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Editorial |

16 Years and Counting? Time to Implement Noninvasive Screening for ARDS FREE TO VIEW

Angela J. Rogers, MD, MPH; Vincent X. Liu, MD
Author and Funding Information

FUNDING/SUPPORT: A. J. R. is supported by the National Institutes of Health (NIH) [Grant K23HL125663]; V. X. L. is supported by NIH [Grant K23GM112018] and The Permanente Medical Group.

FINANCIAL/NONFINANCIAL DISCLOSURES: None declared.

aDivision of Pulmonary and Critical Care Medicine, Stanford University, Stanford, CA

bDivision of Research, Kaiser Permanente, Oakland, CA

CORRESPONDENCE TO: Vincent X Liu, MD, 2000 Broadway, Oakland, CA 94612


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;150(2):266-267. doi:10.1016/j.chest.2016.03.023
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Published online

Prior studies estimate that it takes 17 years to turn efficacious interventions into effective ones: that is, to turn high-quality research evidence into real-world clinical practice. In the case of ARDS—a major cause of morbidity and mortality in the ICU—it has been exactly 16 years since the ARDS Network convincingly established the benefits of lung-protective ventilation. And, in line with those estimates, we continue to woefully underperform when it comes to identifying patients with ARDS and providing evidence-based care.

FOR RELATED ARTICLE SEE PAGE 307

With contemporary data drawn from more than 500 ICUs in 50 countries, Bellani and colleagues found that ARDS was present in 1 in 10 patients with respiratory failure requiring invasive or noninvasive ventilation, with a mortality rate of nearly 40%. Despite the fact that ARDS was both common and deadly, clinicians failed to recognize the syndrome one in three times. This may be a conservative estimate because patients with respiratory failure on noninvasive ventilation were excluded. Given this lack of recognition, it is perhaps not surprising that efficacious ARDS therapies remained similarly underutilized. This may explain the somewhat jarring gap in ARDS mortality observed in this large sample of patients treated in diverse real-world settings (40%) compared with the 24% to 26% mortality rate seen among patients in recent ARDS clinical trials.

ARDS is acute respiratory failure accompanied by three seemingly straightforward criteria: (1) bilateral infiltrates on chest radiograph, (2) the lack of heart failure, and (3) a Pao2/Fio2 ratio (P:F) of < 300 on at least 5 cm H2O of positive end-expiratory pressure. The P:F ratio both defines the cutoff for the presence of ARDS and classifies ARDS severity, with a P:F ratio < 100 defined as severe, a P:F ratio between 100 and 200 as moderate, and a P:F ratio of 200 to 300 as mild ARDS. These definitions have been in common use for at least two decades with the landmark lung-protective ventilation and conservative fluid management trials enrolling patients with ARDS defined by a P:F ratio < 300 for entry., More recent trials of paralysis and prone positioning used a P:F ratio < 150 to identify patients with more severe disease.,

Thus, although there is no question that the P:F ratio remains central to our framework for understanding, describing, and treating ARDS, are there even simpler ways to evaluate the risk and progression of ARDS in patients with respiratory failure, given our persistent failure to identify and treat them appropriately?

Determining a patient’s P:F ratio still requires an arterial blood gas (ABG) measurement, and as easy as it seems, an ABG may not be obtained among patients in whom ARDS is not suspected. Moreover, the ubiquity of intraarterial catheter placement and frequent ABG measurements has been called into question. Further, as demonstrated by Bellani and colleagues, even when the P:F ratio criteria are met clinicians fail to recognize ARDS, perhaps because of the intermittent infrequency of single P:F ratio values over a day. Given this reality, a move to enhance current practice with ubiquitously available and continuously updated oxygen saturation-based Sao2/Fio2 (S:F) ratios seems highly appealing.

In this issue of CHEST, Brown and colleagues extend prior work by validating a nonlinear method for imputing a P:F ratio based on the S:F ratio in ARDS. They compared the imputed P:F ratio values derived from this equation to those derived from two prior methods including a linear method described by Rice et al. and a log-linear method used by Pandharipande et al. These values were based on data from 707 ARDS patients enrolled in three ARDS trials with an oxygen saturation ≤ 96% on the day of enrollment, placing them on the steepest part of the oxygen dissociation curve where S:F determinations could be calculated most accurately.

While all three methods for calculating the S:F ratio were highly correlated with the P:F ratio (range, 0.88-0.90), the nonlinear method had the lowest rate of error, particularly in patients with a P:F ratio < 150. In the range of a P:F ratio > 300, the nonlinear equation tended to overestimate P:F ratios, although in this range patients do not meet ARDS criteria so this shortcoming is not critical. Even with this seemingly superior approach, categorizing ARDS severity was imperfect. Six percent of patients yielded false-negative results: they had moderate-severe ARDS but were classified as mild using the nonlinear S:F calculation. Nine percent yielded false-positive results: they met the threshold based on S:F calculations but in fact had P:F ratios > 200. Although these rates of misclassification seem small, incorporation of misclassified patients into research studies can lead to underpowered and biased results.

Despite these limitations, the benefits of using S:F ratios to evaluate patients in ARDS research studies are already being established. For example, derived P:F ratios based on S:F ratio calculations have already been shown to be highly associated with actual P:F ratios as well as ARDS outcomes using data from prior ARDS and observational studies. The nonlinear S:F ratio approximation method is also being used as an entry criteria for the new PETAL-ROSE trial of neuromuscular blockade in severe ARDS (Clinicaltrials.gov No.: NCT02509078).

Given its emerging use in ARDS clinical trials, how should we incorporate the S:F ratio into clinical practice? We would argue that anything that alerts clinicians to the potential presence of ARDS is a good thing. Increasing numbers of patients are cared for in ICUs equipped with advanced electronic medical records or physiologic monitors; these could readily be enabled to enhance continuous screening for ARDS based on S:F ratios. Resulting alerting systems that lead to earlier, or any, recognition of ARDS patients are likely to save lives with highly favorable cost-effectiveness, as delays in the use of lung-protective therapy are known to worsen outcomes. Fortunately, Brown and colleagues have established a set of excellent methods to leverage S:F ratio data to further maximize the likelihood that flagged patients truly have the disease. The time is ripe to make use of these ubiquitous data to drive improved ARDS care and make our 17th year a win for patients, clinicians, and researchers alike.

References

Westfall J.M. .Mold J. .Fagnan L. . Practice-based research—“Blue Highways” on the NIH roadmap. JAMA. 2007;297:403-406 [PubMed]journal. [CrossRef] [PubMed]
 
The Acute Respiratory Distress Syndrome Network Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342:1301-1308 [PubMed]journal. [CrossRef] [PubMed]
 
Bellani G. .Laffey J.G. .Pham T. . LUNG SAFE Investigators; ESICM Trials Groupet al Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA. 2016;315:788-800 [PubMed]journal. [CrossRef] [PubMed]
 
Ferguson N.D. .Fan E. .Camporota L. .et al The Berlin definition of ARDS: an expanded rationale, justification, and supplementary material. Intensive Care Med. 2012;38:1573-1582 [PubMed]journal. [CrossRef] [PubMed]
 
Wiedemann H.P. .Wheeler A.P. .Bernard G.R. . National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Networket al Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006;354:2564-2575 [PubMed]journal. [CrossRef] [PubMed]
 
Guérin C. .Reignier J. .Richard J.C. . Prone positioning in the acute respiratory distress syndrome. N Engl J Med. 2013;369:980-981 [PubMed]journal
 
Papazian L. .Forel J.M. .Gacouin A. . ACURASYS Study Investigatorset al Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010;363:1107-1116 [PubMed]journal. [CrossRef] [PubMed]
 
Garland A. .Connors A.F. Jr.. Indwelling arterial catheters in the intensive care unit: necessary and beneficial, or a harmful crutch? Am J Respir Crit Care Med. 2010;182:133-134 [PubMed]journal. [CrossRef] [PubMed]
 
Brown S.M. .Grissom C.K. .Moss M. . NIH/NHLBI PETAL Network Collaboratorset al Non-linear imputation of Pao2/Fio2 from Spo2/Fio2 among patients with acute respiratory distress syndrome. Chest. 2016;150:307-313 [PubMed]journal
 
Rice T.W. .Wheeler A.P. .Bernard G.R. .et al Comparison of the SpO2/FIO2 ratio and the PaO2/FIO2 ratio in patients with acute lung injury or ARDS. Chest. 2007;132:410-417 [PubMed]journal. [CrossRef] [PubMed]
 
Pandharipande P.P. .Shintani A.K. .Hagerman H.E. .et al Derivation and validation of Spo2/Fio2 ratio to impute for Pao2/Fio2 ratio in the respiratory component of the Sequential Organ Failure Assessment score. Crit Care Med. 2009;37:1317-1321 [PubMed]journal. [CrossRef] [PubMed]
 
Copeland K.T. .Checkoway H. .McMichael A.J. .Holbrook R.H. . Bias due to misclassification in the estimation of relative risk. Am J Epidemiol. 1977;105:488-495 [PubMed]journal. [PubMed]
 
Chen W. .Janz D.R. .Shaver C.M. .Bernard G.R. .Bastarache J.A. .Ware L.B. . Clinical characteristics and outcomes are similar in ARDS diagnosed by oxygen saturation/Fio2 ratio compared with Pao2/Fio2 ratio. Chest. 2015;148:1477-1483 [PubMed]journal. [CrossRef] [PubMed]
 
Needham D.M. .Yang T. .Dinglas V.D. .et al Timing of low tidal volume ventilation and intensive care unit mortality in acute respiratory distress syndrome. A prospective cohort study. Am J Respir Crit Care Med. 2015;191:177-185 [PubMed]journal. [CrossRef] [PubMed]
 

Figures

Tables

References

Westfall J.M. .Mold J. .Fagnan L. . Practice-based research—“Blue Highways” on the NIH roadmap. JAMA. 2007;297:403-406 [PubMed]journal. [CrossRef] [PubMed]
 
The Acute Respiratory Distress Syndrome Network Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342:1301-1308 [PubMed]journal. [CrossRef] [PubMed]
 
Bellani G. .Laffey J.G. .Pham T. . LUNG SAFE Investigators; ESICM Trials Groupet al Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA. 2016;315:788-800 [PubMed]journal. [CrossRef] [PubMed]
 
Ferguson N.D. .Fan E. .Camporota L. .et al The Berlin definition of ARDS: an expanded rationale, justification, and supplementary material. Intensive Care Med. 2012;38:1573-1582 [PubMed]journal. [CrossRef] [PubMed]
 
Wiedemann H.P. .Wheeler A.P. .Bernard G.R. . National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Networket al Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006;354:2564-2575 [PubMed]journal. [CrossRef] [PubMed]
 
Guérin C. .Reignier J. .Richard J.C. . Prone positioning in the acute respiratory distress syndrome. N Engl J Med. 2013;369:980-981 [PubMed]journal
 
Papazian L. .Forel J.M. .Gacouin A. . ACURASYS Study Investigatorset al Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010;363:1107-1116 [PubMed]journal. [CrossRef] [PubMed]
 
Garland A. .Connors A.F. Jr.. Indwelling arterial catheters in the intensive care unit: necessary and beneficial, or a harmful crutch? Am J Respir Crit Care Med. 2010;182:133-134 [PubMed]journal. [CrossRef] [PubMed]
 
Brown S.M. .Grissom C.K. .Moss M. . NIH/NHLBI PETAL Network Collaboratorset al Non-linear imputation of Pao2/Fio2 from Spo2/Fio2 among patients with acute respiratory distress syndrome. Chest. 2016;150:307-313 [PubMed]journal
 
Rice T.W. .Wheeler A.P. .Bernard G.R. .et al Comparison of the SpO2/FIO2 ratio and the PaO2/FIO2 ratio in patients with acute lung injury or ARDS. Chest. 2007;132:410-417 [PubMed]journal. [CrossRef] [PubMed]
 
Pandharipande P.P. .Shintani A.K. .Hagerman H.E. .et al Derivation and validation of Spo2/Fio2 ratio to impute for Pao2/Fio2 ratio in the respiratory component of the Sequential Organ Failure Assessment score. Crit Care Med. 2009;37:1317-1321 [PubMed]journal. [CrossRef] [PubMed]
 
Copeland K.T. .Checkoway H. .McMichael A.J. .Holbrook R.H. . Bias due to misclassification in the estimation of relative risk. Am J Epidemiol. 1977;105:488-495 [PubMed]journal. [PubMed]
 
Chen W. .Janz D.R. .Shaver C.M. .Bernard G.R. .Bastarache J.A. .Ware L.B. . Clinical characteristics and outcomes are similar in ARDS diagnosed by oxygen saturation/Fio2 ratio compared with Pao2/Fio2 ratio. Chest. 2015;148:1477-1483 [PubMed]journal. [CrossRef] [PubMed]
 
Needham D.M. .Yang T. .Dinglas V.D. .et al Timing of low tidal volume ventilation and intensive care unit mortality in acute respiratory distress syndrome. A prospective cohort study. Am J Respir Crit Care Med. 2015;191:177-185 [PubMed]journal. [CrossRef] [PubMed]
 
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