Clinical paperThe acute respiratory distress syndrome after out-of-hospital cardiac arrest: Incidence, risk factors, and outcomes
Introduction
Approximately 350,000 persons in the United States suffer out-of-hospital cardiac arrest (OHCA) each year.1 Many who survive the initial event will suffer from the post-cardiac arrest syndrome (PCAS), a highly inflammatory state characterized by reperfusion injury, oxidative stress, and multi organ dysfunction.2, 3, 4, 5, 6
The acute respiratory distress syndrome (ARDS) is defined, according to the Berlin definition, by hypoxemia and bilateral radiographic opacities not fully explained by volume overload, that occur acutely in relation to a clinical insult.7 Cardiac arrest is not listed among the traditional “clinical insults” known to cause ARDS.8 Possible mechanisms of ARDS development in patients with PCAS might include reperfusion injury, oxidative stress, pulmonary contusion from chest compressions, ventilator-induced lung injury, aspiration, and infection. Additionally, there is substantial overlap between the pathophysiology of ARDS and PCAS, including inflammation, leukocyte activation, activation of coagulation pathways, and altered permeability of alveolar endothelial and epithelial barriers.9, 10
The exact incidence of ARDS after OHCA is unknown. One study described an 5% incidence of post-arrest ARDS, while another study reported that 65% of patients had a ratio of the partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2:FIO2)≤ 300, implying a much higher incidence.11, 12 Because prior studies report widely variable incidences, we sought to describe the epidemiology of ARDS in a modern OHCA cohort using the contemporary Berlin definition.7 Further, while ARDS itself is associated with a mortality of up to 40% (depending on severity), the impact of ARDS after OHCA on overall outcome has not been described.13, 14 Our primary aim is to describe the incidence of ARDS in patients who have suffered OHCA. We also test the association between ARDS and survival and favorable neurologic outcome at hospital discharge.
Section snippets
Ethics approval and setting
The University of Washington Human Subjects Division approved this study (Study ID #49480). This study site was Seattle, Washington, a U.S. city with 725,000 residents and 83.9 square miles. The Seattle Fire Department’s emergency medical services system, Seattle Medic One, has been described previously.15
Harborview Medical Center (HMC) is a 413-bed public hospital and trauma center. University of Washington Medical Center (UWMC) is a 450-bed quaternary, University-affiliated hospital. HMC and
Statistical analysis
Baseline demographic characteristics, clinical variables, and outcomes were compared according to ARDS status using two-sample t-tests for means, Mann–Whitney tests for medians, and Chi-squared tests for categorical variables.
Using multivariable logistic regression, we fit models to evaluate the associations between ARDS and hospital mortality and ARDS neurologic outcome at hospital discharge. We adjusted the models for age, Charlson index (coded as binary with a cutoff of 2), and the presence
Sensitivity analyses
We performed a sensitivity analysis to elucidate the relative contribution of cardiac dysfunction to patients’ hypoxemic respiratory failure. We excluded patients with the following markers of cardiac dysfunction: (1) a mechanical circulatory support device (most likely to have the highest severity of heart failure), (2) left ventricular ejection fraction <40% within the first 48 h after ROSC, and (3) percutaneous coronary intervention within the first 24 h after ROSC. We also performed a
Patient characteristics and cardiac arrest care
A total of 978 OHCA patients were transported to the study hospitals from 2007 to 2014 (Fig. 1). Of these, 600 met eligibility criteria and were included. Mean age was 56 ± 16 years, 74% were male, and 69% were white (Table 1). Overall survival to hospital discharge was 60% (95% CI 55–64%), with 328 patients (55%, 95% CI 51–59%) surviving with complete neurologic recovery or mild impairment (CPC 1 or 2).
A total of 45% had an initial shockable cardiac arrest rhythm (ventricular fibrillation or
Discussion
We found that nearly half of OHCA patients surviving for at least 48 h following resuscitation develop ARDS, and that early ARDS is associated with poor outcome and increased healthcare resource utilization. The study results advance our growing understanding of an association between respiratory complications and outcome after cardiac arrest.11, 20, 21, 22, 23, 24 Early recognition of ARDS after OHCA may allow for prompt application of therapies known to improve outcome in ARDS such as low
Limitations
Previous studies in other disease states, such as subarachnoid hemorrhage, documented that longer ICU stay is associated with development of ARDS.47 To reduce the effect of competing risk of death from other causes and to avoid including patients who develop ARDS for reasons other than those directly related to the initial OHCA event, such as ventilator-associated pneumonia, we screened for ARDS within 48 h of admission. It is therefore possible that we underestimate the true incidence of ARDS
Conclusions
Nearly half of all out-of-hospital cardiac arrest survivors develop ARDS within 48 h of hospital admission. Early ARDS is associated with lower survival, worse neurologic outcome, and increased resource utilization in this population. OHCA should be considered among the traditional risk factors for ARDS. Future studies should prospectively evaluate whether specific mechanical ventilation strategies, such as low tidal volume ventilation and avoidance of hyperoxia, might reduce the incidence of
Funding sources/Disclosures
This study was funded by a research grant from the Medic One Foundation. NJ and CTH also receive funding from the National Institutes of Health (U01HL123008-02). The authors have no other disclosures.
Acknowledgements
NJ conceived the study, drafted manuscript, and takes primary responsibility. EC collected and analyzed data. MP, DC, DG, TR, and CLH all reviewed and edited the manuscript. The authors have no conflicts of interest. The study was funded by the Medic One Foundation.
References (50)
- et al.
Visceral, hematologic and bacteriologic changes and neurologic outcome after cardiac arrest in dogs. The visceral post-resuscitation syndrome
Resuscitation
(1993) - et al.
Coagulopathy after successful cardiopulmonary resuscitation following cardiac arrest: implication of the protein C anticoagulant pathway
J Am Coll Cardiol
(2005) - et al.
Survival and outcome prediction using the Apache III and the out-of-hospital cardiac arrest (OHCA) score in patients treated in the intensive care unit (ICU) following out-of-hospital, in-hospital or ICU cardiac arrest
Resuscitation
(2012) - et al.
The effect of hyperoxia following cardiac arrest — a systematic review and meta-analysis of animal trials
Resuscitation
(2012) - et al.
Hyperoxia, hypocapnia and hypercapnia as outcome factors after cardiac arrest in children
Resuscitation
(2012) - et al.
Effects of PaCO2 derangements on clinical outcomes after cerebral injury: a systematic review
Resuscitation
(2015) - et al.
Ventilator management and respiratory care after cardiac arrest: oxygenation, ventilation, infection, and injury
Chest
(2018) - et al.
Arterial carbon dioxide tension and outcome in patients admitted to the intensive care unit after cardiac arrest
Resuscitation
(2013) - et al.
Association between mean arterial blood gas tension and outcome in cardiac arrest patients treated with therapeutic hypothermia
Am J Emerg Med
(2014) - et al.
Initial arterial carbon dioxide tension is associated with neurological outcome after resuscitation from cardiac arrest
Resuscitation
(2017)
Association between early arterial blood gas tensions and neurological outcome in adult patients following in-hospital cardiac arrest
Resuscitation
A systematic review and meta-analysis of the association between arterial carbon dioxide tension and outcomes after cardiac arrest
Resuscitation
Echocardiographic left ventricular systolic dysfunction early after resuscitation from cardiac arrest does not predict mortality or vasopressor requirements
Resuscitation
The incidence and significance of emesis associated with out-of-hospital cardiac arrest
Resuscitation
The incidence and significance of bacteremia in out of hospital cardiac arrest
Resuscitation
Emergency percutaneous coronary intervention in post–cardiac arrest patients without st-segment elevation pattern
JACC Cardiovasc Interv
Strategies to improve survival from cardiac arrest: a report from the institute of medicine
JAMA
Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication. A consensus statement from the International Liaison Committee on Resuscitation (American Heart Association, Australian and New Zealand Council on Resuscitation
Circulation
Successful cardiopulmonary resuscitation after cardiac arrest as a “sepsis-like” syndrome
Circulation
Activation of blood coagulation after cardiac arrest is not balanced adequately by activation of endogenous fibrinolysis
Circulation
Acute respiratory distress syndrome: the Berlin definition
JAMA
The Berlin definition of ARDS: an expanded rationale, justification, and supplementary material
Intensive Care Med
Rosuvastatin for sepsis-associated acute respiratory distress syndrome
N Engl J Med
Post-cardiac arrest syndrome
Circulation
Exposure to high concentrations of inspired oxygen does not worsen lung injury after cardiac arrest
Crit Care
Cited by (45)
Acute Respiratory Failure in Severe Acute Brain Injury
2024, Critical Care Clinics