Time to Extubation Among ARDS Subjects With and Without COVID-19 Pneumonia.

BACKGROUND: Pneumonia from COVID-19 that results in ARDS may require invasive mechanical ventilation. This retrospective study assessed the characteristics and outcomes of subjects with COVID-19-associated ARDS versus ARDS (non-COVID) during the first 6 months of the COVID-19 pandemic in 2020. The primary objective was to determine whether mechanical ventilation duration differed between these cohorts and identify other potential contributory factors. METHODS: We retrospectively identified 73 subjects admitted between March 1 and August 12, 2020, with either COVID-19-associated ARDS (37) or ARDS (36) who were managed with the lung protective ventilator protocol and required >48 h of mechanical ventilation. Exclusion criteria were the following: <18 years old or the patient required tracheostomy or interfacility transfer. Demographic and baseline clinical data were collected at ARDS onset (ARDS day 0), with subsequent data collected on ARDS days 1-3, 5, 7, 10, 14, and 21. Comparisons were made by using the Wilcoxon rank-sum test (continuous variables) and chi-square test (categorical variables) stratified by COVID-19 status. A Cox proportional hazards model assessed the cause-specific hazard ratio for extubation. RESULTS: The median (interquartile range) mechanical ventilation duration among the subjects who survived to extubation was longer in those with COVID-19-ARDS versus the subjects with non-COVID ARDS: 10 (6-20) d versus 4 (2-8) d; P < .001. Hospital mortality was not different between the two groups (22% vs 39%; P = .11). The competing risks Cox proportional hazard analysis (fit among the total sample, including non-survivors) revealed that improved compliance of the respiratory system and oxygenation were associated with the probability of extubation. Oxygenation improved at a lower rate in the subjects with COVID-19-associated ARDS than in the subjects with non-COVID ARDS. CONCLUSIONS: Mechanical ventilation duration was longer in subjects with COVID-19-associated ARDS compared with the subjects with non-COVID ARDS, which may be explained by a lower rate of improvement in oxygenation status.

Determining respiratory rate using measured expiratory time constant: A prospective observational study.

PURPOSE: Potential negative implications associated with high respiratory rate (RR) are intrinsic positive end-expiratory pressure (PEEPi) generation, cardiovascular depression and possibly ventilator induced lung injury. Despite these negative consequences, optimal RR remains largely unknown. We hypothesized that without consideration of dynamics of lung emptying (i.e., the expiratory time constant [RCEXP]) clinician settings of RR may exceed the frequency needed for optimal lung emptying. MATERIALS AND METHODS: This prospective multicenter observational study measured RCEXP in 56 intensive care patients receiving pressure-controlled ventilation. We compared set RR to the one predicted with RCEXP (RRP). Also, the subgroup of patients with prolonged RCEXP was analyzed. RESULTS: Overall, the absolute mean difference between the set RR and RRP was 2.8 bpm (95% CI: 2.3-3.2). Twenty-nine (52%) patients had prolonged RCEXP (>0.8 s), mean difference between set RR and RRP of 3.1 bpm (95% CI: 2.3-3.8; p < 0.0001) and significantly higher PEEPi compared to those with RCEXP ≤ 0.8 s: 4.4 (95% CI: 3.6-5.2) versus 1.5 (95% CI: 0.9-2.0) cmH2O respectively, p < 0.0001. CONCLUSIONS: Use of RRP based on measured RCEXP revealed that the clinician-set RR exceeded that predicted by RCEXP in the majority of patients. Measuring RCEXP appears to be a useful variable for adjusting the RR during mandatory mechanical ventilation.

Utilization of a Risk Stratification Tool and Volume-Based Cuff Leak Test to Assess Postextubation Stridor.

BACKGROUND: Postextubation stridor (PES) is an imminently life-threatening event. Maximizing patient safety requires a systematic approach to screen patients for PES risk factors and a standardized test to evaluate that risk. This retrospective study of adult subjects was based on quality assurance data including standardized surveillance screening criteria and a volume-based cuff leak test (CLT) to evaluate PES risk among predominantly surgical-trauma and neurotrauma subjects. Data characterizing PES subjects also were collected. METHODS: Data were collected between May 2010-December 2017 for all intubated subjects in our surgical-trauma, neurotrauma, and medical ICUs. Respiratory therapists were trained in performing both PES risk assessment surveillance and a volume-based CLT. A pre hoc cutoff leak volume of < 110 mL defined a true positive test result when associated with PES, and a leak ≥ 110 mL defined a true negative test if PES was absent. Multiple comparisons were analyzed by Kruskal-Wallis tests and dichotomous variables assessed by Fisher exact tests. Alpha was set at 0.05. RESULTS: In 681 pre-extubation CLTs ∼85% produced true-negative results and 15% consisted of true-positive (∼4%), false-negative (∼5%), and false-positive (∼6%) results. Positive and negative predictive values were 0.42 (0.32-0.54) and 0.94 (0.92-0.96), respectively. The PES likelihood ratio was 7.0, and correct classification was 89%. Of the 115 PES incidences occurring in 112 PES cases, 67% were female and 48% had suffered acute brain injury. CONCLUSIONS: Among predominantly surgical-trauma and neurotrauma subjects with a CLT, leak volume of ≥ 110 mL was associated with a PES risk of ∼6%, whereas the risk of PES was 7 times greater when the leak volume was < 110 mL.

Respiratory Drive, Dyspnea, and Silent Hypoxemia: A Physiological Review in the Context of COVID-19.

Infection with SARS-CoV-2 in select individuals results in viral sepsis, pneumonia, and hypoxemic respiratory failure, collectively known as COVID-19. In the early months of the pandemic, the combination of novel disease presentation, enormous surges of critically ill patients, and severity of illness lent to early observations and pronouncements regarding COVID-19 that could not be scientifically validated owing to crisis circumstances. One of these was a phenomenon referred to as "happy hypoxia." Widely discussed in the lay press, it was thought to represent a novel and perplexing phenomenon: severe hypoxemia coupled with the absence of respiratory distress and dyspnea. Silent hypoxemia is the preferred term describing an apparent lack of distress in the presence of hypoxemia. However, the phenomenon is well known among respiratory physiologists as hypoxic ventilatory decline. Silent hypoxemia can be explained by physiologic mechanisms governing the control of breathing, breathing perception, and cardiovascular compensation. This narrative review examines silent hypoxemia during COVID-19 as well as hypotheses that viral infection of the central and peripheral nervous system may be implicated. Moreover, the credulous embrace of happy hypoxia and the novel hypotheses proposed to explain it has exposed significant misunderstandings among clinicians regarding the physiologic mechanisms governing both the control of breathing and the modulation of breathing sensations. Therefore, a substantial focus of this paper is to provide an in-depth review of these topics.

Mechanical Ventilation in ARDS: Quo Vadis?

Contemplating the future should be grounded in history. The rise of post-polio ICUs was inextricably related to mechanical ventilation. Critically ill patients who developed acute respiratory failure often had "congestive atelectasis" (ie, a term used to describe ARDS prior to 1967). Initial mechanical ventilation strategies for treating this condition and others inadvertently led to ventilator-induced lung injury. Both injurious ventilation and later use of overly cautious weaning practices resulted from both limited technology and understanding of ARDS and other aspects of critical illness. The resulting misperceptions, misconceptions, and missed opportunities took decades to rectify and in some instances still persist. This suggests a reluctance to acknowledge that all therapeutic strategies reflect the historical period in which they were developed and the corresponding limited understanding of ARDS pathophysiology at that time. We are at the threshold of a revolutionary moment in critical care. The confluence of enormous clinical data production, massive computing power, advances in understanding the biomolecular and genetic aspects of critical illness, and the emergence of neural networks will have enormous impact on how critical care is practiced in the decades to come. Therefore, it is imperative we understand the long-crooked path needed to reach the era of protective ventilation in order to avoid similar mistakes moving forward. The emerging era is as difficult to fathom as our current practices and technologies were to those practicing 60 years ago. This review explores the history of mechanical ventilation in treating ARDS, describes current protective ventilation strategies, and speculates how ARDS management might look 20 years from now.

Expiratory Pause Maneuver to Assess Inspiratory Muscle Pressure During Assisted Mechanical Ventilation: A Bench Study.

BACKGROUND: The generation of excessive inspiratory muscle pressure (Pmus) during assisted mechanical ventilation in patients with respiratory failure may result in acute respiratory muscle injury and/or fatigue, and exacerbate ventilator-induced lung injury. A readily available noninvasive surrogate measure of Pmus may help in titrating both mechanical ventilation and sedation to minimize these risks. This bench study explored the feasibility and accuracy of using a ventilator's expiratory pause hold function to measure Pmus across multiple operators. METHODS: A standardized technique for executing a brief (<1 s) expiratory pause maneuver was used to measure the airway occlusion pressure change (Δ Paw) by using 3 simulated Pmus (Δ Pmus: 5, 10, 15 cm H2O) under (1) pressure support ventilation (0, 10, 15 cm H2O), (2) volume and pressure-regulated volume ventilation, (3) flow and pressure-triggering, and (4) varying levels of PEEP and pressure-rise time. Individual and grouped measurements were made by 4-7 clinicians on 3 different ventilators. The concordance between occlusion Δ Paw and Δ Pmus was arbitrarily set at ≤ 2 cm H2O. Data were evaluated by using analysis of variance and the Tukey-Kramer posttest. Correlation was assessed by using the Pearson R test; bias and precision were assessed by using the Bland-Altman method. Alpha was set at 0.05. RESULTS: Grouped expiratory pause maneuver measurements of occlusion Δ Paw across simulated Δ Pmus, mode and level of ventilatory support showed reasonable concordance, regardless of the ventilator used. Occlusion Δ Paw accuracy frequently decreased by ∼3 cm H2O when both pressure support ventilation and Δ Pmus reached 15 cm H2O. Expiratory pause maneuver accuracy was not affected by trigger mechanism and/or sensitivity, PEEP, or the post-trigger pressurization rate. In general, only small differences in Δ Paw occurred among the individual operators. CONCLUSIONS: The expiratory pause maneuver generally provided reproducible, stable approximations of Δ Pmus across ventilators and ventilator settings, and a range of simulated effort. Technique standardization produced relatively consistent results across multiple operators. The expiratory pause maneuver seemed feasible for general use in monitoring inspiratory effort during assisted mechanical ventilation.

2020 Year in Review: Mechanical Ventilation During the First Year of the COVID-19 Pandemic.

Coronavirus disease 2019 (COVID-19) represents the greatest medical crisis encountered in the young history of critical care and respiratory care. During the early months of the pandemic, when little was known about the virus, the acute hypoxemic respiratory failure it caused did not appear to fit conveniently or consistently into our classification of ARDS. This not only re-ignited a half-century's long simmering debate over taxonomy, but also fueled similar debates over how PEEP and lung-protective ventilation should be titrated, as well as the appropriate role of noninvasive ventilation in ARDS. COVID-19 ignited other debates on emerging concepts such as ARDS phenotypes and patient self-inflicted lung injury from vigorous spontaneous breathing. Over a year later, these early perplexities have receded into the background without having been reviewed or resolved. With a full year of evidence having been published, this narrative review systematically analyzes whether COVID-19-associated respiratory failure is essentially ARDS, with perhaps a somewhat different course of presentation. This includes a review of the severity of hypoxemia and derangements in pulmonary mechanics, PEEP requirements, recruitment potential, ability to achieve lung-protective ventilation goals, duration of mechanical ventilation, associated mortality, and response to noninvasive ventilation. This paper also reviews the concepts of ARDS phenotypes and patient self-inflicted lung injury as these are crucial to understanding the contentious debate over the nature and management of COVID-19.

ARDS Outcomes in Non-Research Subjects Assessed by Generalized Prospective Trial Eligibility Criteria and Adherence to Lung-Protective Ventilation.

BACKGROUND: ARDS mortality is lower among subjects participating in randomized controlled trials (RCTs) compared to subjects in observational studies. Excluding potential subjects with inordinately high mortality risk is necessary to prevent masking the impact of potentially effective treatments. We inquired whether observed mortality differed between RCT-eligible and RCT-ineligible subjects managed with varying degrees of lung-protective ventilation in a non-research setting. METHODS: This single-center, retrospective, observational study utilized quality assurance data for monitoring lung-protective ventilation practices based upon National Institutes of Health ARDS Network (ARDSNet) protocols. Between 2002 and 2017, 1,975 subjects meeting the 1994 consensus criteria for acute lung injury/ARDS (later reclassified by the Berlin definition) were prospectively identified and classified as RCT-eligible or RCT-ineligible on the basis of the original ARDSNet exclusion criteria for comorbidities or moribund condition. Demographic and physiologic data from the day of ARDS onset and outcome data were studied. Survival was modeled with a mixed-effect Cox proportional hazard model adjusted for age, both illness and lung injury severity plateau pressure, and formal use of the ARDSNet ventilator protocol. The primary outcome of interest was all-cause mortality during the first 90 d following onset of ARDS. RESULTS: Day 90 mortality was 27.6% in RCT-eligible subjects versus 50.4% in RCT-ineligible subjects (hazard ratio 0.47 [95% CI 0.41-0.54], P < .001). Regardless of eligibility or ineligibility, achieving a plateau pressure ≤ 30 cm H2O was associated with lower mortality. Overall, mortality risk was lower in subjects managed by protocol versus clinician-directed lung-protective ventilation (hazard ratio 0.60 [95% CI 0.52-0.69], P < .001), even among those in whom plateau pressure was ≤ 30 cm H2O (hazard ratio 0.64 [95% CI 0.54-0.76], P < .001). CONCLUSIONS: Mortality in non-research, RCT-eligible subjects was substantially lower compared to RCT-ineligible subjects. Managing non-research patients with ARDS by keeping plateau pressure ≤ 30 cm H2O and formal use of a lung-protective ventilation protocol significantly reduces mortality risk.

The Nature of Recruitment and De-Recruitment and Its Implications for Management of ARDS.

Recruitment maneuvers in ARDS are used to improve oxygenation and lung mechanics by applying high airway pressures to reopen collapsed or obstructed peripheral airways and alveoli. In the early 1990s, recruitment maneuvers became a central feature of a variant form of lung-protective ventilation known as open-lung ventilation. This strategy is based on the belief that repetitive opening and closing of distal airspaces induces shear injury and therefore contributes both to ventilator-induced lung injury and ARDS-associated mortality. However, the largest multi-center randomized controlled trial of open-lung ventilation in moderate to severe ARDS reported that recruitment maneuver plateau pressures of 50-60 cm H2O were associated with significantly higher mortality compared to traditional lung-protective ventilation. Despite being based on well conducted preclinical and clinical recruitment maneuver studies, the higher mortality associated with the open-lung ventilation strategy requires re-examining the assumptions and conclusions drawn from those previous studies. This narrative review examines the evidence used to design recruitment maneuver strategies. We also review the radiologic, rheologic, and histopathologic evidence regarding the nature of lung injury and the phenomena of recruitment and de-recruitment as it informs our perceptions of recruitment potential in ARDS. Major lung-protective ventilation clinical trial data and other clinical data are also examined to assess the practical necessity of recruitment maneuvers in ARDS and whether a subset of cases might benefit from pursuing recruitment maneuver therapy. Finally, a less a radical approach to recruitment maneuvers is offered that might achieve the goals of recruitment maneuvers with less risk of harm.

End-Tidal-to-Arterial PCO2 Ratio as Signifier for Physiologic Dead-Space Ratio and Oxygenation Dysfunction in Acute Respiratory Distress Syndrome.

BACKGROUND: The ratio of end-tidal CO2 pressure to arterial partial pressure of CO2 ([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 (VD/VT) 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 VD/VT (r = -0.87 [95% CI -0.89 to -0.85], P < .001). Decreasing [Formula: see text] was associated with increased VD/VT 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 VD/VT (0.82 ± 0.05, P < .001) and high hospital mortality (70%). CONCLUSIONS: Using [Formula: see text] as a surrogate for VD/VT may be a useful and practical measurement for both management and ongoing research into the nature of ARDS.

Effects of Inhaled Epoprostenol and Prone Positioning in Intubated Coronavirus Disease 2019 Patients With Refractory Hypoxemia.

OBJECTIVES: To evaluate the effects of inhaled epoprostenol and prone positioning, individually and in combination in mechanically ventilated patients with coronavirus disease 2019 and refractory hypoxemia. DESIGN: Retrospective study. SETTING: Academic hospital adult ICUs. PATIENTS: Adult patients who received inhaled epoprostenol and prone positioning during invasive ventilation were enrolled. Patients were excluded if inhaled epoprostenol was initiated: 1) at an outside hospital, 2) after prone positioning was terminated, 3) during extracorporeal membrane oxygenation or cardiopulmonary resuscitation, and 4) with Pao2/Fio2 greater than 150 mm Hg. INTERVENTIONS: Inhaled epoprostenol and prone positioning. RESULTS: Of the 43 eligible patients, 22 and seven received prone positioning and inhaled epoprostenol alone, respectively, prior to their use in combination, Pao2/Fio2 was not different pre- and post-prone positioning or inhaled epoprostenol individually (89.1 [30.6] vs 97.6 [30.2] mm Hg; p = 0.393) but improved after the combined use of inhaled epoprostenol and prone positioning (84.0 [25.6] vs 124.7 [62.7] mm Hg; p < 0.001). While inhaled epoprostenol and prone positioning were instituted simultaneously in 14 patients, Pao2/Fio2 was significantly improved (78.9 [27.0] vs 150.2 [56.2] mm Hg, p = 0.005) with the combination. Twenty-seven patients (63%) had greater than 20% improvement in oxygenation with the combination of inhaled epoprostenol and prone positioning, and responders had lower mortality than nonresponders (52 vs 81%; p = 0.025). CONCLUSIONS: In critically ill, mechanically ventilated patients with coronavirus disease 2019 who had refractory hypoxemia, oxygenation improved to a greater extent with combined use of inhaled epoprostenol and prone positioning than with each treatment individually. A higher proportion of responders to combined inhaled epoprostenol and prone positioning survived compared with nonresponders. These findings need to be validated by randomized, prospective clinical trials.

Developing a Research Program Within a Respiratory Care Department.

Scientific research traditionally has been the domain of graduate school training, and it is based on higher cognitive levels associated with reflective thought. Such skills differ markedly from those needed to train competent respiratory therapists at the undergraduate level. Trainees at the undergraduate level need to acquire, comprehend, and apply large amounts of functional knowledge within a relatively brief time period. As a consequence, there is a pragmatic restriction on the level of complexity that characterizes pathophysiology, therapeutics, and associated technology that can be taught without causing confusion and thereby impeding the learning process. The era of evidence-based medicine is characterized both by the increasing complexity of medical technology and therapeutics. Because respiratory care is fundamentally a technology-driven profession, cultivating research skills among a select group of motivated practitioners is essential. Moreover, it is incumbent on all respiratory therapists to possess a rudimentary understanding of scientific methodology and a familiarity with the processes of reflective thought to become more discerning consumers of medical information. Organizing and implementing a research program within a respiratory care department or training program require forethought and devoted leadership. Crucial to this endeavor is developing mentors to guide those with little or no exposure to scientific inquiry. This article provides an overview of the pedagogical issues that underlie this predicament and then describes practical steps that can be taken to slowly build such a program.

Ventilator Bundles in Transition: From Prevention of Ventilator-Associated Pneumonia to Prevention of Ventilator-Associated Events.

Implementation of ventilator bundles is associated with reductions in ventilator-associated pneumonia (VAP). However, the new surveillance model of ventilator-associated events (VAEs) has shifted the focus from VAP to objective, generalized signs of pulmonary decompensation not specific to VAP. This raises the question of whether the ventilator bundle also is effective in reducing VAE. This narrative review examined 6 studies published since 2013 that assessed the impact of ventilator bundles on the incidence of VAE, and a seventh study that examined its impact on mortality. All 7 studies were low-level evidence, and only 1 study was prospective. The findings among the studies were inconsistent, and the only prospective study found no difference in bundle adherence between those who did and did not develop VAE. However numerous factors may explain the apparent lack of efficacy. Most of these factors were related to the retrospective nature of the studies, such as suboptimal documentation of bundle procedures and the presence of potential non-modifiable risk factors, as well as insufficient performance of most bundle components. In some studies, low VAE incidence also raised uncertainty about the veracity of results. Despite these limitations, there was evidence suggesting that stress ulcer prophylaxis may increase VAE risk, and oral care with chlorhexidine may increase both VAE and mortality risk. The largest study found significant reductions in duration of intubation with weaning, sedation, and head of bed elevation, as well as reduced mortality risk with weaning and sedation bundle elements. Nonetheless, these studies should be useful in designing future prospective controlled studies to determine what elements of a future prevention bundle might be effective in reducing VAEs. At this juncture, and based on the limited evidence to date, it appears that incorporating daily sedation interruptions and spontaneous breathing trials are the factors most likely to reduce VAEs.

Characteristics of Nonpulmonary Organ Dysfunction at Onset of ARDS Based on the Berlin Definition.

BACKGROUND: The Berlin definition of ARDS does not account for nonpulmonary organ failure, which is a major determinant of outcome. We examined whether an increasing severity of hypoxemia across the Berlin definition classifications also corresponded with evidence of multiple organ dysfunction on the day of ARDS onset. We also examined the representation of major etiologies for ARDS across the Berlin definition classifications. METHODS: This single-center, retrospective study examined 15 years of data from a quality assurance program that monitored the use of lung-protective ventilation in ARDS. We analyzed 1,747 subjects without chronic kidney disease or severe chronic liver disease at ARDS onset. The most abnormal laboratory values at ARDS onset were analyzed as cutoff values to assess organ dysfunction. Data were analyzed by using non-parametric analysis of variance (Kruskall-Wallis test) and the Dunn post test. Categorical variables were compared by using the Fisher exact test. Alpha was set at 0.05. Factors independently associated with mortality were assessed by multivariate logistic regression modeling. RESULTS: Nonpulmonary organ dysfunction was present in at least 1 system at ARDS onset that increased with severity: 80% (mild), 83% (moderate), and 90% (severe). ARDS etiologies varied as severity increased: trauma-associated lung injury steadily decreased, whereas lung injury associated with aspiration and pneumonia steadily increased. Hospital mortality also increased significantly with the Berlin definition classifications: mild (22%), moderate (30%), and severe (47%). Multivariate logistic regression modeling revealed that the Berlin definition of severe ARDS was independently associated with mortality, as were cutoff values for renal and hepatic function as well as acidemia. Normal hematologic function and the absence of standard exclusion criteria used for therapeutic clinical trials in ARDS were protective. CONCLUSIONS: Nonpulmonary organ dysfunction was present at ARDS onset in most subjects and was more pronounced as ARDS severity increased. The Berlin definition classification of ARDS provided an elegant scheme for studying the syndrome because it coincided with increasing multiple organ dysfunction.

Physiologic Analysis and Clinical Performance of the Ventilatory Ratio in Acute Respiratory Distress Syndrome.

RATIONALE: Pulmonary dead space fraction (Vd/Vt) is an independent predictor of mortality in acute respiratory distress syndrome (ARDS). Yet, it is seldom used in practice. The ventilatory ratio is a simple bedside index that can be calculated using routinely measured respiratory variables and is a measure of impaired ventilation. Ventilatory ratio is defined as [minute ventilation (ml/min) × PaCO2 (mm Hg)]/(predicted body weight × 100 × 37.5). OBJECTIVES: To determine the relation of ventilatory ratio with Vd/Vt in ARDS. METHODS: First, in a single-center, prospective observational study of ARDS, we tested the association of Vd/Vt with ventilatory ratio. With in-hospital mortality as the primary outcome and ventilator-free days as the secondary outcome, we tested the role of ventilatory ratio as an outcome predictor. The findings from this study were further verified in secondary analyses of two NHLBI ARDS Network randomized controlled trials. MEASUREMENTS AND MAIN RESULTS: Ventilatory ratio positively correlated with Vd/Vt. Ordinal groups of ventilatory ratio had significantly higher Vd/Vt. Ventilatory ratio was independently associated with increased risk of mortality after adjusting for PaO2/FiO2, and positive end-expiratory pressure (odds ratio, 1.51; P = 0.024) and after adjusting for Acute Physiologic Assessment and Chronic Health Evaluation II score (odds ratio, 1.59; P = 0.04). These findings were further replicated in secondary analyses of two separate NHLBI randomized controlled trials. CONCLUSIONS: Ventilatory ratio correlates well with Vd/Vt 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.