., Conclusions: Automated displayed calculations of respiratory mechanics were not dependable or accurate in active breathing conditions. The calculations were clinically more reliable in passive conditions. We propose different methods of calculating P mus , which, if incorporated into the calculations, would improve the accuracy of respiratory mechanics made via the least squares fitting method in actively breathing conditions., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2019 by Daedalus Enterprises.)

Background: ARDS is a highly morbid condition characterized by diffuse pulmonary inflammation, which results in hypoxemic respiratory failure. Approximately 25% of patients with ARDS develop right ventricular dysfunction, with cor pulmonale being a common final pathway in a significant number of non-survivors. ARDS-related right ventricular dysfunction occurs due to acute elevation in ventricular afterload caused by mechanisms that are associated with increased pulmonary dead space fraction. Thus, we hypothesized that changes in pulmonary dead space fraction may reflect changes in pulmonary hemodynamics., Methods: This was a prospective single-center study of 21 subjects with ARDS who underwent serial determination of pulmonary dead space fraction and pulmonary hemodynamics via transthoracic echocardiography. Linear mixed-effects modeling was performed to test for an association between a change in pulmonary dead space and a change in pulmonary hemodynamics., Results: The tricuspid regurgitation velocity to right ventricular outflow track velocity time integral ratio, an echocardiographic surrogate for pulmonary vascular resistance, increased by 0.16 Wood units (Coefficient 0.16, 95% CI 0.09-0.23; P < .001), and the tricuspid regurgitation pressure gradient increased by 3.7 mm Hg (Coefficient 3.7, 95% CI 1.74-5.63, P < .001) for every 10% increase in pulmonary dead space fraction., Conclusions: Increases in the pulmonary dead space fraction were associated with relative increases in both the tricuspid regurgitation velocity to right ventricular outflow track velocity time integral ratio and the tricuspid regurgitation pressure gradient, which likely contributed to the high incidence of ARDS-related right ventricular dysfunction encountered in clinical practice. Pulmonary dead space monitoring may serve as a clinical indicator to identify patients with ARDS at risk of developing right ventricular dysfunction and acute cor pulmonale., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2019 by Daedalus Enterprises.)

The use of extracorporeal membrane oxygenation in the management of ARDS has grown considerably in the past decade, largely as a consequence of improvements in extracorporeal technology and management techniques. Recently published data has helped clarify the use of ECMO in ARDS, and its role in optimizing lung-protective ventilation and minimizing ventilator-induced lung injury has the potential to have a substantial impact on ARDS management and outcomes. In the future, novel extracorporeal management strategies may lead to a new paradigm in our approach to patients with ARDS., (Copyright © 2018 by Daedalus Enterprises.)

Background: Simulation studies are often used to examine ventilator performance. However, there are no standards for selecting simulation parameters. This study collected data in passively-ventilated adult human subjects and summarized the results as a set of parameters that can be used for simulation studies of intubated, passive, adult subjects with normal lungs, COPD, or ARDS., Methods: Consecutive adult patients admitted to the ICU were included if they were deeply sedated and mechanically ventilated for <48 h without any spontaneous breathing activity. Subjects were classified as having normal lungs, COPD, or ARDS. Respiratory mechanics variables were collected once per subject. Static compliance was calculated as the ratio between tidal volume and driving pressure. Inspiratory resistance was measured by the least-squares fitting method. The expiratory time constant was estimated by the tidal volume/flow ratio., Results: Of the 359 subjects included, 138 were classified as having normal lungs, 181 as ARDS, and 40 as COPD. Median (interquartile range) static compliance was significantly lower in ARDS subjects as compared with normal lung and COPD subjects (39 [32-50] mL/cm H 2 O vs 54 [44-64] and 59 [43-75] mL/cm H 2 O, respectively, P < .001). Inspiratory resistance was significantly higher in COPD subjects as compared with normal lung and ARDS subjects (22 [16-33] cm H 2 O/L/s vs 13 [10-15] and 12 [9-14] cm H 2 O/L/s, respectively, P < .001). The expiratory time constant was significantly different for each lung condition (0.60 [0.51-0.71], 1.07 [0.68-2.14], and 0.46 [0.40-0.55] s for normal lung, COPD, and ARDS subjects, respectively, P < .001). In the subgroup of subjects with ARDS, there were no significant differences in respiratory mechanics variables among mild, moderate, and severe ARDS., Conclusions: This study provides educators, researchers, and manufacturers with a standard set of practical parameters for simulating the respiratory system's mechanical properties in passive conditions., (Copyright © 2018 by Daedalus Enterprises.)

Background: Esophageal balloon inflation volume may affect the accuracy of transpulmo-nary pressure estimates in adults, but the effect is unknown in pediatrics. Using a combination bench and human study, we sought to determine a range of optimal filling volumes for esophageal balloon catheters and to derive a technique to inflate catheters to yield the most accurate estimates of pleural pressure., Methods: In the laboratory study, we evaluated 4 pediatric and adult esophageal balloon catheters, a liquid-filled catheter, and a micro-tip catheter, both with and without a model esophagus. We compared the measured esophageal pressure for each type of catheter within a pressurized chamber. Esophageal balloon catheters were also tested by manipulating the esophageal balloon inflation volume, and we attempted to derive a filling-volume technique that would assure accuracy. We then tested the feasibility of this technique in 5 mechanically ventilated pediatric subjects with ARDS., Results: In the laboratory study, smaller inflation volumes underestimated the chamber pressure at higher chamber pressures, and larger inflation volumes overestimated the chamber pressure at lower chamber pressures. Using an optimal filling-volume technique resulted in a mean total error that ranged from -0.53 to -0.10 cm H 2 O. The optimal filling-volume values for the pediatric catheters were 0.2-0.6 mL, and 0.4-0.8 mL for the adult catheters. When correctly positioned and calibrated, the micro-tip transducer and liquid-filled catheters were within ± 1 cm H 2 O of chamber pressure for all ranges of pressure. In the clinical study, high variability in measured esophageal pressure and subsequent transpulmonary pressure during exhalation and during inhalation was observed within the manufacturer's recommended esophageal balloon inflation ranges., Conclusions: Manufacturer-recommended esophageal balloon inflation ranges do not assure accuracy. Individual titration of esophageal balloon volume may improve accuracy. Better esophageal catheters are needed to provide reliable esophageal pressure measurements in children., (Copyright © 2018 by Daedalus Enterprises.)

This review describes the current understanding of the lungs' response to deforming stress under conditions of both normal physiology and acute lung injury. Several limiting assumptions are needed to infer lung parenchymal stress and strain from airway pressure, volume, and flow data from mechanically ventilated patients with injured lungs. These assumptions include the effects of the chest wall on lung-surface pressure, its topographical distribution, and the effects of non-uniform tissue properties on local parenchymal stresses. In addition, there is a spectrum of biophysical lung injury mechanisms that involves normal as well as tangential alveolar wall stresses. To these are added important secondary effects on pulmonary vascular resistance and right heart function. Understanding both the assumptions of lung mechanics and the scope of injury mechanisms operating during ARDS is necessary to interpret the results of clinical trials that inform prevailing ventilator-management guidelines. The implications issuing from these 3 topics inform a safer approach to setting and adjusting the ventilator to minimize the risk of ventilator-induced lung injury. This is enumerated in a 5-step approach that can be used to guide ventilator management of unstable patients with severe lung injury., (Copyright © 2018 by Daedalus Enterprises.)

Background: Limiting tidal volume (V T ) in patients with ARDS may not be achieved once patient-triggered breaths occur. Furthermore, ICU ventilators offer numerous patient-triggered modes that work differently across brands. We systematically investigated, using a bench model, the effect of patient-triggered modes on the size and variability of V T at different breathing frequencies (f), patient effort, and ARDS severity., Methods: We used a V500 Infinity ICU ventilator connected to an ASL 5000 lung model whose compliance was mimicking mild, moderate, and severe ARDS. Thirteen patient-triggered modes were tested, falling into 3 categories, namely volume control ventilation with mandatory minute ventilation; pressure control ventilation, including airway pressure release ventilation (APRV); and pressure support ventilation. Two levels of f and effort were tested for each ARDS severity in each mode. Median (first-third quartiles) V T was compared across modes using non-parametric tests. The probability of V T > 6 mL/kg ideal body weight was assessed by binomial regression and expressed as the odds ratio (OR) with 95% CI. V T variability was measured from the coefficient of variation., Results: V T distribution over all f, effort, and ARDS categories significantly differed across modes ( P < .001, Kruskal-Wallis test). V T was significantly greater with pressure support (OR 420 mL, 95% CI 332-527 mL) than with any other mode except for variable pressure support level. Risk for V T to be > 6 mL/kg was significantly increased with spontaneous breaths patient-triggered by pressure support (OR 19.36, 95% CI 12.37-30.65) and significantly reduced in APRV (OR 0.44, 95% CI 0.26-0.72) and pressure support with guaranteed volume mode. The risk increased with increasing effort and decreasing f. Coefficient of variation of V T was greater for low f and volume control-mandatory minute ventilation and pressure control modes. APRV had the greatest within-mode variability., Conclusions: Risk of V T > 6 mL/kg was significantly reduced in APRV and pressure support with guaranteed volume mode. APRV had the highest variability. Pressure support with guaranteed volume could be tested in patients with ARDS., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2017 by Daedalus Enterprises.)

Background: In ARDS, elevated pulmonary dead-space fraction (V D /V T ) is a particularly strong indicator of mortality risk. Whether the magnitude of V D /V T is modified by the underlying etiology of ARDS and whether this influences the strength of its association with mortality remains unknown. We sought to elucidate the impact of ARDS etiology on V D /V T and also to determine whether ARDS severity, as classified by the Berlin definition, has correspondence with changes in V D /V T ., Methods: This single-center, retrospective, observational study (2010-2016) measured V D /V T in 685 subjects with ARDS as part of clinical management with lung-protective ventilation. Volumetric capnography was used to measure V D /V T with 99% of measurements occurring within 48 h of ARDS onset. Demographic information as well as illness severity scores and pulmonary mechanics data also were collected. Multivariate logistic regression modeling was done to assess the strength of association between V D /V T and mortality., Results: V D /V T was elevated across etiologies, with aspiration and pneumonia having significantly higher V D /V T than non-pulmonary sepsis or trauma. Differences in the magnitude of V D /V T across etiologies did not necessarily correspond with mortality between etiologies. However, within each etiology grouping, V D /V T was significantly elevated in non-survivors versus survivors. The same results were found in both moderate and severe (but not mild) ARDS using the Berlin definition. In the final adjusted model, the strongest mortality risk was V D /V T , wherein the risk of death increased by 22% for every 0.05 increase in V D /V T ., Conclusions: V D /V T magnitude varies by ARDS etiology, as does mortality. Only in mild ARDS does V D /V T fail to distinguish non-survivors from survivors. Nonetheless, V D /V T has the strongest association with mortality risk in those with ARDS., Competing Interests: Mr Kallet discloses relationships with Philips Respironics and Nihon Koden. The other authors have no conflicts to disclose., (Copyright © 2017 by Daedalus Enterprises.)

Background: ARDS is characterized by decreased functional residual capacity (FRC), heterogeneous lung injury, and severe hypoxemia. Tidal ventilation is preferentially distributed to ventilated alveoli. Aerosolized prostaglandin I 2 exploits this pathophysiology by inducing local vasodilation, thereby increasing ventilation-perfusion matching and reducing hypoxemia. Therefore, aerosolized prostaglandin I 2 efficacy may depend upon FRC. Both P aO 2 /F IO 2 and compliance of the respiratory system (C RS ) are indirect signifiers of FRC and thus may partly determine the response to aerosolized prostaglandin I 2 ., Methods: We reviewed the records of 208 ARDS subjects who received aerosolized prostaglandin I 2 and had arterial blood gases done before and after the initiation of therapy, without other ventilator manipulations. Subjects were grouped according to baseline P aO 2 /F IO 2 (lowest: < 60, intermediate: 60-90, highest: > 90 mm Hg) and C RS (< 20, 20-29, 30-39, and ≥ 40 mL/cm H 2 O) and by other factors, such as sepsis. Comparisons were analyzed by paired t tests, or Kruskal-Wallis and Dunn post-tests. Multivariate logistic regression modeling was done to determine which of 18 clinically relevant factors were most predictive for responding to aerosolized prostaglandin I 2 . α was set at .05., Results: Mean P aO 2 /F IO 2 increased by 33 mm Hg (42%) upon initiation of prostaglandin I 2 , with a responder rate of 62%. P aO 2 /F IO 2 increased significantly in all oxygenation groups. The highest baseline P aO 2 /F IO 2 group had the greatest improvement and responder rate (51 ± 63 mm Hg, and 82%). In addition, those with sepsis had a smaller improvement in P aO 2 /F IO 2 compared with those without sepsis (18 ± 35 vs 40 ± 55 mm Hg, P = .002). Both P aO 2 /F IO 2 and responder rate increased as C RS improved, but between-group improvements were not as consistent. In the final model, the only factors that predicted a positive response to aerosolized prostaglandin I 2 were baseline P aO 2 /F IO 2 (odds ratio 1.10 [1.004-1.205], P = .042) and C RS (odds ratio 1.04 [1.01-1.08], P = .02)., Conclusions: Aerosolized prostaglandin I 2 improves oxygenation in approximately 60% of ARDS cases. A favorable response was most strongly associated with baseline P aO 2 /F IO 2 and C RS ., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2017 by Daedalus Enterprises.)

The prone posture is known to have numerous effects on gas exchange, both under normal conditions and in patients with ARDS. Clinical studies have consistently demonstrated improvements in oxygenation, and a multi-center randomized trial found that, when implemented within 48 h of moderate-to-severe ARDS, placing subjects in the prone posture decreased mortality. Improvements in gas exchange occur via several mechanisms: alterations in the distribution of alveolar ventilation, redistribution of blood flow, improved matching of local ventilation and perfusion, and reduction in regions of low ventilation/perfusion ratios. Ventilation heterogeneity is reduced in the prone posture due to more uniform alveolar size secondary to a more uniform vertical pleural pressure gradient. The prone posture results in more uniform pulmonary blood flow when compared with the supine posture, due to an anatomical bias for greater blood flow to dorsal lung regions. Because both ventilation and perfusion heterogeneity decrease in the prone posture, gas exchange improves. Other benefits include a more uniform distribution of alveolar stress, relief of left-lower-lobe lung compression by the heart, enhanced secretion clearance, and favorable right-ventricular and systemic hemodynamics., (Copyright © 2017 by Daedalus Enterprises.)

Background: Administration of cisatracurium in severe ARDS decreases in-hospital mortality. Whether clinical outcomes are cisatracurium-specific or related with all neuromuscular blockers is unknown. This study aimed to compare outcomes in severe ARDS patients treated with cisatracurium versus atracurium., Methods: Patients admitted in ICUs with a diagnosis of severe ARDS and treated with neuromuscular blocking agents within 72 h of diagnosis were included. Subjects treated with cisatracurium versus atracurium were compared. The primary outcome was improvement in oxygenation, defined as the difference of P aO 2 /F IO 2 at 72 h post-initiation of neuromuscular blocking agents. Secondary outcomes were ventilator-free days at day 28, ICU and hospital lengths of stay, and hospital mortality., Results: Seventy-six subjects with ARDS were included in the study. Eighteen subjects (24%) were treated with atracurium, whereas 58 (76%) were treated with cisatracurium. Equivalent dosages of sedation and analgesia as well as use of brain function monitoring technology were similar between both groups. There were no differences in clinical outcomes. Specifically, improvement of P aO 2 /F IO 2 was a median (interquartile range [IQR]) of 65 (25-162) in the atracurium group and 66 (IQR 16-147) in the cisatracurium group ( P = .65). Ventilator-free days at day 28 were 13 d (IQR 0-22 d) and 15 d (IQR 8-21 d) in the atracurium and cisatracurium groups, respectively ( P = .72). ICU length or stay was 18 d (IQR 8-34 d) in the atracurium group and 15 d (IQR 9-22 d) in the cisatracurium group ( P = .34). In-hospital mortality was 50% for the atracurium population and 62% for the cisatracurium group ( P = .42) CONCLUSIONS: Among subjects with early severe ARDS, the utilization of atracurium versus cisatracurium within 72 h of admission was not associated with significant differences in clinical outcomes., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2017 by Daedalus Enterprises.)

Background: Recent findings suggest that using alveolar P CO 2 (P ACO 2 ) estimated by volumetric capnography in the Bohr equation instead of P aCO 2 (Enghoff modification) could be appropriate for the calculation of physiological dead space to tidal volume ratio (V D /V T Bohr and V D /V T Enghoff , respectively). We aimed to describe the relationship between these 2 measurements in mechanically ventilated children and their significance in cases of ARDS., Methods: From June 2013 to December 2013, mechanically ventilated children with various respiratory conditions were included in this study. Demographic data, medical history, and ventilatory parameters were recorded. Volumetric capnography indices (NM3 monitor) were obtained over a period of 5 min preceding a blood sample. Bohr's and Enghoff's dead space, S2 and S3 slopes, and the S2/S3 ratio were calculated breath-by-breath using dedicated software (FlowTool). This study was approved by Ste-Justine research ethics review board., Results: Thirty-four subjects were analyzed. Mean V D /V T Bohr was 0.39 ± 0.12, and V D /V T Enghoff was 0.47 ± 0.13 ( P = .02). The difference between V D /V T Bohr and V D /V T Enghoff was correlated with P aO 2 /F IO 2 and with S2/S3. In subjects without lung disease (P aO 2 /F IO 2 ≥ 300), mean V D /V T Bohr was 0.36 ± 0.11, and V D /V T Enghoff was 0.39 ± 0.11 ( P = .056). Two children with status asthmaticus had a major difference between V D /V T Bohr and V D /V T Enghoff in the absence of a low P aO 2 /F IO 2 ., Conclusions: This study suggests that V D /V T Bohr and V D /V T Enghoff are not different when there is no hypoxemia (P aO 2 /F IO 2 > 300) except in the case of status asthmaticus. In subjects with a low P aO 2 /F IO 2 , the method to measure V D /V T must be reported, and results cannot be easily compared if the measurement methods are not the same., (Copyright © 2017 by Daedalus Enterprises.)

Pulmonary vascular dysfunction is associated with ARDS and leads to increased right-ventricular afterload and eventually right-ventricular failure, also called acute cor pulmonale. Interest in acute cor pulmonale and its negative impact on outcome in patients with ARDS has grown in recent years. Right-ventricular function in these patients should be closely monitored, and this is helped by the widespread use of echocardiography in intensive care units. Because mechanical ventilation may worsen right-ventricular failure, the interaction between the lungs and the right ventricle appears to be a key factor in the ventilation strategy. In this review, a rationale for a right ventricle-protective ventilation approach is provided, and such a strategy is described, including the reduction of lung stress (ie, the limitation of plateau pressure and driving pressure), the reduction of PaCO2 , and the improvement of oxygenation. Prone positioning seems to be a crucial part of this strategy by protecting both the lungs and the right ventricle, resulting in increased survival of patients with ARDS. Further studies are required to validate the positive impact on prognosis of right ventricle-protective mechanical ventilation., (Copyright © 2016 by Daedalus Enterprises.)

High-frequency oscillatory ventilation (HFOV) can improve ventilation-perfusion matching without excessive alveolar tidal stretching or collapse-reopening phenomenon. This is an attractive feature in the ventilation of patients with ARDS. However, two recent large multi-center trials of HFOV failed to show benefits in this patient population. The following review addresses whether, in view of these trails, HFOV should be abandoned in the adult population?, (Copyright © 2016 by Daedalus Enterprises.)

Functional residual capacity (FRC) is essentially the alveolar volume and a determinant of both oxygenation and respiratory system compliance (CRS). ARDS decreases FRC, and sufficient PEEP restores FRC; thus, assessments of PEEP by its impact on oxygenation and CRS are intimately linked. PEEP also can ameliorate or aggravate ventilator-induced lung injury. Therefore, it can be argued that PEEP should be titrated primarily by its impact on CRS The pro position argues that the heterogeneous nature of lung injury and its unique presentation in individual patients results in an uncoupling between oxygenation and CRS Therefore, relying upon oxygenation alone may enhance lung injury and mortality risk, particularly in those with severe ARDS. The con argument is that the preponderance of preclinical and clinical evidence suggests that a relatively narrow range of PEEP is required to manage all but the most severe cases of ARDS. In addition, pathological alterations in chest wall compliance confuse the interpretation of chest mechanics. Moreover, ambiguities and technical limitations in advanced techniques, such as esophageal manometry and pressure-volume curves, add a layer of complexity that renders its broader application in all ARDS patients both impractical and unnecessary. Whether sophisticated monitoring of chest mechanics in severe ARDS might improve outcomes further is open to question and should be studied further. However, it is highly improbable that we will ever discover a PEEP strategy that optimizes all aspects of cardiorespiratory function and chest mechanics for individual patients suffering from ARDS., (Copyright © 2016 by Daedalus Enterprises.)

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. Moreover, 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 (PaO2 /FIO2 < 150 mm Hg). Moreover, survival is enhanced when patients are managed with a smaller tidal volume (≤ 8 mL/kg), higher PEEP (10-13 cm H2O), 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., (Copyright © 2015 by Daedalus Enterprises.)

The injurious effects of alveolar overdistention are well accepted, and there is little debate regarding the importance of pressure and volume limitation during mechanical ventilation. The role of recruitment maneuvers is more controversial. Alveolar recruitment is desirable if it can be achieved, but the potential for recruitment is variable among patients with ARDS. A stepwise recruitment maneuver, similar to an incremental PEEP titration, is favored over sustained inflation recruitment maneuvers. Many approaches to PEEP titration have been proposed, and the best method to choose the most appropriate level for an individual patient is unclear. A PEEP level should be selected that balances alveolar recruitment against overdistention. The easiest approach to select PEEP might be according to the severity of the disease: 5-10 cm H2O PEEP in mild ARDS, 10-15 cm H2O PEEP in moderate ARDS, and 15-20 cm H2O PEEP in severe ARDS. Recruitment maneuvers and PEEP should be used within the context of lung protection and not just as a means of improving oxygenation., (Copyright © 2015 by Daedalus Enterprises.)

Background: The literature generally describes the trachea as oriented toward the right and back, but there is very little detailed characterization. Therefore, the aim of this study was to precisely determine the spatial orientation and to better characterize the physical properties of the human trachea., Methods: We analyzed lung computed tomography scans of 68 intubated and mechanically ventilated subjects suffering from acute lung injury/ARDS at airway pressures (Paw) of 5, 15, and 45 cm H2O. At each Paw, the inner edge of the trachea from the subglottal space to the carina was captured. Tracheal length and diameter were measured. Tracheal orientation and compliance were estimated from processing barycenter and surface tracheal sections., Results: Tracheal orientation at a Paw of 5 cm H2O showed a 4.2 ± 5.3° angle toward the right and a 20.6 ± 6.9° angle downward toward the back, which decreased significantly while increasing Paw (19.4 ± 6.9° at 15 cm H2O and 17.1 ± 6.8° at 45 cm H2O, P < .001). Tracheal compliance was 0.0113 ± 0.0131 mL/cm H2O/cm of trachea length from 5 to 15 cm H2O and 0.004 ± 0.0041 mL/cm H2O/cm of trachea length from 15 to 45 cm H2O (P < .001). Tracheal diameter was 19.6 ± 3.4 mm on the medial-lateral axis and 21.0 ± 4.3 mm on the sternal-vertebral axis., Conclusions: The trachea is oriented downward toward the back at a 20.6 ± 6.9° angle and slightly toward the right at a 4.2 ± 5.3° angle. Understanding tracheal orientation may help in enhancing postural drainage and respiratory physiotherapy, and knowing the physical properties of the trachea may aid in endotracheal tube cuff design., (Copyright © 2015 by Daedalus Enterprises.)

Respiratory mechanics refers to the expression of lung function through measures of pressure and flow. From these measurements, a variety of derived indices can be determined, such as volume, compliance, resistance, and work of breathing. Plateau pressure is a measure of end-inspiratory distending pressure. It has become increasingly appreciated that end-inspiratory transpulmonary pressure (stress) might be a better indicator of the potential for lung injury than plateau pressure alone. This has resulted in a resurgence of interest in the use of esophageal manometry in mechanically ventilated patients. End-expiratory transpulmonary pressure might also be useful to guide the setting of PEEP to counterbalance the collapsing effects of the chest wall. The shape of the pressure-time curve might also be useful to guide the setting of PEEP (stress index). This has focused interest in the roles of stress and strain to assess the potential for lung injury during mechanical ventilation. This paper covers both basic and advanced respiratory mechanics during mechanical ventilation., (Copyright © 2014 by Daedalus Enterprises.)

Background: We tested the association between pulmonary dead-space fraction (ratio of dead space to tidal volume [V(D)/V(T)]) and mortality in subjects with ARDS (Berlin definition, P(aO2)/F(IO2) ≤ 300 mm Hg; PEEP ≥ 5 cm H2O) enrolled into a clinical trial incorporating lung-protective ventilation., Methods: We conducted a prospective, multi-center study at medical-surgical ICUs in the United States. A total of 126 ALI subjects with acute lung injury were enrolled into a phase 3 randomized, placebo-controlled study of aerosolized albuterol. V(D)/V(T) and pulmonary mechanics were measured within 4 h of enrollment and repeated daily on study days 1 and 2 in subjects requiring arterial blood gases for clinical management., Results: At baseline, non-survivors had a trend toward higher V(D)/V(T) compared with survivors (0.62 ± 0.11 vs 0.56 ± 0.11, respectively, P = .08). Differences in V(D)/V(T) between non-survivors and survivors became significant on study days 1 (0.64 ± 0.12 vs 0.55 ± 0.11, respectively, P = .01) and 2 (0.67 ± 0.12 vs 0.56 ± 0.11, respectively, P = .004). Likewise, the association between VD/VT and mortality was significant on study day 1 (odds ratio per 0.10 change in V(D)/V(T) [95% CI]: 6.84 [1.62-28.84] P = .01; and study day 2: 4.90 [1.28-18.73] P = .02) after adjusting for V(D)/V(T), P(aO2)/F(IO2), oxygenation index, vasopressor use, and the primary risk for ARDS. Using a Cox proportional hazard model, V(D)/V(T) was associated with a trend toward higher mortality (HR = 4.37 [CI 0.99-19.32], P = .052) that became significant when the analysis was adjusted for daily oxygenation index (HR = 1.74 [95% CI 1.12-3.35] P = .04)., Conclusions: Markedly elevated V(D)/V(T) (≥ 0.60) in early ARDS is associated with higher mortality. Measuring V(D)/V(T) may be useful in identifying ARDS patients at increased risk of death who are enrolled into a therapeutic trial., (Copyright © 2014 by Daedalus Enterprises.)

Background: Daily routine ventilator-filter exchange interrupts the integrity of the ventilator circuit. We hypothesized that this might reduce positive airway pressure in mechanically ventilated ICU patients, inducing alveolar collapse and causing impaired oxygenation and compliance of the respiratory system., Methods: We studied 40 consecutive ICU subjects (P(aO2)/F(IO2) ratio ≤ 300 mm Hg), mechanically ventilated with pressure-regulated volume control or pressure support and PEEP ≥ 5 cm H2O. Before the filter exchange, (baseline) tidal volume, breathing frequency, end-inspiratory plateau pressure, and PEEP were recorded. Compliance of the respiratory system was calculated; F(IO2), blood pressure, and pulse rate were registered; and P(aO2), P(aCO2), pH, and base excess were measured. Measurements were repeated 15 and 60 min after the filter exchange. In addition, a bench test was performed with a precision test lung with similar compliance and resistance as in the clinical study., Results: The exchange of the filter took 3.5 ± 1.2 s (mean ± SD). There was no significant change in P(aO2) (89 ± 16 mm Hg at baseline vs 86 ± 16 mm Hg at 15 min and 88 ± 18 mm Hg at 60 min, P = .24) or in compliance of the respiratory system (41 ± 11 mL/cm H2O at baseline vs 40 ± 12 mL/cm H2O at 15 min and 40 ± 12 mL/cm H2O at 60 min, P = .32). The bench study showed that auto-triggering by the ventilator when disconnecting from the expiratory circuit kept the tracheal pressure above PEEP for at least 3 s with pressure controlled ventilation., Conclusions: This study showed that a short disconnection of the expiratory ventilator circuit from the ventilator during filter exchange was not associated with any significant deterioration in lung function 15 and 60 min later. This result may be explained by auto-triggering of the ventilator with high inspiratory flows during the filter exchange, maintaining airway pressure.

Background: Although leak compensation has been widely introduced to acute care ventilators to improve patient-ventilator synchronization in the presence of system leaks, there are no data on these ventilators' ability to prevent triggering and cycling asynchrony. The goal of this study was to evaluate the ability of leak compensation in acute care ventilators during invasive and noninvasive ventilation (NIV)., Methods: Using a lung simulator, the impact of system leaks was compared on 7 ICU ventilators and 1 dedicated NIV ventilator during triggering and cycling at 2 respiratory mechanics (COPD and ARDS models) settings, various modes of ventilation (NIV mode [pressure support ventilation], and invasive mode [pressure support and continuous mandatory ventilation]), and 2 PEEP levels (5 and 10 cm H(2)O). Leak levels used were up to 35-36 L/min in NIV mode and 26-27 L/min in invasive mode., Results: Although all of the ventilators were able to synchronize with the simulator at baseline, only 4 of the 8 ventilators synchronized to all leaks in NIV mode, and 2 of the 8 ventilators in invasive mode. The number of breaths to synchronization was higher during increasing than during decreasing leak. In the COPD model, miss-triggering occurred more frequently and required a longer time to stabilize tidal volume than in the ARDS model. The PB840 required fewer breaths to synchronize in both invasive and noninvasive modes, compared with the other ventilators (P < .001)., Conclusions: Leak compensation in invasive and noninvasive modes has wide variations between ventilators. The PB840 and the V60 were the only ventilators to acclimate to all leaks, but there were differences in performance between these 2 ventilators. It is not clear if these differences have clinical importance.

Background: Growth-arrest-specific protein 6 (GAS6) is a vitamin K-dependent protein expressed by endothelial cells and leukocytes participating in cell survival, migration and proliferation and involved in many pathological situations. The aim of our study was to assess its implication in ARDS and its variation according to PEEP setting, considering that different cyclic stresses could alter GAS6 plasma levels., Methods: Our subjects were enrolled in the ExPress study comparing a minimal alveolar distention (low-PEEP) ventilatory strategy to a maximal alveolar recruitment (high-PEEP) strategy in ARDS. Plasma GAS6, interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF) levels were measured at day 0 and day 3 by enzyme-linked immunosorbent assay in blood samples prospectively collected during the study for a subset of 52 subjects included in 8 centers during year 2005., Results: We found that GAS6 plasma level was elevated in the whole population at day 0: median 106 ng/mL IQR 77-139 ng/mL, with significant correlations with IL-8, the Simplified Acute Physiology Score II and the Organ Dysfunction and Infection scores. Statistically significant decreases in GAS6 and IL-8 plasma levels were observed between day 0 and day 3 in the high-PEEP group (P = .02); while there were no differences between day 0 and day 3 in the low-PEEP group., Conclusions: GAS6 plasma level is elevated in ARDS patients. The high-PEEP strategy is associated with a decrease in GAS6 and IL-8 plasma levels at day 3, without significant differences in day 28 mortality between the 2 groups. (Clinicaltrials.gov NCT00188058).

Background: Calculation of physiologic dead space (dead space divided by tidal volume [VD/VT]) using the Enghoff modification of the Bohr equation requires measurement of the partial pressure of mean expired CO2 (PĒCO2) by exhaled gas collection and analysis, use of a metabolic analyzer, or use of a volumetric CO2 monitor. The Dräger XL ventilator is equipped with integrated volumetric CO2 monitoring and calculates minute CO2 production (VCO2). We calculated PĒCO2 and VD/VT from ventilator derived volumetric CO2 measurements of VCO2 and compared them to metabolic analyzer and volumetric CO2 monitor measurements., Methods: A total of 67 measurements in 36 subjects recovering from acute lung injury or ARDS were compared. Thirty-one ventilator derived measurements were compared to measurements using 3 different metabolic analyzers, and 36 ventilator derived measurements were compared to measurements from a volumetric CO2 monitor., Results: There was a strong agreement between ventilator derived measurements and metabolic analyzer or volumetric CO2 monitor measurements of PĒCO2 and VD/VT. The correlations, bias, and precision between the ventilator and metabolic analyzer measurements for PĒCO2 were r = 0.97, r(2) = 0.93 (P < .001), bias -1.04 mm Hg, and precision ± 1.47 mm Hg. For VD/VT the correlations were r = 0.95 and r(2) = 0.91 (P < .001), and the bias and precision were 0.02 ± 0.04. The correlations between the ventilator and the volumetric CO2 monitor for PĒCO2 were r = 0.96 and r(2) = 0.92 (P < .001), and the bias and precision were -0.19 ± 1.58 mm Hg. The correlations between the ventilator and the volumetric CO2 monitor for VD/VT were r = 0.97 and r(2) = 0.95 (P < .001), and the bias and precision were 0.01 ± 0.03., Conclusions: PĒCO2, and therefore VD/VT, can be accurately calculated directly from the Dräger XL ventilator volumetric capnography measurements without use of a metabolic analyzer or volumetric CO2 monitor.

Background: Selection of the PEEP associated with the best compliance of the respiratory system during decremental PEEP titration can be used for the treatment of patients suffering from ARDS. We describe changes in transpulmonary pressure (Ptp) and gas exchange during a decremental PEEP titration maneuver in subjects with pulmonary ARDS., Methods: Eleven subjects with early ARDS were included. After a recruitment maneuver they were ventilated in volume-controlled ventilation and PEEP was decreased from 30 to 0 cm H2O by steps of 3 cm H2O. Static airway pressure (Paw), esophageal pressure (Pes), Ptp (Paw - Pes), the ratio of dead space to tidal volume (VD/VT), and PaO2 were recorded at each step., Results: A linear correlation was found between Paw and Ptp. Expiratory Ptp became negative in all subjects when PEEP decreased below 8.9 ± 5.2 cm H2O. VD/VT was 0.67 ± 0.06 with 30 cm H2O of PEEP, and decreased 15.4 ± 8.5% during the maneuver, when PEEP and expiratory Ptp were 10.6 ± 4.1 cm H2O and 1.2 ± 2.8 cm H2O, respectively. VD/VT was significantly higher during ventilation at high (> 18 cm H2O), compared to low, inspiratory Ptp values (P < .001). PaO2 decreased when expiratory Ptp became negative (P < .001)., Conclusions: During decremental PEEP titration we sequentially observed high inspiratory Ptp that stressed lung tissue and increased VD/VT, and negative Ptp, indicating high risk of alveolar collapse, explaining worse oxygenation. PEEP selection based on Ptp and VD/VT in ARDS may help to avoid these situations.

Background: We wanted to assess whether there was a significant relationship between recruited lung volume (V(rec)) and change in density on digital processed chest x-ray measured at 2 different levels of inspiratory plateau pressure corresponding to 2 PEEP levels in patients with acute lung injury or ARDS., Methods: In 14 subjects, PEEP 5 cm H2O and 15 cm H2O were prospectively applied in a random order for 10 min. At the end of each period, chest x-ray was taken using a digital portable device, and a pressure-volume curve of the respiratory system was performed. We also assessed P(aO2), and the static and the dynamic (C(dyn,rs)) compliance of the respiratory system. Change in end-expiratory lung volume between tidal breath and relaxation volume of the respiratory system was determined. Radiological attenuation was measured on chest x-rays in 4 regions of interest in the right lung, and in 3 regions of interest in the left lung, drawn in posterior intercostal spaces from top to bottom, by using dedicated software. The ratio of lung density in each region between PEEP 15 and PEEP 5 (rP15/P5) and their arithmetic mean (μP15/P5) were computed. V(rec) was determined from the pressure-volume curves., Results: The median value of rP15/P5 in the 98 lung levels was 0.91 (0.80-1.01), which was significantly different from 1 (P < .001). The values of rP15/P5 were not significantly different between the lung levels. The median values of V(rec) and μP15/P5 were 288 (173-402) mL and 0.90 (0.80-0.97), respectively. There was a significant negative correlation between V(rec) and μP15/P5 (R = -0.77, P = .01). The reduction in μP15/P5 tended to correlate with the increase in C(dyn,rs) (R = -0.49, P = .077) or in P(aO2) (R = -0.53, P = .05) between PEEP 15 cm H2O and PEEP 5 cm H2O., Conclusions: Digital chest x-ray done at the bedside in acute lung injury/ARDS subjects was able to detect a reduction in density between PEEP 5 cm H2O and PEEP 15 cm H2O, which correlated with V(rec).

Background: A recent trial showed that setting PEEP according to end-expiratory transpulmonary pressure (P(pl,ee)) in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) might improve patient outcome. P(pl,ee) was obtained by subtracting the absolute value of esophageal pressure (P(es)) from airway pressure an invariant value of 5 cm H(2)O. The goal of the present study was to compare 2 methods for correcting absolute P(es) values in terms of resulting P(pl,ee) and recommended PEEP., Methods: Measurements collected prospectively from 42 subjects with various forms of acute hypoxemic respiratory failure receiving mechanical ventilation in ICU were analyzed. P(es) was measured at PEEP (P(es,ee)) and at relaxation volume of the respiratory system Vr (P(es,Vr)), obtained by allowing the subject to exhale into the atmosphere (zero PEEP). Two methods for correcting P(es) were compared: Talmor method (P(pl,ee,Talmor) = P(es,ee) - 5 cm H(2)O), and Vr method (P(es,ee,Vr) = P(es,ee) - P(es,Vr)). The rationale was that P(es,Vr) was a more physiologically based correction factor than an invariant value of 5 cm H(2)O applied to all subjects., Results: Over the 42 subjects, median and interquartile range of P(es,ee) and P(es,Vr) were 11 (7-14) cm H(2)O and 8 (4-11) cm H(2)O, respectively. P(pl,ee,Talmor) was 6 (1-8) cm H(2)O, and P(es,ee,Vr) was 2 (1-5) cm H(2)O (P = .008). Two groups of subjects were defined, based on the difference between the 2 corrected values. In 28 subjects P(pl,ee,Talmor) was ≥ P(es,ee,Vr) (7 [5-9] cm H(2)O vs 2 [1-5] cm H(2)O, respectively), while in 14 subjects P(es,ee,Vr) was > P(pl,ee,Talmor) (2 [0-4] cm H(2)O vs -1 [-3 to 2] cm H(2)O, respectively). P(pl,ee,Vr) was significantly greater than P(pl,ee,Talmor) (7 [5-11] cm H(2)O vs 5 [2-7] cm H(2)O) in the former, and significantly lower in the latter (1 [-2 to 6] cm H(2)O vs 6 [4-9] cm H(2)O)., Conclusions: Referring absolute P(es) values to Vr rather than to an invariant value would be better adapted to a patient's physiological background. Further studies are required to determine whether this correction method might improve patient outcome.

Objective: Heated and humidified high flow nasal cannula oxygen therapy (HFNC) represents a new alternative to conventional oxygen therapy that has not been evaluated in the emergency department (ED). We aimed to study its feasibility and efficacy in patients exhibiting acute respiratory failure presenting to the ED., Methods: Prospective, observational study in a university hospital's ED. Patients with acute respiratory failure requiring > 9 L/min oxygen or with ongoing clinical signs of respiratory distress despite oxygen therapy were included. The device of oxygen administration was then switched from non-rebreathing mask to HFNC. Dyspnea, rated by the Borg scale and a visual analog scale, respiratory rate, and S(pO(2)) were collected before and 15, 30, and 60 min after beginning HFNC. Feasibility was assessed through caregivers' acceptance of the device in terms of practicality and perceived effect on the subjects, evaluated by questionnaire., Results: Seventeen subjects, median age 64 y (46-84.7 y), were studied. Pneumonia was the most common reason for oxygen therapy (n = 9). HFNC was associated with a significant decrease in both dyspnea scores: Borg scale from 6 (5-7) to 3 (2-4) (P < .001), and visual analog scale from 7 (5-8) to 3 (1-5) (P < .01). Respiratory rate decreased from 28 breaths/min (25-32 breaths/min) to 25 breaths/min (21-28 breaths/min) (P < .001), and S(pO(2)) increased from 90% (88.5-94%) to 97% (92.5-100%) (P < .001). Fewer subjects exhibited clinical signs of respiratory distress (10/17 vs 3/17, P = .03). HFNC was well tolerated and no adverse event was noted. Altogether, 76% of healthcare givers declared preferring HFNC, as compared to conventional oxygen therapy., Conclusions: HFNC is possible in the ED, and it alleviated dyspnea and improved respiratory parameters in subjects with acute hypoxemic respiratory failure.

Background: High-frequency oscillatory ventilation (HFOV) has been utilized as a rescue oxygenation therapy in adults with ARDS over the last decade. The HFOV oscillating piston can generate negative pressure during the exhalation cycle, which has been termed active exhalation. We hypothesized that this characteristic of HFOV entrains CO(2) into the inspiratory limb of the circuit and increases the total dead space. The purpose of this study was to determine if retrograde CO(2) entrainment occurs and how it is altered by HFOV parameter settings., Methods: An HFOV was interfaced to a cuffed endotracheal tube and connected to a mechanical test lung. Negative pressure changes within the circuit's inspiratory limb were measured while HFOV settings were manipulated. Retrograde CO(2) entrainment was evaluated by insufflating CO(2) into the test lung to achieve 40 mm Hg at the carina. Inspiratory limb CO(2) entrainment was measured at incremental distances from the Y-piece. HFOV settings and cuff leak were varied to assess their effect on CO(2) entrainment. Control experiments were conducted using a conventional ventilator. Test lung results were validated on a large hypercapnic swine., Results: Negative pressure was detectable within the inspiratory limb of the HFOV circuit and varied inversely with mean airway pressure (P(-)(aw)) and directly with oscillatory pressure amplitude (ΔP). CO(2) was readily detectable within the inspiratory limb and was proportional to the negative pressure that was generated. Factors that decreased CO(2) entrainment in both the test lung and swine included low ΔP, high mean airway pressure, high oscillatory frequency (Hz), high bias flow, and endotracheal tube cuff leak placement. CO(2) entrainment was also reduced by utilizing a higher bias flow strategy at any targeted mean airway pressure., Conclusions: Retrograde CO(2) entrainment occurs during HFOV use and can be manipulated with the ventilator settings. This phenomenon may have clinical implications on the development or persistence of hypercapnia.

Background: Elevated dead space fraction (the ratio of dead space to tidal volume [V(D)/V(T)]) is a feature of ARDS. PEEP can partially reverse atelectasis, prevent alveoli recollapse, and improve lung compliance and gas exchange in patients with ARDS. However, whether V(D)/V(T) variables have a close relationship with PEEP and collapse alveolar recruitment remains under recognized. Meanwhile, few clinicians titrate PEEP in consideration of changes in V(D)/V(T). Therefore, we performed the study to evaluate V(D)/V(T), arterial oxygenation, and compliance changes during PEEP titration following lung recruitment in ARDS patients., Methods: Twenty-three ARDS patients ventilated in volume-controlled mode were enrolled in the study. Sustained inflation (40 cm H₂O, 30 s) was used as a recruitment maneuver, followed by decremental PEEP changes from 20 to 6 cm H₂O, in steps of 2 cm H₂O, and then to 0 cm H₂O. V(D)/V(T), pulmonary mechanics parameters, gas exchange parameters, and hemodynamic parameters were recorded after 20 min at each PEEP step., Results: Compared with V(D)/V(T) at the PEEP levels of 20 cm H₂O and 0 cm H₂O, V(D)/V(T) was significantly lower at 12 cm H₂O (P = .02), and compliance of the static respiratory system (C(RS)) was significantly higher at pressure step 12/10 cm H₂O (P < .001). Compared with P(aCO₂) at the PEEP level of 20 cm H₂O, P(aCO₂) was significantly lower at 12 cm H₂O (P < .001). Arterial oxygenation values and functional residual capacity were reduced gradually during PEEP, decreasing from 20 cm H₂O to 0 cm H₂O., Conclusions: A significant change of V(D)/V(T), compliance and arterial oxygenation could be induced by PEEP titration in subjects with ARDS. Optimal PEEP in these subjects was 12 cm H₂O, because at this pressure level the highest compliance in conjunction with the lowest V(D)/V(T) indicated a maximum amount of effectively expanded alveoli. Monitoring of V(D)/V(T) was useful for detecting lung collapse and for establishing open-lung PEEP after a recruitment maneuver.

Airway pressure-release ventilation (APRV) is used in the management of patients with severe or refractory respiratory failure. In addition to reversal of inspiratory-expiratory ratios, this pressure control mode also allows unrestricted spontaneous breathing. The spontaneous tidal volume (V(T)), as well as the V(T) resulting from transition between the high and low airway pressures, is uncontrolled. There are limited data on the within-patient variation of actual V(T) and the safety of these modes. The authors present a patient with severe ARDS who was managed with biphasic modes (APRV and bi-level positive airway pressure). Serial V(T) measurements showed that V(T) ranged from 4 to 12 mL/kg predicted body weight. Computed tomography scan images and chest radiographs obtained before and following APRV showed lung parenchyma changes that may be related to ventilator-induced lung injury. We also present a mathematical model that is useful for simulating APRV and demonstrating the issues related to volume delivery for mandatory breaths during the transition between the 2 pressure levels. A key finding of this analysis is the interdependence of release volume, autoPEEP, and the T(low) time setting. Furthermore, it is virtually impossible to target a specific P(aCO(2)) with a desired level V(T) and autoPEEP in a passive model, emphasizing the importance of spontaneous breathing with this mode. This case report suggests caution when using these modes, and that end-inspiratory lung volumes and V(T) should be limited to avoid lung injury. The important point of this case study and model analysis is that the application of APRV is more complex than it appears to be. It requires a lot more knowledge and skill than may be apparent from descriptions in the literature.

Background: Increased dead-space fraction is common in patients with persistent acute respiratory distress syndrome (ARDS). We evaluated the changes in the oxygenation and dead-space fraction in patients with persistent ARDS after corticosteroid therapy., Methods: This was a non-randomized non-placebo, controlled observational study including 19 patients with persistent ARDS treated with corticosteroids. We measured P(aO(2))/F(IO(2)) and dead-space fraction at days 0, 4, and 7 after corticosteroids treatment (methylprednisolone) initiation. Patients were classified in intermediate group when corticosteroids were initiated between days 8-14 after ARDS onset, and in late group when initiated after 14 days., Results: Mean time from the diagnosis of the ARDS to methylprednisolone treatment was 11 ± 2 days in the intermediate group (10 patients) and 21 ± 8 days in the late group (9 patients). When comparing days 0, 4, and 7 after methylprednisolone treatment, we found an increase in the P(aO(2))/F(IO(2)) (145 ± 64 mm Hg, 190 ± 68 mm Hg, and 226 ± 84 mm Hg, respectively, P < .001) and a decrease in the physiological dead-space fraction (0.66 ± 0.10, 0.58 ± 0.12, and 0.53 ± 0.11, respectively, P < .001). No differences were found between the intermediate and late groups., Conclusions: In patients with persistent ARDS, the increase in oxygenation was accompanied by a decrease in the dead-space fraction after a few days of corticosteroid treatment. To confirm potential benefit of corticosteroids on physiological parameters and mortality will require a powered randomized placebo controlled trial.

Background: The ability to rapidly and precisely evaluate patients in respiratory distress is essential. Due to limited opportunities for formal instruction during training, textbooks are the main educational source to teach junior physicians how to interpret the signs of respiratory distress. The quality of the textbook content relevant to respiratory distress is unknown., Objective: To examine the content on the evaluation of a patient in respiratory distress in a representative sample of textbooks and Internet resources., Methods: Two physicians individually reviewed the most recent edition of 21 standard textbooks from a variety of specialties. Smartphone applications, UptoDate, and MD Consult were examined. Each physician reviewed the source for 14 different signs. For each sign, the reviewers determined 3 parameters: a mention of the sign, its pathophysiology, and its detection. The reviews were compared for discrepancies, and a third reviewer resolved them., Results: The normal respiratory rate was mentioned in 10 (48%) of textbooks, and ranged between 10 and 22 breaths/min. Each sign was mentioned by a mean of 45 ± 26% of the textbooks. The pathophysiology of the signs was described by a mean of 33 ± 30% of the textbooks. The most and least commonly mentioned inspection signs were cyanosis and retraction of suprasternal notch, respectively. They were mentioned in 20 (95%) and 4 (19%) textbooks, respectively. The most and least commonly mentioned palpation signs were thoracoabdominal asynchrony or paradox and tracheal tug, respectively. They were mentioned in 17 (81%) and 4 (19%) textbooks, and their pathophysiology was described in 15 (71%) and 4 (19%) textbooks, respectively. The reviewers also found inconsistency in the descriptions of the meaning of scalene muscle contraction and thoracoabdominal asynchrony and paradox., Conclusions: The content of the reviewed textbooks on the evaluation of respiratory distress is inconsistent and deficient.

Airway pressure release ventilation (APRV) is inverse ratio, pressure controlled, intermittent mandatory ventilation with unrestricted spontaneous breathing. It is based on the principle of open lung approach. It has many purported advantages over conventional ventilation, including alveolar recruitment, improved oxygenation, preservation of spontaneous breathing, improved hemodynamics, and potential lung-protective effects. It has many claimed disadvantages related to risks of volutrauma, increased work of breathing, and increased energy expenditure related to spontaneous breathing. APRV is used mainly as a rescue therapy for the difficult to oxygenate patients with acute respiratory distress syndrome (ARDS). There is confusion regarding this mode of ventilation, due to the different terminology used in the literature. APRV settings include the "P high," "T high," "P low," and "T low". Physicians and respiratory therapists should be aware of the different ways and the rationales for setting these variables on the ventilators. Also, they should be familiar with the differences between APRV, biphasic positive airway pressure (BIPAP), and other conventional and nonconventional modes of ventilation. There is no solid proof that APRV improves mortality; however, there are ongoing studies that may reveal further information about this mode of ventilation. This paper reviews the different methods proposed for APRV settings, and summarizes the different studies comparing APRV and BIPAP, and the potential benefits and pitfalls for APRV.

The data available to guide clinical management of acute lung injury and acute respiratory distress syndrome are much more limited for infants and children than for adult patients. This paper reviews the available medical data and the pertinent physiology on the management of pediatric patients with acute lung injury. With the collaboration of multicenter investigation networks, definitive pediatric data may be on the horizon to better guide our clinical practice.

It has been known for decades that shock and sepsis can cause a syndrome of acute respiratory failure with characteristics of non-cardiogenic pulmonary edema. Over the years, this syndrome has been given a number of names, including congestive atelectasis, traumatic wet lung, and shock lung. In 1967 the modern counterpart to this syndrome was described and subsequently called the "acute respiratory distress syndrome" (ARDS). This syndrome results from lung injury and inflammation. As with inflammation elsewhere, ARDS is accompanied by many cellular and molecular processes, some of them specific to the syndrome, others perpetuating the syndrome, and others inactivating the by-products of inflammation. Since no specific clinical sign or diagnostic test has yet been described that identifies ARDS, its diagnosis is based on a constellation of clinical, hemodynamic, and oxygenation criteria. Current ARDS treatment is mainly supportive, since these patients frequently have coexisting conditions. Although in 1994 a new standard ARDS definition was accepted, that definition failed to standardize the measurement of the oxygenation defect and does not recognize different severities of pulmonary dysfunction. Based on current evidence there is a need for a better definition and classification system that could help us to identify ARDS patients who would be most responsive to supportive therapies and those unlikely to benefit because of the severity of their disease process. This paper examines our current understanding of ARDS and discusses why the current definition may not be the most appropriate for research and clinical practice.

To minimize ventilator-induced lung injury, attention should be directed toward avoidance of alveolar over-distention and cyclical opening and closure of alveoli. The most impressive study of mechanical ventilation to date is the Acute Respiratory Distress Syndrome (ARDS) Network study of higher versus lower tidal volume (V(T)), which reported a reduction in mortality from 39.8% to 31.0% with 6 mL/kg ideal body weight rather than 12 mL/kg ideal body weight (number-needed-to-treat of 12 patients). To achieve optimal lung protection, the lowest plateau pressure and V(T) possible should be selected. What is most important is limitation of V(T) and alveolar distending pressure, regardless of the mode set on the ventilator. Accumulating observational evidence suggests that V(T) should be limited in all mechanically ventilated patients-even those who do not have ALI/ARDS. Evidence does not support the use of pressure controlled inverse-ratio ventilation. Although zero PEEP is probably injurious, an area of considerable controversy is the optimal setting of PEEP. Available evidence does not support the use of higher PEEP, compared to lower PEEP, in unselected patients with acute lung injury (ALI)/ARDS. However, results of a meta-analysis using individual patients from 3 randomized controlled trials suggest that higher PEEP should be used for ARDS, whereas lower PEEP may be more appropriate in patients with ALI. PEEP should be set to maximize alveolar recruitment while avoiding over-distention. Many approaches for setting PEEP have been described, but evidence is lacking that any one approach is superior to any other. In most, if not all, cases of ALI/ARDS, conventional ventilation strategies can be used effectively to provide lung-protective ventilation strategies.

As the basis for this paper, it must be acknowledged that children are not simply small adults. But this acknowledgment must go further: infants are not simply small adolescents. As data for pediatric mechanical ventilation, in general, and the management for pediatric acute lung injury, more specifically, are very limited, the pediatric critical care clinician must closely assess the available adult data and evaluate its application for infants and children. Given the hurdles in studying pediatric acute lung injury and acute respiratory distress syndrome, clinicians involved with the care of critically ill infants and children are left with extrapolation of data from the neonatal and adult populations, reliance on the limited available pediatric data, careful assessment of the applicable physiologic and pathophysiologic principles, and/or reliance on their own experience and their colleagues' experience. Hopefully, with the collaboration of multicenter investigator networks, additional and definitive pediatric data may be on the horizon. In the meantime, sharing data between adult and pediatric populations seems to be an essential approach to the management of critically ill patients., (2011 Daedalus Enterprises)

Since the early 1970s there has been an ongoing debate regarding the wisdom of promoting unassisted spontaneous breathing throughout the course of critical illness in patients with severe respiratory failure. The basis of this debate has focused on the clinical relevance of opposite problems. Historically, the term "disuse atrophy" has described a situation wherein sustained inactivity of the respiratory muscles (ie, passive ventilation) results in deconditioning and weakness. More recently it has been referred to as "ventilator-induced diaphragmatic dysfunction." In contrast, "use atrophy" describes a situation where chronic high-tension inspiratory work causes structural damage to the diaphragm and weakness. Both laboratory and clinical studies demonstrated that relatively brief periods of complete respiratory muscle inactivity, as well as intense muscle loading, result in acute inflammation, loss of muscle mass, and weakness. Yet in critical illness other factors also affect respiratory muscle function, including prolonged use of neuromuscular blocking agents, administration of corticosteroids, and sepsis. This makes the attribution of acquired respiratory muscle weakness and ventilator-dependence to either ventilator-induced diaphragmatic dysfunction or loaded breathing extremely difficult. Regardless, the clinical implications of this research strongly suggest that passive mechanical ventilation should be avoided whenever possible. However, promotion of unassisted spontaneous breathing in the acute phase of critical illness also may carry a substantial risk of respiratory muscle injury and weakness. Use of mechanical ventilation modes in a manner that induces spontaneous breathing effort, while simultaneously reducing the work load on the respiratory muscles, is probably sufficient to minimize both problems.