Lung-Protective Ventilation Initiated in the Emergency Department (LOV-ED): A Quasi-Experimental, Before-After Trial

doi:10.1016/j.annemergmed.2017.01.013

Annals of Emergency Medicine

Volume 70, Issue 3, September 2017, Pages 406-418.e4

Presented at the American Thoracic Society Conference, May 2016, San Francisco, CA.

https://doi.org/10.1016/j.annemergmed.2017.01.013 Get rights and content

Study objective

We evaluated the efficacy of an emergency department (ED)–based lung-protective mechanical ventilation protocol for the prevention of pulmonary complications.

Methods

This was a quasi-experimental, before-after study that consisted of a preintervention period, a run-in period of approximately 6 months, and a prospective intervention period. The intervention was a multifaceted ED-based mechanical ventilator protocol targeting lung-protective tidal volume, appropriate setting of positive end-expiratory pressure, rapid oxygen weaning, and head-of-bed elevation. A propensity score–matched analysis was used to evaluate the primary outcome, which was the composite incidence of acute respiratory distress syndrome and ventilator-associated conditions.

Results

A total of 1,192 patients in the preintervention group and 513 patients in the intervention group were included. Lung-protective ventilation increased by 48.4% in the intervention group. In the propensity score–matched analysis (n=490 in each group), the primary outcome occurred in 71 patients (14.5%) in the preintervention group compared with 36 patients (7.4%) in the intervention group (adjusted odds ratio 0.47; 95% confidence interval [CI] 0.31 to 0.71). There was an increase in ventilator-free days (mean difference 3.7; 95% CI 2.3 to 5.1), ICU-free days (mean difference 2.4; 95% CI 1.0 to 3.7), and hospital-free days (mean difference 2.4; 95% CI 1.2 to 3.6) associated with the intervention. The mortality rate was 34.1% in the preintervention group and 19.6% in the intervention group (adjusted odds ratio 0.47; 95% CI 0.35 to 0.63).

Conclusion

Implementing a mechanical ventilator protocol in the ED is feasible and is associated with significant improvements in the delivery of safe mechanical ventilation and clinical outcome.

Introduction

Annually, approximately 250,000 patients receive mechanical ventilation in US emergency departments (ED), many of whom have protracted lengths of stay while awaiting ICU admission.1, 2 Pulmonary complications, such as acute respiratory distress syndrome and ventilator-associated conditions, develop in more than 20% of ED patients receiving ventilation and adversely affect outcome and resource use.3, 4, 5, 6, 7, 8, 9 Because there is increased focus on reducing complications in this high-risk cohort, the time spent in the ED represents a vulnerable period in which preventive therapies could have a significant effect. However, the ED has not been targeted as an arena for prevention.¹⁰

Editor’s Capsule Summary

What is already known on this topic

Patients intubated in the emergency department (ED) are at risk for subsequent acute respiratory distress syndrome and other ventilator-associated complications.

What question this study addressed

Can a 4-part “lung-protective” mechanical ventilation protocol decrease the frequency of such complications?

What this study adds to our knowledge

In this before-and-after analysis of 980 intubated ED adults, the frequency of acute respiratory distress syndrome and other ventilator-associated complications decreased after protocol implementation (14.5% to 7.4%), as did mortality (34.1% to 19.6%).

How this is relevant to clinical practice

Although outcome improvement caused by factors other than the intervention cannot be excluded, these data support the efficacy of a 4-part lung-protective protocol.

Lung-protective ventilation, by reducing ventilator-associated lung injury, is one important strategy to aid in prevention of pulmonary complications. Although lung-protective ventilation is associated with a lower incidence of acute respiratory distress syndrome, evidence demonstrates that potentially injurious ventilator practices are common in the ED.4, 5, 8, 9, 11 Lung-protective ventilation in the ED may be effective at reducing pulmonary complications for several reasons. Experimental data have established that ventilator-associated lung injury can occur shortly after the initiation of mechanical ventilation.12, 13 This is supported by evidence showing that initial ventilator settings influence outcome in patients with, and at risk for, acute respiratory distress syndrome.3, 8, 9, 14 Even if delivered for comparatively brief periods, early lung-protective ventilation during vulnerable periods seems to carry subsequent benefit, as demonstrated by data from the operating room and in lung donation.15, 16 Finally, initial ventilator settings influence the future delivery of lung-protective ventilation; it is therefore possible that establishing a lung-protective strategy during the earliest phases of respiratory failure can improve downstream adherence to lung-protective ventilation.¹⁴

The objective of this study was to evaluate the effectiveness of an ED-based lung-protective mechanical ventilation protocol on reducing the incidence of pulmonary complications. Given the high risk of pulmonary complications in mechanically ventilated ED patients, low adherence to lung-protective ventilation, and the association between initial ventilator settings and outcome, we hypothesized that a multifaceted strategy aimed at improving ED mechanical ventilation practices would reduce the incidence of pulmonary complications after ICU admission from the ED.

Section snippets

Study Design and Setting

The Lung-Protective Ventilation Initiated in the Emergency Department (LOV-ED) trial was a quasi-experimental, before-after study. It consisted of a preintervention period (September 2009 to January 2014), a run-in period of approximately 6 months, during which lung-protective ventilation was implemented as the standard approach in the ED, and an intervention period (October 2014 to March 2016). The study was approved with waiver of informed consent because lung-protective ventilation in the ED

Characteristics of Study Subjects

Figure 2 presents the study flow diagram and the final study population.

Baseline characteristics of the study population are shown in Table 1. Matching on the propensity score allowed the selection of 490 pairs of patients with greater similarity in illness severity and clinically relevant predictors of the primary outcome. After the propensity match, there was a significance difference between the 2 groups in patients with dialysis dependence and those intubated as a result of congestive heart

Limitations

There are several limitations to the present study. A before-after study design is prone to temporal trends that may lead to independent changes in care. Analysis of secular changes did not demonstrate this; the greatest change in clinical practice and outcomes was isolated to the intervention period. However, unmeasured confounders that improved overall care during the intervention may have accounted for some of the improved outcomes. The study design can raise concern over proof of causation.

Discussion

The rationale for implementing lung-protective ventilation in the ED hinges on the premise that there is a temporal link between ventilator management during the earliest period of respiratory failure and the development of subsequent complications; early adherence to lung-protective ventilation could therefore improve outcome. Multiple studies show a link between nonprotective ventilation in the ICU and acute respiratory distress syndrome incidence, with syndrome onset typically 2 days after

References (43)

B.D. Easter et al.
The use of mechanical ventilation in the ED
Am J Emerg Med
(2012)
M.R. Dettmer et al.
Sepsis-associated pulmonary complications in emergency department patients monitored with serial lactate: an observational cohort study
J Crit Care
(2015)
B. Fuller et al.
Mechanical ventilation and acute respiratory distress syndrome in the emergency department: a multi-center, observational, prospective, cross-sectional, study
Chest
(2015)
A.F. Boyer et al.
A prospective evaluation of ventilator-associated conditions and infection-related ventilator-associated conditions
Chest
(2015)
R.C. Bone et al.
Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine
Chest
(1992)
X. Jia et al.
Risk factors for ARDS in patients receiving mechanical ventilation for > 48 h
Chest
(2008)
L. Rose et al.
Emergency department length of stay for patients requiring mechanical ventilation: a prospective observational study
Scand J Trauma Resusc Emerg Med
(2012)
B. Fuller 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)
M. Mikkelsen et al.
The epidemiology of acute respiratory distress syndrome in patients presenting to the emergency department with severe sepsis
Shock
(2013)
B.M. Fuller et al.
Lower tidal volume at initiation of mechanical ventilation may reduce progression to acute respiratory distress syndrome: a systematic review
Crit Care
(2013)

A. Neto 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)

R. Spragg et al.

Beyond mortality: future clinical research in acute lung injury

Am J Respir Crit Care Med

(2010)

R. Determann 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)

H.H. Webb et al.

Experimental pulmonary edema due to intermittent positive pressure ventilation with high inflation pressures: protection by positive end-expiratory pressure

Am Rev Respir Dis

(1974)

D. Dreyfuss et al.

High inflation pressure pulmonary edema: respective effects of high airway pressure, high tidal volume, and positive end-expiratory pressure

Am Rev Respir Dis

(1988)

D.M. Needham 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)

E. Futier et al.

A trial of intraoperative low-tidal-volume ventilation in abdominal surgery

N Engl J Med

(2013)

L. Mascia et al.

Effect of a lung protective strategy for organ donors on eligibility and availability of lungs for transplantation: a randomized controlled trial

JAMA

(2010)

B.M. Fuller et al.

Lung-Protective Ventilation Initiated in the Emergency Department (LOV-ED): a study protocol for a quasi-experimental, before-after trial aimed at reducing pulmonary complications

BMJ Open

(2016)

Acute respiratory distress syndrome

JAMA

(2012)

J. Vincent et al.

The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure

Intensive Care Med

(1996)

Cited by (80)

Partial pressure of carbon dioxide/pH interaction and its association with mortality among patients mechanically ventilated in the emergency department
2024, American Journal of Emergency Medicine
There is currently conflicting data as to the effects of hypercapnia on clinical outcomes among mechanically ventilated patients in the emergency department (ED). These conflicting results may be explained by the degree of acidosis. We sought to test the hypothesis that hypercapnia is associated with increased in-hospital mortality and decreased ventilator-free days at lower pH, but associated with decreased in-hospital mortality and increased ventilator-free days at higher pH, among patients requiring mechanical ventilation in the emergency department (ED).
Secondary analysis of patient level data from prior clinical trials and cohort studies that enrolled adult patients who required mechanical ventilation in the ED. Patients who had a documented blood gas while on mechanical ventilation in the ED were included in these analyses. The primary outcome was in-hospital mortality, and secondary outcome was ventilator-free days. Mixed-effects logistic, linear, and survival-time regression models were used to test if pH modified the association between partial pressure of carbon dioxide (pCO₂) and outcome measures.
Of the 2348 subjects included, the median [interquartile range (IQR)] pCO2 was 43 (35–54) and pH was 7.31 (7.22–7.39). Overall, in-hospital mortality was 27%. We found pH modified the association between pCO₂ and outcomes, with higher pCO₂ associated with increased probability of in-hospital mortality when pH is below 7.00, and decreased probability of in-hospital mortality when pH is above 7.10. These results remained consistent across multiple sensitivity and subgroup analyses. A similar relationship was found with ventilator-free days.
Higher pCO₂ is associated with decreased mortality and greater ventilator-free days when pH is >7.10; however, it is associated with increased mortality and fewer ventilator-free days when the pH is below 7.00. Targeting pCO₂ based on pH in the ED may be a potential intervention target for future clinical trials to improve clinical outcomes.
Investigating distributions of inhaled aerosols in the lungs of post-COVID-19 clusters through a unified imaging and modeling approach
2024, European Journal of Pharmaceutical Sciences
Recent studies, based on clinical data, have identified sex and age as significant factors associated with an increased risk of long COVID. These two factors align with the two post-COVID-19 clusters identified by a deep learning algorithm in computed tomography (CT) lung scans: Cluster 1 (C1), comprising predominantly females with small airway diseases, and Cluster 2 (C2), characterized by older individuals with fibrotic-like patterns. This study aims to assess the distributions of inhaled aerosols in these clusters.
140 COVID survivors examined around 112 days post-diagnosis, along with 105 uninfected, non-smoking healthy controls, were studied. Their demographic data and CT scans at full inspiration and expiration were analyzed using a combined imaging and modeling approach. A subject-specific CT-based computational model analysis was utilized to predict airway resistance and particle deposition among C1 and C2 subjects. The cluster-specific structure and function relationships were explored.
In C1 subjects, distinctive features included airway narrowing, a reduced homothety ratio of daughter over parent branch diameter, and increased airway resistance. Airway resistance was concentrated in the distal region, with a higher fraction of particle deposition in the proximal airways. On the other hand, C2 subjects exhibited airway dilation, an increased homothety ratio, reduced airway resistance, and a shift of resistance concentration towards the proximal region, allowing for deeper particle penetration into the lungs.
This study revealed unique mechanistic phenotypes of airway resistance and particle deposition in the two post-COVID-19 clusters. The implications of these findings for inhaled drug delivery effectiveness and susceptibility to air pollutants were explored.
Arterial to end-tidal carbon dioxide gap and its characterization in mechanically ventilated adults in the emergency department
2023, American Journal of Emergency Medicine
To evaluate early measurement of the arterial to end-tidal carbon dioxide (PaCO₂-PetCO₂) gap, a surrogate for physiologic dead space, and its association with clinical outcomes in intubated adults in the emergency department (ED).
Observational cohort study of invasively mechanically ventilated adults in an academic medical center (years 2009 to 2016). The association of the PaCO₂-PetCO₂ gap was evaluated with respect to clinical outcomes; the primary outcome was in-hospital mortality.
519 patients were included. 325 (63%) patients had an elevated (>5 mmHg) PaCO₂-PetCO₂. Patients with an elevated PaCO₂-PetCO₂ were significantly older, had higher APACHE II scores, more frequently had chronic obstructive pulmonary disease (COPD), had lower arterial oxygen to fraction of inspired oxygen (P:F) ratios, and were more likely to be intubated for exacerbation of COPD or sepsis. There was no difference in mortality for patients with an elevated PaCO₂-PetCO₂ (25% vs 26%) in unadjusted analysis (p = 0.829) or adjusted analysis (aOR = 0.81 [95% CI: 0.53–1.26]), as compared to a non-elevated PaCO₂-PetCO₂.
An elevated PaCO₂-PetCO₂ gap is common in the post-intubation period in the ED, but not significantly associated with clinical outcomes.
A NOVEL EQUATION SUCCESSFULLY CALCULATES TIDAL VOLUMES FOR LUNG PROTECTIVE VENTILATION
2023, Journal of Emergency Medicine
Early application of low-tidal-volume ventilation (LTVV) has been associated with improved outcomes in the emergency department (ED) and intensive care unit (ICU), but is not consistently applied. The perceived complexity of calculating an ideal body weight (IBW)-based tidal volume (Vt) may contribute to this disparity. We hypothesized that a simplified equation could successfully predict LTVV.
To create a memorable, single-step, sex-independent equation to estimate LTVV based on height.
We conducted a retrospective observational cohort study of patients who received mechanical ventilation (MV) at 2 EDs from January 2016 to June 2019. Data were abstracted by automatic query. Patients < 18 years old, < 60 inches in height, and with implausible or incomplete data were excluded. LTVV was defined as ≤ 8 mL/kg IBW. We created a formula predicting a 6–8-mL/kg IBW Vt. We applied this formula to a population of ICU patients in the same health care system who received MV from January 2017 to December 2019 using the same exclusion criteria. The outcome was whether the equation predicted a 6–8-mL/kg IBW Vt.
A total of 982 ED patients were included; 753 (76.7%) had an initial Vt < 8 mL/kg IBW. The equation Vt = 20*(Ht-60) + 300 was derived. A total of 3720 ICU patients were included. The Vt equation successfully predicted a Vt of 6–8 mL/kg IBW in 3720 (100%) of ICU patients.
A novel equation successfully predicted a 6–8-mL/kg IBW Vt in a cohort of patients with height ≥ 60 inches.
Utility of solar-powered oxygen delivery in a resource-constrained setting
2023, Pulmonology
Pneumonia is a leading cause of childhood mortality globally. Children with severe pneumonia associated with hypoxaemia require oxygen (O₂) therapy, which is scarce across resource-constrained countries. Solar-powered oxygen (SPO2) is a novel technology developed for delivering therapeutic O₂ in resource-constrained environments.
Is the introduction of SPO2 associated with a reduction in mortality, relative to the existing practice?
This was a pragmatic, quasi-experimental study comparing mortality amongst children < 5 years of age with hypoxaemic respiratory illness before and after the installation of SPO2 in two resource-constrained hospitals.
Participants were children < 5 years old admitted with acute hypoxaemic respiratory illness. The intervention was SPO2, installed at two resource-constrained hospitals. The primary outcome was 30-day mortality. Secondary outcomes included in-hospital mortality (time to death), length of hospital stay among survivors, duration of O₂ therapy (time to wean O₂), and O₂ delivery system failure(s).
Mortality amongst children admitted with acute hypoxaemic respiratory illness decreased from 30/50 (60%) pre-SPO2 to 15/50 (30%) post-SPO2 (relative risk reduction 50%, 95%CI 19 – 69, p = 0.0049). The post-SPO2 period was consistently associated with decreased mortality in statistical models adjusting for potential confounding factors. Likewise, survival curves pre- and post- SPO2 differed significantly (hazard ratio 0.39, 95% CI 0.20 – 0.74, p = 0.0043). A reduction in the frequency of O₂ delivery interruptions due to fuel shortages and multiple patients needing the concentrator at once was observed, explaining the mortality reduction.
Solar-powered oxygen installation was associated with decreased mortality in resource-constrained settings.
What is the Impact of Low Tidal Volume Ventilation for Emergency Department Patients?
2023, Annals of Emergency Medicine

View all citing articles on Scopus

: Please see page 407 for the Editor’s Capsule Summary of this article.

: Supervising editor: Steven M. Green, MD

: Author contributions: BMF, ITF, RSH, and MHK were responsible for study concept and design. BMF, ITF, RJS, CCB, and AAK were responsible for acquisition of data and administrative, technical, or material support. BMF was responsible for management of data and quality control, drafting of the article, and statistical analysis. BMF, ITF, NMM, RSH, and MHK were responsible for analysis and interpretation of data. BMF, ITF, NMM, AMD, CP, BTW, EA, JK, RJS, CCB, AAK, RSH, and MHK were responsible for critical revision and final approval of the article. BMF and MHK were responsible for study supervision. BMF takes responsibility for the paper as a whole.

: All authors attest to meeting the four ICMJE.org authorship criteria: (1) Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; AND (2) Drafting the work or revising it critically for important intellectual content; AND (3) Final approval of the version to be published; AND (4) Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

: Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). The authors have stated that no such relationships exist. Drs. Fuller and Drewry were funded by the KL2 Career Development Award, and this research 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 (NCATS). Dr. Fuller was also funded by the Foundation for Barnes-Jewish Hospital Clinical and Translational Sciences Research Program (grant 8041-88). Dr. Drewry was also funded by the Foundation for Anesthesia Education and Research. Dr. Mohr was supported by grant funds from the Emergency Medicine Foundation and the Health Resources and Services Administration. Dr. Ablordeppey was supported by the Washington University School of Medicine Faculty Scholars grant and the Foundation for Barnes-Jewish Hospital. Mr. Stephens was supported by the Clinical and Translational Science Award program of the NCATS of the National Institutes of Health (NIH) under awards UL1 TR000448 and TL1 TR000449. Mr. Briscoe was supported by the Short-Term Institutional Research Training Grant, NIH T35 (National Heart, Lung, and Blood Institute [NHLBI]). Dr. Hotchkiss was supported by NIH grants R01 GM44118-22 and R01 GM09839. Dr. Kollef was supported by the Barnes-Jewish Hospital Foundation.

: Trial registration number: clinicaltrials.gov NCT02543554

: The funders played no role in the following: design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the article.

: Readers: click on the link to go directly to a survey in which you can provide feedback to Annals on this particular article.

View full text

Pulmonary/original researchLung-Protective Ventilation Initiated in the Emergency Department (LOV-ED): A Quasi-Experimental, Before-After Trial

Study objective

Methods

Results

Conclusion

Introduction

Editor’s Capsule Summary

Section snippets

Study Design and Setting

Characteristics of Study Subjects

Limitations

Discussion

Am J Emerg Med

J Crit Care

Chest

Chest

Chest

Chest

Emergency department length of stay for patients requiring mechanical ventilation: a prospective observational study

Scand J Trauma Resusc Emerg Med

Mechanical ventilation and acute lung injury in emergency department patients with severe sepsis and septic shock: an observational study

Acad Emerg Med

The epidemiology of acute respiratory distress syndrome in patients presenting to the emergency department with severe sepsis

Shock

Lower tidal volume at initiation of mechanical ventilation may reduce progression to acute respiratory distress syndrome: a systematic review

Crit Care

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

Beyond mortality: future clinical research in acute lung injury

Am J Respir Crit Care Med

Ventilation with lower tidal volumes as compared with conventional tidal volumes for patients without acute lung injury: a preventive randomized controlled trial

Crit Care

Experimental pulmonary edema due to intermittent positive pressure ventilation with high inflation pressures: protection by positive end-expiratory pressure

Am Rev Respir Dis

High inflation pressure pulmonary edema: respective effects of high airway pressure, high tidal volume, and positive end-expiratory pressure

Am Rev Respir Dis

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

A trial of intraoperative low-tidal-volume ventilation in abdominal surgery

N Engl J Med

Effect of a lung protective strategy for organ donors on eligibility and availability of lungs for transplantation: a randomized controlled trial

JAMA

Lung-Protective Ventilation Initiated in the Emergency Department (LOV-ED): a study protocol for a quasi-experimental, before-after trial aimed at reducing pulmonary complications

BMJ Open

Acute respiratory distress syndrome

JAMA

The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure

Intensive Care Med

Pulmonary/original research
Lung-Protective Ventilation Initiated in the Emergency Department (LOV-ED): A Quasi-Experimental, Before-After Trial