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Original Research: Critical Care |

Mechanical Ventilation and ARDS in the EDMechanical Ventilation and ARDS in the ED: A Multicenter, Observational, Prospective, Cross-sectional Study FREE TO VIEW

Brian M. Fuller, MD; Nicholas M. Mohr, MD; Christopher N. Miller, MD; Andrew R. Deitchman, MD; Brian J. Levine, MD; Nicole Castagno, MS; Elizabeth C. Hassebroek, MD; Adam Dhedhi, BA; Nicholas Scott-Wittenborn, BA; Edward Grace; Courtney Lehew, MD; Marin H. Kollef, MD, FCCP
Author and Funding Information

From the Department of Emergency Medicine (Drs Fuller and Lehew) and the Department of Anesthesiology (Dr Fuller), Division of Critical Care, and the Department of Medicine (Dr Kollef), Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine in St. Louis, MO; the Departments of Emergency Medicine and Anesthesiology (Dr Mohr), Division of Critical Care, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA; the Department of Emergency Medicine (Dr Miller), University of Cincinnati Medical Center, Cincinnati, OH; the Department of Emergency Medicine (Drs Deitchman and Levine), Christiana Care Health System, Newark, DE; the University of Michigan Medical School (Ms Castagno), Ann Arbor, MI; the Department of Critical Care Medicine (Dr Hassebroek), Mayo Clinic, Rochester, MN; Saint Louis University School of Medicine (Mr Dhedhi), St. Louis, MO; Washington University in St. Louis (Mr Scott-Wittenborn), St. Louis, MO; and Middlebury College (Mr Grace), Middlebury, VT.

CORRESPONDENCE TO: Brian M. Fuller, MD, Departments of Emergency Medicine and Anesthesiology, Division of Critical Care, Washington University School of Medicine in St. Louis, 660 S Euclid Ave, Campus Box 8072, St. Louis, MO 63110; e-mail: fullerb@wusm.wustl.edu


FUNDING/SUPPORT: Dr Fuller was supported by an Emergency Medicine Grant-in-Aid from the Department of Emergency Medicine, Washington University School of Medicine in St. Louis, and by the KL2 Career Development Award. Dr Mohr was supported by the Emergency Medicine Foundation Research Fellowship. Ms Castagno was funded by the University of Cincinnati Department of Emergency Medicine. Mr Grace was supported by the ASPIRE Program at Washington University in St. Louis. Dr Kollef was supported by the Barnes Jewish Hospital Foundation. This publication was supported by the Washington University Institute of Clinical and Translational Sciences [Grants UL1 TR000448 and KL2 TR000450] from the National Center for Advancing Translational Sciences.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;148(2):365-374. doi:10.1378/chest.14-2476
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BACKGROUND:  There are few data regarding mechanical ventilation and ARDS in the ED. This could be a vital arena for prevention and treatment.

METHODS:  This study was a multicenter, observational, prospective, cohort study aimed at analyzing ventilation practices in the ED. The primary outcome was the incidence of ARDS after admission. Multivariable logistic regression was used to determine the predictors of ARDS.

RESULTS:  We analyzed 219 patients receiving mechanical ventilation to assess ED ventilation practices. Median tidal volume was 7.6 mL/kg predicted body weight (PBW) (interquartile range, 6.9-8.9), with a range of 4.3 to 12.2 mL/kg PBW. Lung-protective ventilation was used in 122 patients (55.7%). The incidence of ARDS after admission from the ED was 14.7%, with a mean onset of 2.3 days. Progression to ARDS was associated with higher illness severity and intubation in the prehospital environment or transferring facility. Of the 15 patients with ARDS in the ED (6.8%), lung-protective ventilation was used in seven (46.7%). Patients who progressed to ARDS experienced greater duration in organ failure and ICU length of stay and higher mortality.

CONCLUSIONS:  Lung-protective ventilation is infrequent in patients receiving mechanical ventilation in the ED, regardless of ARDS status. Progression to ARDS is common after admission, occurs early, and worsens outcome. Patient- and treatment-related factors present in the ED are associated with ARDS. Given the limited treatment options for ARDS, and the early onset after admission from the ED, measures to prevent onset and to mitigate severity should be instituted in the ED.

TRIAL REGISTRY:  ClinicalTrials.gov; No.: NCT01628523; URL: www.clinicaltrials.gov

Figures in this Article

The frequency of critically ill patients in the ED and the severity of illness have increased.1 The need for mechanical ventilation is one of the most common indications for ICU admission and has also increased in incidence.2,3 Initiation of mechanical ventilation in the ED is common, and because of the long ED length of stays (LOSs) for critically ill patients, mechanical ventilation hours provided have also increased.413 Despite these trends, there remain relatively few data on ED-based mechanical ventilation practices.14

ARDS exacts a significant toll on patients who are mechanically ventilated in terms of mortality, long-term survivor morbidity, and health-care use.15,16 Compared with those in the ICU, ARDS data in the ED population are sparse. The ED prevalence of ARDS and knowledge of the early factors that may promote its development and modify its severity are incomplete. Observational studies indicate an ARDS prevalence of approximately 9% in patients receiving mechanical ventilation in the ED.14,17,18 Most of these data, however, are restricted to a narrow cohort of patients (ie, those with sepsis) and are single-center investigations.

In patients with ARDS, unequivocal data exist that harmful ventilator settings cause ventilator-associated lung injury (VALI) and worsen outcome.1921 In patients without ARDS but at risk of the syndrome, there are mounting data to suggest that the mechanical ventilator contributes to ARDS development.2231 Most relevant to the ED, the pathophysiology triggered by VALI can occur within hours, and progression to ARDS in at-risk patients typically occurs shortly after admission.29,3235 We hypothesize that modifiable patient characteristics and treatment variables can influence clinical outcome during this most proximal time window. In the future, the ED could, therefore, be a vital arena for the treatment and clinical investigation of patients who are mechanically ventilated to (1) further refine predictive variables of outcome, (2) improve the quality of mechanical ventilation delivered during the early stages of respiratory failure, (3) decrease the incidence of ARDS, and (4) decrease mortality and long-term survivor morbidity.

The objectives of this study were to (1) further characterize ED mechanical ventilation practices, (2) determine the incidence of ARDS after admission and the risk factors associated with this outcome, (3) determine the prevalence of ARDS in the ED and assess ED compliance with lung-protective ventilation, and (4) assess outcome differences between patients with ARDS and those without ARDS.

This was a multicenter, prospective, observational, cross-sectional study conducted at four academic EDs. For each center, data were collected during four temporally distinct 1-month time periods (July 10, 2012, to August 10, 2012; September 1, 2012, to October 2, 2012; January 21, 2013, to February 22, 2013; and July 2, 2013, to August 3, 2013). The study, therefore, spanned a total of 13 months. This observational study is reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for Reporting Observational Studies.36 The institutional review boards at each site approved the study under waiver of informed consent (e-Appendix 1).

Eligible patients were all patients receiving mechanical ventilation in the ED and aged ≥ 18 years. Exclusion criteria were as follows: (1) death in the ED, (2) ED LOS < 1 h, (3) total mechanical ventilation duration < 1 h, and (4) elective extubation while in the ED. To ensure uniform data collection and accuracy, all variables were defined a priori and were recorded in a standardized format during the data collection process.

The baseline patient characteristics included age, sex, race, weight, height, predicted body weight (PBW), BMI, ED LOS, patient comorbidities, home medications, vital signs, hemodynamics, and laboratory values. Modified APACHE (Acute Physiology and Chronic Health Evaluation) II and Sequential Organ Failure Assessment (SOFA) scores and the Lung Injury Prediction Score (LIPS) were determined.3741 PBW in kilograms was calculated according to the following formula: men, 50 + 2.3 (height [inches] – 60); women, 45.5 + 2.3 (height [inches] – 60).42 Process of care variables in the ED (IV fluid, blood products, etc) were collected, as were all ventilator-related variables. All these data were collected prospectively by research assistants and principal investigators (PIs) at each site.

Definitions

Definitions of comorbid conditions are provided in e-Appendix 2. Severe sepsis and septic shock were defined as described previously.43,44 Lung-protective ventilation was defined as the use of tidal volume of < 8 mL/kg PBW, because this was the upper limit of tidal volume allowed by previous investigations of low tidal volume ventilation in ARDS.19 We did not include a pressure limit to define lung protective, because previous data suggest monitoring of inspiratory plateau pressure is rare in intubated patients in the ED.14

Outcomes

All patients were analyzed for ED mechanical ventilation practices. The primary outcome variable of interest was the development of ARDS after admission, and it was defined according to the Berlin definition.45 It was assessed by site PIs at least once daily (based on frequency of chest radiographs and arterial blood gas measurements). Given the focus of this investigation on ED-based factors associated with ARDS development, and data suggesting that the majority of ARDS cases develop in the first 5 days after admission, assessment of the primary outcome was restricted to day 5 after ICU admission (or death if occurring prior to day 5).40 In patients without an arterial blood gas measurement, the oxygenation criteria was determined using the pulse oximeter to Fio2 ratio as described previously.46 When more than one value was present, the worst value was selected.

A detailed description of our standard operating procedure for adjudicating ARDS status is provided in e-Appendix 3. Secondary analyses of interest included clinical outcome differences between patients with ARDS and those without ARDS. These outcomes were assessed daily by research assistants and site PIs until hospital discharge.

Analysis

Descriptive statistics, including mean ± SD, median (interquartile range [IQR]), and frequency distributions were used to assess the characteristics of the patient cohort. The Spearman correlation coefficient (r) was used to assess the relationship between ED and ICU tidal volume. To assess predictors of progression to ARDS, continuous and categorical variables were compared using an unpaired t test, Wilcoxon test, χ2 test, or Fisher exact test, as appropriate. Variables that were statistically significant in univariate analyses at a P ≤ .10 level were candidates for inclusion in a bidirectional, stepwise, multivariable logistic regression analysis. The stepwise regression method selected variables for inclusion or exclusion from the model in a sequential fashion based on the significance level of .10 for entry and .15 for removal. Statistical interactions and collinearity were assessed. The model used variables that contributed information that was statistically independent of the other variables in the model. The model’s goodness of fit was assessed with the Hosmer-Lemeshow test. Adjusted ORs and corresponding 95% CIs are reported for variables in the multivariable model, adjusted for all variables in the model. To assess clinical outcomes based on ARDS status, χ2 and Kruskal-Wallis tests were used to compare groups. The Kaplan-Meier method was used to compare mortality difference. All tests were two-tailed, and a P value < .05 was considered statistically significant. A sample size calculation was not performed a priori, because the primary analysis was descriptive and was to further characterize mechanical ventilation in the ED. Based on previous existing data, our sample size was recognized as likely to be adequate for investigation of ED-based parameters associated with progression to ARDS.14,47 The analysis was conducted in consultation with a biostatistician.

Characteristics of Study Subjects

A total of 259 patients received mechanical ventilation in the ED during the study period (Fig 1); the final study population totaled 219 patients. All patients were assessed for mechanical ventilation practices and clinical outcomes. Fifteen patients (6.8%) had ARDS while in the ED and were excluded from the analysis of risk factors for ARDS progression after ED admission. Table 1 shows the baseline characteristics of the study population. For the entire cohort, the median ED LOS was 3.4 h (IQR, 2.2-5.4 h), with a range of 1.1 to 18.3 h.

Figure Jump LinkFigure 1 –  Flow diagram depicting the patients analyzed to achieve each objective of the study. LOS = length of stay; MV = mechanical ventilation.Grahic Jump Location
Table Graphic Jump Location
TABLE 1 ]  Characteristics of Patients Receiving Mechanical Ventilation in the ED

Variables are reported as No. (%), mean ± SD, or median (interquartile range). APACHE = Acute Physiology and Chronic Health Evaluation; CHF = congestive heart failure; CKD = chronic kidney disease; DBP = diastolic BP; H2 = histamine-2 receptor; HR = heart rate; INR = international normalized ratio; LIPS = Lung Injury Prediction Score; LOS = length of stay; PBW = predicted body weight; PPI = proton pump inhibitor; RR = respiratory rate; SBP = systolic BP; SOFA = Sequential Organ Failure Assessment; Spo2 = pulse oximetry.

a 

Modified score, which excludes Glasgow Coma Scale.

b 

Refers to the 77 patients who received antibiotics while in the ED.

Ventilator Characteristics

Ventilator variables are presented in Table 2. The preferred mode of ventilation across centers was assist-control, volume-control ventilation (65.3%). The median tidal volume delivered was 7.6 mL/kg PBW (IQR, 6.9-8.9 mL/kg PBW), with a range of 4.3-12.2 mL/kg PBW. Figure 2 shows the distribution of tidal volume in the ED. Lung-protective ventilation was used in 122 patients (55.7%), and 25 patients (11.4%) were ventilated with a tidal volume > 10 mL/kg PBW. Of the 97 patients ventilated with non-lung-protective ventilation in the ED, 31 (32%) had their settings changed to protective settings upon ICU arrival. ED tidal volume was significantly correlated to ICU tidal volume (rs = 0.60, P < .001 ). In the subgroup of patients exposed to non-lung-protective ventilator while in the ED, ED tidal volume remained significantly correlated to ICU tidal volume (rs = 0.46, P < .001). Inspiratory plateau pressure was recorded in 78 patients (35.6%). At least one ventilator parameter was changed in 150 patients (68.5%) during their ED stay. The head of bed was elevated in 79 patients (36.1%) while receiving mechanical ventilation in the ED.

Table Graphic Jump Location
TABLE 2 ]  Ventilator Variables and Care in the ED

Variables are reported as No. (%), mean ± SD, or median (interquartile range). There was no significant difference in any variable when comparing patients with ARDS in the ED and those without ARDS in the ED. AC = assist control; PC = pressure control; PEEP = positive end-expiratory pressure; SIMV = synchronized intermittent mandatory ventilation; VC = volume controlled. See Table 1 for expansion of other abbreviation.

Figure Jump LinkFigure 2 –  Delivered Vt in the ED. Of the 219 patients mechanically ventilated in the ED, 122 (55.7%) received lung-protective ventilation (< 8 mL/kg PBW) and 25 (11.4%) were ventilated with a tidal volume > 10 mL/kg PBW. PBW = predicted body weight; Vt = tidal volume.Grahic Jump Location
Analysis of ARDS

The incidence of ARDS after admission from the ED was 14.7% (n = 30), with a mean ± SD onset of 2.3 ± 1.2 days (Fig 3). There were no differences in the ED ventilator variables in these patients (Table 2). Multivariable logistic regression analysis demonstrated that higher ED APACHE II scores and LIPS were associated with progression to ARDS, as was a higher SOFA score (persistent organ failure) on ICU day 2. Intubation occurring prehospital or from a transferring facility was associated with an increased risk of ARDS compared with ED intubation (Table 3).

Figure Jump LinkFigure 3 –  Hospital d 0 refers to the ED. Incidence of ARDS represents the development of new cases of ARDS on an individual hospital day (eg, seven new cases of ARDS development on hospital d 2). Prevalence of ARDS represents the total number of ARDS cases present on an individual hospital d, excluding those cases experiencing death.Grahic Jump Location
Table Graphic Jump Location
TABLE 3 ]  Multivariate Analysis for Factors Associated With Development of ARDS

aOR = adjusted OR. See Table 1 for expansion of other abbreviations.

a 

Refers to intubation in the ED vs prehospital/transferring facility.

Fifteen patients (6.8%) had ARDS during their stay in the ED. Median tidal volume was 8.2 mL/kg PBW (IQR, 7.2-9.0 mL/kg PBW), compared with 7.6 mL/kg PBW (IQR, 6.9-8.9 mL/kg PBW) in patients without ARDS (P = .37). Lung-protective ventilation was used in seven patients with ARDS (46.7%). Inspiratory plateau pressure was monitored in six patients with ARDS in the ED (40%). Exposure to Fio2 of 1.0 in patients with ARDS in the ED was 99.0 min (IQR, 60-198 min) compared with 43.5 min (IQR, 0-117.0 min) in patients without ARDS in the ED. Compared with patients without ARDS, patients who progressed to ARDS experienced a greater duration of organ failure and ICU LOS, and higher mortality (Fig 4, Table 4).

Figure Jump LinkFigure 4 –  Probability of survival to hospital discharge in patients mechanically ventilated in the ED.Grahic Jump Location
Table Graphic Jump Location
TABLE 4 ]  Clinical Outcomes Comparing All Patients Who Progressed to ARDS With Those With No ARDS Progression

Variables are reported as mean ± SD unless indicated otherwise. Δ refers to the change in SOFA score from ED baseline to 48 h. A negative value reflects an improvement in organ function. HLOS = hospital length of stay. See Table 1 for expansion of other abbreviations.

Our first objective was to characterize further the use of mechanical ventilation in the ED across a heterogeneous patient population in multiple centers. To summarize, based on our analysis, mechanical ventilation in the ED is delivered using (1) higher than recommended tidal volumes and infrequent lung-protective ventilation regardless of ARDS status, (2) high Fio2 and low positive end-expiratory pressure, (3) infrequent monitoring of inspiratory plateau pressure, and (4) the supine, flat position.

Previous work in patients with severe sepsis and septic shock (database from 2005 to 2010) showed a median tidal volume of 8.8 mL/kg PBW (IQR, 7.8-10.0 mL/kg PBW), ranging as high as 14.6 mL/kg PBW.14 The current investigation shows a decrease of about 1 mL/kg PBW and overall less variability in practice. However, a significant percentage of patients remain exposed to high tidal volumes while in the ED. Based on three systematic reviews and meta-analyses, non-lung-protective ventilation seems to be associated with VALI and the development of ARDS.29,31,48

Our results highlight the infrequency with which positive end-expiratory pressure is titrated in the ED, in favor of delivery of high levels of oxygen. Increasing evidence suggests excessive oxygen exposure has adverse effects in various conditions, such as cardiac arrest, ARDS, COPD, and acute myocardial infarction.4953 Providing an optimal environment for lung protection, however, probably requires attention to not only tidal volume, but also appropriate lung recruitment and oxygen exposure.

Only one-third of the study cohort had their head of bed elevated while undergoing mechanical ventilation in the ED. Supine head position during the first 24 h of mechanical ventilation is an independent risk factor for pneumonia.54 This is an immediately modifiable process of care variable that could reduce complications in patients receiving mechanical ventilation admitted from the ED.

Prior work showed an ARDS prevalence of 8.8% in patients receiving mechanical ventilation with severe sepsis in the ED and septic shock.14 This current investigation of a heterogeneous ED population demonstrated an ARDS prevalence of 6.8%, which is similar to the findings of work examining ARDS in patients receiving mechanical ventilation in the ED.14,17,18 Combining data from these studies provides some epidemiologic insight into an ED ARDS prevalence of approximately 8.4% in intubated patients. As in previous work, adherence to lung-protective ventilation in patients with ARDS was low (46.7%). With a conservative estimate of 240,000 patients who receive ED mechanical ventilation annually, the sheer number of patients exposed to potentially harmful ventilation presents an opportunity to reexamine clinical practice and to study these patients further.6

VALI and ARDS can evolve quickly.22,24,26,32,33,47,55,56 The ED represents a period of early critical illness during which protective interventions can influence the complications of critical illness.57 However, our data cannot answer the question of whether altering ED ventilator practices will decrease ARDS or mitigate its severity, and our study did not show any association with ventilator variables and incidence of ARDS.57,58 This may indicate that our study was underpowered to detect a small difference that does exist, that there is a true lack of association between ED ventilator management and downstream complications, or that the ED exposure is too short to impact the outcome. However, our data do suggest that ED tidal volume settings influence those delivered in the ICU. This remained true for patients exposed to non-lung-protective ventilation in the ED and suggests that even suboptimal ventilator settings were continued forth into early ICU care. Furthermore, although tidal volume often exceeded 8 mL/kg PBW, rarely did it exceed the levels shown in prior trials to be injurious in patients with established ARDS (ie, 12 mL/kg PBW) or at risk of the syndrome (ie, 10 mL/kg PBW [11.4% of patients in this study]).19,25 Therefore, in a study of this size, deviations of this magnitude may not be enough to cause a measurable clinical difference, both in terms of ARDS mortality and ARDS development. A lack of association between ventilator variables and ARDS incidence may also reflect the fact that the cause of ARDS is heterogeneous; the most appropriate ED intervention may be a bundled, quality-based approach to address ventilator and nonventilator treatments.57

The incidence of ARDS development in this heterogeneous cohort was 14.7%; a previous investigation of patients with severe sepsis and septic shock (perhaps the highest risk cohort for ARDS) showed an ARDS incidence of 27.5% after ED admission.14 This provides further evidence that ARDS prevention strategies should be considered a priority in emergency research and quality initiatives. Clinical ARDS research has historically been confined to the ICU, but as additional preventive therapies are proposed, ED-based trials will be critical to treat high-risk patients early in the course of disease. The results of our multivariable analysis coincide with the findings of prior research and suggest that these high-risk patients are identified by higher illness severity scores (APACHE II) and LIPS.40 Our results also suggest that two potential non-ventilator-related variables could be targets for future ARDS prevention: reversal of early organ failure and prehospital intubation.

This study has important limitations. This was a cross-sectional study conducted over a single time period (ie, 1 month) at each center. ED mechanical ventilation practice patterns and incidence of ARDS may vary in association with seasonal respiratory illnesses such as H1N1 influenza. However, there is a lack of data to support seasonal variation of ARDS, and our study months were temporally distinct and varied seasonally across centers. This temporal distribution offers some assurance that our data represent a national longitudinal sample.59

This was a relatively small study and, therefore, prone to random error. However, our results are consistent with prior evidence. This study was restricted to academic medical centers. It is, therefore, possible that these data are not truly representative of ED-based mechanical ventilation practices and ARDS prevalence in the community as a whole. The multicenter trial design, consistency with the small amount of previously published data, and inclusion of all mechanically ventilated patients do improve the external validity of our results.

Adjudicating ARDS status can be difficult and will always have a subjective component. This potentially exposes the study to ascertainment bias. Our adjudication protocol was systematic, rigorous, and objective. Our event rate for ARDS was also consistent with that of previous investigations. We are, therefore, confident that we adjudicated the syndrome accurately for the purposes of this investigation.

Finally, the trained research assistants played no role in the clinical care of the patients, and the physicians were unaware of our study hypotheses. However, the possibility that the presence of bedside research assistants influenced clinical care and ventilator settings cannot be excluded completely (ie, Hawthorne-like effect). Our findings, particularly suboptimal adherence to best-practice guidelines such as protective lung ventilation strategies and head-of-bed elevation, speak against this possibility.

This multicenter study of patients with respiratory failure in the ED demonstrates a significant opportunity to improve ED-based mechanical ventilation practices. This includes delivery of lung-protective ventilation, monitoring of inspiratory plateau pressure, and head-of-bed elevation. Across a heterogeneous intubated population in the ED, progression to ARDS is a common occurrence, occurs early after ICU admission, and leads to significant negative clinical consequences. Modifiable patient- and treatment-related variables exist that could prevent or mitigate ARDS severity, and the ED and prehospital environments should be investigated further.

Author contributions: B. M. F. takes responsibility for the content of the manuscript, including the data and analysis, and is the guarantor of this study. B. M. F. contributed to the conception and design of the study, obtaining of research funding, supervision of the conduct of the trial, data management, ARDS adjudication as a referee, and analysis and interpretation of data; N. M. M. contributed to the design of the study, supervision of the conduct of the trial, management, analysis, and interpretation of data, and ARDS adjudication as a referee; C. N. M. contributed to the supervision of the conduct of the trial, management, analysis, and interpretation of data, patient recruitment, and ARDS adjudication as a referee; A. R. D. and B. J. L. contributed to the supervision of the conduct of the trial, collection, management, analysis, and interpretation of data, recruitment of patients, and ARDS adjudication as referees; N. C. , E. C. H., A. D., N. S.-W., E. G., and C. L. contributed to the recruitment of patients and the collection, management, analysis, and interpretation of data; M. H. K. contributed to the conception and design of the study and analysis and interpretation of data; and all authors contributed to the drafting of the manuscript, revision of the manuscript, and approval of the final version.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Role of sponsors: The funding sources played no role in the design, conduct, analysis, or interpretation of these data, and played no role in the drafting, revision, or submission of the manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or any of the other supporting bodies.

Other contributions: The authors acknowledge the following people: Karen Steger-May, MA, from the Division of Biostatistics, Washington University in St. Louis, for assistance with the statistical analysis of these data and Lucas Allen Strakowski; John Collier; Bryan English; Brett Faine, PharmD; Courtney Hancock; Willis Hong; Frank Jareczek; Alycia Karsjens; Ashley Mills; Mackenzie Moore; Laura Nielsen; Angela Ohrt; Randi Ryan; Dena Sult; and Kelsey Winnike for assistance with data collection and entry. Dr Fuller acknowledges Brad Echols for a lifetime of friendship and support.

Additional information: The e-Appendixes can be found in the Supplemental Materials section of the online article.

APACHE

Acute Physiology and Chronic Health Evaluation

IQR

interquartile range

LIPS

Lung Injury Prediction Score

LOS

length of stay

PBW

predicted body weight

PI

principal investigator

SOFA

Sequential Organ Failure Assessment

VALI

ventilator-associated lung injury

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Gajic O, Frutos-Vivar F, Esteban A, Hubmayr RD, Anzueto A. Ventilator settings as a risk factor for acute respiratory distress syndrome in mechanically ventilated patients. Intensive Care Med. 2005;31(7):922-926. [CrossRef] [PubMed]
 
Jia X, Malhotra A, Saeed M, Mark RG, Talmor D. Risk factors for ARDS in patients receiving mechanical ventilation for > 48 h. Chest. 2008;133(4):853-861. [CrossRef] [PubMed]
 
Determann RM, Royakkers A, Wolthuis EK, et al. Ventilation with lower tidal volumes as compared with conventional tidal volumes for patients without acute lung injury: a preventive randomized controlled trial. Crit Care. 2010;14(1):R1. [CrossRef] [PubMed]
 
Mascia L, Zavala E, Bosma K, et al; Brain IT group. High tidal volume is associated with the development of acute lung injury after severe brain injury: an international observational study. Crit Care Med. 2007;35(8):1815-1820. [CrossRef] [PubMed]
 
Pasero D, Davi A, Guerriero F, Rana N, Merigo G, Mastromauro I, Viberti S, Mascia L, Rinaldi M, Ranieri M. High tidal volume as an independent risk factor for acute lung injury after cardiac surgery. Intensive Care Med. 2008;34(suppl 1):0398.
 
Yilmaz M, Keegan MT, Iscimen R, et al. Toward the prevention of acute lung injury: protocol-guided limitation of large tidal volume ventilation and inappropriate transfusion. Crit Care Med. 2007;35(7):1660-1666. [CrossRef] [PubMed]
 
Fuller BM, Mohr NM, Drewry AM, Carpenter CR. Lower tidal volume at initiation of mechanical ventilation may reduce progression to acute respiratory distress syndrome: a systematic review. Crit Care. 2013;17(1):R11. [CrossRef] [PubMed]
 
Futier E, Constantin J-M, Paugam-Burtz C, et al; IMPROVE Study Group. A trial of intraoperative low-tidal-volume ventilation in abdominal surgery. N Engl J Med. 2013;369(5):428-437. [CrossRef] [PubMed]
 
Serpa Neto A, Cardoso SO, Manetta JA, et al. Association between use of lung-protective ventilation with lower tidal volumes and clinical outcomes among patients without acute respiratory distress syndrome: a meta-analysis. JAMA. 2012;308(16):1651-1659. [CrossRef] [PubMed]
 
Muscedere JG, Mullen JB, Gan K, Slutsky AS. Tidal ventilation at low airway pressures can augment lung injury. Am J Respir Crit Care Med. 1994;149(5):1327-1334. [CrossRef] [PubMed]
 
Tremblay L, Valenza F, Ribeiro SP, Li J, Slutsky AS. Injurious ventilatory strategies increase cytokines and c-fos m-RNA expression in an isolated rat lung model. J Clin Invest. 1997;99(5):944-952. [CrossRef] [PubMed]
 
Dreyfuss D, Soler P, Basset G, Saumon G. High inflation pressure pulmonary edema. Respective effects of high airway pressure, high tidal volume, and positive end-expiratory pressure. Am Rev Respir Dis. 1988;137(5):1159-1164. [CrossRef] [PubMed]
 
Webb HH, Tierney DF. Experimental pulmonary edema due to intermittent positive pressure ventilation with high inflation pressures. Protection by positive end-expiratory pressure. Am Rev Respir Dis. 1974;110(5):556-565. [PubMed]
 
von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med. 2007;147(8):573-577. [CrossRef] [PubMed]
 
Vincent JL, Angus DC, Artigas A, et al; Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) Study Group. Effects of drotrecogin alfa (activated) on organ dysfunction in the PROWESS trial. Crit Care Med. 2003;31(3):834-840. [CrossRef] [PubMed]
 
Vincent JL, de Mendonça A, Cantraine F, et al. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on “sepsis-related problems” of the European Society of Intensive Care Medicine. Crit Care Med. 1998;26(11):1793-1800. [CrossRef] [PubMed]
 
Vincent JL, Moreno R, Takala J, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22(7):707-710. [CrossRef] [PubMed]
 
Gajic O, Dabbagh O, Park PK, et al; US Critical Illness and Injury Trials Group: Lung Injury Prevention Study Investigators (USCIITG-LIPS). Early identification of patients at risk of acute lung injury: evaluation of lung injury prediction score in a multicenter cohort study. Am J Respir Crit Care Med. 2011;183(4):462-470. [CrossRef] [PubMed]
 
Hou PC, Elie-Turenne MC, Mitani A, et al. Towards prevention of acute lung injury: frequency and outcomes of emergency department patients at-risk—a multicenter cohort study. Int J Emerg Med. 2012;5(1):22. [CrossRef] [PubMed]
 
Predicted body weight calculator. NHLBI ARDS Network website. http://www.ardsnet.org/node/77460. Accessed January 2, 2014.
 
Bone RC, Balk RA, Cerra FB, et al; The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest. 1992;101(6):1644-1655. [CrossRef] [PubMed]
 
Levy MM, Fink MP, Marshall JC, et al; International Sepsis Definitions Conference. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care Med. 2003;29(4):530-538. [CrossRef] [PubMed]
 
Ranieri VM, Rubenfeld GD, Thompson BT, et al; ARDS Definition Task Force. Acute respiratory distress syndrome: the Berlin definition. JAMA. 2012;307(23):2526-2533. [PubMed]
 
Rice TW, Wheeler AP, Bernard GR, Hayden DL, Schoenfeld DA, Ware LB; National Institutes of Health, National Heart, Lung, and Blood Institute ARDS Network. Comparison of the Spo2/Fio2ratio and the Pao2/Fio2ratio in patients with acute lung injury or ARDS. Chest. 2007;132(2):410-417. [CrossRef] [PubMed]
 
Iscimen R, Cartin-Ceba R, Yilmaz M, et al. Risk factors for the development of acute lung injury in patients with septic shock: an observational cohort study. Crit Care Med. 2008;36(5):1518-1522. [CrossRef] [PubMed]
 
Serpa Neto A, Simonis FD, Barbas CS, et al. Association between tidal volume size, duration of ventilation, and sedation needs in patients without acute respiratory distress syndrome: an individual patient data meta-analysis. Intensive Care Med. 2014;40(7):950-970. [CrossRef] [PubMed]
 
Austin MA, Wills KE, Blizzard L, Walters EH, Wood-Baker R. Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial. BMJ. 2010;341:c5462. [CrossRef] [PubMed]
 
Kilgannon JH, Jones AE, Parrillo JE, et al; Emergency Medicine Shock Research Network (EMShockNet) Investigators. Relationship between supranormal oxygen tension and outcome after resuscitation from cardiac arrest. Circulation. 2011;123(23):2717-2722. [CrossRef] [PubMed]
 
Kilgannon JH, Jones AE, Shapiro NI, et al; Emergency Medicine Shock Research Network (EMShockNet) Investigators. Association between arterial hyperoxia following resuscitation from cardiac arrest and in-hospital mortality. JAMA. 2010;303(21):2165-2171. [CrossRef] [PubMed]
 
Rachmale S, Li G, Wilson G, Malinchoc M, Gajic O. Practice of excessive F(IO(2)) and effect on pulmonary outcomes in mechanically ventilated patients with acute lung injury. Respir Care. 2012;57(11):1887-1893. [CrossRef] [PubMed]
 
Wijesinghe M, Perrin K, Ranchord A, Simmonds M, Weatherall M, Beasley R. Routine use of oxygen in the treatment of myocardial infarction: systematic review. Heart. 2009;95(3):198-202. [CrossRef] [PubMed]
 
Kollef MH. Ventilator-associated pneumonia. A multivariate analysis. JAMA. 1993;270(16):1965-1970. [CrossRef] [PubMed]
 
Kahn JM, Caldwell EC, Deem S, Newell DW, Heckbert SR, Rubenfeld GD. Acute lung injury in patients with subarachnoid hemorrhage: incidence, risk factors, and outcome. Crit Care Med. 2006;34(1):196-202. [CrossRef] [PubMed]
 
Pasero D, Davi A., Guerriero F., et al. High tidal volume as an independent risk factor for acute lung injury after cardiac surgery. Intensive Care Med. 2008 2008;34(suppl 1):0398.
 
Fuller BM, Mohr NM, Hotchkiss RS, Kollef MH. Reducing the burden of acute respiratory distress syndrome: the case for early intervention and the potential role of the emergency department. Shock. 2014;41(5):378-387. [CrossRef] [PubMed]
 
Spragg RG, Bernard GR, Checkley W, et al. Beyond mortality: future clinical research in acute lung injury. Am J Respir Crit Care Med. 2010;181(10):1121-1127. [CrossRef] [PubMed]
 
Bersten AD, Edibam C, Hunt T, Moran J; Australian and New Zealand Intensive Care Society Clinical Trials Group. Incidence and mortality of acute lung injury and the acute respiratory distress syndrome in three Australian States. Am J Respir Crit Care Med. 2002;165(4):443-448. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1 –  Flow diagram depicting the patients analyzed to achieve each objective of the study. LOS = length of stay; MV = mechanical ventilation.Grahic Jump Location
Figure Jump LinkFigure 2 –  Delivered Vt in the ED. Of the 219 patients mechanically ventilated in the ED, 122 (55.7%) received lung-protective ventilation (< 8 mL/kg PBW) and 25 (11.4%) were ventilated with a tidal volume > 10 mL/kg PBW. PBW = predicted body weight; Vt = tidal volume.Grahic Jump Location
Figure Jump LinkFigure 3 –  Hospital d 0 refers to the ED. Incidence of ARDS represents the development of new cases of ARDS on an individual hospital day (eg, seven new cases of ARDS development on hospital d 2). Prevalence of ARDS represents the total number of ARDS cases present on an individual hospital d, excluding those cases experiencing death.Grahic Jump Location
Figure Jump LinkFigure 4 –  Probability of survival to hospital discharge in patients mechanically ventilated in the ED.Grahic Jump Location

Tables

Table Graphic Jump Location
TABLE 1 ]  Characteristics of Patients Receiving Mechanical Ventilation in the ED

Variables are reported as No. (%), mean ± SD, or median (interquartile range). APACHE = Acute Physiology and Chronic Health Evaluation; CHF = congestive heart failure; CKD = chronic kidney disease; DBP = diastolic BP; H2 = histamine-2 receptor; HR = heart rate; INR = international normalized ratio; LIPS = Lung Injury Prediction Score; LOS = length of stay; PBW = predicted body weight; PPI = proton pump inhibitor; RR = respiratory rate; SBP = systolic BP; SOFA = Sequential Organ Failure Assessment; Spo2 = pulse oximetry.

a 

Modified score, which excludes Glasgow Coma Scale.

b 

Refers to the 77 patients who received antibiotics while in the ED.

Table Graphic Jump Location
TABLE 2 ]  Ventilator Variables and Care in the ED

Variables are reported as No. (%), mean ± SD, or median (interquartile range). There was no significant difference in any variable when comparing patients with ARDS in the ED and those without ARDS in the ED. AC = assist control; PC = pressure control; PEEP = positive end-expiratory pressure; SIMV = synchronized intermittent mandatory ventilation; VC = volume controlled. See Table 1 for expansion of other abbreviation.

Table Graphic Jump Location
TABLE 3 ]  Multivariate Analysis for Factors Associated With Development of ARDS

aOR = adjusted OR. See Table 1 for expansion of other abbreviations.

a 

Refers to intubation in the ED vs prehospital/transferring facility.

Table Graphic Jump Location
TABLE 4 ]  Clinical Outcomes Comparing All Patients Who Progressed to ARDS With Those With No ARDS Progression

Variables are reported as mean ± SD unless indicated otherwise. Δ refers to the change in SOFA score from ED baseline to 48 h. A negative value reflects an improvement in organ function. HLOS = hospital length of stay. See Table 1 for expansion of other abbreviations.

References

Herring AA, Ginde AA, Fahimi J, et al. Increasing critical care admissions from US emergency departments, 2001-2009. Crit Care Med. 2013;41(5):1197-1204. [CrossRef] [PubMed]
 
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McConnell KJ, Richards CF, Daya M, Bernell SL, Weathers CC, Lowe RA. Effect of increased ICU capacity on emergency department length of stay and ambulance diversion. Ann Emerg Med. 2005;45(5):471-478. [CrossRef] [PubMed]
 
Nelson M, Waldrop RD, Jones J, Randall Z. Critical care provided in an urban emergency department. Am J Emerg Med. 1998;16(1):56-59. [CrossRef] [PubMed]
 
Varon J, Fromm RE Jr, Levine RL. Emergency department procedures and length of stay for critically ill medical patients. Ann Emerg Med. 1994;23(3):546-549. [CrossRef] [PubMed]
 
Trzeciak S, Rivers EP. Emergency department overcrowding in the United States: an emerging threat to patient safety and public health. Emerg Med J. 2003;20(5):402-405. [CrossRef] [PubMed]
 
Fuller BM, Mohr NM, Dettmer M, et al. Mechanical ventilation and acute lung injury in emergency department patients with severe sepsis and septic shock: an observational study. Acad Emerg Med. 2013;20(7):659-669. [CrossRef] [PubMed]
 
Rubenfeld GD, Caldwell E, Peabody E, et al. Incidence and outcomes of acute lung injury. N Engl J Med. 2005;353(16):1685-1693. [CrossRef] [PubMed]
 
Rubenfeld GD, Herridge MS. Epidemiology and outcomes of acute lung injury. Chest. 2007;131(2):554-562. [CrossRef] [PubMed]
 
Mikkelsen MESC, Shah CV, Meyer NJ, et al. The epidemiology of acute respiratory distress syndrome in patients presenting to the emergency department with severe sepsis. Shock. 2013;40(5):375-381. [CrossRef] [PubMed]
 
Goyal M, Houseman D, Johnson NJ, Christie J, Mikkelsen ME, Gaieski DF. Prevalence of acute lung injury among medical patients in the emergency department. Acad Emerg Med. 2012;19(9):E1011-E1018. [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(18):1301-1308. [CrossRef] [PubMed]
 
Amato MBP, Barbas CSV, Medeiros DM, et al. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med. 1998;338(6):347-354. [CrossRef] [PubMed]
 
Villar J, Kacmarek RM, Pérez-Méndez L, Aguirre-Jaime A. A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: a randomized, controlled trial. Crit Care Med. 2006;34(5):1311-1318. [CrossRef] [PubMed]
 
Gajic O, Dara SI, Mendez JL, et al. Ventilator-associated lung injury in patients without acute lung injury at the onset of mechanical ventilation. Crit Care Med. 2004;32(9):1817-1824. [CrossRef] [PubMed]
 
Gajic O, Frutos-Vivar F, Esteban A, Hubmayr RD, Anzueto A. Ventilator settings as a risk factor for acute respiratory distress syndrome in mechanically ventilated patients. Intensive Care Med. 2005;31(7):922-926. [CrossRef] [PubMed]
 
Jia X, Malhotra A, Saeed M, Mark RG, Talmor D. Risk factors for ARDS in patients receiving mechanical ventilation for > 48 h. Chest. 2008;133(4):853-861. [CrossRef] [PubMed]
 
Determann RM, Royakkers A, Wolthuis EK, et al. Ventilation with lower tidal volumes as compared with conventional tidal volumes for patients without acute lung injury: a preventive randomized controlled trial. Crit Care. 2010;14(1):R1. [CrossRef] [PubMed]
 
Mascia L, Zavala E, Bosma K, et al; Brain IT group. High tidal volume is associated with the development of acute lung injury after severe brain injury: an international observational study. Crit Care Med. 2007;35(8):1815-1820. [CrossRef] [PubMed]
 
Pasero D, Davi A, Guerriero F, Rana N, Merigo G, Mastromauro I, Viberti S, Mascia L, Rinaldi M, Ranieri M. High tidal volume as an independent risk factor for acute lung injury after cardiac surgery. Intensive Care Med. 2008;34(suppl 1):0398.
 
Yilmaz M, Keegan MT, Iscimen R, et al. Toward the prevention of acute lung injury: protocol-guided limitation of large tidal volume ventilation and inappropriate transfusion. Crit Care Med. 2007;35(7):1660-1666. [CrossRef] [PubMed]
 
Fuller BM, Mohr NM, Drewry AM, Carpenter CR. Lower tidal volume at initiation of mechanical ventilation may reduce progression to acute respiratory distress syndrome: a systematic review. Crit Care. 2013;17(1):R11. [CrossRef] [PubMed]
 
Futier E, Constantin J-M, Paugam-Burtz C, et al; IMPROVE Study Group. A trial of intraoperative low-tidal-volume ventilation in abdominal surgery. N Engl J Med. 2013;369(5):428-437. [CrossRef] [PubMed]
 
Serpa Neto A, Cardoso SO, Manetta JA, et al. Association between use of lung-protective ventilation with lower tidal volumes and clinical outcomes among patients without acute respiratory distress syndrome: a meta-analysis. JAMA. 2012;308(16):1651-1659. [CrossRef] [PubMed]
 
Muscedere JG, Mullen JB, Gan K, Slutsky AS. Tidal ventilation at low airway pressures can augment lung injury. Am J Respir Crit Care Med. 1994;149(5):1327-1334. [CrossRef] [PubMed]
 
Tremblay L, Valenza F, Ribeiro SP, Li J, Slutsky AS. Injurious ventilatory strategies increase cytokines and c-fos m-RNA expression in an isolated rat lung model. J Clin Invest. 1997;99(5):944-952. [CrossRef] [PubMed]
 
Dreyfuss D, Soler P, Basset G, Saumon G. High inflation pressure pulmonary edema. Respective effects of high airway pressure, high tidal volume, and positive end-expiratory pressure. Am Rev Respir Dis. 1988;137(5):1159-1164. [CrossRef] [PubMed]
 
Webb HH, Tierney DF. Experimental pulmonary edema due to intermittent positive pressure ventilation with high inflation pressures. Protection by positive end-expiratory pressure. Am Rev Respir Dis. 1974;110(5):556-565. [PubMed]
 
von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med. 2007;147(8):573-577. [CrossRef] [PubMed]
 
Vincent JL, Angus DC, Artigas A, et al; Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) Study Group. Effects of drotrecogin alfa (activated) on organ dysfunction in the PROWESS trial. Crit Care Med. 2003;31(3):834-840. [CrossRef] [PubMed]
 
Vincent JL, de Mendonça A, Cantraine F, et al. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on “sepsis-related problems” of the European Society of Intensive Care Medicine. Crit Care Med. 1998;26(11):1793-1800. [CrossRef] [PubMed]
 
Vincent JL, Moreno R, Takala J, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22(7):707-710. [CrossRef] [PubMed]
 
Gajic O, Dabbagh O, Park PK, et al; US Critical Illness and Injury Trials Group: Lung Injury Prevention Study Investigators (USCIITG-LIPS). Early identification of patients at risk of acute lung injury: evaluation of lung injury prediction score in a multicenter cohort study. Am J Respir Crit Care Med. 2011;183(4):462-470. [CrossRef] [PubMed]
 
Hou PC, Elie-Turenne MC, Mitani A, et al. Towards prevention of acute lung injury: frequency and outcomes of emergency department patients at-risk—a multicenter cohort study. Int J Emerg Med. 2012;5(1):22. [CrossRef] [PubMed]
 
Predicted body weight calculator. NHLBI ARDS Network website. http://www.ardsnet.org/node/77460. Accessed January 2, 2014.
 
Bone RC, Balk RA, Cerra FB, et al; The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest. 1992;101(6):1644-1655. [CrossRef] [PubMed]
 
Levy MM, Fink MP, Marshall JC, et al; International Sepsis Definitions Conference. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care Med. 2003;29(4):530-538. [CrossRef] [PubMed]
 
Ranieri VM, Rubenfeld GD, Thompson BT, et al; ARDS Definition Task Force. Acute respiratory distress syndrome: the Berlin definition. JAMA. 2012;307(23):2526-2533. [PubMed]
 
Rice TW, Wheeler AP, Bernard GR, Hayden DL, Schoenfeld DA, Ware LB; National Institutes of Health, National Heart, Lung, and Blood Institute ARDS Network. Comparison of the Spo2/Fio2ratio and the Pao2/Fio2ratio in patients with acute lung injury or ARDS. Chest. 2007;132(2):410-417. [CrossRef] [PubMed]
 
Iscimen R, Cartin-Ceba R, Yilmaz M, et al. Risk factors for the development of acute lung injury in patients with septic shock: an observational cohort study. Crit Care Med. 2008;36(5):1518-1522. [CrossRef] [PubMed]
 
Serpa Neto A, Simonis FD, Barbas CS, et al. Association between tidal volume size, duration of ventilation, and sedation needs in patients without acute respiratory distress syndrome: an individual patient data meta-analysis. Intensive Care Med. 2014;40(7):950-970. [CrossRef] [PubMed]
 
Austin MA, Wills KE, Blizzard L, Walters EH, Wood-Baker R. Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial. BMJ. 2010;341:c5462. [CrossRef] [PubMed]
 
Kilgannon JH, Jones AE, Parrillo JE, et al; Emergency Medicine Shock Research Network (EMShockNet) Investigators. Relationship between supranormal oxygen tension and outcome after resuscitation from cardiac arrest. Circulation. 2011;123(23):2717-2722. [CrossRef] [PubMed]
 
Kilgannon JH, Jones AE, Shapiro NI, et al; Emergency Medicine Shock Research Network (EMShockNet) Investigators. Association between arterial hyperoxia following resuscitation from cardiac arrest and in-hospital mortality. JAMA. 2010;303(21):2165-2171. [CrossRef] [PubMed]
 
Rachmale S, Li G, Wilson G, Malinchoc M, Gajic O. Practice of excessive F(IO(2)) and effect on pulmonary outcomes in mechanically ventilated patients with acute lung injury. Respir Care. 2012;57(11):1887-1893. [CrossRef] [PubMed]
 
Wijesinghe M, Perrin K, Ranchord A, Simmonds M, Weatherall M, Beasley R. Routine use of oxygen in the treatment of myocardial infarction: systematic review. Heart. 2009;95(3):198-202. [CrossRef] [PubMed]
 
Kollef MH. Ventilator-associated pneumonia. A multivariate analysis. JAMA. 1993;270(16):1965-1970. [CrossRef] [PubMed]
 
Kahn JM, Caldwell EC, Deem S, Newell DW, Heckbert SR, Rubenfeld GD. Acute lung injury in patients with subarachnoid hemorrhage: incidence, risk factors, and outcome. Crit Care Med. 2006;34(1):196-202. [CrossRef] [PubMed]
 
Pasero D, Davi A., Guerriero F., et al. High tidal volume as an independent risk factor for acute lung injury after cardiac surgery. Intensive Care Med. 2008 2008;34(suppl 1):0398.
 
Fuller BM, Mohr NM, Hotchkiss RS, Kollef MH. Reducing the burden of acute respiratory distress syndrome: the case for early intervention and the potential role of the emergency department. Shock. 2014;41(5):378-387. [CrossRef] [PubMed]
 
Spragg RG, Bernard GR, Checkley W, et al. Beyond mortality: future clinical research in acute lung injury. Am J Respir Crit Care Med. 2010;181(10):1121-1127. [CrossRef] [PubMed]
 
Bersten AD, Edibam C, Hunt T, Moran J; Australian and New Zealand Intensive Care Society Clinical Trials Group. Incidence and mortality of acute lung injury and the acute respiratory distress syndrome in three Australian States. Am J Respir Crit Care Med. 2002;165(4):443-448. [CrossRef] [PubMed]
 
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  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543