Elsevier

Journal of Critical Care

Volume 30, Issue 1, February 2015, Pages 65-70
Journal of Critical Care

Mechanical Ventilation
The impact of cardiac dysfunction on acute respiratory distress syndrome and mortality in mechanically ventilated patients with severe sepsis and septic shock: An observational study,☆☆,

https://doi.org/10.1016/j.jcrc.2014.07.027Get rights and content

Abstract

Purpose

Acute respiratory distress syndrome (ARDS) is associated with significant mortality and morbidity in survivors. Treatment is only supportive, therefore elucidating modifiable factors that could prevent ARDS could have a profound impact on outcome. The impact that sepsis-associated cardiac dysfunction has on ARDS is not known.

Materials and Methods

In this retrospective observational cohort study of mechanically ventilated patients with severe sepsis and septic shock, 122 patients were assessed for the impact of sepsis-associated cardiac dysfunction on incidence of ARDS (primary outcome) and mortality.

Results

Sepsis-associated cardiac dysfunction occurred in 44 patients (36.1%). There was no association of sepsis-associated cardiac dysfunction with ARDS incidence (p= 0.59) or mortality, and no association with outcomes in patients that did progress to ARDS after admission. Multivariable logistic regression demonstrated that higher BMI was associated with progression to ARDS (adjusted OR 11.84, 95% CI 1.24 to 113.0, p= 0.02).

Conclusions

Cardiac dysfunction in mechanically ventilated patients with sepsis did not impact ARDS incidence, clinical outcome in ARDS patients, or mortality. This contrasts against previous investigations demonstrating an influence of nonpulmonary organ dysfunction on outcome in ARDS. Given the frequency of ARDS as a sequela of sepsis, the impact of cardiac dysfunction on outcome should be further studied.

Introduction

Sepsis and acute respiratory distress syndrome (ARDS) are 2 critical care syndromes that share several features. Both are common, highly lethal, and negatively impact survivors dramatically [1], [2], [3], [4], [5]. Intense investigation into both syndromes has resulted in little success in randomized controlled trials as well [6], [7]. Sepsis carries an estimated incidence of ARDS of more than 40% in some studies and is a leading cause of death in ARDS [8], [9], [10]. Finally, the clinical care and trajectory set forth at the most proximate time of presentation (eg, the emergency department [ED] and early intensive care unit [ICU]) are now recognized as increasingly impactful periods with respect to overall outcome [11], [12].

Cardiac dysfunction is a prominent feature of sepsis, with an incidence as high as 60% [13]. Sepsis-associated cardiac dysfunction has been described for decades[14], [15]. Although the characterization and pathophysiology remain incompletely understood, it typically is described as involving biventricular dysfunction, decreased ejection fraction (EF), and ventricular dilation (eg, increased end-diastolic volume index), which is reversible in survivors over the course of 7 to 10 days [14], [16], [17], [18], [19], [20]. Earlier studies showed a seemingly paradoxical association with decreased cardiac function and survival, although more recent data question this association [13], [14], [21], [22], [23]. Although sepsis-associated cardiac dysfunction has not definitively been linked with worse outcome, critically ill mechanically ventilated patients (including those with ARDS) have worse outcome associated with nonpulmonary organ failure, including cardiovascular dysfunction [17], [23], [24], [25], [26]. It is possible that cardiac dysfunction may carry a more deleterious impact in sepsis patients who are mechanically ventilated and those with ARDS, but this has not been extensively investigated.

There is increasing interest in optimizing the care of mechanically ventilated patients early in the course of respiratory failure. This includes preventing and mitigating the severity of ARDS after ICU admission [27], [28], [29]. The event rate for ARDS after admission from the ED ranges from 6.2% to 44% [12], [30]. Recent data suggest that close to 9% of mechanically ventilated patients have ARDS while in the ED, and around 30% of mechanically ventilated ED patients with severe sepsis will progress to ARDS [31], [32], [33]. However, some of these data excluded potential ARDS patients on the assumption of left atrial hypertension in the presence of an elevated B-type natriuretic peptide (BNP) or history of heart failure or depressed left ventricular (LV) function on echocardiogram [31], [32]. As the new Berlin definition recognizes that cardiac failure and left atrial hypertension can coexist with ARDS and is more inclusionary in the definition of ARDS with respect to the origin of pulmonary edema, it is possible that cardiac dysfunction is a modifiable factor that influences both ARDS incidence and outcome, yet this remains unknown [34].

This study was therefore performed with 2 objectives: (1) to assess the impact of sepsis-associated cardiac dysfunction on the incidence and outcome of ARDS and (2) to assess the impact of sepsis-associated cardiac dysfunction on mortality in mechanically ventilated patients with severe sepsis admitted from the ED. We hypothesized that the presence of cardiac dysfunction would be associated with progression to ARDS, would worsen outcome in ARDS patients, and would be associated with higher mortality.

Section snippets

Methods

This observational study is reported in accordance with The Strengthening the Reporting of Observational Studies in Epidemiology statement: guidelines for reporting observational studies [35]. Financial support for this project was provided in part from the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through grant number UL1 TR000448. The funding organization played no role in the study concept, design, data

Results

A total of 251 patients with severe sepsis or septic shock were mechanically ventilated during the study, and 122 patients were assessed for the primary and secondary outcomes of interest (Fig. 1). Table 1 shows the baseline characteristics of the study population, process of care variables, and echocardiographic findings of the cohort. Independent review of the echocardiograms yielded a κ value of 0.60, indicating moderate agreement. After consensus discussion, there was perfect agreement

Discussion

Because no treatment targeting the underlying pathophysiology of ARDS exists, assessing modifiable patient characteristics or treatment variables is vital to prevent and mitigate the severity of the syndrome. This study targeted a patient cohort that was both septic and mechanically ventilated, 2 factors placing them at high risk for potentially worse outcomes associated with cardiovascular dysfunction. We first sought to determine the influence of cardiac dysfunction on the incidence of ARDS.

Limitations

There are several important limitations to this study. The retrospective design limits ability to draw causation on any effect of cardiac dysfunction on ARDS incidence. However, we excluded patients with ARDS while in the ED (n = 9), suggesting that a temporal relationship would have existed between early cardiac dysfunction and subsequent ARDS development. The retrospective design may have influenced the event rate for cardiac dysfunction as well. Prospective data collection, with uniform

Conclusions

In mechanically ventilated patients with severe sepsis and septic shock, progression to ARDS and cardiac dysfunction is common. Cardiac dysfunction was not associated with outcome across our cohort of patients, nor in the subgroup of patients with ARDS. Further investigation, with adequately powered prospective studies, should be undertaken, as it is possible that cardiac dysfunction could be a modifiable factor in the prevention and treatment of ARDS.

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    Sources of support: BMF was supported by the Emergency Medicine grant-in-aid from the Division of Emergency Medicine, Washington University School of Medicine in St Louis, MO, and the Postdoctoral Mentored Training Program in Clinical Investigation. TC, SG, and RG were supported by the TL1 Predoctoral Program at Washington University in St Louis, MO. This publication was supported by the Washington University Institute of Clinical and Translational Sciences, the National Center for Research Resources, and the National Center for Advancing Translational Sciences, National Institutes of Health, through grant UL1 TR000448 and TL1 TR000449. NMM, TJG, IPL, MD, and KC declare no support.

    ☆☆

    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.

    Conflicts of interest: All authors declare no conflicts of interest.

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